Small pulmonary nodules in baseline and incidence screening rounds of low-dose CT lung cancer screening

PubMed Central

Walter, Joan E.; Oudkerk, Matthijs

2017-01-01

Currently, lung cancer screening by low-dose computed tomography (LDCT) is widely recommended for high-risk individuals by US guidelines, but there still is an ongoing debate concerning respective recommendations for European countries. Nevertheless, the available data regarding pulmonary nodules released by lung cancer screening studies could improve future screening guidelines, as well as the clinical practice of incidentally detected pulmonary nodules on routine CT scans. Most lung cancer screening trials present results for baseline and incidence screening rounds separately, clustering pulmonary nodules initially found at baseline screening and newly detected pulmonary nodules after baseline screening together. This approach does not appreciate possible differences among pulmonary nodules detected at baseline and firstly detected at incidence screening rounds and is heavily influenced by methodological differences of the respective screening trials. This review intends to create a basis for assessing non-calcified pulmonary nodules detected during LDCT lung cancer screening in a more clinical relevant manner. The aim is to present data of non-calcified pulmonary baseline nodules and new non-calcified pulmonary incident nodules without clustering them together, thereby also simplifying translation to the clinical practice of incidentally detected pulmonary nodules. Small pulmonary nodules newly detected at incidence screening rounds of LDCT lung cancer screening may possess a greater lung cancer probability than pulmonary baseline nodules at a smaller size, which is essential for the development of new guidelines. PMID:28331823

Use of responder threshold criteria to evaluate the response to treatment in the phase III CHEST-1 study.

PubMed

D'Armini, Andrea M; Ghofrani, Hossein-Ardeschir; Kim, Nick H; Mayer, Eckhard; Morsolini, Marco; Pulido-Zamudio, Tomás; Simonneau, Gerald; Wilkins, Martin R; Curram, John; Davie, Neil; Hoeper, Marius M

2015-03-01

In the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase - Stimulator Trial 1 (CHEST-1) study, riociguat improved 6-minute walking distance (6MWD) vs placebo in patients with inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. In this study, the proportion of patients who achieved responder thresholds that correlate with improved outcome in patients with pulmonary arterial hypertension was determined at baseline and at the end of CHEST-1. Patients received placebo or riociguat individually adjusted up to 2.5 mg 3 times a day for 16 weeks. Response criteria were defined as follows: 6MWD increase ≥40 m, 6MWD ≥380 m, cardiac index ≥2.5 liters/min/m(2), pulmonary vascular resistance <500 dyn∙sec∙cm(-5), mixed venous oxygen saturation ≥65%, World Health Organization functional class I/II, N-terminal pro-brain natriuretic peptide <1,800 pg/ml, and right atrial pressure <8 mm Hg. Riociguat increased the proportion of patients with 6MWD ≥380 m, World Health Organization functional class I/II, and pulmonary vascular resistance <500 dyn∙sec∙cm(-5) from 37%, 34%, and 25% at baseline to 58%, 57%, and 50% at Week 16, whereas there was little change in placebo-treated patients (6MWD ≥380 m, 43% vs 44%; World Health Organization functional class I/II, 29% vs 38%; pulmonary vascular resistance <500 dyn∙sec∙cm(-5), 27% vs 26%). Similar changes were observed for thresholds for cardiac index, mixed venous oxygen saturation, N-terminal pro-brain natriuretic peptide, and right atrial pressure. In this exploratory analysis, riociguat increased the proportion of patients with inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy achieving criteria defining a positive response to therapy. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Cardiopulmonary function after pulmonary contusion and partial liquid ventilation.

PubMed

Moomey, C B; Fabian, T C; Croce, M A; Melton, S M; Proctor, K G

1998-08-01

To compare the effects of mechanical ventilation with either positive end-expiratory pressure (PEEP) or partial liquid ventilation (PLV) on cardiopulmonary function after severe pulmonary contusion. Mongrel pigs (32 +/- 1 kg) were anesthetized, paralyzed, and mechanically ventilated (8-10 mL/kg tidal volume; 12 breaths/min; FiO2 = 0.5). Systemic hemodynamics and pulmonary function were measured for 7 hours after a captive bolt gun delivered a blunt injury to the right chest. After 5 hours, FiO2 was increased to 1.0 and either PEEP (n = 7) in titrated increments to 25 cm H2O or PLV with perflubron (LiquiVent, 30 mL/kg, endotracheal) and no PEEP (n = 7) was administered for 2 hours. Two control groups received injury without treatment (n = 6) or no injury with PLV (n = 3). Fluids were liberalized with PEEP versus PLV (27 +/- 3 vs. 18 +/- 2 mL.kg-1.h-1) to maintain cardiac filling pressures. Before treatment at 5 hours after injury, physiologic dead space fraction (30 +/- 4%), pulmonary vascular resistance (224 +/- 20% of baseline), and airway resistance (437 +/- 110% of baseline) were all increased (p < 0.05). In addition, PaO2/FiO2 had decreased to 112 +/- 18 mm Hg, compliance was depressed to 11 +/- 1 mL/cm H2O (36 +/- 3% of baseline), and shunt fraction was increased to 22 +/- 4% (all p < 0.05). Blood pressure and cardiac index remained stable relative to baseline, but stroke index and systemic oxygen delivery were depressed by 15 to 30% (both p < 0.05). After 2 hours of treatment with PEEP versus PLV, PO2/FiO2 was higher (427 +/- 20 vs. 263 +/- 37) and dead space ventilation was lower (4 +/- 3 vs. 28 +/- 7%) (both p < 0.05), whereas compliance tended to be higher (26 +/- 2 vs. 20 +/- 2) and shunt fraction tended to be lower (0 +/- 0 vs. 7 +/- 4). With PEEP versus PLV, however, cardiac index, stroke index, and systemic oxygen delivery were 30 to 60% lower (all p < 0.05). Furthermore, although contused lungs showed similar damage with either treatment, the secondary injury in the contralateral lung (as manifested by intra-alveolar hemorrhage) was more severe with PEEP than with PLV. Both PEEP and PLV improved pulmonary function after severe unilateral pulmonary contusion, but negative hemodynamic and histologic changes were associated with PEEP and not with PLV. These data suggest that PLV is a promising novel ventilatory strategy for unilateral pulmonary contusion that might ameliorate secondary injury in the contralateral uninjured lung.

Treatment of idiopathic pulmonary fibrosis with losartan: a pilot project.

PubMed

Couluris, Marisa; Kinder, Brent W; Xu, Ping; Gross-King, Margaret; Krischer, Jeffrey; Panos, Ralph J

2012-10-01

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease with no current effective therapies. Treatment has focused on antifibrotic agents to stop proliferation of fibroblasts and collagen deposition in the lung. We present the first clinical trial data on the use of losartan, an antifibrotic agent, to treat idiopathic pulmonary fibrosis. The primary objective was to evaluate the effect of losartan on progression of idiopathic pulmonary fibrosis measured by the change in percentage of predicted forced vital capacity (%FVC) after 12 months. Secondary outcomes included the change in forced expiratory volume at 1 second, diffusing capacity of carbon monoxide, 6-minute walk test distance, and baseline/transition dyspnea index. Patients with idiopathic pulmonary fibrosis and a baseline %FVC of ≥50 % were treated with losartan 50 mg by mouth daily for 12 months. Pulmonary function testing, 6-minute walk, and breathlessness indices were measured every 3 months. Twenty participants with idiopathic pulmonary fibrosis were enrolled and 17 patients were evaluable for response. Twelve patients had a stable or improved %FVC at study month 12. Similar findings were observed in secondary end-point measures, including 58, 71, and 65 % of patients with stable or improved forced expiratory volume at 1 second, diffusing capacity for carbon monoxide, and 6-minute walk test distance, respectively. No treatment-related adverse events that resulted in early study discontinuation were reported. Losartan stabilized lung function in patients with idiopathic pulmonary fibrosis over 12 months. Losartan is a promising agent for the treatment of idiopathic pulmonary fibrosis and has a low toxicity profile.

Benefits from the correction of vitamin D deficiency in patients with pulmonary hypertension.

PubMed

Mirdamadi, Ahmad; Moshkdar, Pouya

2016-01-01

Vitamin D (Vit D) is linked to various conditions including musculoskeletal, metabolic and cardiopulmonary diseases. However, it is not clear whether correction of vit D deficiency exerts any beneficial effect in patients with pulmonary hypertension. This study was a prospective uncontrolled longitudinal study. Patients with pulmonary hypertension and vit D deficiency were enrolled into this study. All patients in addition to standard treatment for pulmonary hypertension received cholecalciferol at a dose of 50,000 IU weekly plus calcicare (at a dose of 200 mg magnesium + 8 mg zinc + 400 IU vit D) daily for 3 months. Serum level of 25-hydroxy vit D, serum level of pro-brain natriuretic peptide, six minute walk test (6MWT), peak and mean pulmonary artery pressure, right ventricular size and function, ejection fraction (EF) and New York Heart Association (NYHA) functional class were measured at baseline and after 3 months of treatment. Twenty-two patients with pulmonary hypertension and vit D deficiency were enrolled into the study. At endpoint, the serum vit D level increased significantly to 54.8 ng/ml, the mean of baseline distance of 6MWT increased significantly to 81.6 m and the RV size significantly improved. The mean pulmonary artery pressure also improved after the intervention, but their changes did not reach to statistically significant levels. Vit D replacement therapy in patients with pulmonary arterial hypertension and vit D deficiency results in significant improvement of right ventricular size and 6 MWT. Moreover, mean pulmonary artery pressure improves nonsignificantly. This issue requires further studies with long-term follow-up period.

[Analysis of factors related to pulmonary hypertensive crisis in patients with idiopathic pulmonary arterial hypertension].

PubMed

Zhang, Chen; Li, Qiangqiang; Zhu, Yan; Gu, Hong

2014-06-10

To explore the risk and protective factors for pulmonary hypertensive crisis (PHC) in patients with idiopathic pulmonary arterial hypertension (IPAH). A retrospective study was performed for 65 patients with a diagnosis of IPAH between January 2010 and December 2013. According to clinical manifestations, they were divided into two groups of susceptibility and non-susceptibility to PHC. Clinical and hemodynamic parameters were analyzed in univariate and multivariate manners. Among them, there were 32 males and 33 females with a mean age of (14.4 ± 12.3) (10/12-47.3) years. Twenty-three patients had typical manifestations of PHC and 18 of them were induced by exercises.Univariate analysis revealed that the proportion of patients with World Health Organization (WHO) functional class III-IV in PHC-susceptible group was significantly higher than PHC-nonsusceptible group (60.9% vs 23.8%, P = 0.003) while the percentage of patent foramen ovale in PHC-susceptible group was significantly lower than PHC-nonsusceptible group (8.7% vs 45.2%, P = 0.003).In patients with WHO functional classI-II, hemodynamic variables including the decline of pulmonary arterial pressure and positive rate in vasoreactivity testing in PHC-susceptible group were significantly higher than PHC-nonsusceptible group.In patients with WHO functional class III-IV, baseline pulmonary arterial pressure and mean right atrial pressure in PHC-susceptible group were significantly higher than those in PHC-nonsusceptible group. Multivariate Logistic regression analysis revealed that, for those with WHO functional class III-IV (OR = 23.45, 95%CI: 2.85-193.09) and the decline of systolic pulmonary arterial pressure in vasoreactivity testing (OR = 1.12, 95%CI: 1.04-1.22) were independent risk factors for PHC in IPAH patients while patent foramen ovale (OR = 0.01, 95%CI: 0.00-0.52) was a protective factor. PHC in IPAH patients is correlated with WHO functional class, pulmonary vascular reactivity, baseline pulmonary arterial pressure and patent foramen ovale. And exercise is the most common stimulus to PHC.

Ginseng improves pulmonary functions and exercise capacity in patients with COPD.

PubMed

Gross, D; Shenkman, Z; Bleiberg, B; Dayan, M; Gittelson, M; Efrat, R

2002-01-01

Ginseng is a root that has been used to treat patients with various illnesses for the last 2000 years. The purpose of this study was to evaluate the effects of Ginseng extract (G115) on Pulmonary Function Tests (PFTs), Maximum Voluntary Ventilation (MVV), Maximum Inspiratory Pressure (MIP) and Maximal Oxygen Consumption (VO2max) in patients with moderately-severe Chronic Obstructive Pulmonary Disease (COPD). Ninety-two adults were randomly divided into the experimental (n = 49, G115 100 mg bid for three months) and placebo-control (n = 43) groups. PFTs, MVV and MIP were studied before treatment and every two weeks for the 3-month-study period. Exercise test and VO2max measurements were performed before the beginning and after six weeks and three months. P lower than 0.05 was considered significant. Baseline demographics and pulmonary parameters were similar between the groups. In the experimental, but not in the control group, all parameters significantly increased above baseline and compared with the placebo group. Maximum increase, compared with baseline was FVC-32.5%, FEV1.0-27.0%, PEF-27.5%, FEF50-45.4%, FEF75-56.9%, MVV-40.4%, MIP-47.0% and VO2max-37.5%. No side effects were observed. G115 100 mg bid for three months, but not placebo, improved PFTs, MVV, MIP and VO2 max in patients with moderately-severe COPD with no side effects.

Association between marijuana exposure and pulmonary function over 20 years.

PubMed

Pletcher, Mark J; Vittinghoff, Eric; Kalhan, Ravi; Richman, Joshua; Safford, Monika; Sidney, Stephen; Lin, Feng; Kertesz, Stefan

2012-01-11

Marijuana smoke contains many of the same constituents as tobacco smoke, but whether it has similar adverse effects on pulmonary function is unclear. To analyze associations between marijuana (both current and lifetime exposure) and pulmonary function. The Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal study collecting repeated measurements of pulmonary function and smoking over 20 years (March 26, 1985-August 19, 2006) in a cohort of 5115 men and women in 4 US cities. Mixed linear modeling was used to account for individual age-based trajectories of pulmonary function and other covariates including tobacco use, which was analyzed in parallel as a positive control. Lifetime exposure to marijuana joints was expressed in joint-years, with 1 joint-year of exposure equivalent to smoking 365 joints or filled pipe bowls. Forced expiratory volume in the first second of expiration (FEV(1)) and forced vital capacity (FVC). Marijuana exposure was nearly as common as tobacco exposure but was mostly light (median, 2-3 episodes per month). Tobacco exposure, both current and lifetime, was linearly associated with lower FEV(1) and FVC. In contrast, the association between marijuana exposure and pulmonary function was nonlinear (P < .001): at low levels of exposure, FEV(1) increased by 13 mL/joint-year (95% CI, 6.4 to 20; P < .001) and FVC by 20 mL/joint-year (95% CI, 12 to 27; P < .001), but at higher levels of exposure, these associations leveled or even reversed. The slope for FEV(1) was -2.2 mL/joint-year (95% CI, -4.6 to 0.3; P = .08) at more than 10 joint-years and -3.2 mL per marijuana smoking episode/mo (95% CI, -5.8 to -0.6; P = .02) at more than 20 episodes/mo. With very heavy marijuana use, the net association with FEV(1) was not significantly different from baseline, and the net association with FVC remained significantly greater than baseline (eg, at 20 joint-years, 76 mL [95% CI, 34 to 117]; P < .001). Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.

Pulmonary function and the risk of functional limitation in chronic obstructive pulmonary disease.

PubMed

Eisner, Mark D; Iribarren, Carlos; Yelin, Edward H; Sidney, Stephen; Katz, Patricia P; Ackerson, Lynn; Lathon, Phenius; Tolstykh, Irina; Omachi, Theodore; Byl, Nancy; Blanc, Paul D

2008-05-01

The authors' objective was to analyze the impact of respiratory impairment on the risk of physical functional limitations among adults with chronic obstructive pulmonary disease (COPD). They hypothesized that greater pulmonary function decrement would result in a broad array of physical functional limitations involving organ systems remote from the lung, a key step in the pathway leading to overall disability. The authors used baseline data from the Function, Living, Outcomes, and Work (FLOW) study, a prospective cohort study of adults with COPD recruited from northern California in 2005-2007. They studied the impact of pulmonary function impairment on the risk of functional limitations using validated measures: lower extremity function (Short Physical Performance Battery), submaximal exercise performance (6-Minute Walk Test), standing balance (Functional Reach Test), skeletal muscle strength (manual muscle testing with dynamometry), and self-reported functional limitation (standardized item battery). Multiple variable analysis was used to control for confounding by age, sex, race, height, educational attainment, and cigarette smoking. Greater pulmonary function impairment, as evidenced by lower forced expiratory volume in 1 second (FEV(1)), was associated with poorer Short Physical Performance Battery scores and less distance walked during the 6-Minute Walk Test. Lower forced expiratory volume in 1 second was also associated with weaker muscle strength and with a greater risk of self-reported functional limitation (p < 0.05). In conclusion, pulmonary function impairment is associated with multiple manifestations of physical functional limitation among COPD patients. Longitudinal follow-up can delineate the impact of these functional limitations on the prospective risk of disability, guiding preventive strategies that could attenuate the disablement process.

Effects of extended pleurectomy and decortication on quality of life and pulmonary function in patients with malignant pleural mesothelioma.

PubMed

Burkholder, David; Hadi, Duraid; Kunnavakkam, Rangesh; Kindler, Hedy; Todd, Kristy; Celauro, Amy Durkin; Vigneswaran, Wickii T

2015-05-01

Maximal cytoreductive surgeries--extrapleural pneumonectomy and extended pleurectomy and decortication (EPD)--are effective surgical treatments in selected patients with malignant pleural mesothelioma. Extended pleurectomy and decortication results in equivalent survival yet better health-related quality of life (HRQoL). Patients with malignant pleural mesothelioma were studied for the effects of EPD on HRQoL and pulmonary function. The European Organization for Research and Treatment of Cancer Core Quality of Life Questionaire-C30 was used to evaluate HRQoL before operation, and at 4 to 5 and 7 to 8 months postoperatively. Pulmonary function tests were measured immediately before and 5 to 7 months after the operation. Patients were compared according to World Health Organization baseline performance status (PS). Of the 36 patients enrolled, 17 were PS 0 and 19 were PS 1 or PS 2 at baseline. Patients in groups PS 1 and PS 2 had significantly worse global health, functional, and symptoms scores. After EPD, PS 0 patients had no change in global health or function and symptoms scores except for emotional function, whereas PS 1 or PS 2 patients showed improvements at 4 to 5 months with further improvements at 7 to 8 months. The PS 0 patients demonstrated a significant decrease in forced vital capacity (p = 0.001), forced expiratory volume in 1 second (p = 0.002), total lung capacity (p = 0.0006) and diffusing capacity of the lung for carbon monoxide (p = 0.003) after EPD, whereas no change was observed in PS 1 and PS 2 patients. Extended pleurectomy and decortication did not improve overall HRQoL and had a negative impact in pulmonary function in minimally symptomatic patients. In symptomatic patients, a significant improvement in HRQoL was observed after EPD, which continued at late follow-up, although the pulmonary function was not affected. As changes in HRQoL are multidimensional, the preservation of the pulmonary function may have contributed to the net benefit observed in PS 1 and PS 2 patients. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of Exercise on Pulmonary Function Tests in Obese Malaysian Patients.

PubMed

Christopher, L K S; Kosai, N R; Reynu, R; Levin, K B; Taher, M M; Sutton, P A; Sukor, N; Das, S

2015-01-01

Obesity has taken the 21st century by storm, posing negative effects on of the various facades of health, healthcare and global economy. With regards to pulmonary performance, numerous studies have proven the detrimental effects of obesity while reinstating the positive effects of weight loss on overall pulmonary function. However, effects of exercise on pulmonary function and correlation between changes in pulmonary function test with weight loss have yet to be described. We performed a prospective interventional study to determine the effects of regular exercise on Pulmonary Function Tests (PFT) and ascertain the relationship between weight loss and change in PFT in obese patients. Twenty-five obese patients were enrolled, giving an 80% power of study. Baseline weight and PFT consisting of FEV1, FVC, TLC, mean ERV and VC were recorded prior to commencement of the 8 week long Standard Exercise Regimen (SER). PFT and weight were recorded again at the end of 8 weeks. All parameters of the PFT studied improved significantly with exercise. The participants lost an average of 1kg of body weight post-exercise (p<0.0005). The correlations between mean changes in weight and PFT were negligible. A period of supervised regular exercise improves the pulmonary function of obese patients and this improvement is independent of the amount of weight loss. Hence, SER should be recommended to all obese patients, especially when bariatric surgery is desired.

Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

PubMed

Stone, Ian S; Barnes, Neil C; James, Wai-Yee; Midwinter, Dawn; Boubertakh, Redha; Follows, Richard; John, Leonette; Petersen, Steffen E

2016-04-01

Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting β2-agonist fluticasone furoate/vilanterol 100/25 μg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).

β-Liddle mutation of the epithelial sodium channel increases alveolar fluid clearance and reduces the severity of hydrostatic pulmonary oedema in mice

PubMed Central

Randrianarison, Nadia; Escoubet, Brigitte; Ferreira, Chrystophe; Fontayne, Alexandre; Fowler-Jaeger, Nicole; Clerici, Christine; Hummler, Edith; Rossier, Bernard C; Planès, Carole

2007-01-01

Transepithelial sodium transport via alveolar epithelial Na+ channels and Na+,K+-ATPase constitutes the driving force for removal of alveolar oedema fluid. Decreased activity of the amiloride-sensitive epithelial Na+ channel (ENaC) in the apical membrane of alveolar epithelial cells impairs sodium-driven alveolar fluid clearance (AFC) and predisposes to pulmonary oedema. We hypothesized that hyperactivity of ENaC in the distal lung could improve AFC and facilitate the resolution of pulmonary oedema. AFC and lung fluid balance were studied at baseline and under conditions of hydrostatic pulmonary oedema in the β-Liddle (L) mouse strain harbouring a gain-of-function mutation (R566stop) within the Scnn1b gene. As compared with wild-type (+/+), baseline AFC was increased by 2- and 3-fold in heterozygous (+/L) and homozygous mutated (L/L) mice, respectively, mainly due to increased amiloride-sensitive AFC. The β2-agonist terbutaline stimulated AFC in +/+ and +/L mice, but not in L/L mice. Acute volume overload induced by saline infusion (40% of body weight over 2 h) significantly increased extravascular (i.e. interstitial and alveolar) lung water as assessed by the bloodless wet-to-dry lung weight ratio in +/+ and L/L mice, as compared with baseline. However, the increase was significantly larger in +/+ than in L/L groups (P= 0.01). Volume overload also increased the volume of the alveolar epithelial lining fluid in +/+ mice, indicating the presence of alveolar oedema, but not in L/L mice. Cardiac function as evaluated by echocardiography was comparable in both groups. These data show that constitutive ENaC activation improved sodium-driven AFC in the mouse lung, and attenuated the severity of hydrostatic pulmonary oedema. PMID:17430990

Longitudinal analysis of pulmonary dysfunction in the initial years of employment in the grain industry.

PubMed

Olfert, S M; Pahwa, P; Dosman, J A

2005-11-01

The negative health effects of exposure to grain dust have previously been examined, but few studies have observed the effects on newly hired employees. Young grain workers are of interest because changes in pulmonary function may occur after a short duration of employment, and because older grain workers may represent a survivor population. The New Grain Workers Study (NGWS), a longitudinal study of 299 newly hired male grain industry workers, was conducted between 1980 and 1985. The objectives were to determine the effects of employment in the grain industry on pulmonary function. Pre-employment physical examinations and pulmonary function tests were conducted on subjects at the Division of Respiratory Medicine, Department of Medicine, Royal University Hospital, University of Saskatchewan. The Grain Dust Medical Surveillance Program (GDMSP) was a Labour Canada program that began in 1978. All subjects were grain workers employed in the grain industry in Saskatchewan. All subjects completed a respiratory symptoms questionnaire and underwent pulmonary function testing. Baseline observations were recorded every three years between 1978 and 1993. Data were available on 2184 grain workers. Generalized estimating equations were used to fit marginal and transitional multivariable regression models to determine the effects of grain dust exposure on pulmonary function. Marginal and transitional models were then compared. Height, exposure weeks, and previous FVC were predictive of FVC in the NGWS, while exposure weeks and previous FEV1 were predictive of FEV1. These models, as well as a transitional regression model built using the GDMSP data, were used to compute predicted mean annual decline inpulmonary function. Non-smoking grain workers in the NGWS had the highest pulmonary function test values, but also had the greatest predicted annual decline in pulmonary function. Ever-smoking grain workers in the GDMSP had the lowest pulmonary function test values. Non-smoking grain workers in the GDMSP had the least predicted annual decline in pulmonary function.

Advantage of impulse oscillometry over spirometry to diagnose chronic obstructive pulmonary disease and monitor pulmonary responses to bronchodilators: An observational study.

PubMed

Saadeh, Constantine; Saadeh, Charles; Cross, Blake; Gaylor, Michael; Griffith, Melissa

2015-01-01

This retrospective study was a comparative analysis of sensitivity of impulse oscillometry and spirometry techniques for use in a mixed chronic obstructive pulmonary disease group for assessing disease severity and inhalation therapy. A total of 30 patients with mild-to-moderate chronic obstructive pulmonary disease were monitored by impulse oscillometry, followed by spirometry. Lung function was measured at baseline after bronchodilation and at follow-up (3-18 months). The impulse oscillometry parameters were resistance in the small and large airways at 5 Hz (R5), resistance in the large airways at 15 Hz (R15), and lung reactance (area under the curve X; AX). After the bronchodilator therapy, forced expiratory volume in 1 second (FEV1) readings evaluated by spirometry were unaffected at baseline and at follow-up, while impulse oscillometry detected an immediate improvement in lung function, in terms of AX (p = 0.043). All impulse oscillometry parameters significantly improved at follow-up, with a decrease in AX by 37% (p = 0.0008), R5 by 20% (p = 0.0011), and R15 by 12% (p = 0.0097). Impulse oscillometry parameters demonstrated greater sensitivity compared with spirometry for monitoring reversibility of airway obstruction and the effect of maintenance therapy. Impulse oscillometry may facilitate early treatment dose optimization and personalized medicine for chronic obstructive pulmonary disease patients.

Prognostic value of exercise pulmonary haemodynamics in pulmonary arterial hypertension.

PubMed

Chaouat, Ari; Sitbon, Olivier; Mercy, Magalie; Ponçot-Mongars, Raphaëlle; Provencher, Steeve; Guillaumot, Anne; Gomez, Emmanuel; Selton-Suty, Christine; Malvestio, Pascale; Regent, Denis; Paris, Christophe; Hervé, Philippe; Chabot, François

2014-09-01

The aim of the study was to investigate the prognostic value of right heart catheterisation variables measured during exercise. 55 incident patients with idiopathic, familial or anorexigen-associated pulmonary arterial hypertension (PAH) underwent right heart catheterisation at rest and during exercise and 6-min walk testing before PAH treatment initiation. Patients were treated according to recommendations within the next 2 weeks. Right heart catheterisation was repeated 3-5 months into the PAH treatment in 20 patients. Exercise cardiac index decreased gradually as New York Heart Association (NYHA) functional class increased whereas cardiac index at rest was not significantly different across NYHA groups. Baseline 6-min walk distance correlated significantly with exercise and change in cardiac index from rest to exercise (r=0.414 and r=0.481, respectively; p<0.01). Change in 6-min walk distance from baseline to 3-5 months under PAH treatment was highly correlated with change in exercise cardiac index (r=0.746, p<0.001). The most significant baseline covariates associated with survival were change in systolic pulmonary artery pressure from rest to exercise and exercise cardiac index (hazard ratio 0.56 (95% CI 0.37-0.86) and 0.14 (95% CI 0.05-0.43), respectively). Change in pulmonary haemodynamics during exercise is an important tool for assessing disease severity and may help devise optimal treat-to-target strategies. ©ERS 2014.

Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: the early intervention in cystic fibrosis exacerbation (eICE) trial.

PubMed

Lechtzin, N; West, N; Allgood, S; Wilhelm, E; Khan, U; Mayer-Hamblett, N; Aitken, M L; Ramsey, B W; Boyle, M P; Mogayzel, P J; Goss, C H

2013-11-01

Acute pulmonary exacerbations are central events in the lives of individuals with cystic fibrosis (CF). Pulmonary exacerbations lead to impaired lung function, worse quality of life, and shorter survival. We hypothesized that aggressive early treatment of acute pulmonary exacerbation may improve clinical outcomes. Describe the rationale of an ongoing trial designed to determine the efficacy of home monitoring of both lung function measurements and symptoms for early detection and subsequent early treatment of acute CF pulmonary exacerbations. A randomized, non-blinded, multi-center trial in 320 individuals with CF aged 14 years and older. The study compares usual care to a twice a week assessment of home spirometry and CF respiratory symptoms using an electronic device with data transmission to the research personnel to identify and trigger early treatment of CF pulmonary exacerbation. Participants will be enrolled in the study for 12 months. The primary endpoint is change in FEV1 (L) from baseline to 12 months determined by a linear mixed effects model incorporating all quarterly FEV1 measurements. Secondary endpoints include time to first acute protocol-defined pulmonary exacerbation, number of acute pulmonary exacerbations, number of hospitalization days for acute pulmonary exacerbation, time from the end of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation, change in health related quality of life, change in treatment burden, change in CF respiratory symptoms, and adherence to the study protocol. This study is a first step in establishing alternative approaches to the care of CF pulmonary exacerbations. We hypothesize that early treatment of pulmonary exacerbations has the potential to slow lung function decline, reduce respiratory symptoms and improve the quality of life for individuals with CF. © 2013.

Effects of pharmacologic treatment based on airflow limitation and breathlessness on daily physical activity in patients with chronic obstructive pulmonary disease.

PubMed

Minakata, Yoshiaki; Morishita, Yukiko; Ichikawa, Tomohiro; Akamatsu, Keiichiro; Hirano, Tsunahiko; Nakanishi, Masanori; Matsunaga, Kazuto; Ichinose, Masakazu

2015-01-01

Improvement in the daily physical activity (PA) is important for the management of chronic obstructive pulmonary disease (COPD). However, the effects of pharmacologic treatment on PA are not well understood. We evaluated the effects of additional medications, including bronchodilator with or without inhaled corticosteroid, based on airflow limitation and breathlessness on the PA in COPD patients and the factors that could predict or affect the improvement in PA. A prospective non-randomized observational study was employed. Twenty-one COPD subjects without any other diseases that might reduce PA were recruited. The PA was measured with a triaxial accelerometer for 2 weeks, and pulmonary function tests and incremental shuttle walking tests were administered before and after 4-week treatment with an additional medication. Bronchodilation was obtained by additional medication. The mean values of PA evaluated by metabolic equivalents (METs) at ≥3.0 METs and the duration of PA at ≥3.0 METs and ≥3.5 METs were improved by medication. The % change in the duration of PA at ≥3.5 METs was significantly correlated with the baseline functional residual capacity (FRC), residual volume, and inspiratory capacity/total lung capacity. However, the % change in the duration of PA at any intensity was not correlated with the % changes of any values of the pulmonary function tests or incremental shuttle walking test except the PA at ≥2.5 METs with FRC. Medication could improve the PA in patients with COPD, especially at a relatively high intensity of activity when medication was administered based on airflow limitation and breathlessness. The improvement was seen in the patients with better baseline lung volume, but was not correlated with the improvements in the pulmonary function tests or exercise capacity.

The effect of ivabradine on functional capacity in patients with chronic obstructive pulmonary disease.

PubMed

Mahmoud, Kareem; Kassem, Hussien Heshmat; Baligh, Essam; ElGameel, Usama; Akl, Yosri; Kandil, Hossam

2016-10-01

Increased sympathetic tone and use of bronchodilators increase heart rate and this may worsen functional capacity in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to look at the short-term effect of the heart rate lowering drug ivabradine on clinical status in COPD patients.We randomised 80 COPD patients with sinus heart rate ≥90 bpm into either taking ivabradine 7.5 mg twice per day or placebo for two weeks. We assessed all patients using the modified Borg scale and 6-minute walk test at baseline and then again 2 weeks after randomisation.There were no significant differences in age, sex, severity of airway obstruction (measured using forceful exhalation), severity of diastolic dysfunction or pulmonary artery systolic pressure between the two groups. The ivabradine group showed significant improvement in 6-minute walk distance (from 192.6±108.8 m at baseline to 285.1±88.9 m at the end of the study) compared with the control group (230.6±68.4 at baseline and 250.4±65.8 m at the end of study) (p<0.001). This improvement in the drug group was associated with significant improvement of dyspnea on modified Borg scale (p=0.007).Lowering heart rate with ivabradine can improve exercise capacity and functional class in COPD patients with resting heart rate >90 bpm. © Royal College of Physicians 2016. All rights reserved.

The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function

PubMed Central

Obad, Ante; Palada, Ivan; Valic, Zoran; Ivančev, Vladimir; Baković, Darija; Wisløff, Ulrik; Brubakk, Alf O; Dujić, Željko

2007-01-01

Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (∼2–3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24–48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects. PMID:17110413

The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function.

PubMed

Obad, Ante; Palada, Ivan; Valic, Zoran; Ivancev, Vladimir; Baković, Darija; Wisløff, Ulrik; Brubakk, Alf O; Dujić, Zeljko

2007-02-01

Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (approximately 2-3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24-48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects.

Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle

PubMed Central

Hartman, William; Helan, Martin; Smelter, Dan; Sathish, Venkatachalem; Thompson, Michael; Pabelick, Christina M.; Johnson, Bruce; Prakash, Y. S.

2015-01-01

Background Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF), can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxia-enhanced BDNF expression and signaling in human pulmonary artery smooth muscle cells (PASMCs). Methods and Results 48h of 1% hypoxia enhanced BDNF and TrkB expression, as well as release of BDNF. In arteries of patients with pulmonary hypertension, BDNF expression and release was higher at baseline. In isolated PASMCs, hypoxia-induced BDNF increased intracellular Ca2+ responses to serotonin: an effect altered by HIF1α inhibition or by neutralization of extracellular BDNF via chimeric TrkB-Fc. Enhanced BDNF/TrkB signaling increased PASMC survival and proliferation, and decreased apoptosis following hypoxia. Conclusions Enhanced expression and signaling of the BDNF-TrkB system in PASMCs is a potential mechanism by which hypoxia can promote changes in pulmonary artery structure and function. Accordingly, the BDNF-TrkB system could be a key player in the pathogenesis of hypoxia-induced pulmonary vascular diseases, and thus a potential target for therapy. PMID:26192455

Clinical characteristics of obesity-hypoventilation syndrome in Japan: a multi-center study.

PubMed

Akashiba, Tsuneto; Akahoshi, Toshiki; Kawahara, Seiji; Uematsu, Akihito; Katsura, Kazuhito; Sakurai, Shigeru; Murata, Akira; Sakakibara, Hiroki; Chin, Kazuo; Hida, Wataru; Nakamura, Hiroshi

2006-01-01

To clarify the prevalence and clinical characteristics of obesity-hypoventilation syndrome (OHS) in a large number of patients with moderate to severe obstructive sleep apnea syndrome (OSAS). Subjects comprised 611 patients with OSAS registered from 7 sleep centers and clinics and analyzed according to the definitions of the Respiratory Failure Research Group of the Japanese Ministry of Health and Welfare. Baseline characteristics, polysomnographic data during sleep, laboratory blood examinations, excessive daytime sleepiness, pulmonary functions, and arterial blood gases were compared between OHS and non-OHS patients. Determinants of daytime hypercapnia were also examined in OHS patients. OHS was identified in 55 of the 611 patients with OSAS (9%). OHS patients were younger, heavier, and more somnolent than non-OHS patients and displayed more severe OSAS, liver dysfunctions, higher total cholesterol, and impaired pulmonary function. However, these differences were resolved except for pulmonary function after correction for obesity. Daytime hypercapnia was associated with impaired pulmonary function. Percent vital capacity (%VC) was most closely correlated with PaCO2 in OHS. OHS patients display numerous abnormalities due to obesity compared with non-OHS patients. Impaired pulmonary function, particularly %VC, may play an important role in the development of daytime hypercapnia independent of obesity in OHS patients.

Use of milrinone to treat cardiac dysfunction in infants with pulmonary hypertension secondary to congenital diaphragmatic hernia: a review of six patients.

PubMed

Patel, Neil

2012-01-01

Pulmonary hypertension and secondary cardiac dysfunction are important contributors of morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). Milrinone, a phosphodiesterase-3 inhibitor, may be useful in this setting for its combined actions as a pulmonary vasodilator and to improve systolic and diastolic function. This study aimed to assess the effects of milrinone on cardiac function and pulmonary artery pressure in infants with CDH. A retrospective review of echocardiograms performed on infants with CDH who received milrinone was performed. Tissue Doppler imaging velocities were used to assess systolic and diastolic function. Pulmonary artery pressure was assessed from the pattern and velocity of ductal shunting. Six infants with CDH and severe pulmonary hypertension were identified. Systolic and diastolic myocardial velocities were reduced in the right ventricle (RV) and interventricular septum (IVS) at baseline. In the 72 h after commencement of milrinone, there was a significant increase in early diastolic myocardial velocities in the RV, accompanied by increasing systolic velocities in the RV and IVS. Oxygenation index was significantly reduced, blood pressure unchanged, and ductal shunt velocity minimally altered over the same time period. Milrinone use was associated with an improvement in systolic and diastolic function in the RV, corresponding to an improvement in clinical status. Copyright © 2012 S. Karger AG, Basel.

Pulmonary involvement in long-term mixed connective tissue disease: functional trends and image findings after 10 years.

PubMed

Kawano-Dourado, Leticia; Baldi, Bruno G; Kay, Fernando U; Dias, Olivia M; Gripp, Thais E H; Gomes, Paula S; Fuller, Ricardo; Caleiro, Maria T C; Kairalla, Ronaldo A; Carvalho, Carlos R R

2015-01-01

Interstitial lung disease (ILD) is highly prevalent in patients with mixed connective tissue disease (MCTD). However, little is known about the long-term progression of ILD in MCTD. The aims of this study were to describe pulmonary function test (PFT) and high-resolution computed tomography (HRCT) results in long-term MCTD patients, to measure changes in PFT and HRCT results over a 10-year period, and to ascertain correlations in functional and imaging data. In this retrospective cohort study, comparison between baseline and follow-up PFT and HRCT data was performed for 39 unselected consecutive MCTD patients. At baseline, 51% of the patients had abnormal PFTs. Forced vital capacity (FVC) was slightly reduced at baseline (77% of predicted), but remained stable after 10 years. A relative decrease of 15% in the diffusion capacity for carbon monoxide (DLCO) was detected (from 84% to 71% of predicted, p<0.001). The median lower lobes ILD-HRCT score progressed from 7.5% at baseline to 11.2% at follow-up (p=0.02), and findings of traction bronchiolectasis and honeycombing increased (p<0.05). A moderate negative correlation was observed between functional parameters and quantification of image findings. Functional and radiologic alterations suggestive of ILD in long-term MCTD patients are prevalent, mild, and progressed slightly over time. The most sensitive parameters for detecting subtle progression of ILD in MCTD patients are trends in DLCO, quantification of lower-lobes disease by HRCT (lower-lobes %ILD-HRCT score), and qualitative analysis of HRCT imaging.

Responses of susceptible subpopulations to nitrogen dioxide. Research report, June 1983-January 1988

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrow, P.E.; Utell, M.J.

1989-02-01

Symptom responses and changes in pulmonary function were investigated in people with asthma or chronic obstructive pulmonary disease (COPD) exposed to 0.3 ppm nitrogen dioxide (NO{sub 2}) for four hours. Nonrespiratory-impaired (normal) subjects of comparable ages constituted the control groups. All exposures included periods of exercise and pulmonary function measurements. No significant symptomatic or physiological responses to NO{sub 2} could be detected in either the young or elderly control group. The asthmatic group did not manifest significant reductions in lung function after exposure to 0.3 ppm NO{sub 2}, compared to their preexposure baseline data or to their responses after amore » comparable four-hour exposure to air. During light exercise, subjects with COPD were progressively responsive to 0.3 ppm NO{sub 2}. Subgroup analyses within the asthmatic, COPD, and elderly normal subject groups and intergroup comparisons yielded significant findings and associations.« less

Pulmonary function and health-related quality of life 1-year follow up after cardiac surgery.

PubMed

Westerdahl, Elisabeth; Jonsson, Marcus; Emtner, Margareta

2016-07-08

Pulmonary function is severely reduced in the early period after cardiac surgery, and impairments have been described up to 4-6 months after surgery. Evaluation of pulmonary function in a longer perspective is lacking. In this prospective study pulmonary function and health-related quality of life were investigated 1 year after cardiac surgery. Pulmonary function measurements, health-related quality of life (SF-36), dyspnoea, subjective breathing and coughing ability and pain were evaluated before and 1 year after surgery in 150 patients undergoing coronary artery bypass grafting, valve surgery or combined surgery. One year after surgery the forced vital capacity and forced expiratory volume in 1 s were significantly decreased (by 4-5 %) compared to preoperative values (p < 0.05). Saturation of peripheral oxygen was unchanged 1 year postoperatively compared to baseline. A significantly improved health-related quality of life was found 1 year after surgery, with improvements in all eight aspects of SF-36 (p < 0.001). Sternotomy-related pain was low 1 year postoperatively at rest (median 0 [min-max; 0-7]), while taking a deep breath (0 [0-4]) and while coughing (0 [0-8]). A more pronounced decrease in pulmonary function was associated with dyspnoea limitations and impaired subjective breathing and coughing ability. One year after cardiac surgery static and dynamic lung function measurements were slightly decreased, while health-related quality of life was improved in comparison to preoperative values. Measured levels of pain were low and saturation of peripheral oxygen was same as preoperatively.

Fitness and lung function in children with primary ciliary dyskinesia and cystic fibrosis.

PubMed

Ring, Astrid M; Buchvald, Frederik F; Holgersen, Mathias G; Green, Kent; Nielsen, Kim G

2018-06-01

Peak oxygen uptake (VO 2peak ) is associated with morbidity and mortality in health and disease, and provides important information of global physical health not achieved from standard pulmonary function tests. Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are genetically determined diseases involving different basic defects, but both showing impaired mucociliary clearance leading to chronic infections and pulmonary destruction early in life. PCD is generally considered a milder disease than CF and it is hypothesized that children with CF would have consistently lower VO 2peak and pulmonary function than children with PCD. We performed a prospective, observational single-center, clinical cohort study of VO 2peak and pulmonary function in age and gender matched schoolchildren, at two occasions 12 months apart. VO 2peak was persistently (at baseline and after 12 months) and significantly reduced in the 22 patients with PCD (z-score = -0.89 and -1.0) and 24 with CF (z-score = -0.94 and -1.1), included in the study. Abnormal VO 2peak was detected in a larger proportion of children with PCD (≈30%) than CF (≈13%). Moreover, children with PCD exhibited persistently lower FEV 1 (p < 0.0001 at first visit and p = 0.001 at second visit) while FEF 25-75 and FVC differed only at baseline. Indeed, a retrospective analysis comparing lung function over the last year in our entire PCD and CF populations between 6 and 18 years of age, revealed lower values in patients with PCD (FEV 1 z-score, p = 0.0004, FVC z-score p < 0.0001, FEF 25-75 z-score p = 0.008). This is the first report indicating that cardiopulmonary fitness is equally and consistently reduced in both children with PCD and CF along with a consistent lower pulmonary function in PCD compared with CF. A certain reservation for possible selection bias and the small number of patients is necessary. However, increased focus on early diagnosis, evidence-based treatment regimens and close clinical monitoring in PCD are warranted. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of daily vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients: a pilot trial.

PubMed

Rafiq, Rachida; Prins, Hendrik J; Boersma, Wim G; Daniels, Johannes Ma; den Heijer, Martin; Lips, Paul; de Jongh, Renate T

2017-01-01

Although vitamin D is well known for its function in calcium homeostasis and bone mineralization, several studies have shown positive effects on muscle strength and physical function. In addition, vitamin D has been associated with pulmonary function and the incidence of airway infections. As vitamin D deficiency is highly prevalent in chronic obstructive pulmonary disease (COPD) patients, supplementation might have a beneficial effect in these patients. To assess the effect of vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients. Secondary outcomes are pulmonary function, handgrip strength, exacerbation rate, and quality of life. We performed a randomized, double-blind, placebo-controlled pilot trial. Participants were randomly allocated to receive 1,200 IU vitamin D3 per day (n=24) or placebo (n=26) during 6 months. Study visits were conducted at baseline, and at 3 and 6 months after randomization. During the visits, blood was collected, respiratory muscle strength was measured (maximum inspiratory and expiratory pressure), physical performance and 6-minute walking tests were performed, and handgrip strength and pulmonary function were assessed. In addition, participants kept a diary card in which they registered respiratory symptoms. At baseline, the mean (standard deviation [SD]) serum 25-hydroxyvitamin D (25(OH)D) concentration (nmol/L) was 42.3 (15.2) in the vitamin D group and 40.6 (17.0) in the placebo group. Participants with vitamin D supplementation had a larger increase in serum 25(OH)D compared to the placebo group after 6 months (mean difference (SD): +52.8 (29.8) vs +12.3 (25.1), P <0.001). Primary outcomes, respiratory muscle strength and physical performance, did not differ between the groups after 6 months. In addition, no differences were found in the 6-minute walking test results, handgrip strength, pulmonary function, exacerbation rate, or quality of life. Vitamin D supplementation did not affect (respiratory) muscle strength or physical performance in this pilot trial in vitamin D-deficient COPD patients.

Influence of Pulmonary Rehabilitation on Lung Function Changes After the Lung Resection for Primary Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Mujovic, Natasa; Mujovic, Nebojsa; Subotic, Dragan; Ercegovac, Maja; Milovanovic, Andjela; Nikcevic, Ljubica; Zugic, Vladimir; Nikolic, Dejan

2015-11-01

Influence of physiotherapy on the outcome of the lung resection is still controversial. Study aim was to assess the influence of physiotherapy program on postoperative lung function and effort tolerance in lung cancer patients with chronic obstructive pulmonary disease (COPD) that are undergoing lobectomy or pneumonectomy. The prospective study included 56 COPD patients who underwent lung resection for primary non small-cell lung cancer after previous physiotherapy (Group A) and 47 COPD patients (Group B) without physiotherapy before lung cancer surgery. In Group A, lung function and effort tolerance on admission were compared with the same parameters after preoperative physiotherapy. Both groups were compared in relation to lung function, effort tolerance and symptoms change after resection. In patients with tumors requiring a lobectomy, after preoperative physiotherapy, a highly significant increase in FEV1, VC, FEF50 and FEF25 of 20%, 17%, 18% and 16% respectively was registered with respect to baseline values. After physiotherapy, a significant improvement in 6-minute walking distance was achieved. After lung resection, the significant loss of FEV1 and VC occurred, together with significant worsening of the small airways function, effort tolerance and symptomatic status. After the surgery, a clear tendency existed towards smaller FEV1 loss in patients with moderate to severe, when compared to patients with mild baseline lung function impairment. A better FEV1 improvement was associated with more significant loss in FEV1. Physiotherapy represents an important part of preoperative and postoperative treatment in COPD patients undergoing a lung resection for primary lung cancer.

Impact of Balloon Pulmonary Angioplasty on Hemodynamics and Clinical Outcomes in Patients with Chronic Thromboembolic Pulmonary Hypertension: the Initial Korean Experience.

PubMed

Kwon, Woochan; Yang, Jeong Hoon; Park, Taek Kyu; Chang, Sung A; Jung, Dong Seop; Cho, Young Seok; Kim, Sung Mok; Kim, Tae Jung; Park, Hye Yoon; Choi, Seung Hyuk; Kim, Duk Kyung

2018-01-22

The treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). However, not all patients are eligible for PEA, and some patients experience recurrence of pulmonary hypertension even after PEA. Patients who underwent balloon pulmonary angioplasty (BPA) between December 2015 and April 2017 were enrolled from the Samsung Medical Center CTEPH registry. Enrolled patients underwent right heart catheterization, echocardiography, and 6-minute walk distance (6MWD) at baseline, 4 and 24 weeks after their first BPA session. We compared clinical and hemodynamic parameters at the baseline and last BPA session. Fifty-two BPA sessions were performed in 15 patients, six of whom had a history of PEA. BPA resulted in improvements in World Health Organization (WHO) functional class (2.9 ± 0.8 to 1.7 ± 0.6, P = 0.002), 6MWD (387.0 ± 86.4 to 453.4 ± 64.8 m, P = 0.01), tricuspid annular plane systolic excursion (14.1 ± 3.6 to 15.6 ± 4.3 mm, P = 0.03) and hemodynamics, including a decline in mean pulmonary artery pressure (41.1 ± 13.1 to 32.1 ± 9.5 mmHg, P < 0.001) and in pulmonary vascular resistance (607.4 ± 452.3 to 406.7 ± 265.4 dyne.sec.cm⁻⁵, P = 0.01) but not in cardiac index (2.94 ± 0.79 to 2.96 ± 0.93 L/min/m², P = 0.92). Six cases of complications were recorded, including two cases of reperfusion injury. BPA might be a safe and effective treatment strategy for both inoperable CTEPH patients and patients with residual pulmonary hypertension after PEA. © 2018 The Korean Academy of Medical Sciences.

Acute right heart failure after hemorrhagic shock and trauma pneumonectomy-a management approach: A blinded randomized controlled animal trial using inhaled nitric oxide.

PubMed

Lubitz, Andrea L; Sjoholm, Lars O; Goldberg, Amy; Pathak, Abhijit; Santora, Thomas; Sharp, Thomas E; Wallner, Markus; Berretta, Remus M; Poole, Lauren A; Wu, Jichuan; Wolfson, Marla R

2017-02-01

Hemorrhagic shock and pneumonectomy causes an acute increase in pulmonary vascular resistance (PVR). The increase in PVR and right ventricular (RV) afterload leads to acute RV failure, thus reducing left ventricular (LV) preload and output. Inhaled nitric oxide (iNO) lowers PVR by relaxing pulmonary arterial smooth muscle without remarkable systemic vascular effects. We hypothesized that with hemorrhagic shock and pneumonectomy, iNO can be used to decrease PVR and mitigate right heart failure. A hemorrhagic shock and pneumonectomy model was developed using sheep. Sheep received lung protective ventilatory support and were instrumented to serially obtain measurements of hemodynamics, gas exchange, and blood chemistry. Heart function was assessed with echocardiography. After randomization to study gas of iNO 20 ppm (n = 9) or nitrogen as placebo (n = 9), baseline measurements were obtained. Hemorrhagic shock was initiated by exsanguination to a target of 50% of the baseline mean arterial pressure. The resuscitation phase was initiated, consisting of simultaneous left pulmonary hilum ligation, via median sternotomy, infusion of autologous blood and initiation of study gas. Animals were monitored for 4 hours. All animals had an initial increase in PVR. PVR remained elevated with placebo; with iNO, PVR decreased to baseline. Echo showed improved RV function in the iNO group while it remained impaired in the placebo group. After an initial increase in shunt and lactate and decrease in SvO2, all returned toward baseline in the iNO group but remained abnormal in the placebo group. These data indicate that by decreasing PVR, iNO decreased RV afterload, preserved RV and LV function, and tissue oxygenation in this hemorrhagic shock and pneumonectomy model. This suggests that iNO may be a useful clinical adjunct to mitigate right heart failure and improve survival when trauma pneumonectomy is required.

Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial

PubMed Central

Ehlken, Nicola; Lichtblau, Mona; Klose, Hans; Weidenhammer, Johannes; Fischer, Christine; Nechwatal, Robert; Uiker, Sören; Halank, Michael; Olsson, Karen; Seeger, Werner; Gall, Henning; Rosenkranz, Stephan; Wilkens, Heinrike; Mertens, Dirk; Seyfarth, Hans-Jürgen; Opitz, Christian; Ulrich, Silvia; Egenlauf, Benjamin; Grünig, Ekkehard

2016-01-01

Abstract Aims The impact of exercise training on the right heart and pulmonary circulation has not yet been invasively assessed in patients with pulmonary hypertension (PH) and right heart failure. This prospective randomized controlled study investigates the effects of exercise training on peak VO2/kg, haemodynamics, and further clinically relevant parameters in PH patients. Methods and results Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic PH (54% female, 56 ± 15 years, 84% World Health Organization functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group. Medication remained unchanged during the study period. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoint was the change in peak VO2/kg. Secondary endpoints included changes in haemodynamics. For missing data, multiple imputation and responder analyses were performed. The study results showed a significant improvement of peak VO2/kg in the training group (difference from baseline to 15 weeks: training +3.1 ± 2.7 mL/min/kg equals +24.3% vs. control −0.2 ± 2.3 mL/min/kg equals +0.9%, P < 0.001). Cardiac index (CI) at rest and during exercise, mean pulmonary arterial pressure, pulmonary vascular resistance, 6 min walking distance, quality of life, and exercise capacity significantly improved by exercise training. Conclusion Low-dose exercise training at 4–7 days/week significantly improved peak VO2/kg, haemodynamics, and further clinically relevant parameters. The improvements of CI at rest and during exercise indicate that exercise training may improve the right ventricular function. Further, large multicentre trials are necessary to confirm these results. PMID:26231884

Effect of Milrinone Infusion on Pulmonary Vasculature and Stroke Work Indices: A Single-Center Retrospective Analysis in 69 Patients Awaiting Cardiac Transplantation.

PubMed

Abramov, Dmitry; Haglund, Nicholas A; Di Salvo, Thomas G

2017-08-01

Although milrinone infusion is reported to benefit left ventricular function in chronic left heart failure, few insights exist regarding its effects on pulmonary circulation and right ventricular function. We retrospectively reviewed right heart catheterization data at baseline and during continuous infusion of milrinone in 69 patients with advanced heart failure and analyzed the effects on ventricular stroke work indices, pulmonary vascular resistance and pulmonary arterial compliance. Compared to baseline, milrinone infusion after a mean 58 ± 61 days improved mean left ventricular stroke work index (1540 ± 656 vs. 2079 ± 919 mmHg·mL/m 2 , p = 0.0007) to a much greater extent than right ventricular stroke work index (616 ± 346 vs. 654 ± 332, p = 0.053); however, patients with below median stroke work indices experienced a significant improvement in both left and right ventricular stroke work performance. Overall, milrinone reduced left and right ventricular filling pressures and pulmonary and systemic vascular resistance by approximately 20%. Despite an increase in pulmonary artery capacitance (2.3 ± 1.6 to 3.0 ± 2.0, p = 0.013) and a reduction in pulmonary vascular resistance (3.8 ± 2.3 to 3.0 ± 1.7 Wood units), milrinone did not reduce the transpulmonary gradient (13 ± 7 vs. 12 ± 6 mmHg, p = 0.252), the pulmonary artery pulse pressure (25 ± 10 vs. 24 ± 10, p = 0.64) or the pulmonary artery diastolic to pulmonary capillary wedge gradient (2.0 ± 6.5 vs. 2.4 ± 6.0, p = 0.353). Milrinone improved left ventricular stroke work indices to a greater extent than right ventricular stroke work indices and had beneficial effects on right ventricular net input impedance, predominantly via augmentation of left ventricular stroke volume and passive unloading of the pulmonary circuit. Patients who had the worst biventricular performance benefited the most from chronic milrinone infusion.

The importance of exercise self-efficacy for clinical outcomes in pulmonary rehabilitation.

PubMed

Selzler, Anne-Marie; Rodgers, Wendy M; Berry, Tanya R; Stickland, Michael K

2016-11-01

Pulmonary rehabilitation (PR) improves functional exercise capacity and health status in people with chronic obstructive pulmonary disease (COPD), although these outcomes are often not maintained following PR. Self-efficacy is a precursor to outcomes achievement, yet few studies have examined the importance of self-efficacy to outcome improvement during PR, or how it develops over time. Further, the contribution of exercise-specific self-efficacy to outcomes in PR is unknown. The aims of this study were to determine (a) whether baseline exercise self-efficacy predicts PR attendance and change in functional exercise capacity and health status over PR, and (b) if exercise self-efficacy changes with PR. Fifty-eight out of 64 patients with COPD completed PR and assessments of exercise self-efficacy (task, coping, scheduling), the 6-minute walk test (6MWT), and St. George's Respiratory Questionnaire (SGRQ) at the beginning and end of PR. Analyses were conducted to predict attendance, and change in 6MWT and SGRQ, while controlling for baseline demographic and clinical indicators. Change in 6MWT, SGRQ, and self-efficacy with PR was also examined. Clinically significant increases in the 6MWT and SGRQ were achieved with PR. Stronger task self-efficacy predicted better attendance, while stronger coping self-efficacy predicted greater 6MWT improvement. No variables predicted SGRQ change. Scheduling self-efficacy significantly improved with PR, whereas task and coping self-efficacy did not. Baseline exercise self-efficacy appears to be a determinant of rehabilitation attendance and functional exercise improvement with PR. Clinicians should evaluate and target exercise self-efficacy to maximize adherence and health outcome improvement with PR. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation.

PubMed

Davies, Jane C; Wainwright, Claire E; Canny, Gerard J; Chilvers, Mark A; Howenstine, Michelle S; Munck, Anne; Mainz, Jochen G; Rodriguez, Sally; Li, Haihong; Yen, Karl; Ordoñez, Claudia L; Ahrens, Richard

2013-06-01

Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, has been shown to improve lung function, pulmonary exacerbation rate, respiratory symptoms, and weight gain compared with placebo in patients with cystic fibrosis aged 12 years or older with a G551D-CFTR mutation. This randomized, double-blind, placebo-controlled trial evaluated ivacaftor in patients with cystic fibrosis aged 6-11 years with a G551D-CFTR mutation on at least one allele. Patients were randomly assigned to receive ivacaftor administered orally at 150 mg (n = 26) or placebo (n = 26) every 12 hours for 48 weeks in addition to existing prescribed cystic fibrosis therapies. Despite near-normal mean baseline values in FEV1, patients receiving ivacaftor had a significant increase in percent predicted FEV1 from baseline through Week 24 versus placebo group (treatment effect, 12.5 percentage points; P < 0.001). Effects on pulmonary function were evident by 2 weeks, and a significant treatment effect was maintained through Week 48. Patients treated with ivacaftor gained, on average, 2.8 kg more than those receiving placebo at Week 48 (P < 0.001). The change from baseline through Week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor was -53.5 mmol/L (P < 0.001) versus placebo. The incidence of adverse events was similar in the two groups. In patients who are younger and healthier than those in previously studied populations, ivacaftor demonstrated a significant improvement in pulmonary function, weight, and CFTR activity compared with placebo. Clinical trial registered with www.clinicaltrials.gov (NCT00909727).

Efficacy and Safety of Ivacaftor in Patients Aged 6 to 11 Years with Cystic Fibrosis with a G551D Mutation

PubMed Central

Wainwright, Claire E.; Canny, Gerard J.; Chilvers, Mark A.; Howenstine, Michelle S.; Munck, Anne; Mainz, Jochen G.; Rodriguez, Sally; Li, Haihong; Yen, Karl; Ordoñez, Claudia L.; Ahrens, Richard

2013-01-01

Rationale: Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, has been shown to improve lung function, pulmonary exacerbation rate, respiratory symptoms, and weight gain compared with placebo in patients with cystic fibrosis aged 12 years or older with a G551D-CFTR mutation. Objectives: This randomized, double-blind, placebo-controlled trial evaluated ivacaftor in patients with cystic fibrosis aged 6–11 years with a G551D-CFTR mutation on at least one allele. Methods: Patients were randomly assigned to receive ivacaftor administered orally at 150 mg (n = 26) or placebo (n = 26) every 12 hours for 48 weeks in addition to existing prescribed cystic fibrosis therapies. Measurements and Main Results: Despite near-normal mean baseline values in FEV1, patients receiving ivacaftor had a significant increase in percent predicted FEV1 from baseline through Week 24 versus placebo group (treatment effect, 12.5 percentage points; P < 0.001). Effects on pulmonary function were evident by 2 weeks, and a significant treatment effect was maintained through Week 48. Patients treated with ivacaftor gained, on average, 2.8 kg more than those receiving placebo at Week 48 (P < 0.001). The change from baseline through Week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor was −53.5 mmol/L (P < 0.001) versus placebo. The incidence of adverse events was similar in the two groups. Conclusions: In patients who are younger and healthier than those in previously studied populations, ivacaftor demonstrated a significant improvement in pulmonary function, weight, and CFTR activity compared with placebo. Clinical trial registered with www.clinicaltrials.gov (NCT00909727). PMID:23590265

The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis.

PubMed

Amin, Reshma; Dupuis, Annie; Aaron, Shawn D; Ratjen, Felix

2010-01-01

The relevance of Aspergillus fumigatus in patients with cystic fibrosis (CF) not affected by allergic bronchopulmonary aspergillosis is unclear. Our aim was to determine the effect of persistent infection with A fumigatus on pulmonary exacerbations and lung function in children with CF. This was a retrospective cohort study of patients with CF followed at The Hospital for Sick Children from 1999 to 2006. Persistent A fumigatus infection was defined as the presence of two or more positive sputum or bronchoalveolar cultures for A fumigatus in a given year. The primary outcome measure was the annual number of hospitalizations for pulmonary exacerbations. Two hundred thirty patients with CF were included in the analysis. The FEV(1) of patients persistently infected with A fumigatus was 3.61% (P< or =.0001) lower during the study period compared with uninfected patients. There was a significant interaction between A fumigatus and Pseudomonas aeruginosa on lung function (P=.0006). Patients not infected with either organism had the highest pulmonary function. Persistent A fumigatus infection (relative risk [RR]=1.94, P=.0002) and CF-related diabetes (RR=1.64, P=.028) were associated with an increased risk of pulmonary exacerbations requiring hospitalization, whereas there was no increased risk of pulmonary exacerbations among patients with allergic bronchopulmonary aspergillosis (RR=1.02, P=.94). When adjusted for baseline pulmonary function, none of these variables were associated with a significantly increased risk of pulmonary exacerbations, with only chronic A fumigatus infection trending toward significance (RR=1.40, P=.065). Persistent A fumigatus infection is an independent risk factor for hospital admissions in patients with CF.

Respiratory effects of work in retail food stores. III. Pulmonary function findings.

PubMed

Wegman, D H; Eisen, E A; Smith, T J; Greaves, I A; Fine, L J

1987-06-01

Findings are reported from a prospective morbidity study which examined the effects on pulmonary function associated with the particulate and gaseous air contaminants to which retail food store workers are exposed. A total of 685 supermarket employees (including meat wrappers, meat cutters and store clerks) performed standard ventilatory function tests [forced expiratory volume in 1 s (FEV1.0) and forced vital capacity (FVC)] during a base-line survey. Those available four years later (305) were resurveyed in a similar manner. A suggestive chronic effect on pulmonary function was shown in those with high cumulative exposures and allergic history. Among those workers who had continuous exposure to air contaminants in settings with "hot-wire" plastic wrap film cutters the annual rates of change in FEV1.0 and FVC were twice as great as the changes found among comparable workers who were not exposed to fumes from wrapping film. Those who switched from the "hot-wire" to the "cool-rod" cutters during the course of the follow-up had intermediate rates of change in lung function.

Spatial distribution of venous gas emboli in the lungs

NASA Technical Reports Server (NTRS)

Souders, J. E.; Doshier, J. B.; Polissar, N. L.; Hlastala, M. P.

1999-01-01

The distribution of gaseous pulmonary emboli is presumed to be determined by their buoyancy. We hypothesized that regional pulmonary blood flow may also influence their distribution. Therefore, pulmonary blood flow was measured in supine, anesthetized dogs with use of 15-microm fluorescent microspheres at baseline and during N(2) embolism. The animals were killed, and the lungs were excised, air-dried, and diced into approximately 2-cm(3) pieces with weights and spatial coordinates recorded. Embolism was defined as a >10% flow decrease relative to baseline. Vertically, the incidence of embolism increased substantially by 6 +/- 1% per additional centimeter in height compared with baseline (P = 0.0003). Embolism also increased radially by 3 +/- 1%/cm from the hilum (P = 0.002). There was a weaker but statistically significant increase in embolism to pieces with greater baseline flow, 9 +/- 2% for every 1. 0 increase in relative baseline flow (P = 0.008). We conclude that the distribution of gaseous emboli is influenced by buoyancy and flow dynamics within the pulmonary vasculature.

Impact of customized videotape education on quality of life in patients with chronic obstructive pulmonary disease.

PubMed

Petty, Thomas L; Dempsey, Edward C; Collins, Timothy; Pluss, William; Lipkus, Isaac; Cutter, Gary R; Chalmers, Robin; Mitchell, Amy; Weil, Kenneth C

2006-01-01

To compare the impact of a library of pulmonary rehabilitation videotapes versus an older videotape and usual care on quality of life and ability to perform activities of daily living in persons with chronic obstructive pulmonary disease. Two hundred fourteen patients diagnosed with chronic obstructive pulmonary disease, emphysema, or chronic bronchitis were recruited and randomized to receive customized videotapes, standard videotapes, or usual care. Outcome measures included the Fatigue Impact Scale, Seattle Obstructive Lung Disease Questionnaire, and the SF-36(R) Health Survey. Differences in coping skills and emotional functioning on the Seattle Obstructive Lung Disease Questionnaire were found among the 174 subjects who completed the study. The customized videotape group improved by 8.6 and 4.8 points, respectively, whereas the score of the other groups decreased by less than 1 point for the coping skills, and the scores of the standard video and the control groups decreased by 3.0 and 2.1 points, respectively, for emotional functioning (P < .05, all comparisons). The scores using the Fatigue Impact Scale also improved for the customized videotape group, whereas the scores of the others remained unchanged. Videotape users demonstrated better conversion to and retention of exercise habits, with over 80% of customized videotape subjects who reported exercise habits at baseline continuing the habits as compared with 40% in the usual care group. Sedentary subjects at baseline were more likely to begin and maintain exercise if randomized to videotapes. These findings demonstrate increased quality of life, lower fatigue, and better compliance with a prescribed exercise regimen among subjects using the customized videotapes. There was a significant improvement in emotional functioning and coping skills among customized videotape subjects.

The effect of duration of exposure on sulfuric acid-induced pulmonary function changes in asthmatic adolescent subjects: A dose-response study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koenig, J.Q.; Covert, D.S.; Larson, T.V.

To evaluate the pulmonary effects of varying doses of sulfuric acid, adolescent subjects with asthma were exposed to 35 or 70 micrograms/m3 sulfuric acid for 45 or 90 min. Exposure was carried out during intermittent moderate exercise. The pulmonary functions measured before and after exposure were FEV1, FVC, and total respiratory resistance. The 45 min exposures were associated with larger decreases in FEV1 (-6% or -3%) than the 90 min exposures (-1% or +2%). Analysis of variance of the change in FEV1 among the exposures revealed that the 45 min exposure to 35 micrograms/m3 was significant (p = 0.03). Themore » p value for 45 min exposure to 70 micrograms/m3 was not significant (p = 0.08). Using analysis of variance, neither of the 90 min exposures was associated with a significant decrease in FEV1 compared to air exposure. Also, none of the changes in FVC or RT was significant. When baseline to post-exposure changes were compared for each of the five test atmospheres using paired t tests, both of the 45 min exposures were associated with statistical significance (p < 0.001 for 35 micrograms/m3 and p < 0.005 for 70 micrograms/m3). This baseline to post exposure change was not statistically significant for the 90 min exposures. The reason for the lesser effect on pulmonary function at increased exposure duration is not known; it may be due to changes in either varying deposition patterns or changes in buffering capacity of the cells lining the airways. With respect to individual sensitivities to H2SO4, the data showed a significant consistency across test atmospheres.« less

Reversibility of trapped air on chest computed tomography in cystic fibrosis patients.

PubMed

Loeve, Martine; Rosenow, Tim; Gorbunova, Vladlena; Hop, Wim C J; Tiddens, Harm A W M; de Bruijne, Marleen

2015-06-01

To investigate changes in trapped air volume and distribution over time and compare computed tomography (CT) with pulmonary function tests for determining trapped air. Thirty children contributed two CTs and pulmonary function tests over 2 years. Localized changes in trapped air on CT were assessed using image analysis software, by deforming the CT at timepoint 2 to match timepoint 1, and measuring the volume of stable (TAstable), disappeared (TAdisappeared) and new (TAnew) trapped air as a proportion of total lung volume. We used the difference between total lung capacity measured by plethysmography and helium dilution, residual volume to total lung capacity ratio, forced expiratory flow at 75% of vital capacity, and maximum mid-expiratory flow as pulmonary function test markers of trapped air. Statistical analysis included Wilcoxon's signed rank test and Spearman correlation coefficients. Median (range) age at baseline was 11.9 (5-17) years. Median (range) of trapped air was 9.5 (2-33)% at timepoint 1 and 9.0 (0-25)% at timepoint 2 (p=0.49). Median (range) TAstable, TAdisappeared and TAnew were respectively 3.0 (0-12)%, 5.0 (1-22)% and 7.0 (0-20)%. Trapped air on CT correlated statistically significantly with all pulmonary function measures (p<0.01), other than residual volume to total lung capacity ratio (p=0.37). Trapped air on CT did not significantly progress over 2 years, may have a substantial stable component, and is significantly correlated with pulmonary function markers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pulmonary function derangements in isolated or predominant mitral stenosis - Preoperative evaluation with clinico-hemodynamic correlation.

PubMed

Parvathy, Usha T; Rajan, Rajesh; Faybushevich, Alexander Georgevich

2014-06-01

It is well known that mitral stenosis (MS) is complicated by pulmonary hypertension (PH) of varying degrees. The hemodynamic derangement is associated with structural changes in the pulmonary vessels and parenchyma and also functional derangements. This article analyzes the pulmonary function derangements in 25 patients with isolated/predominant mitral stenosis of varying severity. THE AIM OF THE STUDY WAS TO CORRELATE THE PULMONARY FUNCTION TEST (PFT) DERANGEMENTS (DONE BY SIMPLE METHODS) WITH: a) patient demographics and clinical profile, b) severity of the mitral stenosis, and c) severity of pulmonary artery hypertension (PAH) and d) to evaluate its significance in preoperative assessment. This cross-sectional study was conducted in 25 patients with mitral stenosis who were selected for mitral valve (MV) surgery. The patients were evaluated for clinical class, echocardiographic severity of mitral stenosis and pulmonary hypertension, and with simple methods of assessment of pulmonary function with spirometry and blood gas analysis. The diagnosis and classification were made on standardized criteria. The associations and correlations of parameters, and the difference in groups of severity were analyzed statistically with Statistical Package for Social Sciences (SPSS), using nonparametric measures. THE SPIROMETRIC PARAMETERS SHOWED SIGNIFICANT CORRELATION WITH INCREASING NEW YORK HEART ASSOCIATION (NYHA) FUNCTIONAL CLASS (FC): forced vital capacity (FVC, r = -0.4*, p = 0.04), forced expiratory volume in one second (FEV1, r = -0.5*, p = 0.01), FEV1/FVC (r = -0.44*, p = 0.02), and with pulmonary venous congestion (PVC): FVC (r = -0.41*, p = 0.04) and FEV1 (r = -0.41*, p = 0.04). Cardiothoracic ratio (CTR) correlated only with FEV1 (r = -0.461*, p = 0.02) and peripheral saturation of oxygen (SPO2, r = -0.401*, p = 0.04). There was no linear correlation to duration of symptoms, mitral valve orifice area, or pulmonary hypertension, except for MV gradient with PCO2 (r = 0.594**, p = 0.002). The decreased oxygenation status correlated significantly with FC, CTR, PVC, and with deranged spirometry (r = 0.495*, p = 0.02). PFT derangements are seen in all grades of severity of MS and correlate well with the functional class, though no significant linear correlation with grades of severity of stenosis or pulmonary hypertension. Even the early or mild derangements in pulmonary function such as small airway obstruction in the less severe cases of normal or mild PH can be detected by simple and inexpensive methods when the conventional parameters are normal. The supplementary data from baseline arterial blood gas analysis is informative and relevant. This reclassified pulmonary function status might be prognostically predictive.

Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

PubMed

Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

1999-12-01

Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

Effects of Aerobic Exercise on the Pulmonary Functions, Respiratory Symptoms and Psychological Status of People Living With HIV.

PubMed

Aweto, Happiness Anulika; Aiyegbusi, Ayoola Ibifubara; Ugonabo, Adaora Justina; Adeyemo, Titilope Adenike

2016-01-01

Pulmonary complications, respiratory symptoms and depression are common occurrences which contribute to the morbidity and mortality seen in individuals living with HIV/AIDS. This study investigated the effect of aerobic exercise on the pulmonary functions, respiratory symptoms and psychological status of people living with HIV. This study was conducted in Lagos, Nigeria from October 2014 to May 2015. Forty eligible individuals with HIV aged 18 yr and above participated, of which 33 cooperated to the end. They were recruited from the HIV/AIDS Prevention and Intervention Initiative (APIN) Clinic, Lagos University Teaching Hospital, Nigeria and were randomly assigned to either the study or the control group. The study group received aerobic exercise training three times a week for six weeks and counselling while the control group received only counselling. Pulmonary functions, respiratory symptoms and psychological status were evaluated at baseline and at six weeks. Inferential statistics of paired and independent t-test were used to analyse the data. Comparison of mean changes in the pulmonary variables of the study group with those of the control group showed significant differences in all but in the respiratory rate (RR) - [Forced Expiratory Volume in one second: P=0.001, Forced Vital Capacity: P=0.001, Peak Expiratory Flow: P=0.001]. There were also significant differences between the mean changes in respiratory symptoms (P=0.001) and depressive symptoms (P=0.001) of study group and those of the control group. Aerobic exercise training significantly improved pulmonary functions as well as significantly reduced respiratory and depressive symptoms in people living with HIV.

Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension

PubMed Central

Morris, Claudia R.; Kim, Hae-Young; Wood, John; Porter, John B.; Klings, Elizabeth S.; Trachtenberg, Felicia L.; Sweeters, Nancy; Olivieri, Nancy F.; Kwiatkowski, Janet L.; Virzi, Lisa; Singer, Sylvia T.; Taher, Ali; Neufeld, Ellis J.; Thompson, Alexis A.; Sachdev, Vandana; Larkin, Sandra; Suh, Jung H.; Kuypers, Frans A.; Vichinsky, Elliott P.

2013-01-01

Pulmonary hypertension is a common but often overlooked complication associated with thalassemia syndromes. There are limited data on the safety and efficacy of selective pulmonary vasodilators in this at-risk population. We, therefore, designed a 12-week, open-label, phase 1/2, pilot-scale, proof-of-principle trial of sildenafil therapy in 10 patients with β-thalassemia and at increased risk of pulmonary hypertension based on an elevated tricuspid regurgitant jet velocity >2.5 m/s on Doppler-echocardiography. Variables compared at baseline and after 12 weeks of sildenafil treatment included Doppler-echocardiographic parameters, 6-minute walked distance, Borg Dyspnea Score, New York Heart Association functional class, pulmonary function, and laboratory parameters. Treatment with sildenafil resulted in a significant decrease in tricuspid regurgitant jet velocity by 13.3% (3.0±0.7 versus 2.6±0.5 m/s, P=0.04), improved left ventricular end systolic/diastolic volume, and a trend towards a improved New York Heart Association functional class. No significant change in 6-minute walked distance was noted. Sildenafil was well tolerated, although minor expected adverse events were commonly reported. The total dose of sildenafil (mg) was strongly correlated with percent change in nitric oxide metabolite concentration in the plasma (ρ=0.80, P=0.01). There were also significant increases in plasma and erythrocyte arginine concentrations. Our study suggests that sildenafil is safe and may improve pulmonary hemodynamics in patients at risk of pulmonary hypertension; however, it was not demonstrated to improve the distance walked in 6 minutes. Clinical trials are needed to identify the best treatment strategy for pulmonary hypertension in patients with β-thalassemia. (clinicaltrials.gov identifier: NCT00872170) PMID:23585527

Comparative Effect of Levosimendan and Milrinone in Cardiac Surgery Patients With Pulmonary Hypertension and Left Ventricular Dysfunction.

PubMed

Mishra, Abhi; Kumar, Bhupesh; Dutta, Vikas; Arya, V K; Mishra, Anand Kumar

2016-06-01

To compare the effects of levosimendan with milrinone in cardiac surgical patients with pulmonary hypertension and left ventricular dysfunction. A prospective, randomized study. Tertiary care teaching hospital. The study included patients with valvular heart disease and pulmonary artery hypertension undergoing valve surgery. Forty patients were allocated randomly to receive either milrinone, 50 µg/kg bolus followed by infusion at a rate of 0.5 µg/kg/min (group 1), or levosimendan, 10 µg/kg bolus followed by infusion at a rate of 0.1 µg/kg/min (group 2) for 24 hours after surgery. Hemodynamic parameters were measured using a pulmonary artery catheter, and biventricular functions were assessed using echocardiography. Mean pulmonary artery pressures and the pulmonary vascular resistance index were comparable between the 2 groups at several time points in the intensive care unit. Biventricular function was comparable between both groups. Postcardiopulmonary bypass right ventricular systolic and diastolic functions decreased in both groups compared with baseline, whereas 6 hours postbypass left ventricular ejection fraction improved in patients with stenotic valvular lesions. Levosimendan use was associated with higher heart rate, increased cardiac index, decreased systemic vascular resistance index, and increased requirement of norepinephrine infusion compared with milrinone. The results of this study demonstrated that levosimendan was not clinically better than milrinone. Levosimendan therapy resulted in a greater increase in heart rate, decrease in systemic vascular resistance, and a greater need for norepinephrine than in patients who received milrinone. Copyright © 2016 Elsevier Inc. All rights reserved.

Pulmonary function, respiratory symptoms, and dust exposures among workers engaged in early manufacturing processes of tea: a cohort study.

PubMed

Shieh, Tzong-Shiun; Chung, Jui-Jung; Wang, Chung-Jing; Tsai, Perng-Jy; Kuo, Yau-Chang; Guo, How-Ran

2012-02-13

To evaluate pulmonary function and respiratory symptoms in workers engaged in the early manufacturing processes of tea and to identify the associated factors, we conducted a study in a tea production area in Taiwan. We recruited tea workers who engaged in the early manufacturing process in the Mountain Ali area in Taiwan and a comparison group of local office workers who were matched for age, gender, and smoking habits. We performed questionnaire interviews, pulmonary function tests, skin prick tests, and measurement of specific IgE for tea on the participants and assessed tea dust exposures in the tea factories. The 91 participating tea workers had higher prevalence of respiratory symptoms than the comparison group (32 participants). Among tea workers, ball-rolling workers had the highest prevalence of symptoms and the highest exposures of inhalable dusts. At baseline, tea workers had similar pulmonary functions as the comparison group, but compared to the other tea workers ball-rolling workers had a lower ratio of the 1-second forced expiratory volume to forced vital capacity (FEV1/FVC) and a lower maximal mid-expiratory flow rate expressed as% of the predicted value--MMF (%pred). A total of 58 tea workers participated in the on-site investigation and the cross-shift lung function measurements. We found ball-rolling yielded the highest inhalable dust level, panning yielded the highest respirable dust level, and withering yielded the lowest levels of both dusts. Ball-rolling also yielded the highest coarse fraction (defined as inhalable dusts minus respirable dusts), which represented exposures from nose to tracheobronchial tract. During the shift, we observed significant declines in pulmonary function, especially in ball-rolling workers. Multiple regressions showed that age, height, work tasks, coarse fraction, and number of months working in tea manufacturing each year were independent predictors of certain pulmonary function parameters in tea workers. Tea workers engaged in early manufacturing processes of tea have higher prevalence of respiratory symptoms and pulmonary function impairment, which might be related to tea dust exposures, especially the coarse fraction.

Inhaled dry powder mannitol in children with cystic fibrosis: A randomised efficacy and safety trial.

PubMed

De Boeck, K; Haarman, E; Hull, J; Lands, L C; Moeller, A; Munck, A; Riethmüller, J; Tiddens, H; Volpi, S; Leadbetter, J; Charlton, B; Malfroot, A

2017-05-01

Inhaled mannitol has beneficial effects on lung function, mucociliary clearance, quality of life and sputum properties. This trial examined the efficacy of inhaled mannitol in children with cystic fibrosis (CF). The efficacy of inhaled mannitol in children with CF aged 6-17years was assessed in a phase 2, randomised, placebo-controlled crossover study. Subjects were randomly assigned to mannitol 400mg every 12h or matching placebo for 8weeks, followed by an 8week washout and an 8week period with the alternate treatment. The primary endpoint was the absolute change from baseline in ppFEV1 (percent predicted FEV1). A total of 92 subjects were studied, with a mean age of 12years and mean baseline ppFEV1 of 72.2%. During mannitol treatment ppFEV1 was 3.42% (p=0.004) higher compared to placebo or a 4.97% (p=0.005) relative difference; relative change from baseline FEF25-75 was 10.52% (p=0.013). During mannitol treatment, acute post-treatment sputum weight was higher (p=0.012). In pre-specified subgroups (rhDNase use, age, and disease severity), the treatment differences consistently favoured mannitol. The most common AEs were cough and pulmonary exacerbations. Pulmonary exacerbation AEs were approximately 30% lower in the mannitol group. In children with CF, inhaled mannitol was associated with significant improvements in lung function and sputum weight, irrespective of rhDNase use, age or disease severity. Inhaled mannitol was well tolerated and was associated with a reduced incidence of pulmonary exacerbation AEs. (Clinical Trials.Gov: NCT 01883531). Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Interstitial pneumonia associated to peginterferon alpha-2a: A focus on lung function

PubMed Central

Cortés-Telles, Arturo

2016-01-01

Pulmonary toxicity related to the use of pegylated interferon alpha-2a during treatment of hepatitis C infections is rare; nonetheless, some cases with fatal outcomes have been reported. Evaluating patients’ pulmonary function is a key to diagnosis, follow-up and prognosis of several respiratory diseases, but case reports of respiratory manifestations related to the use of pegylated interferon alpha-2a have limited their findings to only baseline measurements. This paper examines the case of a 65-year-old woman with chronic hepatitis C virus infection who developed interstitial pneumonitis associated with pegylated interferon alpha-2a. Initial lung function evaluation revealed a marked reduction compared to an earlier assessment; the results were consistent with a moderate restricted pattern. Fortunately, over the ensuing 8 weeks of follow-up after discontinuing the drug, the patient recovered her lung function and experienced an overall improvement in her respiratory symptoms. PMID:27051119

The long-term effects of using telehomecare technology on functional health literacy: results from a randomized trial.

PubMed

Hæsum, L K E; Ehlers, L H; Hejlesen, O K

2017-09-01

The association between the use of telehomecare technology and functional health literacy is rather unexplored in the current literature. This relationship could prove important in the future management of chronic diseases, as technology has become a more integrated part of modern healthcare systems. Therefore, the purpose of this study was to explore how the use of telehomecare technology affects the level of functional health literacy over a period of 10 months. Randomized controlled trial. Our sample comprised 116 patients diagnosed with chronic obstructive pulmonary disease. A face-to-face interview and an objective test of functional health literacy were conducted with each patient at baseline and again at follow-up after 10 months. Twenty-six patients were lost to follow-up and thus, providing a total of 47 chronic obstructive pulmonary disease patients in the intervention group and 43 in the control group for this follow-up study. The level of functional health literacy was assessed with the Danish Test of Functional Health Literacy in Adults. The difference from baseline to follow-up, in both the functional health literacy score and the mean response time to the entire Danish Test of Functional Health Literacy in Adults (TOFHLA), was tested for statistical significance between the intervention group and the control group. A significant increase in functional health literacy is observed in both the groups from baseline to follow-up, but there is no statistical difference between groups (P-value = 0.62). A significant increase in the functional health literacy score was observed in both groups, but the findings of this present study provide no information on what causes the increase, so further research is needed to explore the increase in functional health literacy score more thoroughly and establish if the use of telehomecare technology is a part of the explanation. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

The Effects of a Telehealth Coping Skills Intervention on Outcomes in Chronic Obstructive Pulmonary Disease: Primary Results from the INSPIRE-II Study

PubMed Central

Blumenthal, James A.; Emery, Charles F.; Smith, Patrick J.; Keefe, Francis J.; Welty-Wolf, Karen; Mabe, Stephanie; Martinu, Tereza; Johnson, Julie J.; Babyak, Michael A.; O’Hayer, Virginia F.; Diaz, Philip T.; Durheim, Michael; Baucom, Donald; Palmer, Scott M.

2014-01-01

Objective Chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality and reduced quality of life. Novel interventions are needed to improve outcomes in COPD patients. The present study assessed the effects of a telephone-based coping skills intervention on psychological and somatic quality of life and on the combined medical endpoint of COPD-related hospitalizations and all-cause mortality. Methods We conducted a dual-site, randomized clinical trial with assessments at baseline and after 16 weeks of treatment. The study population comprised 326 outpatients with COPD aged 38 to 81 years, randomized to Coping Skills training (CST) or to COPD Education (COPD-ED). Patients completed a battery of quality of life (QoL) instruments, pulmonary function tests, and functional measures and were followed for up to 4.4 years to assess medical outcomes. Results The CST group exhibited greater improvements in psychological QoL compared to controls (P = .001), including less depression (Cohen’s d=0.22 [95%CI 0.08, 0.36]) and anxiety (d=0.17 [95%CI 0.02, 0.33]), and better overall mental health (d=0.17 [95%CI 0.03, 0.32]), emotional role functioning (d= 0.29 [95%CI 0.10, 0.48]), vitality (d= 0.27 [95%CI 0.11, 0.42]), and social functioning (d= 0.21 [95%CI 0.03, 0.38]). A significant baseline psychological QoL by Treatment group interaction revealed that CST with lower QoL at baseline achieved even greater improvements in psychological QoL compared to COPE-ED. CST participants also exhibited greater improvements in Somatic QoL (P = .042), including greater improvements in pulmonary QoL (d= 0.13 [95%CI 0.01, 0.24]), less fatigue (d= 0.34 [95%CI 0.18, 0.50]), and less shortness of breath (d= 0.11 [95%CI −0.01, 0.23]) and greater improvement in distance walked on the 6 Minute Walk Test (d= 0.09 [95%CI 0.01, 0.16]). However, there was no significant difference in risk of time to COPD-related hospitalization or all-cause mortality between CST (34 events) and COPD-ED (32 events) (P= 0.430). Conclusions A telehealth coping skills training intervention produced clinically meaningful improvements in quality of life and functional capacity, but no overall improvement in risk of COPD-related hospitalization and all-cause mortality. Trial Registration clinicaltrials.gov Identifier NCT00736268 PMID:25251888

Statistical Modeling of Disease Progression for Chronic Obstructive Pulmonary Disease Using Data from the ECLIPSE Study.

PubMed

Exuzides, Alex; Colby, Chris; Briggs, Andrew H; Lomas, David A; Rutten-van Mölken, Maureen P M H; Tabberer, Maggie; Chambers, Mike; Muellerova, Hana; Locantore, Nicholas; Risebrough, Nancy A; Ismaila, Afisi S; Gonzalez-McQuire, Sebastian

2017-05-01

To develop statistical models predicting disease progression and outcomes in chronic obstructive pulmonary disease (COPD), using data from ECLIPSE, a large, observational study of current and former smokers with COPD. Based on a conceptual model of COPD disease progression and data from 2164 patients, associations were made between baseline characteristics, COPD disease progression attributes (exacerbations, lung function, exercise capacity, and symptoms), health-related quality of life (HRQoL), and survival. Linear and nonlinear functional forms of random intercept models were used to characterize these relationships. Endogeneity was addressed by time-lagging variables in the regression models. At the 5% significance level, an exacerbation history in the year before baseline was associated with increased risk of future exacerbations (moderate: +125.8%; severe: +89.2%) and decline in lung function (forced expiratory volume in 1 second [FEV 1 ]) (-94.20 mL per year). Each 1% increase in FEV 1 % predicted was associated with decreased risk of exacerbations (moderate: -1.1%; severe: -3.0%) and increased 6-minute walk test distance (6MWD) (+1.5 m). Increases in baseline exercise capacity (6MWD, per meter) were associated with slightly increased risk of moderate exacerbations (+0.04%) and increased FEV 1 (+0.62 mL). Symptoms (dyspnea, cough, and/or sputum) were associated with an increased risk of moderate exacerbations (+13.4% to +31.1%), and baseline dyspnea (modified Medical Research Council score ≥2 v. <2) was associated with lower FEV 1 (-112.3 mL). A series of linked statistical regression equations have been developed to express associations between indicators of COPD disease severity and HRQoL and survival. These can be used to represent disease progression, for example, in new economic models of COPD.

Design, baseline characteristics, and early findings of the MPS VI (mucopolysaccharidosis VI) Clinical Surveillance Program (CSP).

PubMed

Hendriksz, Christian J; Giugliani, Roberto; Harmatz, Paul; Lampe, Christina; Martins, Ana Maria; Pastores, Gregory M; Steiner, Robert D; Leão Teles, Elisa; Valayannopoulos, Vassili

2013-03-01

To outline the design, baseline data, and 5-year follow-up data of patients with mucopolysaccharidosis (MPS) VI enrolled in the Clinical Surveillance Program (CSP), a voluntary, multinational, observational program. The MPS VI CSP was opened in 2005 to collect, for at least 15 years, observational data from standard clinical and laboratory assessments of patients with MPS VI. Baseline and follow-up data are documented by participating physicians in electronic case report forms. Between September 2005 and March 2010 the CSP enrolled 132 patients, including 123 who received enzyme replacement therapy (ERT) with galsulfase. Median age at enrolment was 13 years (range 1-59). Mean baseline data showed impaired growth, hepatosplenomegaly, and reduced endurance and pulmonary function. The most common findings were heart valve disease (90%), reduced visual acuity (79%), impaired hearing (59%), and hepatosplenomegaly (54%). Follow-up data up to 5 years in patients with pre- and post-ERT measurements showed a decrease in urinary glycosaminoglycans and increases in height and weight in patients <16 years and suggested reductions in liver and spleen size and improvements in endurance and pulmonary function after ERT was started. Vision, hearing, and cardiac function were unchanged. Safety data were in line with previous reports. The CSP represents the largest cross-sectional study of MPS VI to date. This first report provides information on the design and implementation of the program and population statistics for several clinical variables in patients with MPS VI. Data collected over 5 years suggest that ERT provides clinical benefit and is well-tolerated with no new safety concerns.

Mitochondrial iron chelation ameliorates cigarette-smoke induced bronchitis and emphysema in mice

PubMed Central

Cloonan, Suzanne M.; Glass, Kimberly; Laucho-Contreras, Maria E.; Bhashyam, Abhiram R.; Cervo, Morgan; Pabón, Maria A.; Konrad, Csaba; Polverino, Francesca; Siempos, Ilias I.; Perez, Elizabeth; Mizumura, Kenji; Ghosh, Manik C.; Parameswaran, Harikrishnan; Williams, Niamh C.; Rooney, Kristen T.; Chen, Zhi-Hua; Goldklang, Monica P.; Yuan, Guo-Cheng; Moore, Stephen C.; Demeo, Dawn L.; Rouault, Tracey A.; D’Armiento, Jeanine M.; Schon, Eric A.; Manfredi, Giovanni; Quackenbush, John; Mahmood, Ashfaq; Silverman, Edwin K.; Owen, Caroline A.; Choi, Augustine M.K.

2015-01-01

Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung. IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. PMID:26752519

Respiratory dysfunction in swine production facility workers: dose-response relationships of environmental exposures and pulmonary function.

PubMed

Donham, K J; Reynolds, S J; Whitten, P; Merchant, J A; Burmeister, L; Popendorf, W J

1995-03-01

Human respiratory health hazards for people working in livestock confinement buildings have been recognized since 1974. However, before comprehensive control programs can be implemented, more knowledge is needed of specific hazardous substances present in the air of these buildings, and at what concentrations they are harmful. Therefore, a medical epidemiological and exposure-response study was conducted on 207 swine producers using intensive housing systems (108 farms). Dose-response relationships between pulmonary function and exposures are reported here. Positive correlations were seen between change in pulmonary function over a work period and exposure to total dust, respirable dust, ammonia, respirable endotoxin, and the interactions of age-of-producer and dust exposure and years-of-working-in-the-facility and dust exposure. Relationships between baseline pulmonary function and exposures were not strong and therefore, not pursued in this study. The correlations between exposure and response were stronger after 6 years of exposure. Multiple regression models were used to identify total dust and ammonia as the two primary environmental predictors of pulmonary function decrements over a work period. The regression models were then used to determine exposure concentrations related to pulmonary function decrements suggestive of a health hazard. Total dust concentrations > or = 2.8 mg/m3 were predictive of a work period decrement of > or = 10% in FEV1. Ammonia concentrations of > or = 7.5 ppm were predictive of a > or = 3% work period decrement in FEV1. These predictive concentrations were similar to a previous dose-response study, which suggested 2.5 mg/m3 of total dust and 7 ppm of NH3 were associated with significant work period decrements. Therefore, dust > or = 2.8 mg/m3 and ammonia > or = 7.5 ppm should be considered reasonable evidence for guidelines regarding hazardous exposure concentrations in this work environment.

Effect of high altitude exposure on the hemodynamics of the bidirectional Glenn physiology: modeling incremented pulmonary vascular resistance and heart rate.

PubMed

Vallecilla, Carolina; Khiabani, Reza H; Sandoval, Néstor; Fogel, Mark; Briceño, Juan Carlos; Yoganathan, Ajit P

2014-06-03

The considerable blood mixing in the bidirectional Glenn (BDG) physiology further limits the capacity of the single working ventricle to pump enough oxygenated blood to the circulatory system. This condition is exacerbated under severe conditions such as physical activity or high altitude. In this study, the effect of high altitude exposure on hemodynamics and ventricular function of the BDG physiology is investigated. For this purpose, a mathematical approach based on a lumped parameter model was developed to model the BDG circulation. Catheterization data from 39 BDG patients at stabilized oxygen conditions was used to determine baseline flows and pressures for the model. The effect of high altitude exposure was modeled by increasing the pulmonary vascular resistance (PVR) and heart rate (HR) in increments up to 80% and 40%, respectively. The resulting differences in vascular flows, pressures and ventricular function parameters were analyzed. By simultaneously increasing PVR and HR, significant changes (p <0.05) were observed in cardiac index (11% increase at an 80% PVR and 40% HR increase) and pulmonary flow (26% decrease at an 80% PVR and 40% HR increase). Significant increase in mean systemic pressure (9%) was observed at 80% PVR (40% HR) increase. The results show that the poor ventricular function fails to overcome the increased preload and implied low oxygenation in BDG patients at higher altitudes, especially for those with high baseline PVRs. The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different PVR increments. Copyright © 2014 Elsevier Ltd. All rights reserved.

Efficacy of pirfenidone and disease severity of idiopathic pulmonary fibrosis: Extended analysis of phase III trial in Japan.

PubMed

Taguchi, Yoshio; Ebina, Masahito; Hashimoto, Seishu; Ogura, Takashi; Azuma, Arata; Taniguchi, Hiroyuki; Kondoh, Yasuhiro; Suga, Moritaka; Takahashi, Hiroki; Nakata, Koichiro; Sugiyama, Yukihiko; Kudoh, Shoji; Nukiwa, Toshihiro

2015-11-01

A phase III clinical trial of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) in Japan has revealed that pirfenidone attenuated the decline in vital capacity (VC) and improved progression-free survival (PFS). We conducted an extended analysis of the pirfenidone trial to investigate its efficacy with respect to IPF severity in the trial population. Patients in the phase III trial were stratified by baseline pulmonary functions including %VC predicted, %diffusion capacity for carbon monoxide predicted, and oxygen saturation by pulse oximetry on exertion and were categorized into mild, moderate, and severe groups of functional impairment. The efficacy of pirfenidone for VC and PFS over 52 weeks was compared among the three sub-populations. Of 264 patients, 102 (39%), 90 (34%), and 72 patients (27%) were classified as having mild, moderate, and severe grades of functional impairment, respectively. This classification was associated with arterial oxygen partial pressure at rest and degree of dyspnea at baseline. While pirfenidone attenuated VC decline at all grades of severity, covariance analysis revealed pirfenidone to have better efficacy in the sub-population with mild-grade IPF. Mixed model repeated measures analysis confirmed that pirfenidone markedly attenuated VC decline in patients with mild-grade IPF compared to its effects in patients with moderate or severe IPF. Pirfenidone also improved PFS markedly in patients with mild-grade IPF. This extended analysis suggested that pirfenidone exerted better therapeutic effects in patients with milder IPF. Further analysis with a larger population is needed to confirm these results. Copyright © 2015. Published by Elsevier B.V.

Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: data from the CHEST-2 open-label, randomised, long-term extension trial.

PubMed

Simonneau, Gérald; D'Armini, Andrea M; Ghofrani, Hossein-Ardeschir; Grimminger, Friedrich; Jansa, Pavel; Kim, Nick H; Mayer, Eckhard; Pulido, Tomas; Wang, Chen; Colorado, Pablo; Fritsch, Arno; Meier, Christian; Nikkho, Sylvia; Hoeper, Marius M

2016-05-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, debilitating, and life-threatening disease. We investigated associations between markers of disease severity and long-term outcomes in patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) who were receiving the soluble guanylate cyclase stimulator riociguat. We also present safety and efficacy from the final data cutoff of CHEST-2, where most patients had received riociguat for at least 2 years. Eligible patients from the CHEST-1 study entered the CHEST-2 open-label extension study, in which all patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times per day. The primary endpoint was safety and tolerability. We did exploratory assessments of associations between markers of disease severity (6-min walking distance [6MWD], N-terminal prohormone of brain natriuretic peptide [NT-proBNP] concentration, and WHO functional class) at baseline and follow-up with overall survival and clinical worsening-free survival. We used Kaplan-Meier and Cox proportional hazards analyses. CHEST-2 is registered at ClinicalTrials.gov, number NCT00910429. 237 patients entered CHEST-2. At 2 years, overall survival was 93% (95% CI 89-96) and clinical worsening-free survival was 82% (77-87). A significant association with overall survival was seen for 6MWD and NT-proBNP concentration at baseline (p=0·0199 and p=0·0183, respectively) and at follow-up (p=0·0385 and p=0·0068, respectively). Change from baseline in 6MWD was also significantly associated with survival (p=0·0047). WHO functional class at baseline and follow-up showed no significant association with overall survival but was associated with clinical worsening-free survival. Riociguat was well tolerated by most patients and no new safety signals were identified. Serious adverse events were seen in 129 (54%) of 237 patients, and 14 (6%) discontinued riociguat therapy because of adverse events. Riociguat may be used long term in patients with CTEPH. 6MWD and NT-proBNP concentration are good prognostic markers. Bayer Pharma AG. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pulmonary performance of elderly normal subjects and subjects with chronic obstructive pulmonary disease exposed to 0. 3 ppm nitrogen dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrow, P.E.; Utell, M.J.; Bauer, M.A.

1992-02-01

Symptoms and changes in pulmonary function of subjects with chronic obstructive pulmonary disease (COPD) and elderly normal subjects, induced by a 4-h exposure to 0.3 ppm NO2, were investigated using a double-blind, crossover design with purified air. The 5-day experimental protocol required approximately 2 wk with at least a 5-day separation between randomized 4-h exposures to either NO2 or air which included several periods of exercise. Over a 2-yr period, COPD subjects, all with a history of smoking, consisting of 13 men and 7 women (mean age of 60.0 yr) and 20 elderly normal subjects of comparable age and sexmore » were evaluated. During intermittent light exercise, COPD subjects demonstrated progressive decrements in FVC and FEV1 compared with baseline with 0.3 ppm NO2, but not with air. Differences in percent changes from baseline data (air-NO2) showed an equivocal reduction in FVC by repeated measures of analysis of variance and cross-over t tests (p less than 0.10). Subgroup analyses suggested that responsiveness to NO2 decreased with severity of COPD; in elderly normal subjects, NO2-induced reduction in FEV1 was greater among smokers than never-smokers. A comparison of COPD and elderly normal subjects also revealed distinctions in NO2-induced responsiveness.« less

Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study.

PubMed

Ghofrani, Hossein-Ardeschir; Simonneau, Gérald; D'Armini, Andrea M; Fedullo, Peter; Howard, Luke S; Jaïs, Xavier; Jenkins, David P; Jing, Zhi-Cheng; Madani, Michael M; Martin, Nicolas; Mayer, Eckhard; Papadakis, Kelly; Richard, Dominik; Kim, Nick H

2017-10-01

Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm 5 and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292. Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 73·0% of baseline in the macitentan group and to 87·2% in the placebo group (geometric means ratio 0·84, 95% CI 0·70-0·99, p=0·041). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]). In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. Actelion Pharmaceuticals Ltd. Copyright © 2017 Elsevier Ltd. All rights reserved.

Incentive spirometry with expiratory positive airway pressure reduces pulmonary complications, improves pulmonary function and 6-minute walk distance in patients undergoing coronary artery bypass graft surgery.

PubMed

Haeffener, Mauren Porto; Ferreira, Glória Menz; Barreto, Sérgio Saldanha Menna; Arena, Ross; Dall'Ago, Pedro

2008-11-01

The use of the incentive spirometry (IS) with expiratory positive airway pressure (EPAP) to prevent postoperative pulmonary complications (PPC) after coronary artery bypass graft (CABG) is not well established. This study sought to determine the effects of IS+EPAP after CABG. Thirty-four patients undergoing CABG were randomly assigned to a control group or IS+EPAP group. Maximal respiratory pressures, pulmonary function test, 6-minute walk test and chest x-ray were performed at baseline as well as 1 week and 1 month after CABG. Maximal inspiratory pressure was significantly higher in the IS+EPAP group compared to controls at both 1 week and 1 month (P<.001). Maximal expiratory pressure was significantly higher at 1 month compared to 1 week in IS+EPAP group (P<.01). At 1 month, forced vital capacity and forced expiratory volume in 1 second was significantly higher in IS+EPAP compared to controls (P<.05). Inspiratory capacity was higher at 1 month in IS+EPAP group compared to controls (P<.05). The distance walked in 6-minute walk test was higher at 1 month in IS+EPAP group (P<.001) compared to controls. Lastly, radiological injury score at 1 week was lower in IS+EPAP compared to controls (P<.004). In patients undergoing CABG, IS+EPAP results in improved pulmonary function and 6-minute walk distance as well as a reduction in PPC.

Effect of fenspiride on pulmonary function in the rat and guinea pig.

PubMed

Bee, D; Laude, E A; Emery, C J; Howard, P

1995-03-01

1. Fenspiride is an anti-inflammatory agent that may have a role in reversible obstructive airways disease. Small, but significant, improvements have been seen in airways function and arterial oxygen tension in patients with mild chronic obstructive pulmonary disease. These changes have been attributed to the anti-inflammatory properties of the drug. However, airways function can be improved by other means, e.g. improved ventilation/perfusion ratio or reduced airways resistance. The possibility that fenspiride may have actions other than anti-inflammatory was investigated in two animal species. 2. In the rat, actions on the pulmonary circulation were investigated in the isolated perfused lung, but fenspiride proved to be a poor pulmonary vasodilator, showing only a small reversal of the raised pulmonary artery pressure induced by hypoxia. 3. Ventilation was measured in the anaesthetized rat using whole-body plethysmography. Fenspiride caused no increase in ventilation or changes in arterial blood gases. However, a profound hypotensive action was observed with high doses. 4. The possibility that a decrease in airways resistance (R(aw)) might occur with fenspiride was investigated in anaesthetized guinea pigs. Capsaicin (30 mumol/l) was used to increase baseline R(aw) through bronchoconstriction. Fenspiride gave a dose-dependent partial reversal of the raised R(aw), and its administration by aerosol proved as efficacious as the intravenous route. In addition, the hypotensive side-effect found with intravenous injection was alleviated by aerosolized fenspiride.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchodilator efficacy of tiotropium in patients with mild to moderate COPD.

PubMed

Johansson, Gunnar; Lindberg, Anne; Romberg, Kerstin; Nordström, Lars; Gerken, Fronke; Roquet, Annika

2008-09-01

Evaluation of tiotropium efficacy in patients with mild chronic obstructive pulmonary disease (COPD) defined by the 2003 Swedish Society of Respiratory Medicine guidelines (post-bronchodilator FEV1/FVC <70%; FEV1 >60% predicted). In this 12-week, randomised, double-blind, placebo-controlled study of tiotropium 18 mcg once daily versus placebo, respiratory function was assessed on Days 1, 15 and 85 (baseline: pre-dose Day 1). Mean+/-SD baseline FEV1 (% predicted) was 73.4+/-12.5 (tiotropium, n=107; placebo, n=117). Tiotropium significantly improved change from baseline in area under the curve from pre-dose to 2 hours post-dose (AUC0-2 h) FEV1 versus placebo, by 166+/-26 mL (mean+/-SE) at study end (p<0.0001). With tiotropium, there were significant increases in the change in AUC0-2 h FVC versus baseline, and trough FEV1 and FVC, versus placebo, on all test days (p<0.01). Adverse event rates were similar. Compared with placebo, tiotropium improved lung function in patients with mild COPD.

Pulmonary function and adverse cardiovascular outcomes: Can cardiac function explain the link?

PubMed

Burroughs Peña, Melissa S; Dunning, Allison; Schulte, Phillip J; Durheim, Michael T; Kussin, Peter; Checkley, William; Velazquez, Eric J

2016-12-01

The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization. This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation. We also used Cox proportional hazards models to examine the relationship between FVC and FEV1 with all-cause mortality and cardiac hospitalization. A total of 1807 patients were included in this analysis with a median age of 61 years and 50% were female. Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals with FVC less than 2.75 L, decreased FVC was associated with increased all-cause mortality after adjusting for left and right heart echocardiographic variables (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was associated with increased cardiac hospitalization after adjusting for left heart size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75, 95% CI 0.57, 0.97). In a tertiary care center reduced pulmonary function was associated with adverse cardiovascular events, a relationship that is not fully explained by left heart remodeling or right heart dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pulmonary Predictors of Incident Diabetes in Smokers

PubMed Central

Kinney, Gregory L.; Baker, Emma H.; Klein, Oana L.; Black-Shinn, Jennifer L.; Wan, Emily S.; Make, Barry; Regan, Elizabeth; Bowler, Russell P.; Lutz, Sharon M.; Young, Kendra A.; Duca, Lindsey M.; Washko, George R.; Silverman, Edwin K.; Crapo, James D.; Hokanson, John E.

2016-01-01

Background: Diabetes mellitus and its complications are a large and increasing burden for health care worldwide. Reduced pulmonary function has been observed in diabetes (both type 1 and type 2), and this reduction is thought to occur prior to diagnosis. Other measures of pulmonary health are associated with diabetes, including lower exercise tolerance, greater dyspnea, lower quality of life (as measured by the St. George’s Respiratory Questionaire [SGRQ]) and susceptibility to lung infection and these measures may also predate diabetes diagnosis. Methods: We examined 7080 participants in the COPD Genetic Epidemiology (COPDGene) study who did not report diabetes at their baseline visit and who provided health status updates during 4.2 years of longitudinal follow-up (LFU). We used Cox proportional hazards modeling, censoring participants at final LFU contact, reported mortality or report of incident diabetes to model predictors of diabetes. These models were constructed using known risk factors as well as proposed markers related to pulmonary health, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, respiratory exacerbations (RE), 6-minute walk distance (6MWD), pulmonary associated quality of life (as measured by the SGRQ), corticosteroid use, chronic bronchitis and dyspnea. Results: Over 21,519 person years of follow-up, 392 of 7080 participants reported incident diabetes which was associated with expected predictors; increased body mass index (BMI), high blood pressure, high cholesterol and current smoking status. Age, gender and accumulated smoking exposure were not associated with incident diabetes. Additionally, preserved ratio with impaired spirometry (PRISm) pattern pulmonary function, reduced 6MWD and any report of serious pulmonary events were associated with incident diabetes. Conclusions: This cluster of pulmonary indicators may aid clinicians in identifying and treating patients with pre- or undiagnosed diabetes. PMID:27795984

Evaluation of respiratory variables in smelter and control workers before and during a shutdown period

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holness, D.L.; Batten, B.; Broder, I.

1985-05-01

Thirty-six smelter workers examined in this pilot study were found to have a higher prevalence of cough and dyspnea and lower baseline lung function than did 31 controls. They also experienced decreases in forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1) over the workweek while the controls did not. Baseline airflow rates and change in FVC and FEV1 over the workweek varied with levels of sulfur dioxide and particulates. Twenty-three smelter workers and 21 controls were seen on a second occasion, six months into an extended shutdown. The smelter workers continued to have a higher prevalence ofmore » cough and dyspnea and lower baseline lung function than the controls. There was, however, a slight increase in lung function in both the exposed workers and the controls during the shutdown. The results suggest that smelter workers may develop both acute and chronic work-related pulmonary effects and that the chronic effects may be nonreversible.« less

Enhanced ventricular pump function and decreased reservoir backflow sustain rise in pulmonary blood flow after reduction of lung liquid volume in fetal lambs.

PubMed

Smolich, Joseph J

2014-02-15

Although a reduction in lung liquid volume increases fetal pulmonary blood flow, the changes in central flow patterns that sustain this increased pulmonary perfusion are unknown. To address this issue, eight anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), ductus arteriosus (DA), and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes, with blood flow profile and wave intensity analyses performed at baseline and after withdrawal of lung liquid via an endotracheal tube. Reducing lung liquid volume by 19 ± 6 ml/kg (mean ± SD) augmented right ventricular power by 34% (P < 0.001), with distribution of an accompanying increase in mean PT blood flow (245 ± 63 ml/min, P < 0.001) to the lungs (169 ± 91 ml/min, P = 0.001) and across the DA (77 ± 92 ml/min, P = 0.04). However, although PT and DA flow increments were confined to systole and were related to an increased magnitude of flow-increasing, forward-running compression waves, the rise in PA flow spanned both systole (108 ± 66 ml/min) and diastole (61 ± 32 ml/min). Flow profile analysis showed that the step-up in PA diastolic flow was associated with diminished PA diastolic backflow and accompanied by a lesser degree of diastolic right-to-left DA shunting. These data suggest that an increased pulmonary blood flow after reduction of lung liquid volume is associated with substantial changes in PT-DA-PA interactions and underpinned by two main factors: 1) enhanced right ventricular pump function that increases PA systolic inflow and 2) decreased PA diastolic backflow that arises from a fundamental change in PA reservoir function, thereby resulting in greater passage of systolic inflow through the lungs.

Contribution of the bronchial circulation to lung preservation.

PubMed

LoCicero, J; Massad, M; Matano, J; Greene, R; Dunn, M; Michaelis, L L

1991-05-01

Short preservation time still severely limits lung transplantation. To determine the effect of bronchial arterial flush preservation, we studied 54 dogs using the isolated perfused working lung model. After baseline measurements, lungs were flushed with lactated Ringer's solution (60 ml/kg at 8 degrees C) by one of three methods: pulmonary artery perfusion, bronchial artery perfusion through a 15 cm closed aortic segment, or simultaneous pulmonary-bronchial artery perfusion. These groups were further subdivided and tested after 0, 4, and 17 hours of storage at 4 degrees C (n = 6 each). Lungs were ventilated (flow rate 140 ml/kg/min; inspired oxygen fraction 0.21) and continuously reperfused with normothermic deoxygenated autologous blood in a closed loop. Measured variables were hemodynamics, aerodynamics, and leukocytes in bronchoalveolar lavage. Survival time was determined from initial reperfusion to failure of the lung to oxygenate. After 0 and 4 hours of storage, there was no significant difference in survival times. After 17 hours, lungs subjected to pulmonary-bronchial artery perfusion survived longer than those perfused via either the pulmonary or bronchial arteries alone (120 +/- 24 versus 38 +/- 14 or 52 +/- 16 minutes; p less than 0.01). Pulmonary artery pressure and resistance in all groups except at failure were never different from baseline values in the intact animal. Shunts in the pulmonary-bronchial artery perfusion groups were closest to baseline at onset (8% +/- 4%) and remained lower throughout reperfusion than in the groups subjected to pulmonary or bronchial artery perfusion alone. After 17 hours, static compliance of pulmonary artery-perfused lungs was worse than baseline (1.1 +/- 0.2 x 10(-2) versus 3.2 +/- 0.7 x 10(-2) L/cm H2O/sec; p less than 0.05), whereas compliance in the pulmonary-bronchial artery perfusion groups remained constant (3.6 +/- 1.5 x 10(-2) L/cm H2O/sec). Elastic work performed by lungs subjected to pulmonary-bronchial artery flushing at onset was significantly lower when these lungs were reperfused immediately (201 +/- 14 versus 295 +/- 35 gm-m/min for pulmonary artery-flushed lungs) or after 4 hours of storage (229 +/- 30 versus 290 +/- 24 gm-m/min for pulmonary artery-flushed lungs). Bronchoalveolar lavage after 17 hours in the group subjected to pulmonary bronchial artery flushing demonstrated leukocyte counts similar to those of intact lungs (45 +/- 5 versus 29 +/- 8/mm3) and significantly less than in lungs subjected to pulmonary or bronchial artery flushing (137 +/- 18 or 82 +/- 10/mm3, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

An encapsulated juice powder concentrate improves markers of pulmonary function and cardiovascular risk factors in heavy smokers.

PubMed

Bamonti, Fabrizia; Pellegatta, Marco; Novembrino, Cristina; Vigna, Luisella; De Giuseppe, Rachele; de Liso, Federica; Gregori, Dario; Noce, Cinzia Della; Patrini, Lorenzo; Schiraldi, Gianfranco; Bonara, Paola; Calvelli, Laura; Maiavacca, Rita; Cighetti, Giuliana

2013-01-01

Cigarette smoking is associated with reduced pulmonary function and increased risk factors for cardiovascular disease. This randomized placebo-controlled double-blind study evaluated the effects of two different combinations of mixed fruit and vegetable juice powder concentrate (Juice Plus+, NSA, Collierville, TN) on heavy smokers. At baseline (T 0) and after 3 months' supplementation (T 1), pulmonary function parameters and cardiovascular risk factors-that is, plasma total homocysteine (tHcy) with related B vitamins and cysteine (tCys) concentrations-were assessed in 75 apparently healthy smokers (aged 49.2 ± 10.6 years, >20 cigarettes/d, duration ≥10 years) randomized into 3 groups: placebo (P), fruit/vegetable (FV) and fruit/vegetable/berry (FVB). T 0: most smokers showed abnormalities in tHcy and tCys concentrations. T 1: respiratory function was unchanged in P and slightly, but not significantly, improved in FV, whereas FVB showed a significant improvement in forced expiratory flow at 25% (FEF25; p < 0.0001 vs P and FV) and significant improvement in CO diffusion lung/alveolar volume (DLCO/VA). FV and FVB (50%) showed significant reduction in tHcy and tCys compared to T 0 ( p < 0.0001) and P ( p < 0.0001). At T 1, both supplemented groups, but to a greater extent the FVB group, showed improvements in some pulmonary parameters, cardiovascular risk factors, and folate status. The beneficial effects of Juice Plus+ supplementation could potentially help smokers, even if smoking cessation is advisable.

Can patients with pulmonary hypertension travel to high altitude?

PubMed

Luks, Andrew M

2009-01-01

With the increasing popularity of adventure travel and mountain activities, it is likely that many high altitude travelers will have underlying medical problems and approach clinicians for advice about ensuring a safe sojourn. Patients with underlying pulmonary hypertension are one group who warrants significant concern during high altitude travel, because ambient hypoxia at high altitude will trigger hypoxic pulmonary vasoconstriction and cause further increases in pulmonary artery (PA) pressure, which may worsen hemodynamics and also predispose to acute altitude illness. After addressing basic information about pulmonary hypertension and pulmonary vascular responses to acute hypoxia, this review discusses the evidence supporting an increased risk for high altitude pulmonary edema in these patients, concerns regarding worsening oxygenation and right-heart function, the degree of underlying pulmonary hypertension necessary to increase risk, and the altitude at which such problems may occur. These patients may be able to travel to high altitude, but they require careful pre-trip assessment, including echocardiography and, when feasible, high altitude simulation testing with echocardiography to assess changes in PA pressure and oxygenation under hypoxic conditions. Those with mean PA pressure > or =35 mm Hg or systolic PA pressure > or =50 mm Hg at baseline should avoid travel to >2000 m; but if such travel is necessary or strongly desired, they should use supplemental oxygen during the sojourn. Patients with milder degrees of pulmonary hypertension may travel to altitudes <3000 m, but should consider prophylactic measures, including pulmonary vasodilators or supplemental oxygen.

The pulmonary response of white and black adults to six concentrations of ozone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seal, E. Jr.; McDonnell, W.F.; House, D.E.

1993-04-01

Many early studies of respiratory responsiveness to ozone (O3) were done on healthy, young, white males. The purpose of this study was to determine whether gender or race differences in O3 response exist among white and black, males and females, and to develop concentration-response curves for each of the gender-race groups. Three hundred seventy-two subjects (n > 90 in each gender-race group), ages 18 to 35 yr, were exposed once for 2.33 h to 0.0 (purified air), 0.12, 0.18, 0.24, 0.30, or 0.40 ppm O3. Each exposure was preceded by baseline pulmonary function tests and a symptom questionnaire. The firstmore » 2 h of exposure included alternating 15-min periods of rest and exercise on a motorized treadmill producing a minute ventilation (VE) of 25 L/min/m2 body surface area (BSA). After exposure, subjects completed a set of pulmonary function tests and a symptom questionnaire. Lung function and symptom responses were expressed as percent change from baseline and analyzed using a nonparametric two factor analysis of variance. Three primary variables were analyzed: FEV1, specific airway resistance (SRaw), and cough. Statistical analysis demonstrated no significant differences in response to O3 among the individual gender-race groups. For the group as a whole, changes in the variables FEV1, SRaw, and cough were first noted at 0.12, 0.18, and 0.18 ppm O3, respectively. Adjusted for exercise difference, concentration-response curves for FEV1 and cough among white males were consistent with previous reports (1).« less

Genetic Ancestry-Smoking Interactions and Lung Function in African Americans: A Cohort Study

PubMed Central

Colangelo, Laura A.; Williams, L. Keoki; Sen, Saunak; Kritchevsky, Stephen B.; Meibohm, Bernd; Galanter, Joshua; Hu, Donglei; Gignoux, Christopher R.; Liu, Yongmei; Harris, Tamara B.; Ziv, Elad; Zmuda, Joseph; Garcia, Melissa; Leak, Tennille S.; Foreman, Marilyn G.; Smith, Lewis J.; Fornage, Myriam; Liu, Kiang; Burchard, Esteban G.

2012-01-01

Background Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans. Methodology/Principal Findings We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA) Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV1) per pack-year of smoking (−5.7 ml FEV1/ smoking pack-year) compared with smokers with lower African ancestry (−4.6 ml in FEV1/ smoking pack-year) (interaction P value  = 0.17). Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV1 decline in Health ABC and independently replicated in CARDIA. Conclusions/Significance African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking. PMID:22737244

Efficacy of concomitant administration of clarithromycin and acetylcysteine in bronchiolitis obliterans in seventeen sulfur mustard—exposed patients: An open-label study

PubMed Central

Ghanei, Mostafa; Abolmaali, Kamran; Aslani, Jafar

2004-01-01

Background: Victims of sulfur mustard (SM) gas exposure experience different types of chronic pulmonary disease, manifested as cough, sputum production, and dyspnea. Conventional therapies (eg, immunosuppressive drugs, corticosteroids) have not been effective in these patients. Objective: This study was carried out to determine the efficacy of concomitant administration of the macrolide clarithromycin and the mucolytic agent acetylcysteine in the treatment of bronchiolitis obliterans in SM-exposed patients. Methods: This open-label clinical study was conducted at the Research Center of Chemical Injuries, Baqiyatallah Medical Sciences University, Tehran, Iran. Clarithromycin and acetylcysteine were administered concomitantly for 6 months to male SM-exposed patients with chronic bronchitis and bronchiolitis obliterans who were nonresponsive to conventional treatments. Efficacy analysis included symptom assessment and pulmonary function tests (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and FEV1/FVC ratio) using spirometry, performed at baseline and after 2 and 6 months of treatment. Results: Seventeen male patients (mean [SD] age, 38.3 [5.3] years [range, 31–50 years]; mean [SD] body weight, 77.9 [15.7] kg) were included in the study. Cough and sputum production were each found in 10 of 17 patients (58.8%) at baseline and were improved in all 10 patients after the administration of clarithromycin and acetylcysteine. FEV1 and FVC also were improved, by mean (SD) 10.6% (9.7%) (P < 0.001 vs baseline) and 12.9% (13.6%) (P = 0.001 vs baseline). No significant change in FEV1/FVC ratio was found. Conclusions: In this study of concomitant administration of clarithromycin and acetylcysteine for the treatment of bronchiolitis obliterans in SM-exposed patients, symptoms and pulmonary function were improved. These results may have been related to the therapeutic effects of a macrolide antibiotic on chronic bronchitis and bronchiolitis obliterans in these patients. Based on the results of this study, we recommend this treatment for chemical warfare victims with recurrent exacerbation of bronchitis who do not respond to conventional treatment. PMID:24672101

Agents Which Mediate Pulmonary Edema

DTIC Science & Technology

1990-12-01

described in this report has focused on delineating various approach s to understanding mechanisms of pathological changes leading to pulmonary edema... pathological changes leading to pulmonary edema. Baseline parameters including hemodynamics, gas exchange and lymph flow were determined for the sheep...mediastinal lymph node is catheterized permitting frequent sampling of lung lymph. This model permits the monitoring of changes in pulmonary vascular

Correlation of pulmonary function and usual interstitial pneumonia computed tomography patterns in idiopathic pulmonary fibrosis.

PubMed

Arcadu, Antonella; Byrne, Suzanne C; Pirina, Pietro; Hartman, Thomas E; Bartholmai, Brian J; Moua, Teng

2017-08-01

Little is known about presenting 'inconsistent' or 'possible' usual interstitial pneumonia (UIP) computed tomography (CT) patterns advancing to 'consistent' UIP as disease progresses in idiopathic pulmonary fibrosis (IPF). We hypothesized that if 'consistent' UIP represented more advanced disease, such a pattern on presentation should also correlate with more severe pulmonary function test (PFT) abnormalities. Consecutive IPF patients (2005-2013) diagnosed by international criteria with baseline PFT and CT were included. Presenting CTs were assessed by three expert radiologists for consensus UIP pattern ('consistent', 'possible', and 'inconsistent'). Approximation of individual and combined interstitial abnormalities was also performed with correlation of interstitial abnormalities and UIP CT pattern made with PFT findings and survival. Three-hundred and fifty patients (70% male) were included with a mean age of 68.3 years. Mean percent predicted forced vital capacity (FVC%) and diffusion capacity (DLCO%) was 64% and 45.5% respectively. Older age and male gender correlated more with 'consistent' UIP CT pattern. FVC% was not associated with any UIP pattern but did correlate with total volume of radiologist assessed interstitial abnormalities. DLCO% was lower in those with 'consistent' UIP pattern. A 'consistent' UIP CT pattern was also not independently predictive of survival after correction for age, gender, FVC%, and DLCO%. PFT findings appear to correlate with extent of radiologic disease but not specific morphologic patterns. Whether such UIP patterns represent different stages of disease severity or radiologic progression is not supported by coinciding pulmonary function decline. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sildenafil improves renal function in patients with pulmonary arterial hypertension

PubMed Central

Webb, David J; Vachiery, Jean-Luc; Hwang, Lie-Ju; Maurey, Julie O

2015-01-01

Aim Elevated serum creatinine (sCr) and low estimated glomerular filtration rate (eGFR) are associated with poor outcomes in patients with pulmonary arterial hypertension (PAH) whereas sildenafil treatment improves PAH outcomes. This post hoc analysis assessed the effect of sildenafil on kidney function and links with clinical outcomes including 6-min walk distance, functional class, time to clinical worsening and survival. Methods Patients with PAH received placebo or sildenafil 20, 40 or 80 mg three times daily in the SUPER-1 study and open-label sildenafil titrated to 80 mg three times daily (as tolerated) in the extension study. Results Baseline characteristics were similar among groups (n = 277). PAH was mostly idiopathic (63%) and functional class II (39%) or III (58%). From baseline to week 12, kidney function improved (increased eGFR, decreased sCr) with sildenafil and worsened with placebo. In univariate logistic regression, improved kidney function was associated with significantly improved exercise and functional class (odds ratios 1.17 [95% CI 1.01, 1.36] and 1.21 [95% CI 1.03, 1.41], respectively, for sCr and 0.97 [95% CI 0.94, 0.99] and 0.97 [95% CI 0.94, 0.99] for eGFR, all P < 0.05). In patients who maintained or improved kidney function, time to worsening was significantly delayed (P < 0.02 for both kidney parameters). Observed trends towards improved survival were not significant. Patients with eGFR <60 (vs. ≥60) ml min–1 1.73 m–2 appeared to have worse survival. Conclusions Sildenafil treatment was associated with improved kidney function in patients with PAH, which was in turn associated with improved exercise capacity and functional class, a reduced risk of clinical worsening, and a trend towards reduced mortality. PMID:25727860

Trial occlusion to assess the risk of persistent pulmonary arterial hypertension after closure of a large patent ductus arteriosus in adolescents and adults with elevated pulmonary artery pressure.

PubMed

Zhang, Duan-Zhen; Zhu, Xian-Yang; Lv, Bei; Cui, Chun-Sheng; Han, Xiu-Min; Sheng, Xiao-Tang; Wang, Qi-Guang; Zhang, Po

2014-08-01

No method is available to predict whether patients with patent ductus arteriosus (PDA) and severe pulmonary arterial hypertension (PAH) will show persistent postprocedural PAH (PP-PAH) after PDA closure. This study evaluated the usefulness of trial occlusion for predicting PP-PAH after transcatheter PDA closure in patients with severe PAH. Trial occlusion was performed in 137 patients (age ≥12 years) with PDA and severe PAH. All patients undergoing trial occlusion had a mean pulmonary artery pressure ≥45 mm Hg, pulmonary:systemic flow (Qp/Qs) ratio >1.5, and pulmonary:systemic resistance (Rp/Rs) ratio <0.7. A total of 135 patients (98%) showing stable hemodynamics during occlusion trial underwent successful device closure. Linear correlation analysis revealed weak or moderate relationships between the baseline and post-trial pulmonary artery pressures and pulmonary:systemic pressure (Pp/Ps) ratios. Patients were followed up for 1 to 10 years (median: 5 years). PP-PAH (systolic pulmonary artery pressure >50 mm Hg by Doppler echocardiography) was detected in 17 patients (13%), who displayed no significant differences in sex and age compared with patients without PP-PAH. According to discriminant analysis, the strongest discriminators between patients with and without PP-PAH were the baseline left ventricular end-diastolic volume and the baseline and post-trial systolic Pp/Ps ratios. In particular, a post-trial systolic Pp/Ps ratio >0.5 correctly classified 100% of the PP-PAH and non-PAH patients. Trial occlusion is a feasible method to predict PP-PAH in patients with PDA and severe PAH. A post-trial systolic Pp/Ps ratio >0.5 indicates a high risk of PP-PAH occurrence after device closure. © 2014 American Heart Association, Inc.

Effect of Treatment of Cystic Fibrosis Pulmonary Exacerbations on Systemic Inflammation

PubMed Central

Thompson, Valeria; Chmiel, James F.; Montgomery, Gregory S.; Nasr, Samya Z.; Perkett, Elizabeth; Saavedra, Milene T.; Slovis, Bonnie; Anthony, Margaret M.; Emmett, Peggy; Heltshe, Sonya L.

2015-01-01

Rationale: In cystic fibrosis (CF), pulmonary exacerbations present an opportunity to define the effect of antibiotic therapy on systemic measures of inflammation. Objectives: Investigate whether plasma inflammatory proteins demonstrate and predict a clinical response to antibiotic therapy and determine which proteins are associated with measures of clinical improvement. Methods: In this multicenter study, a panel of 15 plasma proteins was measured at the onset and end of treatment for pulmonary exacerbation and at a clinically stable visit in patients with CF who were 10 years of age or older. Measurements and Main Results: Significant reductions in 10 plasma proteins were observed in 103 patients who had paired blood collections during antibiotic treatment for pulmonary exacerbations. Plasma C-reactive protein, serum amyloid A, calprotectin, and neutrophil elastase antiprotease complexes correlated most strongly with clinical measures at exacerbation onset. Reductions in C-reactive protein, serum amyloid A, IL-1ra, and haptoglobin were most associated with improvements in lung function with antibiotic therapy. Having higher IL-6, IL-8, and α1-antitrypsin (α1AT) levels at exacerbation onset were associated with an increased risk of being a nonresponder (i.e., failing to recover to baseline FEV1). Baseline IL-8, neutrophil elastase antiprotease complexes, and α1AT along with changes in several plasma proteins with antibiotic treatment, in combination with FEV1 at exacerbation onset, were predictive of being a treatment responder. Conclusions: Circulating inflammatory proteins demonstrate and predict a response to treatment of CF pulmonary exacerbations. A systemic biomarker panel could speed up drug discovery, leading to a quicker, more efficient drug development process for the CF community. PMID:25714657

Thrombus resolution and right ventricular functional recovery using ultrasound-accelerated thrombolysis in acute massive and submassive pulmonary embolism.

PubMed

Ozcinar, Evren; Cakici, Mehmet; Dikmen Yaman, Nur; Baran, Cagdas; Aliyev, Anar; Inan, Bahadir; Durdu, Serkan; Akar, Ahmet R; Sirlak, Mustafa

2017-10-01

This study aims to evaluate the efficacy and safety of ultrasound-accelerated catheter-directed thrombolysis (UACDT) in the treatment of massive and submassive pulmonary embolism (PE). We conducted a prospective, observational cohort study of consequtive patients with massive or submassive PE treated with low-dose UACDT using EKOS EkoSonic® system at single center from May 2014 until April 2015. Overall, thirty-eight patients (median age, 64.5 years) were included. The primary safety outcomes were change in right ventricular (RV) to left ventricular (LV) diameter ratio within 24 hours of procedure initiation, at 1- and 6-month follow-up and major bleeding within 96 hours of the procedure initiation. BNP, troponin and D-dimer levels were also measured. The ultrasound-accelerated thrombolytic catheters were bilaterally placed in 25 (65.8%) patients. The median tissue plasminogen activator (tPA) dose for all patients in our study was 21.0 mg and the median infusion time was 15 hours. Measurements before and after treatment showed a decrease in pulmonary artery pressure. The median value of RV/LV diameter ratio decreased from 0.9 (0.7-1.1) at baseline to 0.7 (0-0.97) at 6-month follow-up (P=0.001) and pulmonary artery pressure from 61.4 ±16.7 to 37.2±9.1 mmHg (P=0.001). The median BNP level at baseline was 169 (29-721) pg/mL and 45.5 (0-328) pg/mL at 6 month follow-up (P=0.001). Of 38 patients with PE, one had intracranial hemorrage, one gastrointestinal bleeding and two developed puncture site bleeding. This prospective study provides alternative treatment option and an addition to the treatment algorithm for the management of pulmonary embolism.

Deployment Pulmonary Health

DTIC Science & Technology

2015-02-11

A similar risk-based approach may be appropriate for deploying military personnel. e) If DoD were to consider implementing a large- scale pre...quality of existing spirometry programs prior to considering a larger scale pre-deployment effort. Identifying an accelerated decrease in spirometry...baseline spirometry on a wider scale . e) Conduct pre-deployment baseline spirometry if there is a significant risk of exposure to a pulmonary hazard based

Characteristics and survival of adult Swedish PAH and CTEPH patients 2000-2014.

PubMed

Rådegran, Göran; Kjellström, Barbro; Ekmehag, Björn; Larsen, Flemming; Rundqvist, Bengt; Blomquist, Sofia Berg; Gustafsson, Carola; Hesselstrand, Roger; Karlsson, Monica; Kornhall, Björn; Nisell, Magnus; Persson, Liselotte; Ryftenius, Henrik; Selin, Maria; Ullman, Bengt; Wall, Kent; Wikström, Gerhard; Willehadson, Maria; Jansson, Kjell

2016-08-01

The Swedish Pulmonary Arterial Hypertension Register (SPAHR) is an open continuous register, including pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients from 2000 and onwards. We hereby launch the first data from SPAHR, defining baseline characteristics and survival of Swedish PAH and CTEPH patients. Incident PAH and CTEPH patients 2008-2014 from all seven Swedish PAH-centres were specifically reviewed. There were 457 PAH (median age: 67 years, 64% female) and 183 CTEPH (median age: 70 years, 50% female) patients, whereof 77 and 81%, respectively, were in functional class III-IV at diagnosis. Systemic hypertension, diabetes, ischaemic heart disease and atrial fibrillation were common comorbidities, particularly in those >65 years. One-, 3- and 5-year survival was 85%, 71% and 59% for PAH patients. Corresponding numbers for CTEPH patients with versus without pulmonary endarterectomy were 96%, 89% and 86% versus 91%, 75% and 69%, respectively. In 2014, the incidence of IPAH/HPAH, associated PAH and CTEPH was 5, 3 and 2 per million inhabitants and year, and the prevalence was 25, 24 and 19 per million inhabitants. The majority of the PAH and CTEPH patients were diagnosed at age >65 years, in functional class III-IV, and exhibiting several comorbidities. PAH survival in SPAHR was similar to other registers.

Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep

PubMed Central

Seedorf, Gregory J.; Brown, Alicia; Roe, Gates; O'Meara, Meghan C.; Gien, Jason; Tang, Jen-Ruey; Abman, Steven H.

2011-01-01

Intrauterine growth restriction (IUGR) increases the risk for bronchopulmonary dysplasia (BPD). Abnormal lung structure has been noted in animal models of IUGR, but whether IUGR adversely impacts fetal pulmonary vascular development and pulmonary artery endothelial cell (PAEC) function is unknown. We hypothesized that IUGR would decrease fetal pulmonary alveolarization, vascular growth, and in vitro PAEC function. Studies were performed in an established model of severe placental insufficiency and IUGR induced by exposing pregnant sheep to elevated temperatures. Alveolarization, quantified by radial alveolar counts, was decreased 20% (P < 0.005) in IUGR fetuses. Pulmonary vessel density was decreased 44% (P < 0.01) in IUGR fetuses. In vitro, insulin increased control PAEC migration, tube formation, and nitric oxide (NO) production. This response was absent in IUGR PAECs. VEGFA stimulated tube formation, and NO production also was absent. In control PAECs, insulin increased cell growth by 68% (P < 0.0001). Cell growth was reduced in IUGR PAECs by 29% at baseline (P < 0.01), and the response to insulin was attenuated (P < 0.005). Despite increased basal and insulin-stimulated Akt phosphorylation in IUGR PAECs, endothelial NO synthase (eNOS) protein expression as well as basal and insulin-stimulated eNOS phosphorylation were decreased in IUGR PAECs. Both VEGFA and VEGFR2 also were decreased in IUGR PAECs. We conclude that fetuses with IUGR are characterized by decreased alveolar and vascular growth and PAEC dysfunction in vitro. This may contribute to the increased risk for adverse respiratory outcomes and BPD in infants with IUGR. PMID:21873446

Incremental value of right atrial strain for early diagnosis of hemodynamic deterioration in pulmonary hypertension: a new noninvasive tool for a more comprehensive diagnostic paradigma.

PubMed

Piccinino, Cristina; Giubertoni, Ailia; Zanaboni, Jacopo; Gravellone, Miriam; Sola, Daniele; Rosso, Roberta; Ferrarotti, Lorena; Marino, Paolo Nicola

2017-11-01

Increased right atrial size is related to adverse prognosis in pulmonary hypertension. The potential incremental value of right atrial function assessment is still unclear. We tested the relationship between right atrial two-dimensional speckle-tracking echocardiography impairment and hemodynamic, functional and clinical deterioration in patients with pulmonary hypertension. We prospectively evaluated 36 patients (27 female, 9 male; mean age 68 ± 13 years) with suspected pulmonary hypertension undergoing right heart catheterization and 16 matched controls. All patients underwent baseline evaluation by New York Heart Association functional class, 6-min walking test, brain natriuretic peptide (BNP), and standard two-dimensional echocardiography in less than 48 h of right heart catheterization. Right atrial two-dimensional speckle-tracking echocardiography was assessed by averaging all segments in standard four-chamber apical view. Right atrial global integral strain was significantly lower in patients compared with controls (11.40 ± 5.22% vs. 25.72 ± 5.95 P < 0.001). Moreover, right atrial global strain, but not right atrial area or volume, was correlated with invasively measured cardiac index (CI) (r = 0.72; P < 0.0001) and pulmonary vascular resistances in all patients, even though stronger in subjects with precapillary pulmonary hypertension (r = -0.42, P = 0.018; r = -0.54, P = 0.007 respectively; P = 0.007). It was also correlated with New York Heart Association (P = 0.027), BNP (P = 0.002), and 6-min walking test (P = 0.006). After multivariate analysis including right atrial volume, tricuspid annular plane systolic excursion, left atrial strain, and BNP, right atrial global strain showed the strongest correlation with CI. Area under the curve optimal cutoff for predicting CI at least 2.4 l/min/m was 17% (area under the curve: 0.83, sensitivity: 90%, specificity: 54%). Right atrial global strain can identify right atrial functional impairment before structural changes and may be implemented in a comprehensive, noninvasive right heart assessment for diagnosis and follow-up of pulmonary hypertension patients.

High-resolution CT evaluation of bronchial lumen to vertebral body, pulmonary artery to vertebral body and bronchial lumen to pulmonary artery ratios in Dirofilaria immitis-infected cats with and without selamectin administration.

PubMed

Lee-Fowler, Tekla M; Cole, Robert C; Dillon, A Ray; Graham, Shannon; Tillson, D Michael; Barney, Sharron

2017-10-01

Objectives The bronchial lumen to pulmonary artery (BA) ratio is utilized to evaluate pulmonary pathology on CT images. The BA ratio may be unreliable when changes are present in bronchial and pulmonary arteries concurrently. Bronchial lumen to vertebral body (BV) and pulmonary artery to vertebral body (AV) ratios have been established in normal cats and may serve as an alternative. This study aimed to evaluate the BV, AV and BA ratios in cats before and after infection with Dirofilaria immitis, with and without selamectin administration, and to characterize the distribution of disease. Methods Archived CT images were reviewed from three groups of cats: D immitis-infected untreated (n = 6); infected pretreated with selamectin (n = 6); uninfected untreated (n = 5). The BV, AV and BA ratios were calculated for all lung lobes for baseline (D0) and day 240 (D240) postinfection. Ratios and percentage change from baseline were compared between lobes and between groups. Results BV and AV ratios were more consistent in identifying abnormalities when disease was present in bronchial and arteries concurrently than BA ratios. Infected untreated cats had significant changes in both BV and AV ratios and percentage change from baseline. Abnormal BV and AV ratios were noted in the infected selamectin group, although less widely distributed. Conclusions and relevance The BV and AV ratios more accurately identified bronchial and pulmonary artery abnormalities in D immitis-infected cats. Both bronchial and pulmonary artery changes were present in infected cats, decreasing the diagnostic application of the BA ratio. Pulmonary artery changes were more widely distributed than bronchial changes in the lung. Heartworm-infected cats receiving selamectin had bronchial and pulmonary artery changes but to a lesser extent than untreated heartworm-infected cats. The CT-derived BV and AV ratios are a useful measure to evaluate lung disease of cats.

Impact of Net Atrioventricular Compliance on Clinical Outcome in Mitral Stenosis

PubMed Central

Nunes, Maria Carmo P.; Hung, Judy; Barbosa, Marcia M.; Esteves, William A.; Carvalho, Vinicius T.; Lodi-Junqueira, Lucas; Fonseca Neto, Cirilo P.; Tan, Timothy C.; Levine, Robert A.

2014-01-01

Background Net atrioventricular compliance (Cn) has been reported to be an important determinant of pulmonary hypertension in mitral stenosis (MS). We hypothesized that, as Cn reflects hemodynamic consequences of MS, it may be useful in assessing prognosis. To date, limited data with an assumed Cn cutoff have indicated the need for larger prospective studies. This prospective study was designed to determine the impact of Cn on clinical outcome and its contribution to pulmonary pressure in MS. In addition, we aimed to identify a cutoff value of Cn for outcome prediction in this setting. Methods and Results A total of 128 patients with rheumatic MS without other significant valve disease were prospectively enrolled. Comprehensive echocardiography was performed and Doppler-derived Cn estimated using a previously validated equation. The endpoint was either mitral valve intervention or death. Cn was an important predictor of pulmonary pressure, regardless of classic measures of MS severity. During a median follow-up of 22 months, the endpoint was reached in 45 patients (35%). Baseline Cn predicted outcome, adding prognostic information beyond that provided by mitral valve area and functional status. Cn ≤ 4 mL/mmHg best predicted unfavorable outcome in derivation and validation sets. A subgroup analysis including only initially asymptomatic patients with moderate to severe MS without initial indication for intervention (40.6 % of total) demonstrated that baseline Cn predicted subsequent adverse outcome even after adjusting for classic measures of hemodynamic MS severity (hazard ratio [HR] 0.33, 95% confidence interval [CI] 0.14–0.79, p = 0.013). Conclusions Cn contributes to pulmonary hypertension beyond of stenosis severity itself. In a wide spectrum of MS severity, Cn is a powerful predictor of adverse outcome, adding prognostic value to clinical data and mitral valve area. Importantly, baseline Cn predicts a progressive course with subsequent need for intervention in initially asymptomatic patients. Cn assessment therefore has potential value for clinical risk stratification and monitoring in MS patients. PMID:24097419

Restrictive allograft syndrome (RAS): a novel form of chronic lung allograft dysfunction.

PubMed

Sato, Masaaki; Waddell, Thomas K; Wagnetz, Ute; Roberts, Heidi C; Hwang, David M; Haroon, Ayesha; Wagnetz, Dirk; Chaparro, Cecilia; Singer, Lianne G; Hutcheon, Michael A; Keshavjee, Shaf

2011-07-01

Bronchiolitis obliterans syndrome (BOS) with small-airway pathology and obstructive pulmonary physiology may not be the only form of chronic lung allograft dysfunction (CLAD) after lung transplantation. Characteristics of a form of CLAD consisting of restrictive functional changes involving peripheral lung pathology were investigated. Patients who received bilateral lung transplantation from 1996 to 2009 were retrospectively analyzed. Baseline pulmonary function was taken as the time of peak forced expiratory volume in 1 second (FEV(1)). CLAD was defined as irreversible decline in FEV(1) < 80% baseline. The most accurate threshold to predict irreversible decline in total lung capacity and thus restrictive functional change was at 90% baseline. Restrictive allograft syndrome (RAS) was defined as CLAD meeting this threshold. BOS was defined as CLAD without RAS. To estimate the effect on survival, Cox proportional hazards models and Kaplan-Meier analyses were used. Among 468 patients, CLAD developed in 156; of those, 47 (30%) showed the RAS phenotype. Compared with the 109 BOS patients, RAS patients showed significant computed tomography findings of interstitial lung disease (p < 0.0001). Prevalence of RAS was approximately 25% to 35% of all CLAD over time. Patient survival of RAS was significantly worse than BOS after CLAD onset (median survival, 541 vs 1,421 days; p = 0.0003). The RAS phenotype was the most significant risk factor of death among other variables after CLAD onset (hazard ratio, 1.60; confidential interval, 1.23-2.07). RAS is a novel form of CLAD that exhibits characteristics of peripheral lung fibrosis and significantly affects survival of lung transplant patients. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn

PubMed Central

Gien, Jason; Roe, Gates; Isenberg, Nicole; Kailey, Jenai; Abman, Steven H.

2013-01-01

Although past studies demonstrate that altered serotonin (5-HT) signaling is present in adults with idiopathic pulmonary arterial hypertension, whether serotonin contributes to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) is unknown. We hypothesized that 5-HT contributes to increased pulmonary vascular resistance (PVR) in a sheep model of PPHN and that selective 5-HT reuptake inhibitor (SSRI) treatment increases PVR in this model. We studied the hemodynamic effects of 5-HT, ketanserin (5-HT2A receptor antagonist), and sertraline, an SSRI, on pulmonary hemodynamics of the late gestation fetal sheep with PPHN caused by prolonged constriction of the ductus arteriosis. Brief intrapulmonary infusions of 5-HT increased PVR from 1.0 ± 0.07 (baseline) to 1.4 ± 0.22 mmHg/ml per minute of treatment (P < 0.05). Ketanserin decreased PVR from 1.1 ± 0.15 (baseline) to 0.82 ± 0.09 mmHg/ml per minute of treatment (P < 0.05). Sertraline increased PVR from 1.1 ± 0.17 (baseline) to 1.4 ± 0.17 mmHg/ml per minute of treatment (P = 0.01). In addition, we studied 5-HT production and activity in vitro in experimental PPHN. Compared with controls, pulmonary artery endothelial cells from fetal sheep with PPHN exhibited increased expression of tryptophan hydroxylase 1 and 5-HT production by twofold and 56%, respectively. Compared with controls, 5-HT2A R expression was increased in lung homogenates and pulmonary artery smooth muscle cell lysates by 35% and 32%, respectively. We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT2A receptor and that SSRI infusion further increases PVR in this model. PMID:23605003

The effects of oxygen induced pulmonary vasoconstriction on bedside measurement of pulmonary gas exchange.

PubMed

Weinreich, Ulla M; Thomsen, Lars P; Rees, Stephen E; Rasmussen, Bodil S

2016-04-01

In patients with respiratory failure measurements of pulmonary gas exchange are of importance. The bedside automatic lung parameter estimator (ALPE) of pulmonary gas exchange is based on changes in inspired oxygen (FiO2) assuming that these changes do not affect pulmonary circulation. This assumption is investigated in this study. Forty-two out of 65 patients undergoing coronary artery bypass grafting (CABG) had measurements of mean pulmonary arterial pressure (MPAP), cardiac output and pulmonary capillary wedge pressure thus enabling the calculation of pulmonary vascular resistance (PVR) at each FiO2 level. The research version of ALPE was used and FiO2 was step-wise reduced a median of 0.20 and ultimately returned towards baseline values, allowing 6-8 min' steady state period at each of 4-6 levels before recording the oxygen saturation (SpO2). FiO2 reduction led to median decrease in SpO2 from 99 to 92 %, an increase in MPAP of 4 mmHg and an increase in PVR of 36 dyn s cm(-5). Changes were immediately reversed on returning FiO2 towards baseline. In this study changes in MPAP and PVR are small and immediately reversible consistent with small changes in pulmonary gas exchange. This indicates that mild deoxygenation induced pulmonary vasoconstriction does not have significant influences on the ALPE parameters in patients after CABG.

The Right Ventricle Explains Sex Differences in Survival in Idiopathic Pulmonary Arterial Hypertension

PubMed Central

Jacobs, Wouter; van de Veerdonk, Mariëlle C.; Trip, Pia; de Man, Frances; Heymans, Martijn W.; Marcus, Johannes T.; Kawut, Steven M.; Bogaard, Harm-Jan; Boonstra, Anco

2014-01-01

Background: Male sex is an independent predictor of worse survival in pulmonary arterial hypertension (PAH). This finding might be explained by more severe pulmonary vascular disease, worse right ventricular (RV) function, or different response to therapy. The aim of this study was to investigate the underlying cause of sex differences in survival in patients treated for PAH. Methods: This was a retrospective cohort study of 101 patients with PAH (82 idiopathic, 15 heritable, four anorexigen associated) who were diagnosed at VU University Medical Centre between February 1999 and January 2011 and underwent right-sided heart catheterization and cardiac MRI to assess RV function. Change in pulmonary vascular resistance (PVR) was taken as a measure of treatment response in the pulmonary vasculature, whereas change in RV ejection fraction (RVEF) was used to assess RV response to therapy. Results: PVR and RVEF were comparable between men and women at baseline; however, male patients had a worse transplant-free survival compared with female patients (P = .002). Although male and female patients showed a similar reduction in PVR after 1 year, RVEF improved in female patients, whereas it deteriorated in male patients. In a mediator analysis, after correcting for confounders, 39.0% of the difference in transplant-free survival between men and women was mediated through changes in RVEF after initiating PAH medical therapies. Conclusions: This study suggests that differences in RVEF response with initiation of medical therapy in idiopathic PAH explain a significant portion of the worse survival seen in men. PMID:24306900

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chance, William W.; Rice, David C.; Allen, Pamela K.

Purpose: To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). Methods and Materials: In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or outmore » of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. Results: Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). Conclusions: Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but led to progressive declines in pulmonary function; OS and PFS were better in PD-IMRT compared with EPP-IMRT.« less

Longitudinal In Vivo SPECT/CT Imaging Reveals Morphological Changes and Cardiopulmonary Apoptosis in a Rodent Model of Pulmonary Arterial Hypertension

PubMed Central

Paffett, Michael L.; Hesterman, Jacob; Candelaria, Gabriel; Lucas, Selita; Anderson, Tamara; Irwin, Daniel; Hoppin, Jack; Norenberg, Jeffrey; Campen, Matthew J.

2012-01-01

Pulmonary arterial hypertension (PAH) has a complex pathogenesis involving both heart and lungs. Animal models can reflect aspects of the human pathology and provide insights into the development and underlying mechanisms of disease. Because of the variability of most animal models of PAH, serial in vivo measurements of cardiopulmonary function, morphology, and markers of pathology can enhance the value of such studies. Therefore, quantitative in vivo SPECT/CT imaging was performed to assess cardiac function, morphology and cardiac perfusion utilizing 201Thallium (201Tl) in control and monocrotaline-treated rats. In addition, lung and heart apoptosis was examined with 99mTc-Annexin V (99mTc-Annexin) in these cohorts. Following baseline imaging, rats were injected with saline or monocrotaline (50 mg/kg, i.p.) and imaged weekly for 6 weeks. To assess a therapeutic response in an established pulmonary hypertensive state, a cohort of rats received resveratrol in drinking water (3 mg/kg/day) on days 28–42 post-monocrotaline injection to monitor regression of cardiopulmonary apoptosis. PAH in monocrotaline-treated rats was verified by conventional hemodynamic techniques on day 42 (right ventricular systolic pressure (RSVP) = 66.2 mmHg in monocrotaline vs 28.8 mmHg in controls) and in terms of right ventricular hypertrophy (RV/LVS = 0.70 in monocrotaline vs 0.32 in controls). Resveratrol partially reversed both RVSP (41.4 mmHg) and RV/LVS (0.46), as well as lung edema and RV contractility +dP/dtmax. Serial 99mTc-Annexin V imaging showed clear increases in pulmonary and cardiac apoptosis when compared to baseline, which regressed following resveratrol treatment. Monocrotaline induced modest changes in whole-heart perfusion as assessed by 201TI imaging and cardiac morphological changes consistent with septal deviation and enlarged RV. This study demonstrates the utility of functional in vivo SPECT/CT imaging in rodent models of PAH and further confirms the efficacy of resveratrol in reversing established monocrotaline-induced PAH presumably by attenuation of cardiopulmonary apoptosis. PMID:22815866

Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma: toxicity, patterns of failure, and a matched survival analysis.

PubMed

Chance, William W; Rice, David C; Allen, Pamela K; Tsao, Anne S; Fontanilla, Hiral P; Liao, Zhongxing; Chang, Joe Y; Tang, Chad; Pan, Hubert Y; Welsh, James W; Mehran, Reza J; Gomez, Daniel R

2015-01-01

To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or out of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but led to progressive declines in pulmonary function; OS and PFS were better in PD-IMRT compared with EPP-IMRT. Copyright © 2015 Elsevier Inc. All rights reserved.

Is there an optimal level of positive expiratory pressure (PEP) to improve walking tolerance in patients with severe COPD?

PubMed

Russo, Davide; Simonelli, Carla; Paneroni, Mara; Saleri, Manuela; Piroddi, Ines Maria Grazia; Cardinale, Francesco; Vitacca, Michele; Nicolini, Antonello

2016-07-01

The application of positive expiratory pressure (PEP) devices during exercise had been proposed in order to counteract the pulmonary hyperinflation, reduce the dyspnea and thus increase the exercise tolerance in patients with severe chronic obstructive pulmonary disease (COPD). This randomized controlled crossover trial investigated the effect of two different levels of PEP (1 cmH2O and 10 cmH2O) on distance covered at 6minute walk test (6MWT) in patients with severe COPD. Secondary outcomes were the evaluation of PEP effects on physiological and pulmonary function variables. Seventy-two severe COPD patients, referred to our hospitals as in and out patients, were recruited. A basal 6MWT without devices was performed on the first day, and then repeated with PEP 1 cmH2O (PEP1) and 10 cmH2O (PEP10), with a randomized crossover design. Slow and forced spirometries, including the inspiratory capacity measure, were repeated before and after each 6MWT. 50 patients (average age 69,92 year, mean FEV1 41,42% of predicted) concluded the trial. The 6MWT improved significantly among both PEP levels and baseline (323,8 mt at baseline vs. 337,8 PEP1 and 341,8 PEP10; p<.002 and p<.018, respectively). The difference between PEP10 and PEP1 did not reach the significance. No improvements were found in pulmonary function, symptoms and physiological variables after the 6MWT. In patients with severe COPD, the application of 1 cmH2O of PEP seems to improve the exercise tolerance as 10 cmH2O, with similar dyspnea. Further studies should investigate the effects of low levels of PEP on aerobic training programs. Copyright © 2016 SEPAR. Published by Elsevier Espana. All rights reserved.

Novel insights in cough and breathing patterns of patients with idiopathic pulmonary fibrosis performing repeated 24-hour-respiratory polygraphies.

PubMed

Schertel, Anke; Funke-Chambour, Manuela; Geiser, Thomas; Brill, Anne-Kathrin

2017-11-13

The main symptoms of patients with idiopathic pulmonary fibrosis (IPF) are cough and dyspnea. IPF leads to a restrictive lung disorder impacting daytime and nocturnal breathing patterns. In this pilot study we assessed the course of day- and nighttime respiration, oxygenation, and cough over a period of 8 months as well as differences between wakefulness and sleep in IPF patients. Repetitive 24-h respiratory polygraphies (RP) and pulmonary function tests were performed at baseline and after 3, 4, 7 and 8 months. Cough-index, oxygenation parameters (SpO2, time with SpO2 < 90%, desaturation index), respiratory rate and heart rate were assessed for differences between wakefulness and sleep. The first and the last RP were compared to identify changes of these parameters over time. Statistical analyses were performed with Wilcoxon signed rank tests. Nine IPF patients (8 male, median age 67 years (IQR 60, 77) with 37 valid 24-h RPs were included. Eight patients (88.9%) received antifibrotic treatment. Cough was more prevalent during wakefulness with a median cough-index of 14.8/h (IQR 10.9, 16.8) and 1.6/h (IQR 1.3-2.8) during sleep, p = 0.0039. Oxygenation parameters showed no difference, while respiratory- and heart rate were significantly higher during wakefulness. Despite stable pulmonary function tests over 8 months, the initially elevated respiratory rate increased further during wakefulness (baseline RR median 25.7/min (IQR 19.8, 26.6) vs. RR median 32.2/min (IQR 26.5, 40.9) at follow-up, p = 0.0273). The other respiratory parameters remained stable over time. Cough in IPF patients is more prevalent during wakefulness than during sleep. Further studies with a larger sample size and longer a follow-up period are needed to evaluate the role of the respiratory rate during wakefulness as a potential clinical follow up parameter in IPF.

Uncoupling protein 2 deficiency mimics the effects of hypoxia and endoplasmic reticulum stress on mitochondria and triggers pseudohypoxic pulmonary vascular remodeling and pulmonary hypertension.

PubMed

Dromparis, Peter; Paulin, Roxane; Sutendra, Gopinath; Qi, Andrew C; Bonnet, Sébastien; Michelakis, Evangelos D

2013-07-05

Mitochondrial signaling regulates both the acute and the chronic response of the pulmonary circulation to hypoxia, and suppressed mitochondrial glucose oxidation contributes to the apoptosis-resistance and proliferative diathesis in the vascular remodeling in pulmonary hypertension. Hypoxia directly inhibits glucose oxidation, whereas endoplasmic reticulum (ER)-stress can indirectly inhibit glucose oxidation by decreasing mitochondrial calcium (Ca²⁺m levels). Both hypoxia and ER stress promote proliferative pulmonary vascular remodeling. Uncoupling protein 2 (UCP2) has been shown to conduct calcium from the ER to mitochondria and suppress mitochondrial function. We hypothesized that UCP2 deficiency reduces Ca²⁺m in pulmonary artery smooth muscle cells (PASMCs), mimicking the effects of hypoxia and ER stress on mitochondria in vitro and in vivo, promoting normoxic hypoxia inducible factor-1α activation and pulmonary hypertension. Ucp2 knockout (KO)-PASMCs had lower mitochondrial calcium than Ucp2 wildtype (WT)-PASMCs at baseline and during histamine-stimulated ER-Ca²⁺ release. Normoxic Ucp2KO-PASMCs had mitochondrial hyperpolarization, lower Ca²⁺-sensitive mitochondrial enzyme activity, reduced levels of mitochondrial reactive oxygen species and Krebs' cycle intermediates, and increased resistance to apoptosis, mimicking the hypoxia-induced changes in Ucp2WT-PASMC. Ucp2KO mice spontaneously developed pulmonary vascular remodeling and pulmonary hypertension and exhibited a pseudohypoxic state with pulmonary vascular and systemic hypoxia inducible factor-1α activation (increased hematocrit), not exacerbated further by chronic hypoxia. This first description of the role of UCP2 in oxygen sensing and in pulmonary hypertension vascular remodeling may open a new window in biomarker and therapeutic strategies.

Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone.

PubMed

Ikeda, Kimiyuki; Shiratori, Masanori; Chiba, Hirofumi; Nishikiori, Hirotaka; Yokoo, Keiki; Saito, Atsushi; Hasegawa, Yoshihiro; Kuronuma, Koji; Otsuka, Mitsuo; Yamada, Gen; Takahashi, Hiroki

2017-10-01

Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disease with poor prognosis. Pirfenidone, the first antifibrotic drug, suppresses the decline in forced vital capacity (FVC) and improves prognosis in some, but not all, patients with IPF; therefore, an indicator for identifying improved outcomes in pirfenidone therapy is desirable. This study aims to clarify whether baseline parameters can be predictors of disease progression and prognosis in patients with IPF treated with pirfenidone. We retrospectively investigated patients with IPF who started treatment with pirfenidone between December 2008 and November 2014 at the Sapporo Medical University Hospital. Patients treated with pirfenidone for ≥6 months were enrolled in this study and were observed until November 2015. We investigated the association of clinical characteristics, pulmonary function test results, and blood examination results at the start of pirfenidone with the outcome of patients. Sixty patients were included in this study. In multivariate logistic regression analysis, % predicted FVC and serum surfactant protein (SP)-D levels were predictors of a ≥10% decline in FVC in the initial 12 months. In the Cox proportional hazards model, these two factors predicted progression-free survival. Pack-years, % predicted diffusing capacity for carbon monoxide, and SP-D levels predicted overall survival. The serum SP-D level was a predictor of disease progression and prognosis in patients with IPF treated with pirfenidone. In addition, this analysis describes the relative usefulness of other clinical parameters at baseline in estimating the prognosis of patients with IPF who are candidates for pirfenidone therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison between conventional and protective one-lung ventilation for ventilator-assisted thoracic surgery.

PubMed

Ahn, H J; Kim, J A; Yang, M; Shim, W S; Park, K J; Lee, J J

2012-09-01

Recent papers suggest protective ventilation (PV) as a primary ventilation strategy during one-lung ventilation (OLV) to reduce postoperative pulmonary morbidity. However, data regarding the advantage of the PV strategy in patients with normal preoperative pulmonary function are inconsistent, especially in the case of minimally invasive thoracic surgery. Therefore we compared conventional OLV (VT 10 ml/kg, FiO2 1.0, zero PEEP) to protective OLV (VT 6 ml/kg, FiO2 0.5, PEEP 5 cmH2O) in patients with normal preoperative pulmonary function tests undergoing video-assisted thoracic surgery. Oxygenation, respiratory mechanics, plasma interleukin-6 and malondialdehyde levels were measured at baseline, 15 and 60 minutes after OLV and 15 minutes after restoration of two-lung ventilation. PaO2 and PaO2/FiO2 were higher in conventional OLV than in protective OLV (P<0.001). Interleukin-6 and malondialdehyde increased over time in both groups (P<0.05); however, the magnitudes of increase were not different between the groups. Postoperatively there were no differences in the number of patients with PaO2/FiO2<300 mmHg or abnormalities on chest radiography. Protective ventilation did not provide advantages over conventional ventilation for video-assisted thoracic surgery in this group of patients with normal lung function.

Endothelin B receptor blockade attenuates pulmonary vasodilation in oxygen-ventilated fetal lambs.

PubMed

Ivy, D Dunbar; Lee, Dong-Seok; Rairigh, Robyn L; Parker, Thomas A; Abman, Steven H

2004-01-01

Endothelin-1 (ET-1) contributes to the regulation of pulmonary vascular tone in the normal ovine fetus and in models of perinatal pulmonary hypertension. In the fetal lamb lung, the effects of ET-1 depend on the balance of at least two endothelin receptor subtypes: ETA and ETB. ETA receptors are located on smooth muscle cells and mediate vasoconstriction and smooth muscle proliferation. Stimulation of endothelial ETB receptors causes vasodilation through release of nitric oxide and also functions to remove ET-1 from the circulation. However, whether activation of ETB receptors contributes to the fall in pulmonary vascular tone at birth is unknown. To determine the role of acute ETB receptor blockade in pulmonary vasodilation in response to birth-related stimuli, we studied the hemodynamic effects of selective ETB receptor blockade with BQ-788 during mechanical ventilation with low (<10%) and high FiO2 (100%) in near-term fetal sheep. Intrapulmonary infusion of BQ-788 did not change left pulmonary artery (LPA) blood flow and pulmonary vascular resistance (PVR) at baseline. In comparison with controls, BQ-788 treatment attenuated the rise in LPA flow with low and high FiO2 ventilation (p <0.001 vs. control for each FiO2 concentration). PVR progressively decreased during mechanical ventilation with low and high FiO2 in both groups, but PVR remained higher after BQ-788 treatment throughout the study period (p <0.001). We conclude that selective ETB receptor blockade attenuates pulmonary vasodilation at birth. We speculate that ETB receptor stimulation contributes to pulmonary vasodilation at birth in the ovine fetus.

Functional and prognostic effects when emphysema complicates idiopathic pulmonary fibrosis.

PubMed

Jacob, Joseph; Bartholmai, Brian J; Rajagopalan, Srinivasan; Kokosi, Maria; Maher, Toby M; Nair, Arjun; Karwoski, Ronald; Renzoni, Elisabetta; Walsh, Simon L F; Hansell, David M; Wells, Athol U

2017-07-01

This study aimed to investigate whether the combination of fibrosis and emphysema has a greater effect than the sum of its parts on functional indices and outcome in idiopathic pulmonary fibrosis (IPF), using visual and computer-based (CALIPER) computed tomography (CT) analysis.Consecutive patients (n=272) with a multidisciplinary IPF diagnosis had the extent of interstitial lung disease (ILD) scored visually and by CALIPER. Visually scored emphysema was subcategorised as isolated or mixed with fibrotic lung. The CT scores were evaluated against functional indices forced vital capacity (FVC), diffusing capacity of the lungs for carbon monoxide ( D LCO ), transfer coefficient of the lung for carbon monoxide ( K CO ), composite physiologic index (CPI)) and mortality.The presence and extent of emphysema had no impact on survival. Results were maintained following correction for age, gender, smoking status and baseline severity using D LCO , and combined visual emphysema and ILD extent. Visual emphysema quantitation indicated that relative preservation of lung volumes (FVC) resulted from tractionally dilated airways within fibrotic lung, ventilating areas of admixed emphysema (p<0.0001), with no independent effect on FVC from isolated emphysema. Conversely, only isolated emphysema (p<0.0001) reduced gas transfer ( D LCO ).There is no prognostic impact of emphysema in IPF, beyond that explained by the additive extents of both fibrosis and emphysema. With respect to the location of pulmonary fibrosis, emphysema distribution determines the functional effects of emphysema. Copyright ©ERS 2017.

Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation.

PubMed

Butler, Javed; Stankewicz, Mark A; Wu, Jack; Chomsky, Don B; Howser, Renee L; Khadim, Ghazanfar; Davis, Stacy F; Pierson, Richard N; Wilson, John R

2005-02-01

Pre-transplant fixed pulmonary hypertension is associated with higher post-transplant mortality. In this study, we assessed the significance of pre-transplant reversible pulmonary hypertension in patients undergoing cardiac transplantation. Overall, we studied 182 patients with baseline normal pulmonary pressures or reversible pulmonary hypertension, defined as a decrease in pulmonary vascular resistance (PVR) to < or =2.5 Wood units (WU), who underwent cardiac transplantation. Multiple recipient and donor characteristics were assessed to identify independent predictors of mortality. The average duration of follow-up was 42 +/- 28 months. Forty patients (22%) died during the follow-up period. Baseline hemodynamics for alive vs dead patients were as follows: pulmonary artery systolic (PAS) 42 +/- 15 vs 52 +/- 15 mm Hg; PA diastolic 21 +/- 9 vs 25 +/- 9 mm Hg; PA mean 28 +/- 11 vs 35 +/- 10 mm Hg; transpulmonary gradient (TPG) 9 +/- 4 vs 11 +/- 7 mm Hg (all p < 0.05); total pulmonary resistance 7.7 +/- 4.8 vs 8.8 +/- 3.2 WU (p = 0.08); and PVR 2.3 +/- 1.5 vs 2.9 +/- 1.6 WU (p = 0.06). In an unadjusted analysis, patients with PAS >50 mm Hg had a higher risk of death (odds ratio [OR] 5.96, 95% confidence interval [CI] 1.46 to 19.84 as compared with PAS < or =30 mm Hg). There was no significant difference in survival among patients with baseline PVR <2.5, 2.5 to 4.0 or >4.0 WU, but patients with TPG > or =16 had a higher risk of mortality (OR 4.93, 95% CI 1.84 to 13.17). PAS pressure was an independent predictor of mortality (OR 1.04, 95% CI 1.02 to 1.06). Recipient body mass index, history of sternotomy; and donor ischemic time were the other independent predictors of mortality. Pre-transplant pulmonary hypertension, even when reversible to a PVR of < or =2.5 WU, is associated with a higher mortality post-transplant.

The Effects of Statins on Pulmonary Artery Pressure in Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial

PubMed Central

Arian, Anahita; Moghadam, Sayyed Gholamreza Mortazavi; Kazemi, Toba; Hajihosseini, Morteza

2017-01-01

Objective: Pulmonary hypertension is a serious complication in patients suffering from chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the effects of atorvastatin in reducing pulmonary arterial pressure in COPD patients. Methods: This double-blind, randomized trial was conducted on 42 known cases of COPD with systolic pulmonary arterial pressure of more than 25 mmHg. The patients were randomly assigned into two groups, 21 patients with atorvastatin treatment (40 mg/daily for 6 months) and 21 patients without receiving atorvastatin. All the patients participated voluntarily and provided written informed consent. The trial was registered in the Iranian Registry of Clinical Trials. Pulmonary pressure was also anticipated by Doppler echocardiography with peak pressure gradient of tricuspid regurgitation. Both groups were tested with echocardiography to measure systolic pulmonary pressure at baseline and posttreatment. Statistical analysis includes Chi-square, Student's t-test, and Wilcoxon test. P < 0.05 was considered statistically significant. Findings: The mean age was 65.8 ± 11.5 years for atorvastatin group and 63.7 ± 7.6 years for control group (P = 0.45). Baseline and posttreatment mean systolic pulmonary artery pressure (PAP) levels in the atorvastatin group were 48.9 ± 3.3 and 38.4 ± 1.9 mmHg, respectively (P = 0.007). In the control group, mean systolic PAP levels at baseline and 6 months later were 45.6 ± 3.1 and 38.9 ± 2.4 mmHg, respectively (P = 0.073). The patients treated with atorvastatin showed significant decrease in total cholesterol (P = 0.001) and low-density lipoprotein cholesterol (P = 0.008). Conclusion: A 40 mg dose of atorvastatin daily for 6 months may have beneficial effects in reducing PAP in patients with COPD. Further studies are necessary to find long-term effects of statins in COPD patients. PMID:28331863

The Effects of Statins on Pulmonary Artery Pressure in Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

PubMed

Arian, Anahita; Moghadam, Sayyed Gholamreza Mortazavi; Kazemi, Toba; Hajihosseini, Morteza

2017-01-01

Pulmonary hypertension is a serious complication in patients suffering from chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the effects of atorvastatin in reducing pulmonary arterial pressure in COPD patients. This double-blind, randomized trial was conducted on 42 known cases of COPD with systolic pulmonary arterial pressure of more than 25 mmHg. The patients were randomly assigned into two groups, 21 patients with atorvastatin treatment (40 mg/daily for 6 months) and 21 patients without receiving atorvastatin. All the patients participated voluntarily and provided written informed consent. The trial was registered in the Iranian Registry of Clinical Trials. Pulmonary pressure was also anticipated by Doppler echocardiography with peak pressure gradient of tricuspid regurgitation. Both groups were tested with echocardiography to measure systolic pulmonary pressure at baseline and posttreatment. Statistical analysis includes Chi-square, Student's t -test, and Wilcoxon test. P < 0.05 was considered statistically significant. The mean age was 65.8 ± 11.5 years for atorvastatin group and 63.7 ± 7.6 years for control group ( P = 0.45). Baseline and posttreatment mean systolic pulmonary artery pressure (PAP) levels in the atorvastatin group were 48.9 ± 3.3 and 38.4 ± 1.9 mmHg, respectively ( P = 0.007). In the control group, mean systolic PAP levels at baseline and 6 months later were 45.6 ± 3.1 and 38.9 ± 2.4 mmHg, respectively ( P = 0.073). The patients treated with atorvastatin showed significant decrease in total cholesterol ( P = 0.001) and low-density lipoprotein cholesterol ( P = 0.008). A 40 mg dose of atorvastatin daily for 6 months may have beneficial effects in reducing PAP in patients with COPD. Further studies are necessary to find long-term effects of statins in COPD patients.

Role of Vitamin D in reducing number of acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) patients.

PubMed

Khan, Dur Muhammad; Ullah, Aziz; Randhawa, Fawad Ahmad; Iqtadar, Somia; Butt, Nasir Farooq; Waheed, Khadija

2017-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by chronic incompletely reversible poor airflow and air trapping and usually this debilitating disorder limits the outside activities of the patients depriving them of sunlight which is a rich source of Vitamin D. The objective of this study was to determine the effect of vitamin D supplementation in reducing number of acute exacerbation in COPD patients. This randomized control trial was conducted at East Medical Ward Mayo Hospital Lahore from January to December 2015 as exacerbations of COPD are season dependent. Diagnosis was confirmed by performing Pulmonary Function Tests (PFTs). Basic demographical information was obtained and baseline PFTs of the patient was done. Only Group A patients was treated with oral vitamin D intake of 2000 IU daily for 6 months. Vitamin D level was measured at 0, 2, 4, and 6 months and exacerbation of COPD, FEV1 and FVC was measured weekly. Both the groups were given standard treatment for exacerbation of COPD. Spirometry was repeated at each visit. Blood samples were collected every 2 months for vitamin D. Supplementation was stopped if vitamin D level exceeded 100ng/ml. The mean age of the patients was 46.28±8.83 years, the male to female ratio was 1.8:1. The mean 25(OH) level at baseline was 24.08±2.58 and at 6th month was 29.60±8.74. The mean FVC at baseline was 77.83±5.49 and at 6th month was 91.34±5.52. The exacerbation at baseline was present in all 120(100%) patients and at 6th month was reduced to 4(3.3%). Vitamin D supplementation has significant effect in reducing number of acute exacerbation in COPD patients when it is given for prolonged period.

Smallest worthwhile effect of land-based and water-based pulmonary rehabilitation for COPD.

PubMed

McNamara, Renae J; Elkins, Mark R; Ferreira, Manuela L; Spencer, Lissa M; Herbert, Robert D

2015-05-01

This study aimed to determine the smallest worthwhile effect of land-based and water-based pulmonary rehabilitation on 6-min walk distance among people with chronic obstructive pulmonary disease (COPD). Using a benefit-harm trade-off method, people with COPD who had completed two baseline 6-min walk tests at the commencement of outpatient pulmonary rehabilitation were presented with two scenarios: 8 weeks of land-based and 8 weeks of water-based pulmonary rehabilitation. Participants were guided through an iterative process allowing them to progressively refine their estimates of the smallest improvement due to each form of rehabilitation that would outweigh the associated costs, risks and inconvenience presented in the scenario. 100 people with COPD participated (mean±sd age 72±9 years, forced expiratory volume in 1 s 54±16% predicted and baseline 6-min walk distance 377±101 m). For land-based pulmonary rehabilitation, the median smallest worthwhile effect was 20 m (95% CI 15-37 m). For water-based pulmonary rehabilitation, the median smallest worthwhile effect was 26 m (95% CI 15-33 m). These estimates did not differ significantly (p=0.10). People with COPD typically perceive that pulmonary rehabilitation would be worthwhile if it increased the 6-min walk distance by about 6%. The smallest worthwhile effects of land- and water-based pulmonary rehabilitation were similar.

Interstage evaluation of homograft-valved right ventricle to pulmonary artery conduits for palliation of hypoplastic left heart syndrome.

PubMed

Sandeep, Nefthi; Punn, Rajesh; Balasubramanian, Sowmya; Smith, Shea N; Reinhartz, Olaf; Zhang, Yulin; Wright, Gail E; Peng, Lynn F; Wise-Faberowski, Lisa; Hanley, Frank L; McElhinney, Doff B

2018-04-01

Palliation of hypoplastic left heart syndrome with a standard nonvalved right ventricle to pulmonary artery conduit results in an inefficient circulation in part due to diastolic regurgitation. A composite right ventricle pulmonary artery conduit with a homograft valve has a hypothetical advantage of reducing regurgitation, but may differ in the propensity for stenosis because of valve remodeling. This retrospective cohort study included 130 patients with hypoplastic left heart syndrome who underwent a modified stage 1 procedure with a right ventricle to pulmonary artery conduit from 2002 to 2015. A composite valved conduit (cryopreserved homograft valve anastomosed to a polytetrafluoroethylene tube) was placed in 100 patients (47 aortic, 32 pulmonary, 13 femoral/saphenous vein, 8 unknown), and a nonvalved conduit was used in 30 patients. Echocardiographic functional parameters were evaluated before and after stage 1 palliation and before the bidirectional Glenn procedure, and interstage interventions were assessed. On competing risk analysis, survival over time was better in the valved conduit group (P = .040), but this difference was no longer significant after adjustment for surgical era. There was no significant difference between groups in the cumulative incidence of bidirectional Glenn completion (P = .15). Patients with a valved conduit underwent more interventions for conduit obstruction in the interstage period, but this difference did not reach significance (P = .16). There were no differences between groups in echocardiographic parameters of right ventricle function at baseline or pre-Glenn. In this cohort of patients with hypoplastic left heart syndrome, inclusion of a valved right ventricle to pulmonary artery conduit was not associated with any difference in survival on adjusted analysis and did not confer an identifiable benefit on right ventricle function. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Establishment of a canine model of acute pulmonary embolism with definite right ventricular dysfunction through introduced autologous blood clots.

PubMed

Zhao, Lin-Bo; Jia, Zhen-Yu; Lu, Guang-Dong; Zhu, Yin-Su; Jing, Lei; Shi, Hai-Bin

2015-04-01

To establish a canine model of acute pulmonary embolism (PE) with right ventricular (RV) dysfunction using autologous blood clots and evaluate by echocardiography and contrast-enhanced Computed Tomography (CT). Autologous blood clots formed in vitro were introduced sequentially into the pulmonary arteries of eight healthy mixed-breed dogs while monitoring pulmonary and systemic hemodynamic function. Blood clots were injected until the mean pulmonary artery pressure (MPAP) reached two-three times the baseline pressure, which was maintained up to 1 hour. The RV function was assessed by echocardiography and ECG-gated dual-source contrast CT. All animals survived the imaging procedure. The post-injection pulmonary angiograms showed extensive PE, and MPAP increased from 16.50±2.45 mmHg to 43.13±4.91 mmHg (P<0.001). On echocardiography, the RV fractional area change decreased from 42.06±3.36 to 27.96±3.54 (P<0.001), and the RV myocardial performance increased from 0.20±0.05 to 0.63±0.16 (P<0.001). On CT, the RV end-systolic volume increased from 11.11±1.81 ml to 24.71±4.60 ml (P<0.001), RV end-diastolic volume from 20.73±2.83 ml to 34.63±5.76 ml (P<0.001), and the four-chamber RV/left ventricular diameter ratio from 0.38±0.07 to 0.81±0.14 (P<0.001). Acute PE with RV dysfunction was established in a large animal model through controlled injection of autologous blood clots, which may be useful for developing and evaluating new therapeutic approaches for acute PE with RV dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis of lung function and survival in RECAP: An open-label extension study of pirfenidone in patients with idiopathic pulmonary fibrosis.

PubMed

Costabel, Ulrich; Albera, Carlo; Bradford, Williamson Z; Hormel, Phil; King, Talmadge E; Noble, Paul W; Sahn, Steven A; Valeyre, Dominique; du Bois, Roland M

2014-10-20

RECAP is an open-label extension study evaluating pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) who completed the Phase 3 CAPACITY program. We examined the effect of pirfenidone on lung function and survival in patients who were previously randomised to the placebo group in one of the two CAPACITY studies and received pirfenidone for the first time in RECAP. Eligible patients received oral pirfenidone 2403 mg/day. Forced vital capacity (FVC) was measured at baseline and at weeks 12, 36, and 60. To facilitate comparison with CAPACITY outcomes, analyses were based on patients newly treated with pirfenidone in RECAP who had baseline FVC and carbon monoxide diffusing capacity (DLCO) values that met CAPACITY entry criteria. A total of 178 patients were included in the analysis. Among these, 16.3% experienced an FVC decline ≥10% at week 60, compared with 16.8% and 24.8%, respectively, in the CAPACITY pirfenidone (n=345) and placebo (n=347) groups. The mean change from baseline to week 60 in %FVC was -5.9%, compared with -7.0% and -9.4% in the CAPACITY pirfenidone and placebo groups. Overall survival was similar to that of pirfenidone treated patients in CAPACITY. Treatment was safe and generally well tolerated; the type and frequency of adverse events were consistent with previous clinical experience. FVC and survival outcomes in IPF patients newly treated with pirfenidone in RECAP were similar to those in the CAPACITY pirfenidone group. These data provide further evidence to support the use of pirfenidone in patients with IPF.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jingbo; Department of Radiation Oncology, Cancer Hospital, Chinese Academic Medical Sciences and Peking Union Medical College, Beijing; Cao, Jianzhong

Purpose: Poor pulmonary function (PF) is often considered a contraindication to definitive radiation therapy for lung cancer. This study investigated whether baseline PF was associated with radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC) receiving conformal radiation therapy (CRT). Methods and Materials: NSCLC patients treated with CRT and tested for PF at baseline were eligible. Baseline predicted values of forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and diffusion capacity of lung for carbon monoxide (DLCO) were analyzed. Additional factors included age, gender, smoking status, Karnofsky performance status, coexisting chronic obstructive pulmonary diseasemore » (COPD), tumor location, histology, concurrent chemotherapy, radiation dose, and mean lung dose (MLD) were evaluated for RILT. The primary endpoint was symptomatic RILT (SRILT), including grade ≥2 radiation pneumonitis and fibrosis. Results: There was a total of 260 patients, and SRILT occurred in 58 (22.3%) of them. Mean FEV1 values for SRILT and non-SRILT patients were 71.7% and 65.9% (P=.077). Under univariate analysis, risk of SRILT increased with MLD (P=.008), the absence of COPD (P=.047), and FEV1 (P=.077). Age (65 split) and MLD were significantly associated with SRILT in multivariate analysis. The addition of FEV1 and age with the MLD-based model slightly improved the predictability of SRILT (area under curve from 0.63-0.70, P=.088). Conclusions: Poor baseline PF does not increase the risk of SRILT, and combining FEV1, age, and MLD may improve the predictive ability.« less

Ocular safety of sildenafil citrate when administered chronically for pulmonary arterial hypertension: results from phase III, randomised, double masked, placebo controlled trial and open label extension

PubMed Central

Tressler, Charles; Hwang, Lie-Ju; Burgess, Gary; Laties, Alan M

2012-01-01

Objective To assess the ocular effects and safety profile of chronic sildenafil oral dosing in patients with pulmonary arterial hypertension. Design 12 week, double masked, randomised, placebo controlled, phase III trial with open label extension. Setting 53 institutions worldwide. Participants 277 adults with idiopathic pulmonary arterial hypertension or pulmonary arterial hypertension associated with connective tissue disease or after congenital heart disease repair (mean pulmonary artery pressure ≥25 mm Hg; pulmonary capillary wedge pressure ≤15 mm Hg at rest). Interventions During the double masked study, oral sildenafil 20 mg, 40 mg, or 80 mg or placebo (1:1:1:1) three times daily for 12 weeks was added to baseline drug treatment. In the extension study, the placebo, 20 mg and 40 mg groups received 40 mg three times daily titrated to 80 mg three times daily at week 6. After unmasking, the dose was titrated according to clinical need. Main outcome measure Ocular safety (ocular examinations, visual function tests, participants’ reports of adverse events, and visual disturbance questionnaire completed by investigators) by treatment group at 12 weeks, 24 weeks, 18 months, and yearly. Results Findings of the objective assessments—that is, intraocular pressure and visual function tests (visual acuity, colour vision, and visual field)—were similar across groups (20 mg, n=69; 40 mg, n=67; 80 mg, n=71; placebo, n=70). No clinically significant changes occurred between baseline and 12 weeks, except for an efficacy signal in contrast sensitivity for the sildenafil 40 mg three times daily group. In right eyes, changes in intraocular pressure from baseline to week 12 ranged from a mean of −0.5 (95% confidence interval −1.3 to 0.2) mm Hg with placebo, −0.2 (−0.9 to 0.5) mm Hg with sildenafil 40 mg, and −0.1 (−0.7 to 0.5) mm Hg with 80 mg to 0.3 (−0.4 to 0.9) mm Hg with sildenafil 20 mg (the approved dose for pulmonary arterial hypertension). Mean changes from baseline to week 12 in contrast sensitivity in right eyes were −0.02 (SD 0.12) in the sildenafil 20 mg three times daily group compared with −0.05 (0.18) in the placebo group (P=0.044). Percentages of participants with deterioration in visual acuity (Snellen) from baseline to week 12 ranged from 10% (n=7) in the placebo group to 3% (n=2) in the sildenafil 20 mg three times daily group; the same percentages had visual field changes from normal to abnormal during the period in these two groups. The investigators did not deem any findings on colour vision assessment to be clinically significant. Findings of the objective assessments in the 40 mg and 80 mg three times daily sildenafil treatment groups and in left eyes were not substantially different, nor were any measures different throughout the open label extension compared with week 12. However, objective data were limited after month 18, as most participants had missing data or visual parameters were no longer collected by investigators. Incidence of ocular adverse events reported on the case report forms and assessed by the investigator was low with all doses, but a modest, dose related incidence of chromatopsia, cyanopsia, photophobia, and visual disturbance was reported with 80 mg three times daily consistent with the indicated dosing for erectile dysfunction. Retinal haemorrhages, captured on funduscopy, occurred in 2% (4/207) of sildenafil treated participants and none in the placebo group during the double masked study and in 4% (10/259) during the open label extension. Conclusions Sildenafil dosing up to 80 mg three times daily is safe and well tolerated from an ocular perspective in patients with pulmonary arterial hypertension. Daily chronic dosing in this patient population was not associated with visual change and had no detrimental effect on best corrected visual acuity, contrast sensitivity, colour vision, or visual field, or on slit lamp examinations, funduscopy, or intraocular pressure during the duration of this study. Trial registration Clinical trials NCT00644605 and NCT00159887. PMID:22354598

Association of Transcatheter Aortic Valve Replacement With 30-Day Renal Function and 1-Year Outcomes Among Patients Presenting With Compromised Baseline Renal Function: Experience From the PARTNER 1 Trial and Registry.

PubMed

Beohar, Nirat; Doshi, Darshan; Thourani, Vinod; Jensen, Hanna; Kodali, Susheel; Zhang, Feifan; Zhang, Yiran; Davidson, Charles; McCarthy, Patrick; Mack, Michael; Kapadia, Samir; Leon, Martin; Kirtane, Ajay

2017-07-01

The frequency of baseline renal impairment among high-risk and inoperable patients with severe aortic stenosis undergoing a transcatheter aortic valve replacement (TAVR) and the effect of TAVR on subsequent renal function are, to our knowledge, unknown. To determine the effect of TAVR among patients with baseline renal impairment. This substudy of patients with baseline renal impairment (estimated glomerular filtration rate [eGFR] ≤ 60 mL/min) and paired baseline and 30-day measures of renal function undergoing TAVR in the PARTNER 1 trial and continued access registries was conducted in 25 centers in the United States and Canada. Patients were categorized with improved eGFR (30-day follow-up eGFR≥10% higher than baseline pre-TAVR), worsened eGFR (≥10% lower), or no change in renal function (neither). Baseline characteristics, 30-day to 1-year all-cause mortality, and repeat hospitalization were compared. Multivariable models were constructed to identify predictors of 1-year mortality and of improvement/worsening in eGFR. Of the 821 participants, 401 (48.8%) were women and the mean (SD) age for participants with improved, unchanged, or worsening eGFR was 84.90 (6.91) years, 84.37 (7.13) years, and 85.39 (6.40) years, respectively. The eGFR was 60 mL/min or lower among 821 patients (72%), of whom 345 (42%) improved, 196 (24%) worsened, and 280 (34%) had no change at 30 days. There were no differences in baseline age, body mass index, diabetes, chronic obstructive pulmonary disease, coronary artery disease, peripheral arterial disease, hypertension, pulmonary hypertension, renal or liver disease, New York Heart Association III/IV symptoms, transaortic gradient, left ventricular ejection fraction, or procedural characteristics. The group with improved eGFR had more women, nonsmokers, and a lower cardiac index. Those with worsening eGFR had a higher median Society of Thoracic Surgeons score and left ventricle mass. From 30 days to 1 year, those with improved eGFR had no difference in mortality or repeat hospitalization. Those with worsening eGFR had increased mortality (25.5% vs 19.1%, P = .07) but no significant increases in repeat hospitalization or dialysis. Predictors of improved eGFR were being female (odds ratio [OR], 1.38; 95% CI, 1.03-1.85; P = .03) and nonsmoking status (OR, 1.49; 95% CI, 1.11-1.01; P = .01); predictors of worsening eGFR were baseline left ventricle mass (OR, 1.00; 95% CI, 1.00-1.01; P = .01), smoking (OR, 1.51; 95% CI, 1.06-2.14; P = .02), and age (OR, 1.03; 95% CI, 1.00-1.05; P = .05); and predictors of 1-year mortality were baseline left ventricular ejection fraction (OR, 0.98; 95% CI, 0.97-0.99; P = .003), baseline eGFR (OR, 0.98; 95% CI, 0.96-0.99; P < .001), and worsening eGFR vs no change in eGFR (OR, 1.51; 95% CI, 1.02-2.24; P = .04). Baseline renal impairment was frequent among patients who underwent TAVR. While improved eGFR did not improve 1-year outcomes, worsening eGFR was associated with increased mortality. clinicaltrials.gov Identifier: NCT00530894.

Off-pump grafting does not reduce postoperative pulmonary dysfunction.

PubMed

Izzat, Mohammad Bashar; Almohammad, Farouk; Raslan, Ahmad Fahed

2017-02-01

Objectives Pulmonary dysfunction is a recognized postoperative complication that may be linked to use of cardiopulmonary bypass. The off-pump technique of coronary artery bypass aims to avoid some of the complications that may be related to cardiopulmonary bypass. In this study, we compared the influence of on-pump or off-pump coronary artery bypass on pulmonary gas exchange following routine surgery. Methods Fifty patients (mean age 60.4 ± 8.4 years) with no preexisting lung disease and good left ventricular function undergoing primary coronary artery bypass grafting were prospectively randomized to undergo surgery with or without cardiopulmonary bypass. Alveolar/arterial oxygen pressure gradients were calculated prior to induction of anesthesia while the patients were breathing room air, and repeated postoperatively during mechanical ventilation and after extubation while inspiring 3 specific fractions of oxygen. Results Baseline preoperative arterial blood gases and alveolar/arterial oxygen pressure gradients were similar in both groups. At both postoperative stages, the partial pressure of arterial oxygen and alveolar/arterial oxygen pressure gradients increased with increasing fraction of inspired oxygen, but there were no statistically significant differences between patients who underwent surgery with or without cardiopulmonary bypass, either during ventilation or after extubation. Conclusions Off-pump surgery is not associated with superior pulmonary gas exchange in the early postoperative period following routine coronary artery bypass grafting in patients with good left ventricular function and no preexisting lung disease.

A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial.

PubMed

Elinoff, Jason M; Rame, J Eduardo; Forfia, Paul R; Hall, Mary K; Sun, Junfeng; Gharib, Ahmed M; Abd-Elmoniem, Khaled; Graninger, Grace; Harper, Bonnie; Danner, Robert L; Solomon, Michael A

2013-04-02

Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include the effect of spironolactone on the change in placebo-corrected maximal oxygen consumption; plasma markers of vascular inflammation and peripheral blood mononuclear cell gene expression profiles; sympathetic nervous system activation, renin-angiotensin-aldosterone system activation and sex hormone metabolism; and right ventricular structure and function using echocardiography and novel high-resolution magnetic resonance imaging-based techniques. Safety and tolerability of spironolactone will be assessed with periodic monitoring for hyperkalemia and renal insufficiency as well as the incidence of drug discontinuation for untoward effects. ClinicalTrials.gov: NCT01712620.

A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. Methods/Design Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include the effect of spironolactone on the change in placebo-corrected maximal oxygen consumption; plasma markers of vascular inflammation and peripheral blood mononuclear cell gene expression profiles; sympathetic nervous system activation, renin-angiotensin-aldosterone system activation and sex hormone metabolism; and right ventricular structure and function using echocardiography and novel high-resolution magnetic resonance imaging-based techniques. Safety and tolerability of spironolactone will be assessed with periodic monitoring for hyperkalemia and renal insufficiency as well as the incidence of drug discontinuation for untoward effects. Trial registration ClinicalTrials.gov: NCT01712620 PMID:23547564

Prevalence of Anxiety and Depression in Pulmonary Hypertension and Changes during Therapy.

PubMed

Somaini, Gina; Hasler, Elisabeth D; Saxer, Stéphanie; Huber, Lars C; Lichtblau, Mona; Speich, Rudolf; Bloch, Konrad E; Ulrich, Silvia

2016-01-01

Pulmonary hypertension (PH) leads to reduced health-related quality of life (HRQoL). To investigate the prevalence and course of anxiety and depression and their association with HRQoL, disease severity and survival in PH. 131 PH patients (91 pulmonary arterial, 30 chronic thromboembolic, 10 due to lung disease; 84 female, 47 male) had repeated assessments with the Hospital Anxiety and Depression Scale (HADS), HRQoL, six-minute walk distance and WHO functional class during a mean course of 16 ± 12 months. Among the 49 incident and 82 prevalent PH patients, the HADS score was positive in 53%/21% (depression), 51%/24% (anxiety) and 63%/26% (total score) (all p < 0.05). The HADS score was improved at the second assessment in incident patients. The HADS score correlated with HRQoL at all consecutive assessments and with functional class until the third assessment, but not with baseline hemodynamics, age or gender. Mood disorders remain underdiagnosed in PH. The higher prevalence of anxiety/depression in incident versus prevalent patients and the improvement over time may indicate an amelioration of mood disorders after PH diagnosis and treatment. © 2016 S. Karger AG, Basel.

Effect of supplementing a high-fat, low-carbohydrate enteral formula in COPD patients.

PubMed

Cai, Baiqiang; Zhu, Yuanjue; Ma, Y i; Xu, Zuojun; Zao, Y i; Wang, Jinglan; Lin, Yaoguang; Comer, Gail M

2003-03-01

One of the goals in treating patients with chronic obstructive pulmonary disease (COPD) who suffer from hypoxemia, hypercapnia, and malnutrition is to correct the malnutrition without increasing the respiratory quotient and minimize the production of carbon dioxide. This 3-wk study evaluated the efficacy of feeding a high-fat, low-carbohydrate (CHO) nutritional supplement as opposed to a high-carbohydrate diet in COPD patients on parameters of pulmonary function.S METHODS: Sixty COPD patients with low body weight (<90% ideal body weight) were randomized to the control group, which received dietary counseling for a high-CHO diet (15% protein, 20% to 30% fat, and 60% to 70% CHO), or the experimental group, which received two to three cans (237 mL/can) of a high-fat, low-CHO oral supplement (16.7% protein, 55.1% fat, and 28.2% CHO) in the evening as part of the diet. Measurements of lung function (forced expiratory volume in 1 s or volume of air exhaled in 1 s of maximal expiration, minute ventilation, oxygen consumption per unit time, carbon dioxide production in unit time, and respiratory quotient) and blood gases (pH, arterial carbon dioxide tension, and arterial oxygen tension) were taken at baseline and after 3 wk. Lung function measurements decreased significantly and forced expiratory volume increased significantly in the experimental group. This study demonstrates that pulmonary function in COPD patients can be significantly improved with a high-fat, low-CHO oral supplement as compared with the traditional high-CHO diet.

Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial

PubMed Central

2016-01-01

Background COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2). Methods This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers. Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 μmoles, or 150 μmoles sulforaphane daily by mouth for four weeks. The primary outcomes were changes in Nrf2 target gene expression (NQ01, HO1, AKR1C1 and AKR1C3) in alveolar macrophages and bronchial epithelial cells. Secondary outcomes included measures of oxidative stress and airway inflammation, and pulmonary function tests. Results Between July 2011 and May 2013, 89 patients were enrolled and randomized. Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels. Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 and there was no consistent pattern among the three groups; the changes were not statistically significantly different from baseline. Changes in measures of inflammation and pulmonary function tests were not different among the groups. Sulforaphane was well tolerated at both dose levels. Conclusion Sulforaphane administered for four weeks at doses of 25 μmoles and 150 μmoles to patients with COPD did not stimulate the expression of Nrf2 target genes or have an effect on levels of other anti-oxidants or markers of inflammation. Trial Registration Clinicaltrials.gov: NCT01335971. PMID:27832073

Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.

PubMed

Wise, Robert A; Holbrook, Janet T; Criner, Gerard; Sethi, Sanjay; Rayapudi, Sobharani; Sudini, Kuladeep R; Sugar, Elizabeth A; Burke, Alyce; Thimmulappa, Rajesh; Singh, Anju; Talalay, Paul; Fahey, Jed W; Berenson, Charles S; Jacobs, Michael R; Biswal, Shyam

2016-01-01

COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2). This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers. Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 μmoles, or 150 μmoles sulforaphane daily by mouth for four weeks. The primary outcomes were changes in Nrf2 target gene expression (NQ01, HO1, AKR1C1 and AKR1C3) in alveolar macrophages and bronchial epithelial cells. Secondary outcomes included measures of oxidative stress and airway inflammation, and pulmonary function tests. Between July 2011 and May 2013, 89 patients were enrolled and randomized. Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels. Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 and there was no consistent pattern among the three groups; the changes were not statistically significantly different from baseline. Changes in measures of inflammation and pulmonary function tests were not different among the groups. Sulforaphane was well tolerated at both dose levels. Sulforaphane administered for four weeks at doses of 25 μmoles and 150 μmoles to patients with COPD did not stimulate the expression of Nrf2 target genes or have an effect on levels of other anti-oxidants or markers of inflammation. Clinicaltrials.gov: NCT01335971.

Cystic Fibrosis-Related Diabetes with strict glycaemic control is not associated with frequent intravenous antibiotics use for pulmonary infections.

PubMed

Belle-van Meerkerk, G; de Valk, H W; Stam-Slob, M C; Teding van Berkhout, F; Zanen, P; van de Graaf, E A

2016-06-01

Pulmonary infections are more frequent in and associated with higher mortality in Cystic Fibrosis-Related Diabetes (CFRD) patients compared to CF patients without CFRD. Hyperglycaemia can lead to a higher vulnerability for infections. Aim of the study was to test whether the infection rate in well-controlled CFRD patients was similar to that in CF patients without CFRD. This is a retrospective six-year cohort analysis on a consecutive series of 138 CF patients. They were categorized in two groups with CFRD or without CFRD. Pulmonary infection frequency was defined as the number of intravenous (IV) antibiotic treatments. Clinical factors associated with infection frequency were collected. CFRD was diagnosed in 54 (39%) CF patients of whom 44 (81%) achieved target value for glycaemic control (HbA1c 7.0% (⩽53mmol/mol)). Median frequency of IV antibiotics was 0 without CFRD and 3 episodes in patients with CFRD (rate ratio (RR) 2.9 (95% CI 1.6-5.2)). Multivariate analysis showed that frequency of IV antibiotics was significantly related to Pseudomonas aeruginosa colonization (RR 3.7) and lower lung function at baseline (RR 0.97) but not to CFRD by itself. In this cohort with overall strict glycaemic control, the frequency of IV antibiotics use was related to chronic infection and impaired lung function at baseline, but not to CFRD by itself. Although this study in itself does not prove beneficial effect of strict glycaemic control, it does emphasize the potential role of glycaemic control on infection frequency in CF patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

EPITOME-2: An open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension.

PubMed

Sitbon, Olivier; Delcroix, Marion; Bergot, Emmanuel; Boonstra, Anco B; Granton, John; Langleben, David; Subías, Pilar Escribano; Galiè, Nazzareno; Pfister, Thomas; Lemarié, Jean-Christophe; Simonneau, Gérald

2014-02-01

Continuous infusion of epoprostenol is the treatment of choice in patients with pulmonary arterial hypertension in functional classes III to IV. However, this treatment's limitations include instability at room temperature. A new epoprostenol formulation offers improved storage conditions and patient convenience. The EPITOME-2 trial was an open-label, prospective, multicenter, single-arm, phase IIIb study. Patients with pulmonary arterial hypertension on long-term, stable epoprostenol therapy were transitioned from epoprostenol with glycine and mannitol excipients (Flolan; GlaxoSmithKline, Durham, NC) to epoprostenol with arginine and sucrose excipients (Veletri; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland). Patients were followed up for 3 months, and dose adjustments were recorded. Efficacy measures included the 6-minute walk distance, hemodynamics assessed by right heart catheterization, and New York Heart Association functional class. Safety and tolerability of the transition were also evaluated. Quality of life was assessed using the Treatment Satisfaction Questionnaire for Medication. Forty-two patients enrolled in the study, and 1 patient withdrew consent before treatment; thus, 41 patients received treatment and completed the study. Six patients required dose adjustments. There were no clinically relevant changes from baseline to month 3 in any of the efficacy end points. Adverse events were those previously described with intravenous prostacyclin therapy. Treatment Satisfaction Questionnaire for Medication scores showed an improvement from baseline to month 3 in the domain of treatment convenience. Transition from epoprostenol with glycine and mannitol excipients to epoprostenol with arginine and sucrose excipients did not affect treatment efficacy, raised no new safety or tolerability concerns, and provided patients with an increased sense of treatment convenience. © 2014.

Comparison of valvar and right ventricular function following transcatheter and surgical pulmonary valve replacement.

PubMed

Li, Wendy F; Pollard, Heidi; Karimi, Mohsen; Asnes, Jeremy D; Hellenbrand, William E; Shabanova, Veronika; Weismann, Constance G

2018-01-01

Trans-catheter (TC) pulmonary valve replacement (PVR) has become common practice for patients with right ventricular outflow tract obstruction (RVOTO) and/or pulmonic insufficiency (PI). Our aim was to compare PVR and right ventricular (RV) function of patients who received TC vs surgical PVR. Retrospective review of echocardiograms obtained at three time points: before, immediately after PVR, and most recent. Sixty-two patients (median age 19 years, median follow-up 25 months) following TC (N = 32) or surgical (N = 30) PVR at Yale-New Haven Hospital were included. Pulmonary valve and right ventricular function before, immediately after, and most recently after PVR. At baseline, the TC group had predominant RVOTO (74% vs 10%, P < .001), and moderate-severe PI was less common (61% vs 100%, P < .001). Immediate post-procedural PVR function was good throughout. At last follow-up, the TC group had preserved valve function, but the surgical group did not (moderate RVOTO: 6% vs 41%, P < .001; >mild PI: 0% vs 24%, P = .003). Patients younger than 17 years at surgical PVR had the highest risk of developing PVR dysfunction, while PVR function in follow-up was similar in adults. Looking at RV size and function, both groups had a decline in RV size following PVR. However, while RV function remained stable in the TC group, there was a transient postoperative decline in the surgical group. TC PVR in patients age <17 years is associated with better PVR function in follow-up compared to surgical valves. There was a transient decline in RV function following surgical but not TC PVR. TC PVR should therefore be the first choice in children who are considered for PVR, whenever possible. © 2017 Wiley Periodicals, Inc.

Effect of dobutamine on extravascular lung water index, ventilator function, and perfusion parameters in acute respiratory distress syndrome associated with septic shock.

PubMed

Zhou, Min; Dai, Ji; Du, Min; Wang, Wei; Guo, Changxing; Wang, Yi; Tang, Rui; Xu, Fengling; Rao, Zhuqing; Sun, Gengyun

2016-08-01

The role of dobutamine in the relief of pulmonary edema during septic shock-induced acute respiratory distress syndrome (ARDS) remains undetermined, due to a lack of controllable and quantitative clinical studies. Our objective was to assess the potential effects of dobutamine on extravascular lung water index (ELWI) in septic shock-induced ARDS, reflecting its importance in pulmonary edema. At the same time, ventilator function and perfusion parameters were evaluated. We designed a prospective, non-randomized, non-blinded, controlled study to compare the differences in PiCCO parameters after 6 h of constant dobutamine infusion (15 μg/kg/min), in the baseline parameters in 26 septic shock-related ARDS patients with cardiac index ≥ 2.5I/min/m(2) and hyperlactatemia. These patients (12 survivors/14 non-survivors) were monitored using the PiCCO catheter system within 48 h of onset of septic shock. The dynamic changes in ELWI, which is typically used for quantifying the extent of pulmonary edema, were evaluated, and the corresponding ventilator function and tissue perfusion parameters were also measured. Decreasing ELWI (p = 0.0376) was accompanied by significantly decreased SVRI (p < 0.0001). Despite a significant increase in cardiac output (p < 0.0001), no differences were found in ITBI or GEDI. Moreover, the required dose of norepinephrine was decreased (p = 0.0389), and urine output was increased (p = 0.0358), accompanied by stabilized lactacidemia and MAP. Additionally, airway pressure was moderately improved. During the early stage of septic shock-induced ARDS, dobutamine treatment demonstrated a beneficial effect by relieving pulmonary edema in patients, without a negative elevation in preload or hemodynamics, which might account for the improvements in ventilator function and tissue hypoperfusion.

Study of body composition, lung function, and quality of life following use of anabolic steroids in patients with chronic obstructive pulmonary disease.

PubMed

Daga, Mradul Kumar; Khan, Naushad Ahmad; Malhotra, Varun; Kumar, Suman; Mawari, Govind; Hira, Harmanjit Singh

2014-04-01

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation and is associated with weight loss and decreased muscle strength and exercise capacity. A double-blinded randomized controlled trial of 32 male COPD patients (age, 54.94 ± 11.27 years) was carried out to assess effects of anabolic steroid in terms of a daily high-protein, high-calorie diet alone or one combined with anabolic steroids on body composition, lung function, and health-related quality of life (HRQL). Outcomes were assessed by anthropometric and spirometric measurements, peak expiratory flow rate, partial pressure of oxygen in arterial blood, 6-minute walk test (6MWT), hand grip test, and HRQL index scores. Measurements were made at baseline and end of treatment (6 weeks). All patients showed significant difference (P < .001) in pulmonary function parameters and anthropometric measurements after 6 weeks of intervention (within-group changes); however, no significant improvement occurred in the pulmonary function parameters between the groups. The difference in exercise capacity (6MWT) and HRQL scores in the treatment group were statistically significant (P < .001) compared with control group after 6 weeks of intervention. In the treatment group, the average 6MWT distance increased from 213.5 m to 268.5 m at 6-week follow-up, and HRQL scores increased from 101.25 to 118.45. Also, HRQL and 6MWT parameters were positively correlated in response to steroid supplementation at the end of the study. Weekly administration of anabolic steroids during 6 weeks increased exercise capacity and quality of life in patients with COPD.

Effects of yoga breathing exercises on pulmonary function in patients with Duchenne muscular dystrophy: an exploratory analysis*, **

PubMed Central

Rodrigues, Marcos Rojo; Carvalho, Celso Ricardo Fernandes; Santaella, Danilo Forghieri; Lorenzi-Filho, Geraldo; Marie, Suely Kazue Nagahashi

2014-01-01

OBJECTIVE: Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in children, and children with DMD die prematurely because of respiratory failure. We sought to determine the efficacy and safety of yoga breathing exercises, as well as the effects of those exercises on respiratory function, in such children. METHODS: This was a prospective open-label study of patients with a confirmed diagnosis of DMD, recruited from among those followed at the neurology outpatient clinic of a university hospital in the city of São Paulo, Brazil. Participants were taught how to perform hatha yoga breathing exercises and were instructed to perform the exercises three times a day for 10 months. RESULTS: Of the 76 patients who entered the study, 35 dropped out and 15 were unable to perform the breathing exercises, 26 having therefore completed the study (mean age, 9.5 ± 2.3 years; body mass index, 18.2 ± 3.8 kg/m2). The yoga breathing exercises resulted in a significant increase in FVC (% of predicted: 82.3 ± 18.6% at baseline vs. 90.3 ± 22.5% at 10 months later; p = 0.02) and FEV1 (% of predicted: 83.8 ± 16.6% at baseline vs. 90.1 ± 17.4% at 10 months later; p = 0.04). CONCLUSIONS: Yoga breathing exercises can improve pulmonary function in patients with DMD. PMID:24831396

Lung Mass in Smokers.

PubMed

Washko, George R; Kinney, Gregory L; Ross, James C; San José Estépar, Raúl; Han, MeiLan K; Dransfield, Mark T; Kim, Victor; Hatabu, Hiroto; Come, Carolyn E; Bowler, Russell P; Silverman, Edwin K; Crapo, James; Lynch, David A; Hokanson, John; Diaz, Alejandro A

2017-04-01

Emphysema is characterized by airspace dilation, inflammation, and irregular deposition of elastin and collagen in the interstitium. Computed tomographic studies have reported that lung mass (LM) may be increased in smokers, a finding attributed to inflammatory and parenchymal remodeling processes observed on histopathology. We sought to examine the epidemiologic and clinical associations of LM in smokers. Baseline epidemiologic, clinical, and computed tomography (CT) data (n = 8156) from smokers enrolled into the COPDGene Study were analyzed. LM was calculated from the CT scan. Changes in lung function at 5 years' follow-up were available from 1623 subjects. Regression analysis was performed to assess for associations of LM with forced expiratory volume in 1 second (FEV 1 ) and FEV 1 decline. Subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 chronic obstructive pulmonary disease had greater LM than either smokers with normal lung function or those with GOLD 2-4 chronic obstructive pulmonary disease (P < 0.001 for both comparisons). LM was predictive of the rate of the decline in FEV 1 (decline per 100 g, -4.7 ± 1.7 mL/y, P = 0.006). Our cross-sectional data suggest the presence of a biphasic radiological remodeling process in smokers: the presence of such nonlinearity must be accounted for in longitudinal computed tomographic studies. Baseline LM predicts the decline in lung function. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Long-Term Pulmonary Function in Survivors of Childhood Cancer

PubMed Central

Armenian, Saro H.; Landier, Wendy; Francisco, Liton; Herrera, Claudia; Mills, George; Siyahian, Aida; Supab, Natt; Wilson, Karla; Wolfson, Julie A.; Horak, David; Bhatia, Smita

2015-01-01

Purpose This study was undertaken to determine the magnitude of pulmonary dysfunction in childhood cancer survivors when compared with healthy controls and the extent (and predictors) of decline over time. Patients and Methods Survivors underwent baseline (t1) pulmonary function tests, followed by a second comprehensive evaluation (t2) after a median of 5 years (range, 1.0 to 10.3 years). Survivors were also compared with age- and sex-matched healthy controls at t2. Results Median age at cancer diagnosis was 16.5 years (range, 0.2 to 21.9 years), and time from diagnosis to t2 was 17.1 years (range, 6.3 to 40.1 years). Compared with odds for healthy controls, the odds of restrictive defects were increased 6.5-fold (odds ratio [OR], 6.5; 95% CI, 1.5 to 28.4; P < .01), and the odds of diffusion abnormalities were increased 5.2-fold (OR, 5.2; 95% CI, 1.8 to 15.5; P < .01). Among survivors, age younger than 16 years at diagnosis (OR, 3.0; 95% CI, 1.2 to 7.8; P = .02) and exposure to more than 20 Gy chest radiation (OR, 5.6; 95% CI, 1.5 to 21.0; P = .02, referent, no chest radiation) were associated with restrictive defects. Female sex (OR, 3.9; 95% CI, 1.7 to 9.5; P < .01) and chest radiation dose (referent: no chest radiation; ≤ 20 Gy: OR, 6.4; 95% CI, 1.7 to 24.4; P < .01; > 20 Gy: OR, 11.3; 95% CI, 2.6 to 49.5; P < .01) were associated with diffusion abnormalities. Among survivors with normal pulmonary function tests at t1, females and survivors treated with more than 20 Gy chest radiation demonstrated decline in diffusion function over time. Conclusion Childhood cancer survivors exposed to pulmonary-toxic therapy are significantly more likely to have restrictive and diffusion defects when compared with healthy controls. Diffusion capacity declines with time after exposure to pulmonary-toxic therapy, particularly among females and survivors treated with high-dose chest radiation. These individuals could benefit from subsequent monitoring. PMID:25847925

Impaired Right, Left, or Biventricular Function and Resting Oxygen Saturation Are Associated With Mortality in Eisenmenger Syndrome: A Clinical and Cardiovascular Magnetic Resonance Study.

PubMed

Jensen, Annette S; Broberg, Craig S; Rydman, Riikka; Diller, Gerhard-Paul; Li, Wei; Dimopoulos, Konstantinos; Wort, Stephen J; Pennell, Dudley J; Gatzoulis, Michael A; Babu-Narayan, Sonya V

2015-12-01

Patients with Eisenmenger syndrome (ES) have better survival, despite similar pulmonary vascular pathology, compared with other patients with pulmonary arterial hypertension. Cardiovascular magnetic resonance (CMR) is useful for risk stratification in idiopathic pulmonary arterial hypertension, whereas it has not been evaluated in ES. We studied CMR together with other noninvasive measurements in ES to evaluate its potential role as a noninvasive risk stratification test. Between 2003 and 2005, 48 patients with ES, all with a post-tricuspid shunt, were enrolled in a prospective, longitudinal, single-center study. All patients underwent a standardized baseline assessment with CMR, blood test, echocardiography, and 6-minute walk test and were followed up for mortality until the end of December 2013. Twelve patients (25%) died during follow-up, mostly from heart failure (50%). Impaired ventricular function (right or left ventricular ejection fraction) was associated with increased risk of mortality (lowest quartile: right ventricular ejection fraction, <40%; hazard ratio, 4.4 [95% confidence interval, 1.4-13.5]; P=0.01 and left ventricular ejection fraction, <50%; hazard ratio, 6.6 [95% confidence interval, 2.1-20.8]; P=0.001). Biventricular impairment (lowest quartile left ventricular ejection fraction, <50% and right ventricular ejection fraction, <40%) conveyed an even higher risk of mortality (hazard ratio, 8.0 [95% confidence interval, 2.5-25.1]; P=0.0004). No other CMR or noninvasive measurement besides resting oxygen saturation (hazard ratio, 0.90 [0.83-0.97]/%; P=0.007) was associated with mortality. Impaired right, left, or biventricular systolic function derived from baseline CMR and resting oxygen saturation are associated with mortality in adult patients with ES. CMR is a useful noninvasive tool, which may be incorporated in the risk stratification assessment of ES during lifelong follow-up. © 2015 American Heart Association, Inc.

Impact of sildenafil on survival of patients with idiopathic pulmonary arterial hypertension.

PubMed

Zeng, Wei-Jie; Sun, Yun-Juan; Gu, Qing; Xiong, Chang-Ming; Li, Jian-Jun; He, Jian-Guo

2012-09-01

It has been reported that short-term sildenafil therapy is safe and effective for patients with pulmonary arterial hypertension. However, data regarding the impact of sildenafil on the survival of patients with idiopathic pulmonary arterial hypertension remain limited. The study was conducted on 77 patients with newly diagnosed idiopathic pulmonary arterial hypertension at Fu Wai Hospital between September 2005 and September 2009. Patients were divided into 2 groups: the sildenafil group and the conventional group. Nine patients treated with sildenafil were re-evaluated by right heart catheterization after 3 months. Our data demonstrated that the 6-minute walk distance, World Health Organization functional class, mixed venous oxygen saturation, and hemodynamics significantly improved after 3 months of sildenafil therapy (P < .05). The baseline characteristics of the sildenafil group were similar to those of the conventional group. The 1-, 2-, and 3-year survival rates in the sildenafil group were 88%, 72%, and 68% compared with 61%, 36%, and 27% in the conventional group (P < .001). The absence of sildenafil therapy, lower body mass index, and lower mixed venous oxygen saturation were found to be independent predictors of mortality. In conclusion, sildenafil therapy was found to be associated with improved survival in patients with idiopathic pulmonary arterial hypertension.

Inhaled carbon monoxide does not cause pulmonary vasodilation in the late-gestation fetal lamb.

PubMed

Grover, T R; Rairigh, R L; Zenge, J P; Abman, S H; Kinsella, J P

2000-04-01

As observed with nitric oxide (NO), carbon monoxide (CO) binds and may activate soluble guanylate cyclase and increase cGMP levels in smooth muscle cells in vitro. Because inhaled NO (I(NO)) causes potent and sustained pulmonary vasodilation, we hypothesized that inhaled CO (I(CO)) may have similar effects on the perinatal lung. To determine whether I(CO) can lower pulmonary vascular resistance (PVR) during the perinatal period, we studied the effects of I(CO) on late-gestation fetal lambs. Catheters were placed in the main pulmonary artery, left pulmonary artery (LPA), aorta, and left atrium to measure pressure. An ultrasonic flow transducer was placed on the LPA to measure blood flow to the left lung. After baseline measurements, fetal lambs were mechanically ventilated with a hypoxic gas mixture (inspired O(2) fraction < 0.10) to maintain a constant fetal arterial PO(2). After 60 min (baseline), the lambs were treated with I(CO) [5-2,500 parts/million (ppm)]. Comparisons were made with I(NO) (5 and 20 ppm) and combined I(NO) (5 ppm) and I(CO) (100 and 2,500 ppm). We found that I(CO) did not alter left lung blood flow or PVR at any of the study doses. In contrast, low-dose I(NO) decreased PVR by 47% (P < 0.005). The combination of I(NO) and I(CO) did not enhance the vasodilator response to I(NO). To determine whether endogenous CO contributes to vascular tone in the fetal lung, zinc protoporphyrin IX, an inhibitor of heme oxygenase, was infused into the LPA in three lambs. Zinc protoporphyrin IX had no effect on baseline PVR, aortic pressure, or the pressure gradient across the ductus arteriosus. We conclude that I(CO) does not cause vasodilation in the near-term ovine transitional circulation, and endogenous CO does not contribute significantly to baseline pulmonary vascular tone or ductus arteriosus tone in the late-gestation ovine fetus.

Design and measurement of quality improvement indicators in ambulatory pulmonary care: creating a "culture of quality" in an academic pulmonary division.

PubMed

Roberts, David H; Gilmartin, Geoffrey S; Neeman, Naama; Schulze, Joanne E; Cannistraro, Sabrina; Ngo, Long H; Aronson, Mark D; Weiss, J Woodrow

2009-10-01

Quality improvement (QI) measures often are cited as goals for individual practices and medical centers and may someday form a component of reimbursement guidelines. Relatively few QI metrics relevant to ambulatory pulmonary medicine have been published. We describe the development and implementation of a QI program in an academic pulmonary division, including progress to date and lessons learned. Metrics for the pulmonary QI Dashboard were developed based on an extensive literature review. Patients were identified through International Classification of Diseases-based billing databases, and results data were obtained from a manual and automated review of the electronic medical record. The performance of the division was monitored and presented in regular faculty meetings. Quarterly, confidential, individual scorecards gave each clinician feedback about his or her performance and compared the feedback to that of the faculty of the entire division. Significant improvements were found in many QI measures during a 2-year period. The number of patients with asthma who received appropriately prescribed inhaled corticosteroids increased from a baseline of 76 to 92% to 98%. Flu shot and pneumococcal vaccine administration documentation for patients with COPD increased from baseline values of 11 to 32% and 11 to 34%, respectively, to 90% and 93%, respectively. The COPD Global Initiative for Obstructive Lung Disease pharmacotherapy guidelines adherence increased substantially for patients with all disease stages. Chest CT scan results notification documentation improved from a baseline of 67 to 76% to 98%. Comparison between baseline and QI periods yielded statistically significant increases for these indicators. QI measures for an ambulatory pulmonary practice can be designed, implemented, and monitored. Key components include a well-structured electronic medical record, measurable outcomes, strong QI leadership, and specific interventions, such as providing feedback through QI review meetings and individual "report cards."

Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study.

PubMed

Saggar, Rajeev; Khanna, D; Shapiro, S; Furst, D E; Maranian, P; Clements, P; Abtin, F; Dua, Shiv; Belperio, J; Saggar, Rajan

2012-12-01

Exercise-induced pulmonary hypertension (ePH) may represent an early, clinically relevant phase in the spectrum of pulmonary vascular disease. The purpose of this pilot study was to describe the changes in hemodynamics and exercise capacity in patients with systemic sclerosis (SSc) spectrum-associated ePH treated with open-label daily ambrisentan. Patients were treated with ambrisentan, 5 mg or 10 mg once daily, for 24 weeks. At baseline and 24 weeks, patients with SSc spectrum disorders exercised in a supine position, on a lower extremity cycle ergometer. All patients had normal hemodynamics at rest. We defined baseline ePH as a mean pulmonary artery pressure of >30 mm Hg with maximum exercise and a transpulmonary gradient (TPG) of >15 mm Hg. The primary end point was change in pulmonary vascular resistance (PVR) with exercise. Secondary end points included an improvement from baseline in 6-minute walking distance, health-related quality of life assessments, and cardiopulmonary hemodynamics. Of the 12 enrolled patients, 11 completed the study. At 24 weeks there were improvements in mean exercise PVR (85.8 dynes × second/cm(5) ; P = 0.003) and mean distance covered during 6-minute walk (44.5 meters; P = 0.0007). Improvements were also observed in mean exercise cardiac output (1.4 liters/minute; P = 0.006), mean pulmonary artery pressure (-4.1 mm Hg; P = 0.02), and total pulmonary resistance (-93.0 dynes × seconds/cm(5) ; P = 0.0008). Three patients developed resting pulmonary arterial hypertension during the 24 weeks. Exercise hemodynamics and exercise capacity in patients with SSc spectrum-associated ePH improved over 24 weeks with exposure to ambrisentan. Placebo-controlled studies are needed to confirm whether this is a drug-related effect and to determine optimal therapeutic regimens for patients with ePH. Copyright © 2012 by the American College of Rheumatology.

Smallest worthwhile effect of land-based and water-based pulmonary rehabilitation for COPD

PubMed Central

Elkins, Mark R.; Ferreira, Manuela L.; Spencer, Lissa M.; Herbert, Robert D.

2015-01-01

This study aimed to determine the smallest worthwhile effect of land-based and water-based pulmonary rehabilitation on 6-min walk distance among people with chronic obstructive pulmonary disease (COPD). Using a benefit–harm trade-off method, people with COPD who had completed two baseline 6-min walk tests at the commencement of outpatient pulmonary rehabilitation were presented with two scenarios: 8 weeks of land-based and 8 weeks of water-based pulmonary rehabilitation. Participants were guided through an iterative process allowing them to progressively refine their estimates of the smallest improvement due to each form of rehabilitation that would outweigh the associated costs, risks and inconvenience presented in the scenario. 100 people with COPD participated (mean±sd age 72±9 years, forced expiratory volume in 1 s 54±16% predicted and baseline 6-min walk distance 377±101 m). For land-based pulmonary rehabilitation, the median smallest worthwhile effect was 20 m (95% CI 15–37 m). For water-based pulmonary rehabilitation, the median smallest worthwhile effect was 26 m (95% CI 15–33 m). These estimates did not differ significantly (p=0.10). People with COPD typically perceive that pulmonary rehabilitation would be worthwhile if it increased the 6-min walk distance by about 6%. The smallest worthwhile effects of land- and water-based pulmonary rehabilitation were similar. PMID:27730130

Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease.

PubMed

Fuld, J P; Kilduff, L P; Neder, J A; Pitsiladis, Y; Lean, M E J; Ward, S A; Cotton, M M

2005-07-01

Skeletal muscle wasting and dysfunction are strong independent predictors of mortality in patients with chronic obstructive pulmonary disease (COPD). Creatine nutritional supplementation produces increased muscle mass and exercise performance in health. A controlled study was performed to look for similar effects in 38 patients with COPD. Thirty eight patients with COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 46 (15)% predicted) were randomised to receive placebo (glucose polymer 40.7 g) or creatine (creatine monohydrate 5.7 g, glucose 35 g) supplements in a double blind trial. After 2 weeks loading (one dose three times daily), patients participated in an outpatient pulmonary rehabilitation programme combined with maintenance (once daily) supplementation. Pulmonary function, body composition, and exercise performance (peripheral muscle strength and endurance, shuttle walking, cycle ergometry) took place at baseline (n = 38), post loading (n = 36), and post rehabilitation (n = 25). No difference was found in whole body exercise performance between the groups: for example, incremental shuttle walk distance mean -23.1 m (95% CI -71.7 to 25.5) post loading and -21.5 m (95% CI -90.6 to 47.7) post rehabilitation. Creatine increased fat-free mass by 1.09 kg (95% CI 0.43 to 1.74) post loading and 1.62 kg (95% CI 0.47 to 2.77) post rehabilitation. Peripheral muscle performance improved: knee extensor strength 4.2 N.m (95% CI 1.4 to 7.1) and endurance 411.1 J (95% CI 129.9 to 692.4) post loading, knee extensor strength 7.3 N.m (95% CI 0.69 to 13.92) and endurance 854.3 J (95% CI 131.3 to 1577.4) post rehabilitation. Creatine improved health status between baseline and post rehabilitation (St George's Respiratory Questionnaire total score -7.7 (95% CI -14.9 to -0.5)). Creatine supplementation led to increases in fat-free mass, peripheral muscle strength and endurance, health status, but not exercise capacity. Creatine may constitute a new ergogenic treatment in COPD.

Effects of the endothelin receptor antagonist bosentan on hemodynamics and exercise capacity in Japanese patients with mildly symptomatic pulmonary arterial hypertension.

PubMed

Hatano, Masaru; Yamada, Hidehiro; Fukuda, Keiichi; Yoshioka, Koichiro; Funauchi, Masanori; Kuwana, Masataka; Sata, Masataka; Taniguchi, Mitsugu; Nakanishi, Norifumi; Saito, Takefumi; Saji, Tsutomu; Sasayama, Shigetake

2015-11-01

Pulmonary arterial hypertension (PAH) trial has mostly enrolled patients with World Health Organization functional class (WHO FC) III or IV. However, PAH is rapidly progressive in nature even in patients with less severe forms at diagnosis. Following the recent studies in Western population, here we assessed the efficacy of bosentan in Japanese patients with WHO FCII PAH. In this open-label trial, bosentan 125 mg twice daily was administered for 12 weeks in 16 patients, and a hemodynamic evaluation was performed. Treatment was continued for a further 12 weeks, where the effect on exercise capacity was assessed in 13 patients. In 16 patients, mean pulmonary arterial pressure decreased from 40.4 ± 10.4 to 35.6 ± 12.6 mmHg (p = 0.018) and cardiac index increased from 2.54 ± 0.73 to 2.96 ± 0.82 L/min/m(2) (p = 0.023). Thus, pulmonary vascular resistance decreased from 792 ± 565 to 598 ± 558 dyn·sec/cm(5) (p = 0.006). In 13 patients followed up for 24 weeks, 6-min walking distance increased from baseline at Week 12 (p = 0.003) and Week 24 (p = 0.011). All patients were mildly symptomatic at baseline with dyspnea index (Borg scale) of 2.50 ± 1.58 and the specific activity scale (SAS) of 5.0 ± 1.4 METs. These values remained unchanged throughout the study. These results suggest that bosentan treatment was beneficial for Japanese patients with WHO FC II PAH and treatment should be started in the early stage of the disease.

Short-term Automated Quantification of Radiologic Changes in the Characterization of Idiopathic Pulmonary Fibrosis Versus Nonspecific Interstitial Pneumonia and Prediction of Long-term Survival.

PubMed

De Giacomi, Federica; Raghunath, Sushravya; Karwoski, Ronald; Bartholmai, Brian J; Moua, Teng

2018-03-01

Fibrotic interstitial lung diseases presenting with nonspecific and overlapping radiologic findings may be difficult to diagnose without surgical biopsy. We hypothesized that baseline quantifiable radiologic features and their short-term interval change may be predictive of underlying histologic diagnosis as well as long-term survival in idiopathic pulmonary fibrosis (IPF) presenting without honeycombing versus nonspecific interstitial pneumonia (NSIP). Forty biopsy-confirmed IPF and 20 biopsy-confirmed NSIP patients with available high-resolution chest computed tomography 4 to 24 months apart were studied. CALIPER software was used for the automated characterization and quantification of radiologic findings. IPF subjects were older (66 vs. 48; P<0.0001) with lower diffusion capacity for carbon monoxide and higher volumes of baseline reticulation (193 vs. 83 mL; P<0.0001). Over the interval period, compared with NSIP, IPF patients experienced greater functional decline (forced vital capacity, -6.3% vs. -1.7%; P=0.02) and radiologic progression, as noted by greater increase in reticulation volume (24 vs. 1.74 mL; P=0.048), and decrease in normal (-220 vs. -37.7 mL; P=0.045) and total lung volumes (-198 vs. 58.1 mL; P=0.03). Older age, male gender, higher reticulation volumes at baseline, and greater interval decrease in normal lung volumes were predictive of IPF. Both baseline and short-term changes in quantitative radiologic findings were predictive of mortality. Baseline quantitative radiologic findings and assessment of short-term disease progression may help characterize underlying IPF versus NSIP in those with difficult to differentiate clinicoradiologic presentations. Our study supports the possible utility of assessing serial quantifiable high-resolution chest computed tomographic findings for disease differentiation in these 2 entities.

Pulmonary Hypertension After Heart Transplantation in Patients Bridged with the Total Artificial Heart.

PubMed

Shah, Rachit; Patel, Dhavalkumar B; Mankad, Anit K; Rennyson, Stephen L; Tang, Daniel G; Quader, Mohammed A; Smallfield, Melissa C; Kasirajan, Vigneshwar; Shah, Keyur B

2016-01-01

Pulmonary hypertension (PH) among heart transplant recipients is associated with an increased risk of mortality. Pulmonary hemodynamics improves after left ventricular assist device (LVAD) implantation; however, the impact of PH before total artificial heart (TAH) implantation on posttransplant hemodynamics and survival is unknown. This is a single center retrospective study aimed to evaluate the impact of TAH implantation on posttransplant hemodynamics and mortality in two groups stratified according to severity of PH: high (≥3 Woods units [WU]) and low (<3 WU) baseline pulmonary vascular resistance (PVR). Hemodynamic data were obtained from right heart catheterization performed at baseline (before TAH) and posttransplant at 1 and 12 months. Patients in the high PVR group (n = 12) experienced improvement in PVR (baseline = 4.31 ± 0.7; 1-month = 1.69 ± 0.7, p < 0.001; 12-month = 48 ± 0.9, p < 0.001) and transpulmonary gradient (baseline = 15.8 ± 3.3; 1-month = 11.57 ± 5.0, p = 0.07; 12-month = 8.50 ± 4.0, p = 0.008) after transplantation, reaching similar values as the low PVR group at 12 months. The filling pressures improved in the high PVR group after heart transplantation (HT), but remained elevated. There was no significant difference in survival between the two groups at 12 months follow-up. Patients with high PVR who are bridged to transplant with TAH had improvement in PVR at 12 months after transplant, and the degree of PVR did not impact posttransplant survival.

Effect of Bhrāmarī Prāṇāyāma Practice on Pulmonary Function in Healthy Adolescents: A Randomized Control Study.

PubMed

Kuppusamy, Maheshkumar; Dilara, K; Ravishankar, P; Julius, A

2017-01-01

Prāṇāyāma , the fourth limb of ancient aṣṭāṅga yoga consists of breathing techniques which produce various physiological and psychological effects. Though various types of prāṇāyāma and their effects have been scientifically established, Bhrāmarī prāṇāyāma (Bhr.P) is the one whose effects still remain understated. The present study was conducted to find the effects of Bhrāmarī prāṇāyāma practice on pulmonary function in healthy adolescents. Randomized control trial. 90 healthy adolescents including 32 females and 58 males participated in the study. They were randomly divided into Bhr.P group ( n = 45) and Control group ( n = 45) by a simple lottery method. Pulmonary function test was done at baseline and at end of 12 th week using RMS Helios spirometry. Prāṇāyāma group students were trained to do Bhr.P as 3 to 4 breaths/min for 5 min followed by 2 min rest. This was one cycle and in this way, they were instructed to do five cycles each time for 45 minutes five days in a week. Control group students were not allowed to practice any kind of exercise throughout the study period. Student paired and unpaired T tests were used to analyse the intra group and intergroup differences using R statistical software. A significant ( P < 0.05) improvement in all pulmonary function parameters; FVC, FEV1, FEV1/FVC ratio, FEF 25%-75% and PEFR was seen in the Bhr.P group than the control group adolescents. Slow vital capacity (SVC) and Maximum Voluntary Volume (MVV) also showed significant improvement in the prāṇāyāma group. Bhrāmarī Prāṇāyāma practice is effective in improving the pulmonary function among the adolescents which could be utilized for further clinical studies.

Lung volume recruitment acutely increases respiratory system compliance in individuals with severe respiratory muscle weakness

PubMed Central

Molgat-Seon, Yannick; Hannan, Liam M.; Dominelli, Paolo B.; Peters, Carli M.; Fougere, Renee J.; McKim, Douglas A.; Sheel, A. William

2017-01-01

The aim of the present study was to determine whether lung volume recruitment (LVR) acutely increases respiratory system compliance (Crs) in individuals with severe respiratory muscle weakness (RMW). Individuals with RMW resulting from neuromuscular disease or quadriplegia (n=12) and healthy controls (n=12) underwent pulmonary function testing and the measurement of Crs at baseline, immediately after, 1 h after and 2 h after a single standardised session of LVR. The LVR session involved 10 consecutive supramaximal lung inflations with a manual resuscitation bag to the highest tolerable mouth pressure or a maximum of 50 cmH2O. Each LVR inflation was followed by brief breath-hold and a maximal expiration to residual volume. At baseline, individuals with RMW had lower Crs than controls (37±5 cmH2O versus 109±10 mL·cmH2O−1, p<0.001). Immediately after LVR, Crs increased by 39.5±9.8% to 50±7 mL·cmH2O−1 in individuals with RMW (p<0.05), while no significant change occurred in controls (p=0.23). At 1 h and 2 h post-treatment, there were no within-group differences in Crs compared to baseline (all p>0.05). LVR had no significant effect on measures of pulmonary function at any time point in either group (all p>0.05). During inflations, mean arterial pressure decreased significantly relative to baseline by 10.4±2.8 mmHg and 17.3±3.0 mmHg in individuals with RMW and controls, respectively (both p<0.05). LVR acutely increases Crs in individuals with RMW. However, the high airway pressures during inflations cause reductions in mean arterial pressure that should be considered when applying this technique. PMID:28326313

Effect of inhaled N-acetylcysteine monotherapy on lung function and redox balance in idiopathic pulmonary fibrosis.

PubMed

Muramatsu, Yoko; Sugino, Keishi; Ishida, Fumiaki; Tatebe, Junko; Morita, Toshisuke; Homma, Sakae

2016-05-01

An oxidant-antioxidant imbalance is considered to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Therefore, administration of antioxidants, such as N-acetylcysteine (NAC), may represent a potential treatment option for IPF patients. The aim of this study was to evaluate the effect of inhaled NAC monotherapy on lung function and redox balance in patients with IPF. A retrospective observational study was done, involving 22 patients with untreated early IPF (19 men; mean [±S.D.] age, 71.8 [±6.3]y). At baseline and at 6 and 12 months after initiating inhaled NAC monotherapy, we assessed forced vital capacity (FVC) and measured the levels of total glutathione, oxidized glutathione (GSSG), and the ratio of reduced to oxidized glutathione in whole blood (hereafter referred to as the ratio), and of 8-hydroxy-2'-deoxyguanosine in urine. To evaluate response to treatment, we defined disease progression as a decrease in FVC of ≥5% from baseline and stable disease as a decrease in FVC of <5%, over a period of 6 months. Change in FVC in the stable group at 6 and 12 months were 95±170mL and -70±120mL, while those in the progressive group at 6 and 12 months were -210±80mL, -320±350mL, respectively. The serial mean change in GSSG from baseline decreased as the ratio of reduced to oxidized glutathione increased in patients with stable disease, while it increased as this ratio decreased in patients with progressive disease. Receiver operating characteristic curve analysis revealed that a baseline GSSG level of ≥1.579μM was optimal for identifying treatment responders. Inhaled NAC monotherapy was associated with improved redox imbalance in patients with early IPF. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Infrared Imaging of Nitric Oxide-Mediated Blood Flow in Human Sickle Cell Disease

PubMed Central

Gorbach, Alexander M.; Ackerman, Hans C.; Liu, Wei-Min; Meyer, Joseph M.; Littel, Patricia L.; Seamon, Catherine; Footman, Eleni; Chi, Amy; Zorca, Suzana; Krajewski, Megan L.; Cuttica, Michael J.; Machado, Roberto F.; Cannon, Richard O.; Kato, Gregory J.

2012-01-01

Vascular dysfunction is an important pathophysiologic manifestation of sickle cell disease (SCD), a condition that increases risk of pulmonary hypertension and stroke. We hypothesized that infrared (IR) imaging would detect changes in cutaneous blood flow reflective of vascular function. We performed IR imaging and conventional strain gauge plethysmography in twenty-five adults with SCD at baseline and during intra-arterial infusions of an endothelium-dependent vasodilator acetylcholine (ACh), an endothelium-independent vasodilator sodium nitroprusside (SNP), and a NOS inhibitor L-NMMA. Skin temperature measured by IR imaging increased in a dose-dependent manner to graded infusions of ACh (+1.1° C, p < 0.0001) and SNP (+0.9° C, p < 0.0001), and correlated with dose-dependent increases in forearm blood flow (ACh: +19.9 mL/min/100mL, p < 0.0001; rs = 0.57, p = 0.003; SNP: +8.6 mL/min/100mL, p < 0.0001; r = 0.70, p = 0.0002). Although IR measurement of skin temperature accurately reflected agonist-induced increases in blood flow, it was less sensitive to decreases in blood flow caused by NOS inhibition. Baseline forearm skin temperature measured by IR imaging correlated significantly with baseline forearm blood flow (31.8±0.2° C, 6.0±0.4 mL/min/100mL; r = 0.58, p = 0.003), and appeared to represent a novel biomarker of vascular function. It predicted a blunted blood flow response to SNP (r = −0.61, p = 0.002), and was independently associated with a marker of pulmonary artery pressure, as well as hemoglobin level, diastolic blood pressure, homocysteine, and cholesterol (R2 = 0.84, p < 0.0001 for the model). IR imaging of agonist-stimulated cutaneous blood flow represents a less cumbersome alternative to plethysmography methodology. Measurement of baseline skin temperature by IR imaging may be a useful new marker of vascular risk in adults with SCD. PMID:22784510

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bookstein, J.J.; Alazraki, N.P.; Jassy, L.N.

An experiment was designed to determine whether or not acute pneumococcal pneumonia in dogs is associated with intravascular thrombosis, or with angiographic features distinguishable from pulmonary embolism. In dogs with normal baseline chest radiographs and perfusion scans, pneumonia was produced by transbronchial instillation of type III pneumococcus. After 2 days, perfusion scans demonstrated discrete appropriate defects. In vivo magnification pulmonary arteriography, postmortem pulmonary arteriography, and histologic examination disclosed no evidence of thrombi.

Sing Your Lungs Out—a community singing group for chronic obstructive pulmonary disease: a 1-year pilot study

PubMed Central

McNaughton, Amanda; Weatherall, Mark; Williams, Mathew; McNaughton, Harry; Aldington, Sarah; Williams, Gayle; Beasley, Richard

2017-01-01

Objective Singing group participation may benefit patients with chronic obstructive pulmonary disease (COPD). Previous studies are limited by small numbers of participants and short duration of generally hospital-based singing group intervention. This study examines the feasibility of long-term participation in a community singing group for patients with COPD who had completed pulmonary rehabilitation (PR). Methods This was a feasibility cohort study. Patients with COPD who had completed PR and were enrolled in a weekly community exercise group were recruited to a new community-based singing group which met weekly for over 1 year. Measurements at baseline, 4 months and 1 year comprised comprehensive pulmonary function tests including lung volumes, 6 min walk test (6MWT), Clinical COPD Questionnaire (CCQ), Hospital Anxiety and Depression Scale (HADS) and hospital admission days for acute exacerbation of COPD (AECOPD) for 1 year before and after the first singing group session. Findings There were 28 participants with chronic lung disease recruited from 140 people approached. Five withdrew in the first month. 21 participants meeting Global Initiative for Chronic Obstructive Lung Disease criteria for COPD completed 4-month and 18 completed 1-year assessments. The mean attendance was 85%. For the prespecified primary outcome measure, total HADS score, difference between baseline and 12 months was −0.9, 95% CI −3.0 to 1.2, p=0.37. Of the secondary measures, a significant reduction was observed for HADS anxiety score after 1 year of −0.9 (95% CI −1.8 to −0.1) points, p=0.038 and an increase in the 6MWT at 1 year, of 65 (95% CI 35 to 99) m compared with baseline p<0.001. Conclusions Our findings support the feasibility of long-term participation in a community singing group for adults with COPD who have completed PR and are enrolled in a weekly community exercise group and provide evidence of improved exercise capacity and a reduction in anxiety. Trial registration number ACTRN12615000736549; Results. PMID:28119393

Effect of PAH specific therapy on pulmonary hemodynamics and six-minute walk distance in portopulmonary hypertension: a systematic review and meta-analysis.

PubMed

Faisal, Muhammad; Siddiqi, Furqan; Alkaddour, Ahmad; Bajwa, Abubakr A; Shujaat, Adil

2014-01-01

Little is known about the effect of pulmonary arterial hypertension (PAH) specific therapy on pulmonary hemodynamics and exercise capacity in patients with portopulmonary hypertension (PoPH) because such patients are usually excluded from randomized clinical trials (RCT) of such therapy. We searched PUBMED using the terms "(Therapy/Broad (filter)) AND (portopulmonary hypertension)." We included studies that met the following criteria: ≥5 patients, AND PoPH confirmed by right heart catheterization (RHC), AND follow-up RHC data, AND/OR baseline and follow-up 6MWD available. 12 studies met our inclusion criteria. None was a RCT. The baseline mPAP was 48.6 ± 4.4 mmHg, cardiac output (CO) 5.6 ± 0.9 L/min, and pulmonary vascular resistance (PVR) 668.6 ± 219.1 dynes.sec/cm(5). The baseline 6MWD was 348.2 ± 35.6 meters. The use of PAH specific therapy improved mPAP by 7.54 mmHg (95% CI 10.2 to 4.9), CO by 1.77 L/min (95% CI 1.1 to 2.4), and PVR by 253 dynes.sec/cm(5) (95% CI 291.4 to 214.6) (n = 135) and 6MWD by 61.8 meters (95% CI 47.5 to 76) (n = 122). The use of PAH specific therapy in PoPH results in significant improvement in both pulmonary hemodynamics and 6MWD.

Evaluation of Inhaled Procaterol for Potential Assist Use in Patients with Stable Chronic Obstructive Pulmonary Disease.

PubMed

Kodaka, Norio; Yamagishi, Toru; Watanabe, Kayo; Kishimoto, Kumiko; Nakano, Chihiro; Oshio, Takeshi; Niitsuma, Kumiko; Shimada, Nagashige; Matsuse, Hiroto

2018-05-17

International guidelines recommend the use of long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease (COPD), but the usefulness of short-acting bronchodilator assist use for stable COPD remains uncertain. The purpose of the present study was to objectively demonstrate the effects of assist use of procaterol, a short-acting -agonist, on the respiratory mechanics of stable COPD patients treated with a long-acting bronchodilator using forced oscillation technique (FOT) and conventional spirometry. We also confirmed the length of time for which procaterol assist could significantly improve pulmonary function. We enrolled 28 outpatients with mild to severe COPD (GOLD stages I-III), who had used the same long-acting bronchodilator for longer than 3 months and who were in stable condition. All measures were performed using both FOT and spirometry sequentially from 15 min to 2 h after inhalation. Compared to baseline, inhaled procaterol assist use modestly but significantly improved spirometric and FOT measurements within 2 h after inhalation. These significant effects continued for at least 2 h. Significant correlations were found between parameters measured by spirometry and those measured by FOT. Procaterol assist use modestly but significantly improved pulmonary function determined by spirometry and respiratory mechanics in patients with stable COPD treated with long-acting bronchodilators. Thus, inhaled procaterol has potential for assist use for COPD. ©2018The Author(s). Published by S. Karger AG, Basel.

Differential roles of endothelin-1 ETA and ETB receptors and vasoactive intestinal polypeptide in regulation of the airways and the pulmonary vasculature in isolated rat lung.

PubMed

Janosi, Tibor; Peták, Ferenc; Fontao, Fabienne; Morel, Denis R; Beghetti, Maurice; Habre, Walid

2008-11-01

The available treatment strategies against pulmonary hypertension include the administration of endothelin-1 (ET-1) receptor subtype blockers (ET(A) and ET(B) antagonists); vasoactive intestinal polypeptide (VIP) has recently been suggested as a potential new therapeutic agent. We set out to investigate the ability of these agents to protect against the vasoconstriction and impairment of lung function commonly observed in patients with pulmonary hypertension. An ET(A) blocker (BQ123), ET(B) blocker (BQ788), a combination of these selective blockers (ET(A) + ET(B) blockers) or VIP (V6130) was administered into the pulmonary circulation in four groups of perfused normal rat lungs. Pulmonary vascular resistance (PVR) and forced oscillatory lung input impedance (Z(L)) were measured in all groups under baseline conditions and at 1 min intervals following ET-1 administrations. The airway resistance, inertance, tissue damping and elastance were extracted from the Z(L) spectra. While VIP, ET(A) blocker and combined ET(A) and ET(B) blockers significantly prevented the pulmonary vasoconstriction induced by ET-1, ET(B) blockade enhanced the ET-1-induced increases in PVR. In contrast, the ET(A) and ET(B) blockers markedly elevated the ET-1-induced increases in airway resistance, while VIP blunted this constrictor response. Our results suggest that VIP potently acts against the airway and pulmonary vascular constriction mediated by endothelin-1, while the ET(A) and ET(B) blockers exert a differential effect between airway resistance and PVR.

Perfusion redistribution after a pulmonary-embolism-like event with contrast enhanced EIT.

PubMed

Nguyen, D T; Bhaskaran, A; Chik, W; Barry, M A; Pouliopoulos, J; Kosobrodov, R; Jin, C; Oh, T I; Thiagalingam, A; McEwan, A L

2015-06-01

Recent studies showed that regional pulmonary perfusion can be reliably estimated using electrical impedance tomography (EIT) with the aid of hypertonic saline based contrast enhancement. Building on these successful studies, we studied contrast EIT for pulmonary perfusion defect caused by an artificially induced pulmonary embolism (PE) in a large ovine model (N = 8, 78 ± 7.8 kg). Furthermore, the efficacy of a less invasive contrast bolus of 0.77 ml kg(-1) of NaCl 3% was compared with a more concentrated bolus of 0.13 ml kg(-1) of NaCl 20%. Prior to the injection of each contrast bolus injection, ventilation was turned off to provide a total of 40 to 45 s of apnoea. Each bolus of impedance contrast was injected through a catheter into the right atrium. Pulmonary embolisation was performed by balloon occlusion of part of the right branch of the pulmonary trunk. Four parameters representing the kinetics of the contrast dilution in the lung were evaluated for statistical differences between baseline and PE, including peak value, maximum uptake, maximum washout and area under the curve of the averaged contrast dilution curve in each lung. Furthermore, the right lung to left lung (R2L) ratio of each the aforementioned parameters were assessed. While all of the R2L ratios yielded significantly different means between baseline and PE, it can be concluded that the R2L ratios of area under the curve and peak value of the averaged contrast dilution curve are the most promising and reliable in assessing PE. It was also found that the efficacy of the two types of impedance contrasts were not significantly different in distinguishing PE from baseline in our model.

Exercise-induced Pulmonary Hypertension

PubMed Central

Vanderpool, Rebecca; Dhakal, Bishnu P.; Saggar, Rajeev; Saggar, Rajan; Vachiery, Jean-Luc; Lewis, Gregory D.

2013-01-01

Exercise stresses the pulmonary circulation through increases in cardiac output (Q.) and left atrial pressure. Invasive as well as noninvasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure (mPAP)–flow relationships ranges from 0.5 to 3 mm Hg⋅min⋅L−1. The upper limit of normal mPAP at exercise thus approximates 30 mm Hg at a Q. of less than 10 L⋅min−1 or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to PAP in a close to one-for-one mm Hg fashion. Multipoint PAP–flow relationships are usually described by a linear approximation, but present with a slight curvilinearity, which is explained by resistive vessel distensibility. When mPAP is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase Q. at the highest levels of exercise. Exercise has to be dynamic to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Postexercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in PAP to a mean higher than 30 mm Hg may be associated with dyspnea-fatigue symptomatology. PMID:23348976

Factor analysis in the Genetics of Asthma International Network family study identifies five major quantitative asthma phenotypes.

PubMed

Pillai, S G; Tang, Y; van den Oord, E; Klotsman, M; Barnes, K; Carlsen, K; Gerritsen, J; Lenney, W; Silverman, M; Sly, P; Sundy, J; Tsanakas, J; von Berg, A; Whyte, M; Ortega, H G; Anderson, W H; Helms, P J

2008-03-01

Asthma is a clinically heterogeneous disease caused by a complex interaction between genetic susceptibility and diverse environmental factors. In common with other complex diseases the lack of a standardized scheme to evaluate the phenotypic variability poses challenges in identifying the contribution of genes and environments to disease expression. To determine the minimum number of sets of features required to characterize subjects with asthma which will be useful in identifying important genetic and environmental contributors. Methods Probands aged 7-35 years with physician diagnosed asthma and symptomatic siblings were identified in 1022 nuclear families from 11 centres in six countries forming the Genetics of Asthma International Network. Factor analysis was used to identify distinct phenotypes from questionnaire, clinical, and laboratory data, including baseline pulmonary function, allergen skin prick test (SPT). Five distinct factors were identified:(1) baseline pulmonary function measures [forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)], (2) specific allergen sensitization by SPT, (3) self-reported allergies, (4) symptoms characteristic of rhinitis and (5) symptoms characteristic of asthma. Replication in symptomatic siblings was consistent with shared genetic and/or environmental effects, and was robust across age groups, gender, and centres. Cronbach's alpha ranged from 0.719 to 0.983 suggesting acceptable internal scale consistencies. Derived scales were correlated with serum IgE, methacholine PC(20), age and asthma severity (interrupted sleep). IgE correlated with all three atopy-related factors, the strongest with the SPT factor whereas severity only correlated with baseline lung function, and with symptoms characteristic of rhinitis and of asthma. In children and adolescents with established asthma, five distinct sets of correlated patient characteristics appear to represent important aspects of the disease. Factor scores as quantitative traits may be better phenotypes in epidemiological and genetic analyses than those categories derived from the presence or absence of combinations of +ve SPTs and/or elevated IgE.

Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension

PubMed Central

Howard, Luke S.G.E.; Watson, Geoffrey M.J.; Wharton, John; Rhodes, Christopher J.; Chan, Kakit; Khengar, Rajeshree; Robbins, Peter A.; Kiely, David G.; Condliffe, Robin; Elliott, Charlie A.; Pepke-Zaba, Joanna; Sheares, Karen; Morrell, Nicholas W.; Davies, Rachel; Ashby, Deborah; Gibbs, J. Simon R.; Wilkins, Martin R.

2013-01-01

Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy. PMID:23662181

Acute effect of L-arginine on hemodynamics and vascular capacitance in the canine pacing model of heart failure.

PubMed

Ogilvie, R I; Zborowska-Sluis, D

1995-09-01

The effect of L-arginine, 250 mg/kg over 10 min, on hemodynamics and venous function was studied in nine splenectomized dogs under light pentobarbital anesthesia before and after 17 +/- 1 days of rapid right ventricular pacing (RRVP) at 250 beats/min. Chronic RRVP induced mild congestive heart failure with increased mean circulatory filling (Pmcf), right atrial (Pra) and pulmonary capillary wedge pressures (Ppcw), and reduced cardiac output (CO). During the development of heart failure, total vascular compliance assessed from Pmcf-blood volume relationships during circulatory arrest was unchanged, but total vascular capacitance was markedly reduced, with an increase in stressed and reduction in unstressed blood volumes. At baseline but not after RRVP, L-arginine increased CO and reduced pulmonary vascular resistance. There were no significant changes in Pra, Ppcw, or total peripheral resistance. L-Arginine failed to alter total vascular compliance and capacitance or central blood volume in the baseline or failure state. These results do not support the hypothesis that increased Pmcf and reduced total vascular capacitance in the early stages of pacing-induced heart failure are caused by reduced substrate availability for or an endogenous competitive antagonist of NO synthase in venous endothelial cells.

Six-minute-walk test in idiopathic pulmonary fibrosis: test validation and minimal clinically important difference.

PubMed

du Bois, Roland M; Weycker, Derek; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; Kartashov, Alex; Lancaster, Lisa; Noble, Paul W; Sahn, Steven A; Szwarcberg, Javier; Thomeer, Michiel; Valeyre, Dominique; King, Talmadge E

2011-05-01

The 6-minute-walk test (6MWT) is a practical and clinically meaningful measure of exercise tolerance with favorable performance characteristics in various cardiac and pulmonary diseases. Performance characteristics in patients with idiopathic pulmonary fibrosis (IPF) have not been systematically evaluated. To assess the reliability, validity, and responsiveness of the 6MWT and estimate the minimal clinically important difference (MCID) in patients with IPF. The study population included all subjects completing a 6MWT in a clinical trial evaluating interferon gamma-1b (n = 822). Six-minute walk distance (6MWD) and other parameters were measured at baseline and at 24-week intervals using a standardized protocol. Parametric and distribution-independent correlation coefficients were used to assess the strength of the relationships between 6MWD and measures of pulmonary function, dyspnea, and health-related quality of life. Both distribution-based and anchor-based methods were used to estimate the MCID. Comparison of two proximal measures of 6MWD (mean interval, 24 d) demonstrated good reliability (coefficient = 0.83; P < 0.001). 6MWD was weakly correlated with measures of physiologic function and health-related quality of life; however, values were consistently and significantly lower for patients with the poorest functional status, suggesting good construct validity. Importantly, change in 6MWD was highly predictive of mortality; a 24-week decline of greater than 50 m was associated with a fourfold increase in risk of death at 1 year (hazard ratio, 4.27; 95% confidence interval, 2.57- 7.10; P < 0.001). The estimated MCID was 24-45 m. The 6MWT is a reliable, valid, and responsive measure of disease status and a valid endpoint for clinical trials in IPF.

Marihuana use. Biologic and behavioral aspects.

PubMed

Mendelson, J H

1976-11-01

More than 70 male chronic marihuana users were studied under research ward conditions for a 31-day period consisting of 5 days of baseline assessment, 21 days of marihuana availability, and 5 days of postsmoking assessment. Biological findings were for the most part within normal limits. Blood chemistry studies showed no abnormalities. Plasma testosterone levels for all subjects at all times during the study were well within normal limits, suggesting that previous reports of testosterone suppression by marihuana may have statistical but not biologic singificance. A significant reduction in baseline vital capacity was observed in six subjects, a compromise in pulmonary function similar to that characteristically produced by chronic inhalation of substances, such as tobacco smoke, which are irritants to the lung. Increased caloric intake and weight gain occurred in virtually all subjects and were causally related to marihuana smoking. The weight gain may be attributable to water retention as well as increased caloric intake. Behavioral findings indicated that no uniform alteration in mood is produced by marihuana smoking--all subjects reported becoming "high", but experienced no consistent degree of euphoria. Mood changes which occurred were relatively mild and were largely dependent on group determinants rather than individual experience. No relationship could be established between marihuana use and motivation to work or engage in socially desirable activities. Evidence that pulmonary function may be compromised as a function of marihuana smoking suggests the need for alerting individuals to this potential health hazard. As was true of cigarette smoking, the eventual public health consequences of marihuana use may become apparent only after large numbers of individuals have smoked marihuana for two or three decades.

Pulmonary rehabilitation in lymphangioleiomyomatosis: a controlled clinical trial.

PubMed

Araujo, Mariana S; Baldi, Bruno G; Freitas, Carolina S G; Albuquerque, André L P; Marques da Silva, Cibele C B; Kairalla, Ronaldo A; Carvalho, Celso R F; Carvalho, Carlos R R

2016-05-01

Lymphangioleiomyomatosis (LAM) is a cystic lung disease frequently associated with reduced exercise capacity. The aim of this study was to assess safety and efficacy of pulmonary rehabilitation in LAM.This controlled clinical trial included 40 patients with LAM and a low physical activity level. The pulmonary rehabilitation programme comprised 24 aerobic and muscle strength training sessions and education. The primary outcome was exercise capacity (endurance time during a constant work rate exercise test). Secondary outcomes included health-related quality of life (St George's Respiratory Questionnaire (SGRQ)), 6-min walking distance (6MWD), dyspnoea, peak oxygen consumption (V'O2 ), daily physical activity (pedometer), symptoms of anxiety and depression, lung function and peripheral muscle strength (one-repetition maximum).The baseline characteristics were well balanced between the groups. The pulmonary rehabilitation group exhibited improvements in the following outcomes versus controls: endurance time (median (interquartile range) 169 (2-303) s versus -33 (-129-39) s; p=0.001), SGRQ (median (interquartile range) -8 (-16-2) versus 2 (-4-5); p=0.002) and 6MWD (median (interquartile range) 59 (13-81) m versus 20 (-12-30) m; p=0.002). Dyspnoea, peak V'O2 , daily physical activity and muscle strength also improved significantly. No serious adverse events were observed.Pulmonary rehabilitation is a safe intervention and improves exercise capacity, dyspnoea, daily physical activity, quality of life and muscle strength in LAM. Copyright ©ERS 2016.

Source-specific pollution exposure and associations with pulmonary response in the Atlanta Commuters Exposure Studies.

PubMed

Krall, Jenna R; Ladva, Chandresh N; Russell, Armistead G; Golan, Rachel; Peng, Xing; Shi, Guoliang; Greenwald, Roby; Raysoni, Amit U; Waller, Lance A; Sarnat, Jeremy A

2018-06-01

Concentrations of traffic-related air pollutants are frequently higher within commuting vehicles than in ambient air. Pollutants found within vehicles may include those generated by tailpipe exhaust, brake wear, and road dust sources, as well as pollutants from in-cabin sources. Source-specific pollution, compared to total pollution, may represent regulation targets that can better protect human health. We estimated source-specific pollution exposures and corresponding pulmonary response in a panel study of commuters. We used constrained positive matrix factorization to estimate source-specific pollution factors and, subsequently, mixed effects models to estimate associations between source-specific pollution and pulmonary response. We identified four pollution factors that we named: crustal, primary tailpipe traffic, non-tailpipe traffic, and secondary. Among asthmatic subjects (N = 48), interquartile range increases in crustal and secondary pollution were associated with changes in lung function of -1.33% (95% confidence interval (CI): -2.45, -0.22) and -2.19% (95% CI: -3.46, -0.92) relative to baseline, respectively. Among non-asthmatic subjects (N = 51), non-tailpipe pollution was associated with pulmonary response only at 2.5 h post-commute. We found no significant associations between pulmonary response and primary tailpipe pollution. Health effects associated with traffic-related pollution may vary by source, and therefore some traffic pollution sources may require targeted interventions to protect health.

SH2 domain-containing protein tyrosine phosphatase 2 and focal adhesion kinase protein interactions regulate pulmonary endothelium barrier function.

PubMed

Chichger, Havovi; Braza, Julie; Duong, Huetran; Harrington, Elizabeth O

2015-06-01

Enhanced protein tyrosine phosphorylation is associated with changes in vascular permeability through formation and dissolution of adherens junctions and regulation of stress fiber formation. Inhibition of the protein tyrosine phosphorylase SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) increases tyrosine phosphorylation of vascular endothelial cadherin and β-catenin, resulting in disruption of the endothelial monolayer and edema formation in the pulmonary endothelium. Vascular permeability is a hallmark of acute lung injury (ALI); thus, enhanced SHP2 activity offers potential therapeutic value for the pulmonary vasculature in diseases such as ALI, but this has not been characterized. To assess whether SHP2 activity mediates protection against edema in the endothelium, we assessed the effect of molecular activation of SHP2 on lung endothelial barrier function in response to the edemagenic agents LPS and thrombin. Both LPS and thrombin reduced SHP2 activity, correlated with decreased focal adhesion kinase (FAK) phosphorylation (Y(397) and Y(925)) and diminished SHP2 protein-protein associations with FAK. Overexpression of constitutively active SHP2 (SHP2(D61A)) enhanced baseline endothelial monolayer resistance and completely blocked LPS- and thrombin-induced permeability in vitro and significantly blunted pulmonary edema formation induced by either endotoxin (LPS) or Pseudomonas aeruginosa exposure in vivo. Chemical inhibition of FAK decreased SHP2 protein-protein interactions with FAK concomitant with increased permeability; however, overexpression of SHP2(D61A) rescued the endothelium and maintained FAK activity and FAK-SHP2 protein interactions. Our data suggest that SHP2 activation offers the pulmonary endothelium protection against barrier permeability mediators downstream of the FAK signaling pathway. We postulate that further studies into the promotion of SHP2 activation in the pulmonary endothelium may offer a therapeutic approach for patients suffering from ALI.

Socioeconomic status and the likelihood of antibiotic treatment for signs and symptoms of pulmonary exacerbation in children with cystic fibrosis.

PubMed

Schechter, Michael S; McColley, Susanna A; Regelmann, Warren; Millar, Stefanie J; Pasta, David J; Wagener, Jeffrey S; Konstan, Michael W; Morgan, Wayne J

2011-11-01

To determine whether socioeconomic status (SES) influences the likelihood of antibiotic treatment of pulmonary exacerbations in patients with cystic fibrosis (CF). We used data on 9895 patients ≤ 18 years old from the Epidemiologic Study of CF. After establishing an individual baseline of clinical signs and symptoms, we ascertained whether antibiotics were prescribed when new signs/symptoms suggested a pulmonary exacerbation, adjusting for sex, presence of Pseudomonas aeruginosa, the number of new signs/symptoms, and baseline disease severity. In a 12-month period, 20.0% of patients <6 years of age, 33.8% of patients 6 to 12 years of age, and 41.4% of patients 13 to 18 years of age were treated with any (oral, intravenous (IV), or inhaled) antibiotics; the percentage receiving IV antibiotics was 7.3%, 15.2%, and 20.9%, respectively. SES had little effect on treatment for pulmonary exacerbation with any antibiotics, but IV antibiotics were prescribed more frequently for patients with lower SES. SES-related disparities in CF health outcomes do not appear to be explained by differential treatment of pulmonary exacerbations. Copyright © 2011 Mosby, Inc. All rights reserved.

Baseline Cardiopulmonary Function as an Independent Prognostic Factor for Survival of Inoperable Non-Small-Cell Lung Cancer After Concurrent Chemoradiotherapy: A Single-Center Analysis of 161 Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Semrau, Sabine, E-mail: sabine.semrau@uk-erlangen.d; Department of Radiation Therapy, University of Rostock, Suedring, Rostock; Klautke, Gunther

2011-01-01

Purpose: Little is known about the effects of cardiopulmonary function on the prognosis of concurrent chemoradiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC). Methods and Materials: A retrospective analysis of the effects of tumor- and patient-related factors and parameters of cardiopulmonary function and heart morphology on the feasibility, toxicity, and prognosis was performed. Results: Cardiopulmonary function had no effect on the toxicity or feasibility of treatment; effects on survival were observed in the univariate analysis. Median survival varied as follows: cardiac function: 13.0 {+-} 1.6 months for left ventricular ejection fraction (LVEF) > 50% vs. 10.0 {+-} 1.9 monthsmore » for LVEF {<=} 50% (p = 0.003); pulmonary function: 16.0 {+-} 0.6 months for no lung function deficits (vital capacity [VC]{>=} 60%, forced expiratory volume in 1 s {>=} 80%, and diffusing capacity of the lung for carbon monoxide (DLCO) {>=}60%) vs. 14.0 {+-} 1.5 months for one or two function deficits vs. 8.0 {+-} 1.5 months for three lung function deficits (p = 0.001); T stage: 19.0 {+-} 3.1 months for rcT0/cT1/cT2 vs. 12.0 {+-} 0.8 months for cT3/cT4 (p = 0.039); and age: 11.0 {+-} 1.5 months for <60 years vs. 18.0 {+-} 2.5 months for 60-69 years vs. 12.0 {+-} 1.2 months for {>=}70 years (p = 0.008). Prognostic factors identified in the multivariate analysis were LVEF {<=}50% (p = 0.043; hazard ratio [HR], 1.74), reduced pulmonary function (p = 0.001; HR, 1.71 or 5.05) and T stage (p = 0.026; HR: 1.71). Conclusions: In addition to T-stage, cardiac and pulmonary function variables affected the survival of non-small-cell lung cancer patients after chemoradiotherapy.« less

IMPACT OF CALCIUM-CHANNEL BLOCKERS ON RIGHT HEART FUNCTION IN A CONTROLLED MODEL OF CHRONIC PULMONARY HYPERTENSION

PubMed Central

Zierer, Andreas; Voeller, Rochus K.; Melby, Spencer J.; Steendijk, Paul; Moon, Marc R.

2009-01-01

Purpose Patients with chronic pulmonary hypertension (CPH) who demonstrate a pulmonary vasodilation following calcium channel blocker (CCB) administration are defined as “responders”. In contrast, “non-responders” are patients who do not show such a pulmonary vasodilation with CCB therapy. The purpose of this investigation was to study the effects of CCB therapy on right heart mechanics in experimental CCB responders versus CCB non-responders. Methods In 12 dogs, right atrial (RA) and ventricular (RV) pressure and volume (conductance catheters) were simultaneously recorded after 3 months of progressive pulmonary artery (PA) banding. Diltiazem was given at 10 mg/hr with the PA constricted (simulated CCB non-responder). Responders were then created by releasing the PA band to unload the ventricle. RA and RV contractility and diastolic stiffness (slope of end-systolic and end-diastolic pressure-volume relations) were calculated and RA reservoir and conduit function were quantified as RA inflow with the tricuspid valve closed versus open, respectively. Results With CCB, RA contractility (p<0.03) and cardiac output (p<0.004) were compromised in simulated non-responders while RA stroke work was pharmacologically depressed in the setting of an unchanged afterload. After simulating a responder by controlled PA band release, the RA became less distensible, causing a shift from reservoir to conduit function (p<0.001) towards physiologic baseline conditions and a recovery in the hyperdynamic compensatory response in both chambers (p<0.007) as evidenced in a declined RA and RV contractility with an improved cardiac output as compared to CPH and simulated non-responders. RA and RV diastolic function in both groups was not affected by CCB. Conclusions CCB did not impact RV function in simulated non-responders, but significantly impaired RA contractility and cardiac output. In simulated responders, afterload fell substantially, thereby allowing the RA and RV to recover from their pathological hyperdynamic contractile response to CPH. This affect was able to outweigh the intrinsic negative effects of CCB therapy on systolic RA function. Current data suggest that the RA in CPH is much more sensitive to CCB therapy than the RV and delineate for the first time why CCB therapy in CPH has been empirically restricted to documented responders. PMID:19237986

Impaired pulmonary function after treatment for tuberculosis: the end of the disease?

PubMed Central

Chushkin, Mikhail Ivanovich; Ots, Oleg Nikolayevich

2017-01-01

ABSTRACT Objective: To evaluate the prevalence of pulmonary function abnormalities and to investigate the factors affecting lung function in patients treated for pulmonary tuberculosis. Methods: A total of 214 consecutive patients (132 men and 82 women; 20-82 years of age), treated for pulmonary tuberculosis and followed at a local dispensary, underwent spirometry and plethysmography at least one year after treatment. Results: Pulmonary impairment was present in 102 (47.7%) of the 214 patients evaluated. The most common functional alteration was obstructive lung disease (seen in 34.6%). Of the 214 patients, 60 (28.0%) showed reduced pulmonary function (FEV1 below the lower limit of normal). Risk factors for reduced pulmonary function were having had culture-positive pulmonary tuberculosis in the past, being over 50 years of age, having recurrent tuberculosis, and having a lower level of education. Conclusions: Nearly half of all tuberculosis patients evolve to impaired pulmonary function. That underscores the need for pulmonary function testing after the end of treatment. PMID:28380187

Effect of Increased Blood Flow on Pulmonary Circulation Before and During High Altitude Acclimatization.

PubMed

Hilty, Matthias Peter; Müller, Andrea; Flück, Daniela; Siebenmann, Christoph; Rasmussen, Peter; Keiser, Stefanie; Auinger, Katja; Lundby, Carsten; Maggiorini, Marco

2016-12-01

Matthias Peter Hilty, Andrea Mueller, Daniela Flück, Christoph Siebenmann, Peter Rasmussen, Stefanie Keiser, Katja Auinger, Carsten Lundby, and Marco Maggiorini. Effect of increased blood flow on the pulmonary circulation before and during high altitude acclimatization. High Alt Med Biol. 17:305-314, 2016.-Introduction and Methods: Acute exposure to high altitude increases pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR). The evolution of Ppa and PVR with continuous hypoxic exposure remains, however, elusive. To test the hypothesis that altitude exposure leads to a persistent elevation in Ppa and PVR throughout acclimatization in seven healthy male subjects, echocardiography was performed at sea level (SL; 488 m) weekly during a 4-week sojourn at 3454 m (HA1-HA4) and upon return (SL2). Pulmonary artery catheterization and bilateral thigh cuff release maneuver were performed at SL and HA3 to study the properties of pulmonary circulation after 3 weeks of acclimatization. Pulmonary artery catheter determined that systolic Ppa (mean ± SEM) was increased from 20 ± 1 at SL to 27 ± 2 mmHg at HA3 (p < 0.01). Echocardiography assessed that systolic Ppa remained equally increased throughout acclimatization (26 ± 2, 25 ± 2, 25 ± 2, and 24 ± 2 mmHg at HA1-HA4; p = 0.93) and returned to baseline upon return (17 ± 2, 18 ± 1 mmHg at SL, SL2; p = 0.3). The same was shown for PVR. Right heart function remained unaffected. Thigh cuff release maneuvers at SL and HA3 resulted in similar increase in cardiac output (2.5 ± 0.5 and 2.2 ± 0.4 L/min; p = 0.61) without affecting mean Ppa. Prolonged altitude exposure leads to a persistent increase in Ppa and PVR without affecting right heart function and is fully reversible within 1 week after return to SL. The thigh cuff release maneuver-induced increase in cardiac output suggests a preserved ability of pulmonary circulation to cope with sudden remarkable increase in pulmonary blood flow throughout acclimatization.

Effect of Baseline Anxiety and Depression Symptoms on Selected Outcomes Following Pulmonary Rehabilitation.

PubMed

Cullen, Kate; Talbot, Daniel; Gillmor, Julie; McGrath, Colin; OʼDonnell, Rory; Baily-Scanlan, Maria; Broderick, Julie

2017-07-01

Anxiety and depression are prevalent comorbidities in people with chronic respiratory diseases (CRDs). This study sought to quantify the influence of varying degrees of anxiety and depression on functional performance and disease impact in a population with CRDs following pulmonary rehabilitation (PR) intervention. The Hospital Anxiety and Depression Scale (HADS), the 6-Minute Walk Test (6MWT), and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT) were assessed pre- and post-PR. Participants were categorized into 3 groups (None, Probable, and Present) based on their level of anxiety and depression. Functional performance and disease impact outcomes were compared pre- and post-PR. Patients consisted of a total of 134 program completers (72 males, 62 females; mean age = 67.8 years). Significant improvements in functional performance with regard to 6MWT scores were observed across all groups postintervention (P < .05). The Present group, in both the anxiety and depression domains, failed to reach a minimally clinically important difference postintervention. The Probable and Present groups achieved a significant improvement in CAT scores postintervention (P < .05). This study showed that symptoms of anxiety and depression in people with CRDs were significantly related to lower exercise tolerance levels and higher levels of disease impact. People with increased levels of anxiety and depression have the potential to significantly improve disease impact outcomes post-PR. The results demonstrated that the detection and treatment of anxiety and depression symptoms in people with CRDs are likely to be clinically important.

The Relationship between Ambient Air Pollution and Heart Rate Variability Differs for Individuals with Heart and Pulmonary Disease

PubMed Central

Wheeler, Amanda; Zanobetti, Antonella; Gold, Diane R.; Schwartz, Joel; Stone, Peter; Suh, Helen H.

2006-01-01

Associations between concentrations of ambient fine particles [particulate matter < 2.5 μ m aerodynamic diameter (PM2.5)] and heart rate variability (HRV) have differed by study population. We examined the effects of ambient pollution on HRV for 18 individuals with chronic obstructive pulmonary disease (COPD) and 12 individuals with recent myocardial infarction (MI) living in Atlanta, Georgia. HRV, baseline pulmonary function, and medication data were collected for each participant on 7 days in fall 1999 and/or spring 2000. Hourly ambient pollution concentrations were obtained from monitoring sites in Atlanta. The association between ambient pollution and HRV was examined using linear mixed-effect models. Ambient pollution had opposing effects on HRV in our COPD and MI participants, resulting in no significant effect of ambient pollution on HRV in the entire population for 1-, 4-, or 24-hr moving averages. For individuals with COPD, interquartile range (IQR) increases in 4-hr ambient PM2.5 (11.65 μ g/m3) and nitrogen dioxide (11.97 ppb) were associated with 8.3% [95% confidence interval (CI), 1.7–15.3%] and 7.7% (95% CI, 0.1–15.9%) increase in the SD of normal R-R intervals (SDNN), respectively. For individuals with MI, IQR increases in 4-hr PM2.5 (8.54 μ g/m3) and NO2 (9.25 ppb) were associated with a nonsignificant 2.9% (95% CI, –7.8 to 2.3) and significant 12.1 (95% CI, –19.5 to –4.0) decrease in SDNN. Beta-blocker and bronchodilator intake and baseline forced expiratory volume in 1 sec modified the PM–SDNN association significantly, with effects consistent with those by disease group. Results indicate heterogeneity in the autonomic response to air pollution due to differences in baseline health, with significant associations for ambient NO2 suggesting an important role for traffic-related pollution. PMID:16581546

Prone position improves lung mechanical behavior and enhances gas exchange efficiency in mechanically ventilated chronic obstructive pulmonary disease patients.

PubMed

Mentzelopoulos, Spyros D; Zakynthinos, Spyros G; Roussos, Charris; Tzoufi, Maria J; Michalopoulos, Argyris S

2003-06-01

Pronation might favorably affect respiratory system (rs) mechanics and function in volume-controlled, mode-ventilated chronic obstructive pulmonary disease (COPD) patients. We studied 10 COPD patients, initially positioned supine (baseline supine [supine(BAS)]) and then randomly and consecutively changed to protocol supine (supine(PROT)), semirecumbent, and prone positions. Rs mechanics and inspiratory work (W(I)) were assessed at baseline (0.6 L) (all postures) and sigh (1.2 L) (supine(BAS) excluded) tidal volume (V(T)) with rapid airway occlusion during constant-flow inflation. Hemodynamics and gas exchange were assessed in all postures. There were no complications. Prone positioning resulted in (a) increased dynamic-static chest wall (cw) elastance (at both V(Ts)) and improved oxygenation versus supine(BAS), supine(PROT), and semirecumbent, (b) decreased additional lung (L) resistance-elastance versus supine(PROT) and semirecumbent at sigh V(T), (c) decreased L-static elastance (at both V(Ts)) and improved CO(2) elimination versus supine(BAS) and supine(PROT), and (d) improved oxygenation versus all other postures. Semirecumbent positioning increased mainly additional cw-resistance versus supine(BAS) and supine(PROT) at baseline. V(T) W(I)-sub-component changes were consistent with changes in rs, cw, and L mechanical properties. Total rs-W(I) and hemodynamics were unaffected by posture change. After pronation, five patients were repositioned supine (supine(POSTPRO)). In supine(POSTPRO), static rs-L elastance were lower, and oxygenation was still improved versus supine(BAS). Pronation of mechanically ventilated COPD patients exhibits applicability and effectiveness and improves oxygenation and sigh-L mechanics versus semirecumbent ("gold standard") positioning. By assessing respiratory mechanics, inspiratory work, hemodynamics, and gas exchange, we showed that prone positioning of mechanically ventilated chronic obstructed pulmonary disease patients improves oxygenation and lung mechanics during sigh versus semirecumbent positioning. Furthermore, certain pronation-related benefits versus preprone-supine positioning (reduced lung elastance and improved oxygenation) are maintained in the postprone supine position.

Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2).

PubMed

Simonneau, Gérald; D'Armini, Andrea M; Ghofrani, Hossein-Ardeschir; Grimminger, Friedrich; Hoeper, Marius M; Jansa, Pavel; Kim, Nick H; Wang, Chen; Wilkins, Martin R; Fritsch, Arno; Davie, Neil; Colorado, Pablo; Mayer, Eckhard

2015-05-01

Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit-risk profile and improved several clinically relevant end-points in patients with CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from CHEST-1 received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was the safety and tolerability of riociguat; exploratory efficacy end-points included 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC). Overall, 237 patients entered CHEST-2 and 211 (89%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±sd 6MWD had changed by +51±62 m (n=172) versus CHEST-1 baseline (n=237), and WHO FC had improved/stabilised/worsened in 47/50/3% of patients (n=176) versus CHEST-1 baseline (n=236). Long-term riociguat had a favourable benefit-risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year. Copyright ©ERS 2015.

Interdisciplinary model of care (RADICALS) for early detection and management of chronic obstructive pulmonary disease (COPD) in Australian primary care: study protocol for a cluster randomised controlled trial

PubMed Central

Liang, Jenifer; Abramson, Michael J; Zwar, Nicholas; Russell, Grant; Holland, Anne E; Bonevski, Billie; Mahal, Ajay; van Hecke, Benjamin; Phillips, Kirsten; Eustace, Paula; Paul, Eldho; Petrie, Kate; Wilson, Sally; George, Johnson

2017-01-01

Introduction Up to half of all smokers develop clinically significant chronic obstructive pulmonary disease (COPD). Gaps exist in the implementation and uptake of evidence-based guidelines for managing COPD in primary care. We describe the methodology of a cluster randomised controlled trial (cRCT) evaluating the efficacy and cost-effectiveness of an interdisciplinary model of care aimed at reducing the burden of smoking and COPD in Australian primary care settings. Methods and analysis A cRCT is being undertaken to evaluate an interdisciplinary model of care (RADICALS — Review of Airway Dysfunction and Interdisciplinary Community-based care of Adult Long-term Smokers). General practice clinics across Melbourne, Australia, are identified and randomised to the intervention group (RADICALS) or usual care. Patients who are current or ex-smokers, of at least 10 pack years, including those with an existing diagnosis of COPD, are being recruited to identify 280 participants with a spirometry-confirmed diagnosis of COPD. Handheld lung function devices are being used to facilitate case-finding. RADICALS includes individualised smoking cessation support, home-based pulmonary rehabilitation and home medicines review. Patients at control group sites receive usual care and Quitline referral, as appropriate. Follow-ups occur at 6 and 12 months from baseline to assess changes in quality of life, abstinence rates, health resource utilisation, symptom severity and lung function. The primary outcome is change in St George’s Respiratory Questionnaire score of patients with COPD at 6 months from baseline. Ethics and dissemination This project has been approved by the Monash University Human Research Ethics Committee and La Trobe University Human Ethics Committee (CF14/1018 – 2014000433). Results of the study will be disseminated in peer-reviewed journals and research conferences. If the intervention is successful, the RADICALS programme could potentially be integrated into general practices across Australia and sustained over time. Trial registration number ACTRN12614001155684; Pre-results. PMID:28928190

Variations in Alveolar Partial Pressure for Carbon Dioxide and Oxygen Have Additive Not Synergistic Acute Effects on Human Pulmonary Vasoconstriction

PubMed Central

Croft, Quentin P. P.; Formenti, Federico; Talbot, Nick P.; Lunn, Daniel; Robbins, Peter A.; Dorrington, Keith L.

2013-01-01

The human pulmonary vasculature constricts in response to hypercapnia and hypoxia, with important consequences for homeostasis and adaptation. One function of these responses is to direct blood flow away from poorly-ventilated regions of the lung. In humans it is not known whether the stimuli of hypercapnia and hypoxia constrict the pulmonary blood vessels independently of each other or whether they act synergistically, such that the combination of hypercapnia and hypoxia is more effective than the sum of the responses to each stimulus on its own. We independently controlled the alveolar partial pressures of carbon dioxide (Paco 2) and oxygen (Pao 2) to examine their possible interaction on human pulmonary vasoconstriction. Nine volunteers each experienced sixteen possible combinations of four levels of Paco 2 (+6, +1, −4 and −9 mmHg, relative to baseline) with four levels of Pao 2 (175, 100, 75 and 50 mmHg). During each of these sixteen protocols Doppler echocardiography was used to evaluate cardiac output and systolic tricuspid pressure gradient, an index of pulmonary vasoconstriction. The degree of constriction varied linearly with both Paco 2 and the calculated haemoglobin oxygen desaturation (1-So 2). Mixed effects modelling delivered coefficients defining the interdependence of cardiac output, systolic tricuspid pressure gradient, ventilation, Paco 2 and So 2. No interaction was observed in the effects on pulmonary vasoconstriction of carbon dioxide and oxygen (p>0.64). Direct effects of the alveolar gases on systolic tricuspid pressure gradient greatly exceeded indirect effects arising from concurrent changes in cardiac output. PMID:23935847

Variations in alveolar partial pressure for carbon dioxide and oxygen have additive not synergistic acute effects on human pulmonary vasoconstriction.

PubMed

Croft, Quentin P P; Formenti, Federico; Talbot, Nick P; Lunn, Daniel; Robbins, Peter A; Dorrington, Keith L

2013-01-01

The human pulmonary vasculature constricts in response to hypercapnia and hypoxia, with important consequences for homeostasis and adaptation. One function of these responses is to direct blood flow away from poorly-ventilated regions of the lung. In humans it is not known whether the stimuli of hypercapnia and hypoxia constrict the pulmonary blood vessels independently of each other or whether they act synergistically, such that the combination of hypercapnia and hypoxia is more effective than the sum of the responses to each stimulus on its own. We independently controlled the alveolar partial pressures of carbon dioxide (Paco 2) and oxygen (Pao 2) to examine their possible interaction on human pulmonary vasoconstriction. Nine volunteers each experienced sixteen possible combinations of four levels of Paco 2 (+6, +1, -4 and -9 mmHg, relative to baseline) with four levels of Pao 2 (175, 100, 75 and 50 mmHg). During each of these sixteen protocols Doppler echocardiography was used to evaluate cardiac output and systolic tricuspid pressure gradient, an index of pulmonary vasoconstriction. The degree of constriction varied linearly with both Paco 2 and the calculated haemoglobin oxygen desaturation (1-So2). Mixed effects modelling delivered coefficients defining the interdependence of cardiac output, systolic tricuspid pressure gradient, ventilation, Paco 2 and So2. No interaction was observed in the effects on pulmonary vasoconstriction of carbon dioxide and oxygen (p>0.64). Direct effects of the alveolar gases on systolic tricuspid pressure gradient greatly exceeded indirect effects arising from concurrent changes in cardiac output.

Pulmonary rehabilitation improves exercise capacity and dyspnea in air pollution-related respiratory disease.

PubMed

Miyamoto, Naomi; Senjyu, Hideaki; Tanaka, Takako; Asai, Masaharu; Yanagita, Yorihide; Yano, Yudai; Nishinakagawa, Tsuyoshi; Kotaki, Kenji; Kitagawa, Chika; Rikitomi, Naoto; Kozu, Ryo; Honda, Sumihisa

2014-01-01

Air pollution in Japan caused respiratory disease, such as chronic bronchitis and asthma, in many individuals in the 1960s. Although air pollution has decreased, many victims of air pollution-related respiratory disease are limited in their activities of daily living because of respiratory symptoms. The purpose of this study was to evaluate the efficacy of pulmonary rehabilitation in victims of air pollution-related chronic bronchitis or asthma. Subjects were enrolled in a 12-week (2-week inpatient followed by 10-week outpatient) pulmonary rehabilitation program. The program comprised conditioning, strength training, endurance training, and patient education. We assessed the Modified Medical Research Council (MMRC) dyspnea grade, pulmonary function, peripheral muscle force, incremental shuttle walk distance (ISWD), and physical activity at baseline and immediately after the program. Twenty-nine subjects (mean age 74.2 ± 10.1 years, 11 males) completed the program, including 11 subjects with COPD and 18 subjects with asthma. Following rehabilitation, the participants (n = 29) showed significant improvements in MMRC dyspnea grade, vital capacity % predicted, quadriceps force and ISWD (all P < 0.05). Sub-group analyses revealed that all these variables were significantly improved in subjects with asthma. In contrast, subjects with COPD showed significant improvements only in quadriceps force and ISWD (both P < 0.05). Thus, pulmonary rehabilitation is an effective method of improving exercise capacity and dyspnea in officially acknowledged victims of air pollution-related asthma. In conclusion, we recommend that patients with chronic bronchitis or asthma, resulting from exposure to air pollution, are referred for pulmonary rehabilitation.

Exercise physiological responses to drug treatments in chronic thromboembolic pulmonary hypertension.

PubMed

Charalampopoulos, Athanasios; Gibbs, J Simon R; Davies, Rachel J; Gin-Sing, Wendy; Murphy, Kevin; Sheares, Karen K; Pepke-Zaba, Joanna; Jenkins, David P; Howard, Luke S

2016-09-01

We tested the hypothesis that patients with chronic thromboembolic pulmonary hypertension (CTEPH) that was deemed to be inoperable were more likely to respond to drugs for treating pulmonary arterial hypertension (PAH) by using cardiopulmonary exercise (CPX) testing than those with CTEPH that was deemed to be operable. We analyzed CPX testing data of all patients with CTEPH who were treated with PAH drugs and had undergone CPX testing before and after treatment at a single pulmonary hypertension center between February 2009 and March 2013. Suitability for pulmonary endarterectomy (PEA) was decided by experts in PEA who were associated with a treatment center. The group with inoperable CTEPH included 16 patients, the operable group included 26 patients. There were no differences in demographics and baseline hemodynamic data between the groups. Unlike patients in the operable group, after drug treatment patients with inoperable CTEPH had a significantly higher peak V̇o2 (P < 0.001), work load (P = 0.002), and oxygen pulse (P < 0.001). In terms of gas exchange, there was an overall net trend toward improved V̇e/V̇co2 in the group with inoperable CTEPH, with an increased PaCO2 (P = 0.01), suggesting reduced hyperventilation. No changes were observed in patients with operable CTEPH. In conclusion, treatment with PAH drug therapy reveals important pathophysiological differences between inoperable and operable CTEPH, with significant pulmonary vascular and cardiac responses in inoperable disease. Drug effects on exercise function observed in inoperable CTEPH cannot be translated to all forms of CTEPH. Copyright © 2016 the American Physiological Society.

The influence of kyphosis correction surgery on pulmonary function and thoracic volume.

PubMed

Zeng, Yan; Chen, Zhongqiang; Ma, Desi; Guo, Zhaoqing; Qi, Qiang; Li, Weishi; Sun, Chuiguo; Liu, Ning; White, Andrew P

2014-10-01

A clinical study. To measure the changes in pulmonary function and thoracic volume associated with surgical correction of kyphotic deformities. No prior study has focused on the pulmonary function and thoracic cavity volume before and after corrective surgery for kyphosis. Thirty-four patients with kyphosis underwent posterior deformity correction with instrumented fusion. Preoperative and postoperative pulmonary function was measured, and pulmonary function grade was evaluated as mild, significant, or severe. The change in preoperative to postoperative pulmonary function was analyzed, using 6 comparative subgroupings of patients on the basis of age, severity of kyphosis, location of kyphosis apex, length of follow-up time after surgery, degree of kyphosis correction, and number of segments fused. A second group of 19 patients also underwent posterior surgical correction of kyphosis, which had thoracic volume measured preoperatively and postoperatively with computed tomographic scanning. All of the pulmonary impairments were found to be restrictive. After surgery, most of the patients had improvement of the pulmonary function. Before surgery, the pulmonary function differences were found to be significant based on both severity of preoperative kyphosis (<60° vs. >60°) and location of the kyphosis apex (above T10 vs. below T10). Younger patients (younger than 35 yr) were more likely to exhibit statistically significant improvements in pulmonary function after surgery. However, thoracic volume was not significantly related to pulmonary function parameters. After surgery, average thoracic volume had no significant change. The major pulmonary impairment caused by kyphosis was found to be restrictive. Patients with kyphosis angle of 60° or greater or with kyphosis apex above T10 had more severe pulmonary dysfunction. Patients' age was significantly related to change in pulmonary function after surgery. However, the average thoracic volume had no significant change after surgery. 3.

Exposure to traffic pollution, acute inflammation and autonomic response in a panel of car commuters.

PubMed

Sarnat, Jeremy A; Golan, Rachel; Greenwald, Roby; Raysoni, Amit U; Kewada, Priya; Winquist, Andrea; Sarnat, Stefanie E; Dana Flanders, W; Mirabelli, Maria C; Zora, Jennifer E; Bergin, Michael H; Yip, Fuyuen

2014-08-01

Exposure to traffic pollution has been linked to numerous adverse health endpoints. Despite this, limited data examining traffic exposures during realistic commutes and acute response exists. We conducted the Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and health study, to measure chemically-resolved in-vehicle exposures and corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary and systemic inflammation and autonomic response. We recruited 42 adults (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle particulate components were measured in the subjects' private vehicles. Biomarker measurements were conducted before, during, and immediately after the commutes and in 3 hourly intervals after commutes. At measurement time points within 3h after the commute, we observed mild to pronounced elevations relative to baseline in exhaled nitric oxide, C-reactive-protein, and exhaled malondialdehyde, indicative of pulmonary and systemic inflammation and oxidative stress initiation, as well as decreases relative to baseline levels in the time-domain heart-rate variability parameters, SDNN and rMSSD, indicative of autonomic dysfunction. We did not observe any detectable changes in lung function measurements (FEV1, FVC), the frequency-domain heart-rate variability parameter or other systemic biomarkers of vascular injury. Water soluble organic carbon was associated with changes in eNO at all post-commute time-points (p<0.0001). Our results point to measureable changes in pulmonary and autonomic biomarkers following a scripted 2-h highway commute. Copyright © 2014 Elsevier Inc. All rights reserved.

Exposure to traffic pollution, acute inflammation and autonomic response in a panel of car commuters

PubMed Central

Sarnat, Jeremy A.; Golan, Rachel; Greenwald, Roby; Raysoni, Amit U.; Kewada, Priya; Winquist, Andrea; Sarnat, Stefanie E.; Flanders, W. Dana; Mirabelli, Maria C.; Zora, Jennifer E.; Bergin, Michael H.; Yip, Fuyuen

2015-01-01

Background Exposure to traffic pollution has been linked to numerous adverse health endpoints. Despite this, limited data examining traffic exposures during realistic commutes and acute response exists. Objectives: We conducted the Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and health study, to measure chemically-resolved in-vehicle exposures and corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary and systemic inflammation and autonomic response. Methods We recruited 42 adults (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle particulate components were measured in the subjects’ private vehicles. Biomarker measurements were conducted before, during, and immediately after the commutes and in 3 hourly intervals after commutes. Results At measurement time points within 3 h after the commute, we observed mild to pronounced elevations relative to baseline in exhaled nitric oxide, C-reactive-protein, and exhaled malondialdehyde, indicative of pulmonary and systemic inflammation and oxidative stress initiation, as well as decreases relative to baseline levels in the time-domain heart-rate variability parameters, SDNN and rMSSD, indicative of autonomic dysfunction. We did not observe any detectable changes in lung function measurements (FEV1, FVC), the frequency-domain heart-rate variability parameter or other systemic biomarkers of vascular injury. Water soluble organic carbon was associated with changes in eNO at all post-commute time-points (p < 0.0001). Conclusions Our results point to measureable changes in pulmonary and autonomic biomarkers following a scripted 2-h highway commute. PMID:24906070

Impaired resolution of inflammatory response in the lungs of JF1/Msf mice following carbon nanoparticle instillation

PubMed Central

2011-01-01

Background Declined lung function is a risk factor for particulate matter associated respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). Carbon nanoparticles (CNP) are a prominent component of outdoor air pollution that causes pulmonary toxicity mainly through inflammation. Recently we demonstrated that mice (C3H/HeJ) with higher than normal pulmonary function resolved the elicited pulmonary inflammation following CNP exposure through activation of defense and homeostasis maintenance pathways. To test whether CNP-induced inflammation is affected by declined lung function, we exposed JF1/Msf (JF1) mice with lower than normal pulmonary function to CNP and studied the pulmonary inflammation and its resolution. Methods 5 μg, 20 μg and 50 μg CNP (Printex 90) were intratracheally instilled in JF1 mice to determine the dose response and the time course of inflammation over 7 days (20 μg dosage). Inflammation was assessed using histology, bronchoalveolar lavage (BAL) analysis and by a panel of 62 protein markers. Results 24 h after instillation, 20 μg and 50 μg CNP caused a 25 fold and 19 fold increased polymorphonuclear leucocytes (PMN) respectively while the 5 μg represented the 'no observable adverse effect level' as reflected by PMN influx (9.7 × 10E3 vs 8.9 × 10E3), and BAL/lung concentrations of pro-inflammatory cytokines. Time course assessment of the inflammatory response revealed that compared to day1 the elevated BAL PMN counts (246.4 × 10E3) were significantly decreased at day 3 (72.9 × 10E3) and day 7 (48.5 × 10E3) but did not reach baseline levels indicating slow PMN resolution kinetics. Strikingly on day 7 the number of macrophages doubled (455.0 × 10E3 vs 204.7 × 10E3) and lymphocytes were 7-fold induced (80.6 × 10E3 vs 11.2 × 10E3) compared to day1. At day 7 elevated levels of IL1B, TNF, IL4, MDC/CCL22, FVII, and vWF were detected in JF1 lungs which can be associated to macrophage and lymphocyte activation. Conclusion This explorative study indicates that JF1 mice with impaired pulmonary function also exhibits delayed resolution of particle mediated lung inflammation as evident from elevated PMN and accumulation of macrophages and lymphocytes on day7. It is plausible that elevated levels of IL1B, IL4, TNF, CCL22/MDC, FVII and vWF counteract defense and homeostatic pathways thereby driving this phenomenon. PMID:21756372

Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease

PubMed Central

Fuld, J; Kilduff, L; Neder, J; Pitsiladis, Y; Lean, M; Ward, S; Cotton, M

2005-01-01

Background: Skeletal muscle wasting and dysfunction are strong independent predictors of mortality in patients with chronic obstructive pulmonary disease (COPD). Creatine nutritional supplementation produces increased muscle mass and exercise performance in health. A controlled study was performed to look for similar effects in 38 patients with COPD. Methods: Thirty eight patients with COPD (mean (SD) forced expiratory volume in 1 second (FEV1) 46 (15)% predicted) were randomised to receive placebo (glucose polymer 40.7 g) or creatine (creatine monohydrate 5.7 g, glucose 35 g) supplements in a double blind trial. After 2 weeks loading (one dose three times daily), patients participated in an outpatient pulmonary rehabilitation programme combined with maintenance (once daily) supplementation. Pulmonary function, body composition, and exercise performance (peripheral muscle strength and endurance, shuttle walking, cycle ergometry) took place at baseline (n = 38), post loading (n = 36), and post rehabilitation (n = 25). Results: No difference was found in whole body exercise performance between the groups: for example, incremental shuttle walk distance mean –23.1 m (95% CI –71.7 to 25.5) post loading and –21.5 m (95% CI –90.6 to 47.7) post rehabilitation. Creatine increased fat-free mass by 1.09 kg (95% CI 0.43 to 1.74) post loading and 1.62 kg (95% CI 0.47 to 2.77) post rehabilitation. Peripheral muscle performance improved: knee extensor strength 4.2 N.m (95% CI 1.4 to 7.1) and endurance 411.1 J (95% CI 129.9 to 692.4) post loading, knee extensor strength 7.3 N.m (95% CI 0.69 to 13.92) and endurance 854.3 J (95% CI 131.3 to 1577.4) post rehabilitation. Creatine improved health status between baseline and post rehabilitation (St George's Respiratory Questionnaire total score –7.7 (95% CI –14.9 to –0.5)). Conclusions: Creatine supplementation led to increases in fat-free mass, peripheral muscle strength and endurance, health status, but not exercise capacity. Creatine may constitute a new ergogenic treatment in COPD. PMID:15994258

Probability of treatment following acute decline in lung function in children with cystic fibrosis is related to baseline pulmonary function.

PubMed

Morgan, Wayne J; Wagener, Jeffrey S; Yegin, Ashley; Pasta, David J; Millar, Stefanie J; Konstan, Michael W

2013-10-01

To determine whether the association between high forced expiratory volume in 1 second (FEV1) and increased rate of decline in FEV1 in children with cystic fibrosis could be due to less frequent intervention after acute declines (sudden decline events) in FEV1. Patients with cystic fibrosis aged 6-17 years enrolled in the Epidemiologic Study of Cystic Fibrosis were assessed for a sudden decline event, defined as a 10% relative decline in FEV1% predicted from an average of 3 consecutive stable baseline spirometries. The likelihood of therapeutic intervention within 14 days before and 56 days after this event was then related to their baseline FEV1% predicted age-specific decile using a logistic regression adjusting for age group (6-12 years, 13-17 years) and presence of Pseudomonas aeruginosa on respiratory culture. A total of 10 888 patients had at least 1 sudden decline event in FEV1. Patients in the highest FEV1 decile were significantly less likely than those in the lowest decile to receive intravenous antibiotics (OR, 0.14; 95% CI, 0.11-0.18; P < .001) or be hospitalized (OR, 0.18; 95% CI, 0.14-0.23; P < .001) following decline. Children and adolescents with high baseline lung function are less likely to receive a therapeutic intervention following an acute decline in FEV1, which may explain their greater rate of FEV1 decline. Copyright © 2013 Mosby, Inc. All rights reserved.

Obstructive lung disease as a complication in post pulmonary TB

NASA Astrophysics Data System (ADS)

Tarigan, A. P.; Pandia, P.; Eyanoer, P.; Tina, D.; Pratama, R.; Fresia, A.; Tamara; Silvanna

2018-03-01

The case of post TB is a problem that arises in the community. Pulmonary tuberculosis (TB) can affect lung function. Therefore, we evaluated impaired pulmonary function in subjects with diagnosed prior pulmonary TB. A Case Series study, pulmonary function test was performed in subjects with a history of pulmonary tuberculosis; aged ≥18 years were included. Exclusion criteria was a subject who had asthma, obesity, abnormal thorax and smoking history. We measured FEV1 and FVC to evaluate pulmonary function. Airflow obstruction was FEV1/FVC%<75 and restriction was FVC<80% according to Indonesia’s pneumomobile project. This study was obtained from 23 patients with post pulmonary TB, 5 subjects (23%) had airflow obstruction with FEV1/FVC% value <75%, 15 subjects (71.4%) had abnormalities restriction with FVC value <80% and 3 subjects (5.6%) had normal lung function. Obstructive lung disease is one of the complications of impaired lung function in post pulmonary TB.

A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.

PubMed

Ramsey, Bonnie W; Davies, Jane; McElvaney, N Gerard; Tullis, Elizabeth; Bell, Scott C; Dřevínek, Pavel; Griese, Matthias; McKone, Edward F; Wainwright, Claire E; Konstan, Michael W; Moss, Richard; Ratjen, Felix; Sermet-Gaudelus, Isabelle; Rowe, Steven M; Dong, Qunming; Rodriguez, Sally; Yen, Karl; Ordoñez, Claudia; Elborn, J Stuart

2011-11-03

Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis. We conducted a randomized, double-blind, placebo-controlled trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation. Subjects were randomly assigned to receive 150 mg of ivacaftor every 12 hours (84 subjects, of whom 83 received at least one dose) or placebo (83, of whom 78 received at least one dose) for 48 weeks. The primary end point was the estimated mean change from baseline through week 24 in the percent of predicted forced expiratory volume in 1 second (FEV(1)). The change from baseline through week 24 in the percent of predicted FEV(1) was greater by 10.6 percentage points in the ivacaftor group than in the placebo group (P<0.001). Effects on pulmonary function were noted by 2 weeks, and a significant treatment effect was maintained through week 48. Subjects receiving ivacaftor were 55% less likely to have a pulmonary exacerbation than were patients receiving placebo, through week 48 (P<0.001). In addition, through week 48, subjects in the ivacaftor group scored 8.6 points higher than did subjects in the placebo group on the respiratory-symptoms domain of the Cystic Fibrosis Questionnaire-revised instrument (a 100-point scale, with higher numbers indicating a lower effect of symptoms on the patient's quality of life) (P<0.001). By 48 weeks, patients treated with ivacaftor had gained, on average, 2.7 kg more weight than had patients receiving placebo (P<0.001). The change from baseline through week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor as compared with placebo was -48.1 mmol per liter (P<0.001). The incidence of adverse events was similar with ivacaftor and placebo, with a lower proportion of serious adverse events with ivacaftor than with placebo (24% vs. 42%). Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks. Substantial improvements were also observed in the risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight, and concentration of sweat chloride. (Funded by Vertex Pharmaceuticals and others; VX08-770-102 ClinicalTrials.gov number, NCT00909532.).

Prognostic factors in a cohort of antisynthetase syndrome (ASS): serologic profile is associated with mortality in patients with interstitial lung disease (ILD).

PubMed

Rojas-Serrano, Jorge; Herrera-Bringas, Denisse; Mejía, Mayra; Rivero, Hermes; Mateos-Toledo, Heidegger; Figueroa, José E

2015-09-01

The objectives of the present study were to compare the survival function of antisynthetase syndrome (ASS) Jo1-positive patients with ASS non-Jo1 patients, all with interstitial lung disease (ILD), and to evaluate other factors such as the extension of pulmonary disease and the time between the onset of symptoms and diagnosis and its association to survival in a cohort of ASS patients. Patients with ASS, all with ILD, were included. At the baseline, pulmonary function tests were realized and a high-resolution chest tomography was obtained; lung inflammation and fibrosis were measured with the Goh score and the Kazerooni index. The following autoantibodies were measured: Jo1, Ej, Oj, PL7, and PL12. Patients had to be positive for one of them in order to be included in the study. The survival function was estimated and compared with the log rank test, and the hazard ratio (HR) was estimated using Cox regression procedure. Forty-three patients were included, of which six patients died (14 %). Patients who died were different in comparison with survivors as regards the frequency of anti-Jo1 positivity: Survivors had anti-Jo1 autoantibodies more frequently (86 %) than patients who died (50 %). The univariate Cox regression analysis identified four variables associated with survival: Jo1 status, arthritis, extent of ground glass, and consolidation (inflammation) in high-resolution computed tomography (HRCT) and baseline forced vital capacity. The serological status of patients (Jo1-positive vs non-Jo1), the extent of lung inflammation in the HRCT scan, a low forced vital capacity, and arthritis are associated with survival in ASS patients.

Relation of exercise capacity with lung volumes before and after 6-minute walk test in subjects with COPD.

PubMed

Wibmer, Thomas; Rüdiger, Stefan; Kropf-Sanchen, Cornelia; Stoiber, Kathrin M; Rottbauer, Wolfgang; Schumann, Christian

2014-11-01

There is growing evidence that exercise-induced variation in lung volumes is an important source of ventilatory limitation and is linked to exercise intolerance in COPD. The aim of this study was to compare the correlations of walk distance and lung volumes measured before and after a 6-min walk test (6MWT) in subjects with COPD. Forty-five subjects with stable COPD (mean pre-bronchodilator FEV1: 47 ± 18% predicted) underwent a 6MWT. Body plethysmography was performed immediately pre- and post-6MWT. Correlations were generally stronger between 6-min walk distance and post-6MWT lung volumes than between 6-min walk distance and pre-6MWT lung volumes, except for FEV1. These differences in Pearson correlation coefficients were significant for residual volume expressed as percent of total lung capacity (-0.67 vs -0.58, P = .043), percent of predicted residual volume expressed as percent of total lung capacity (-0.68 vs -0.59, P = .026), inspiratory vital capacity (0.65 vs 0.54, P = .019), percent of predicted inspiratory vital capacity (0.49 vs 0.38, P = .037), and percent of predicted functional residual capacity (-0.62 vs -0.47, P = .023). In subjects with stable COPD, lung volumes measured immediately after 6MWT are more closely related to exercise limitation than baseline lung volumes measured before 6MWT, except for FEV1. Therefore, pulmonary function testing immediately after exercise should be included in future studies on COPD for the assessment of exercise-induced ventilatory constraints to physical performance that cannot be adequately assessed from baseline pulmonary function testing at rest. Copyright © 2014 by Daedalus Enterprises.

Treatment response of airway clearance assessed by single-breath washout in children with cystic fibrosis.

PubMed

Abbas, Chiara; Singer, Florian; Yammine, Sophie; Casaulta, Carmen; Latzin, Philipp

2013-12-01

We studied the ability of 4 single-breath gas washout (SBW) tests to measure immediate effects of airway clearance in children with CF. 25 children aged 4-16 years with CF performed pulmonary function tests to assess short-term variability at baseline and response to routine airway clearance. Tidal helium and sulfur hexafluoride (double-tracer gas: DTG) SBW, tidal capnography, tidal and vital capacity nitrogen (N2) SBW and spirometry were applied. We analyzed the gasses' phase III slope (SnIII--normalized for tidal volume) and FEV1 from spirometry. SnIII from tidal DTG-SBW, SnIII from vital capacity N2-SBW, and FEV1 improved significantly after airway clearance. From these tests, individual change of SnIII from tidal DTG-SBW and FEV1 exceeded short-term variability in 10 and 6 children. With the tidal DTG-SBW, an easy and promising test for peripheral gas mixing efficiency, immediate pulmonary function response to airway clearance can be assessed in CF children. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Statin Therapy and Outcomes in Trials of Nintedanib in Idiopathic Pulmonary Fibrosis.

PubMed

Kreuter, Michael; Costabel, Ulrich; Richeldi, Luca; Cottin, Vincent; Wijsenbeek, Marlies; Bonella, Francesco; Bendstrup, Elisabeth; Maher, Toby M; Wachtlin, Daniel; Stowasser, Susanne; Kolb, Martin

Cardiovascular comorbidities are frequent in patients with idiopathic pulmonary fibrosis (IPF), and many patients with IPF receive treatment with statins to reduce cardiovascular risk. We investigated whether statin use at baseline was associated with differences in disease progression in placebo-treated patients or influenced the treatment effect of nintedanib in the INPULSIS® trials. Post-hoc subgroup analyses of patients receiving versus not receiving statins at baseline using pooled data from the INPULSIS® trials. At baseline, 312 patients received statins and 749 did not. The annual rates of decline in forced vital capacity (FVC) in patients treated with nintedanib and placebo, respectively, were -78.9 and -187.6 mL/year in patients who received statins at baseline, and -127.9 and -237.9 mL/year in patients who did not. The effect of nintedanib was consistent across subgroups (p = 0.9590). In the INPULSIS® trials, there was a numerically lower FVC decline in placebo-treated patients with IPF who received statins at baseline versus those who did not. Use of statins at baseline did not influence the treatment effect of nintedanib. Prospective data are needed to assess the impact of statins on the course of IPF. © 2018 S. Karger AG, Basel.

Exposure to high concentrations of inspired oxygen does not worsen lung injury after cardiac arrest.

PubMed

Elmer, Jonathan; Wang, Bo; Melhem, Samer; Pullalarevu, Raghavesh; Pullalarevu, Raghevesh; Vaghasia, Nishit; Buddineni, Jaya; Rosario, Bedda L; Doshi, Ankur A; Callaway, Clifton W; Dezfulian, Cameron

2015-03-10

Post-cardiac arrest patients are often exposed to 100% oxygen during cardiopulmonary resuscitation and the early post-arrest period. It is unclear whether this contributes to development of pulmonary dysfunction or other patient outcomes. We performed a retrospective cohort study including post-arrest patients who survived and were mechanically ventilated at least 24 hours after return of spontaneous circulation. Our primary exposure of interest was inspired oxygen, which we operationalized by calculating the area under the curve of the fraction of inspired oxygen (FiO₂AUC) for each patient over 24 hours. We collected baseline demographic, cardiovascular, pulmonary and cardiac arrest-specific covariates. Our main outcomes were change in the respiratory subscale of the Sequential Organ Failure Assessment score (SOFA-R) and change in dynamic pulmonary compliance from baseline to 48 hours. Secondary outcomes were survival to hospital discharge and Cerebral Performance Category at discharge. We included 170 patients. The first partial pressure of arterial oxygen (PaO₂):FiO₂ ratio was 241 ± 137, and 85% of patients had pulmonary failure and 55% had cardiovascular failure at presentation. Higher FiO₂AUC was not associated with change in SOFA-R score or dynamic pulmonary compliance from baseline to 48 hours. However, higher FiO₂AUC was associated with decreased survival to hospital discharge and worse neurological outcomes. This was driven by a 50% decrease in survival in the highest quartile of FiO₂AUC compared to other quartiles (odds ratio for survival in the highest quartile compared to the lowest three quartiles 0.32 (95% confidence interval 0.13 to 0.79), P = 0.003). Higher exposure to inhaled oxygen in the first 24 hours after cardiac arrest was not associated with deterioration in gas exchange or pulmonary compliance after cardiac arrest, but was associated with decreased survival and worse neurological outcomes.

Oral supplement enriched in HMB combined with pulmonary rehabilitation improves body composition and health related quality of life in patients with bronchiectasis (Prospective, Randomised Study).

PubMed

Olveira, Gabriel; Olveira, Casilda; Doña, Esperanza; Palenque, Francisco Javier; Porras, Nuria; Dorado, Antonio; Godoy, Ana M; Rubio-Martínez, Elehazara; Rojo-Martínez, Gemma; Martín-Valero, Rocío

2016-10-01

Pulmonary Rehabilitation (PR) is recommended for bronchiectasis but there is no data about its effect on body composition. The aim of this study is to assess the effect of Pulmonary Rehabilitation (PR) for 12 weeks in normally-nourished non-cystic-fibrosis bronchiectasis patients compared with the effect of PR plus a hyperproteic oral nutritional supplement enriched with beta-hydroxy-beta-methylbutyrate (HMB) on body composition, muscle strength, quality of life and serum biomarkers. single center randomized controlled trial, parallel treatment design: Participants were randomly assigned to receive PR for 12 weeks or PR plus ONS (PRONS) (one can per day). Outcome assessments were performed at baseline, 12 weeks and 24 weeks: body composition (Dual-energy X-Ray Absorptiometry (DEXA), mid-arm muscle circumference (MAMC), phase angle by Bio-impedance), health related quality of life (Spanish QOL-B-V3.0, Physical Functioning Scale), handgrip strength, diet questionnaire, and plasma levels of prealbumin, myostatin and somatomedin-c. Thirty patients were randomized (15 per group) without differences in clinical and respiratory variables. In the PRONS group bone mineral density (BMD), mean and maximum handgrip dynamometry, MAMC, QOLB and prealbumin were significantly increased from baseline at 12 and 24 weeks and Fat free Mass (FFM) and FFM index, at 12 weeks. In the PR group only mean handgrip dynamometry and prealbumin were significantly increased at 12 and 24 weeks. In both groups plasma myostatin was reduced at 12 weeks (without significant differences). The addition of a hyperproteic ONS enriched with HMB to Pulmonary Rehabilitation could improve body composition, BMD, muscle strength and health related quality of life in bronchiectasis patients. Clinical Trials Number NCT02048397. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Contemporary survival of patients with pulmonary arterial hypertension and congenital systemic to pulmonary shunts

PubMed Central

Chungsomprasong, Paweena; Bositthipichet, Densiri; Ketsara, Salisa; Titaram, Yuttapon; Chanthong, Prakul; Kanjanauthai, Supaluck

2018-01-01

Objective To compare survival of patients with newly diagnosed pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) according to various clinical classifications with classifications of anatomical-pathophysiological systemic to pulmonary shunts in a single-center cohort. Methods All prevalent cases of PAH-CHD with hemodynamic confirmation by cardiac catheterization in 1995–2015 were retrospectively reviewed. Patients who were younger than three months of age, or with single ventricle following surgery were excluded. Baseline characteristics and clinical outcomes were retrieved from the database. The survival analysis was performed at the end of 2016. Prognostic factors were identified using multivariate analysis. Results A total of 366 consecutive patients (24.5 ± 17.6 years of age, 40% male) with PAH-CHD were analyzed. Most had simple shunts (85 pre-tricuspid, 105 post-tricuspid, 102 combined shunts). Patients with pre-tricuspid shunts were significantly older at diagnosis in comparison to post-tricuspid, combined, and complex shunts. Clinical classifications identified patients as having Eisenmenger syndrome (ES, 26.8%), prevalent left to right shunt (66.7%), PAH with small defect (3%), or PAH following defect correction (3.5%). At follow-up (median = 5.9 years; 0.1–20.7 years), no statistically significant differences in survival rate were seen among the anatomical-pathophysiological shunts (p = 0.1). Conversely, the clinical classifications revealed that patients with PAH-small defect had inferior survival compared to patients with ES, PAH post-corrective surgery, or PAH with prevalent left to right shunt (p = 0.01). Significant mortality risks were functional class III, age < 10 years, PAH-small defect, elevated right atrial pressure > 15 mmHg, and baseline PVR > 8 WU•m.2 Conclusion Patients with PAH-CHD had a modest long-term survival. Different anatomical-pathophysiological shunts affect the natural presentation, while clinical classifications indicate treatment strategies and survival. Contemporary therapy improves survival in deliberately selected patients. PMID:29664959

Differential modulation of right ventricular strain and right atrial mechanics in mild vs. severe pressure overload

PubMed Central

Voeller, Rochus K.; Aziz, Abdulhameed; Maniar, Hersh S.; Ufere, Nneka N.; Taggar, Ajay K.; Bernabe, Noel J.; Cupps, Brian P.

2011-01-01

Increased right atrial (RA) and ventricular (RV) chamber volumes are a late maladaptive response to chronic pulmonary hypertension. The purpose of the current investigation was to characterize the early compensatory changes that occur in the right heart during chronic RV pressure overload before the development of chamber dilation. Magnetic resonance imaging with radiofrequency tissue tagging was performed on dogs at baseline and after 10 wk of pulmonary artery banding to yield either mild RV pressure overload (36% rise in RV pressure; n = 5) or severe overload (250% rise in RV pressure; n = 4). The RV free wall was divided into three segments within a midventricular plane, and circumferential myocardial strain was calculated for each segment, the septum, and the left ventricle. Chamber volumes were calculated from stacked MRI images, and RA mechanics were characterized by calculating the RA reservoir, conduit, and pump contribution to RV filling. With mild RV overload, there were no changes in RV strain or RA function. With severe RV overload, RV circumferential strain diminished by 62% anterior (P = 0.04), 42% inferior (P = 0.03), and 50% in the septum (P = 0.02), with no change in the left ventricle (P = 0.12). RV filling became more dependent on RA conduit function, which increased from 30 ± 9 to 43 ± 13% (P = 0.01), than on RA reservoir function, which decreased from 47 ± 6 to 33 ± 4% (P = 0.04), with no change in RA pump function (P = 0.94). RA and RV volumes and RV ejection fraction were unchanged from baseline during either mild (P > 0.10) or severe RV pressure overload (P > 0.53). In response to severe RV pressure overload, RV myocardial strain is segmentally diminished and RV filling becomes more dependent on RA conduit rather than reservoir function. These compensatory mechanisms of the right heart occur early in chronic RV pressure overload before chamber dilation develops. PMID:21926343

Acute pulmonary function change associated with work on large dairies in California.

PubMed

Eastman, Chelsea; Schenker, Marc B; Mitchell, Diane C; Tancredi, Daniel J; Bennett, Deborah H; Mitloehner, Frank M

2013-01-01

To study whether dairy workers in California have lower baseline and greater cross-shift decrements in lung function than control employees. A cross-sectional study of 210 dairy and 47 control workers who completed questionnaires and spirometry before and after the work shift. Dairy work was associated with mean baseline differences of -0.132 L (P = 0.07) and -0.131 L (P = 0.13) in forced expiratory volume in 1 second and forced vital capacity, respectively, compared with control employees, adjusting for age, height, smoking status, and days back at work since last day off. Dairy work was associated with a mean cross-shift difference of -65.2 mL (P = 0.02) and -103.1 mL (P < 0.01) in forced expiratory volume in 1 second and forced vital capacity, respectively, adjusting for smoking status and work-shift time. Dairy work in California was associated with mild acute airway obstruction. The unclear long-term effect of dairy work in California merits further investigation.

H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

MCClay, Joseph L.; Adkins, Daniel E.; Isern, Nancy G.

2010-06-04

Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious and growing public health concern. The major environmental risk factor for COPD is tobacco smoking, but the biological mechanisms underlying COPD are not well understood. In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 adults without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correctingmore » for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Two of the three urinary metabolites positively associated with baseline lung function, i.e. hippurate and formate, are often related to gut microflora. This suggests that the microbiome composition is variable between individuals with different lung function. Alternatively, the nature and origins of all three associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of lung disease or disease risk.« less

Sing Your Lungs Out-a community singing group for chronic obstructive pulmonary disease: a 1-year pilot study.

PubMed

McNaughton, Amanda; Weatherall, Mark; Williams, Mathew; McNaughton, Harry; Aldington, Sarah; Williams, Gayle; Beasley, Richard

2017-01-24

Singing group participation may benefit patients with chronic obstructive pulmonary disease (COPD). Previous studies are limited by small numbers of participants and short duration of generally hospital-based singing group intervention. This study examines the feasibility of long-term participation in a community singing group for patients with COPD who had completed pulmonary rehabilitation (PR). This was a feasibility cohort study. Patients with COPD who had completed PR and were enrolled in a weekly community exercise group were recruited to a new community-based singing group which met weekly for over 1 year. Measurements at baseline, 4 months and 1 year comprised comprehensive pulmonary function tests including lung volumes, 6 min walk test (6MWT), Clinical COPD Questionnaire (CCQ), Hospital Anxiety and Depression Scale (HADS) and hospital admission days for acute exacerbation of COPD (AECOPD) for 1 year before and after the first singing group session. There were 28 participants with chronic lung disease recruited from 140 people approached. Five withdrew in the first month. 21 participants meeting Global Initiative for Chronic Obstructive Lung Disease criteria for COPD completed 4-month and 18 completed 1-year assessments. The mean attendance was 85%. For the prespecified primary outcome measure, total HADS score, difference between baseline and 12 months was -0.9, 95% CI -3.0 to 1.2, p=0.37. Of the secondary measures, a significant reduction was observed for HADS anxiety score after 1 year of -0.9 (95% CI -1.8 to -0.1) points, p=0.038 and an increase in the 6MWT at 1 year, of 65 (95% CI 35 to 99) m compared with baseline p<0.001. Our findings support the feasibility of long-term participation in a community singing group for adults with COPD who have completed PR and are enrolled in a weekly community exercise group and provide evidence of improved exercise capacity and a reduction in anxiety. ACTRN12615000736549; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease

PubMed Central

Asai, Kazuhisa; Kobayashi, Akihiro; Makihara, Yukio; Johnson, Malcolm

2015-01-01

Purpose Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese patients with chronic obstructive pulmonary disease (COPD). Patients and methods Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks. At the start and end of treatment, inflammation biomarkers (sputum and serum), lung function, and health status (COPD Assessment Test [CAT] questionnaire) were measured. Results Although a numerical decrease in differential neutrophil count was observed from baseline, SFC 250 did not significantly reduce sputum neutrophils compared with placebo, nor were there significant changes from baseline in the other biomarkers (sputum or serum), lung function, or CAT, versus placebo. Squamous epithelial cell contamination in some sputum samples rendered them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250) and n=10 (placebo). However, inclusion of contaminated samples did not affect the overall trend of the outcome. Ad hoc bootstrap statistical analysis showed a 27.9% (SFC 250) and 1.3% (placebo) decrease in sputum neutrophils. Sputum IL-8 decreased by 43.2% after SFC 250 but increased by 48.3% with placebo. Responder analyses showed 42% of patients had ≥20% decrease in neutrophils from baseline; and 47% of patients had a ≥200 pg/mL change in sputum IL-8 following SFC 250 versus 20% after placebo; both changes are considered clinically relevant. Conclusion This study provides additional information about inflammation in Japanese COPD patients and is the first to study the anti-inflammatory effects of SFC 250 in this context and population. In the primary analysis, SFC 250 did not produce significant changes from baseline in sputum neutrophil levels or other sputum or serum inflammatory markers compared with placebo. Secondary ad hoc statistical analysis showed that SFC 250 reduced the number of sputum neutrophils and IL-8 compared with placebo. PMID:25945045

Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease.

PubMed

Asai, Kazuhisa; Kobayashi, Akihiro; Makihara, Yukio; Johnson, Malcolm

2015-01-01

Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese patients with chronic obstructive pulmonary disease (COPD). Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks. At the start and end of treatment, inflammation biomarkers (sputum and serum), lung function, and health status (COPD Assessment Test [CAT] questionnaire) were measured. Although a numerical decrease in differential neutrophil count was observed from baseline, SFC 250 did not significantly reduce sputum neutrophils compared with placebo, nor were there significant changes from baseline in the other biomarkers (sputum or serum), lung function, or CAT, versus placebo. Squamous epithelial cell contamination in some sputum samples rendered them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250) and n=10 (placebo). However, inclusion of contaminated samples did not affect the overall trend of the outcome. Ad hoc bootstrap statistical analysis showed a 27.9% (SFC 250) and 1.3% (placebo) decrease in sputum neutrophils. Sputum IL-8 decreased by 43.2% after SFC 250 but increased by 48.3% with placebo. Responder analyses showed 42% of patients had ≥20% decrease in neutrophils from baseline; and 47% of patients had a ≥200 pg/mL change in sputum IL-8 following SFC 250 versus 20% after placebo; both changes are considered clinically relevant. This study provides additional information about inflammation in Japanese COPD patients and is the first to study the anti-inflammatory effects of SFC 250 in this context and population. In the primary analysis, SFC 250 did not produce significant changes from baseline in sputum neutrophil levels or other sputum or serum inflammatory markers compared with placebo. Secondary ad hoc statistical analysis showed that SFC 250 reduced the number of sputum neutrophils and IL-8 compared with placebo.

The natural history of adult pulmonary Langerhans cell histiocytosis: a prospective multicentre study.

PubMed

Tazi, Abdellatif; de Margerie, Constance; Naccache, Jean Marc; Fry, Stéphanie; Dominique, Stéphane; Jouneau, Stéphane; Lorillon, Gwenaël; Bugnet, Emmanuelle; Chiron, Raphael; Wallaert, Benoit; Valeyre, Dominique; Chevret, Sylvie

2015-03-14

The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported. In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV1 and/or FVC and/or DLCO, compared with baseline values. At each visit, smoking status was recorded based on the patients' self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders. The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 at inclusion were the only factors associated with the risk of lung function deterioration. The patients' smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients. Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs. ClinicalTrials.gov: No: NCT01225601 .

Is insufficient pulmonary air support the cause of dysphonia in chronic obstructive pulmonary disease?

PubMed

Hassan, Megahed M; Hussein, Mona T; Emam, Ahmed Mamdouh; Rashad, Usama M; Rezk, Ibrahim; Awad, Al Hussein

2018-08-01

Optimal pulmonary air support is essential pre-requisite for efficient phonation. The objective is to correlate pulmonary and vocal functions in chronic obstructive pulmonary disease (COPD) to find out whether the reduced pulmonary function per se could induce dysphonia. In this prospective case-control study, sixty subjects with stable COPD underwent evaluation of pulmonary and vocal functions. The pulmonary functions measured include {Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio, peak expiratory flow (PEF), maximum mid-expiratory flow (MMEF)}. The vocal functions were {jitter, shimmer, noise-to-harmonic ratio, pitch perturbation quotient, amplitude perturbation quotient, maximum phonation time (MPT), sound pressure level, phonatory efficiency, resistance and power. A control group (n=35) underwent the same measurements. These functions were compared between subjects and controls. Also, correlation of the vocal and pulmonary functions was conducted. Thirty five (58.3%) of COPD subjects have dysphonia. The pulmonary functions were lower in all COPD group than in the control group (P<0.001 for all parameters). Also, the FVC, FEV1, PEF and MMEF % of predicted values were significantly lower in subjects with dysphonia (n=35) than those without dysphonia (n=25) with P values 0.0018, <0.001, 0.0011 and 0.0026 respectively. In addition, the MPT in all subjects showed positive correlations to the 5 pulmonary functions (P=0.004 for FEV1/FVC ratio and P<0.001 for the rest). Also, the phonatory efficiency showed significant positive correlations with the pulmonary functions FVC, FEV1, PEF and MMEF (P=0.001, 0.001, 0.002 and 0.001 respectively). Unlike efficiency, the phonatory resistance revealed significant negative correlations with these pulmonary functions in the same order (P=0.001, 0.003, 0.002, 0.001 respectively). Dysphonia is a common comorbidity with COPD which attributed to multifactorial etiologies. The lower the pulmonary function in COPD patients is the more likely to have dysphonia. Decreased pulmonary function was associated with reduced MPT and phonatory efficiency but with increased phonatory resistance. The reduced pulmonary functions in COPD can be the underlying cause of the altered vocal function and dysphonia. Great part of this dysphonia is functional, and hence, can be corrected by voice therapy in compensated subjects. Further researches are needed to evaluate the efficacy of voice therapy in these patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Beta-erythropoietin effects on ventricular remodeling, left and right systolic function, pulmonary pressure, and hospitalizations in patients affected with heart failure and anemia.

PubMed

Palazzuoli, Alberto; Silverberg, Donald S; Calabrò, Anna; Spinelli, Tommaso; Quatrini, Ilaria; Campagna, Maria S; Franci, Beatrice; Nuti, Ranuccio

2009-06-01

Anemia in heart failure is related to advanced New York Heart Association classes, severe systolic dysfunction, and reduced exercise tolerance. Although anemia is frequently found in congestive heart failure (CHF), little is known about the effect of its' correction with erythropoietin (EPO) on cardiac structure and function. The present study examines, in patients with advanced CHF and anemia, the effects of beta-EPO on left ventricular volumes, left ventricular ejection fraction (LVEF), left and right longitudinal function mitral anular plane systolic excursion (MAPSE), tricuspid anular plane excursion (TAPSE), and pulmonary artery pressures in 58 patients during 1-year follow-up in a double-blind controlled study of correction of anemia with subcutaneous beta-EPO. Echocardiographic evaluation, B-Type natriuretic peptide (BNP) levels, and hematological parameters are reported at 4 and 12 months. The patients in group A after 4 months of follow-up period demonstrated an increase in LVEF and MAPSE (P < 0.05 and P < 0.01, respectively) with left ventricular systolic volume reduction (P < 0.02) with respect to baseline and controls. After 12 months, results regarding left ventricular systolic volume LVEF and MAPSE persisted (P < 0.001). In addition, TAPSE increased and pulmonary artery pressures fell significantly in group A (P < 0.01). All these changes occurred together with a significant BNP reduction and significant hemoglobin increase in the treated group. Therefore, we revealed a reduced hospitalization rate in treated patients with respect to the controls (25% in treated vs. 54% in controls). In patients with anemia and CHF, correction of anemia with beta-EPO and oral iron over 1 year leads to an improvement in left and right ventricular systolic function by reducing cardiac remodeling, BNP levels, and hospitalization rate.

Intrauterine growth restriction decreases nuclear factor-kappa B signaling in fetal pulmonary artery endothelial cells of fetal sheep.

PubMed

Dodson, R Blair; Powers, Kyle N; Gien, Jason; Rozance, Paul J; Seedorf, Gregory J; Astling, David; Jones, Kenneth Lloyd; Crombleholme, Timothy M; Abman, Steven H; Alvira, Cristina M

2018-05-03

Intrauterine growth restriction (IUGR) in premature newborns increases the risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted pulmonary angiogenesis and alveolarization. We previously showed that experimental IUGR impairs angiogenesis, however, mechanisms that impair pulmonary artery endothelial cell (PAEC) function are uncertain. The nuclear factor-kappa-B (NFκB) pathway promotes vascular growth in the developing mouse lung, and we hypothesized that IUGR disrupts NFκB-regulated pro-angiogenic targets in fetal PAEC. PAECs were isolated from lungs of control fetal sheep and sheep with experimental IUGR from an established model of chronic placental insufficiency. Microarray analysis identified suppression of NFκB signaling and significant alterations in extracellular matrix (ECM) pathways in IUGR PAEC, including decreases in collagen 4α1 and laminin α4, components of the basement membrane and putative NFκB targets. In comparison with controls: (i) immunostaining of active NFκB complexes; (ii) NFκB-DNA binding; (iii) baseline expression of NFκB subunits, p65 and p50; and (iv) LPS-mediated inducible activation of NFκB signaling were decreased in IUGR PAEC. Although pharmacologic NFκB inhibition did not affect angiogenic function in IUGR PAEC, angiogenic function of control PAEC was reduced to a similar degree as that observed in IUGR PAEC. These data identify reductions in endothelial NFκB signaling as central to the disrupted angiogenesis observed in IUGR, likely by impairing both intrinsic PAEC angiogenic function and NFκB-mediated regulation of ECM components necessary for vascular development. These data further suggest that strategies that preserve endothelial NFκB activation may be useful in lung diseases marked by disrupted angiogenesis such as IUGR.

Residential Proximity to Major Roadways Is Not Associated with Cardiac Function in African Americans: Results from the Jackson Heart Study.

PubMed

Weaver, Anne M; Wellenius, Gregory A; Wu, Wen-Chih; Hickson, DeMarc A; Kamalesh, Masoor; Wang, Yi

2016-06-13

Cardiovascular disease (CVD), including heart failure, is a major cause of morbidity and mortality, particularly among African Americans. Exposure to ambient air pollution, such as that produced by vehicular traffic, is believed to be associated with heart failure, possibly by impairing cardiac function. We evaluated the cross-sectional association between residential proximity to major roads, a marker of long-term exposure to traffic-related pollution, and echocardiographic indicators of left and pulmonary vascular function in African Americans enrolled in the Jackson Heart Study (JHS): left ventricular ejection fraction, E-wave velocity, isovolumic relaxation time, left atrial diameter index, and pulmonary artery systolic pressure. We examined these associations using multivariable linear or logistic regression, adjusting for potential confounders. Of 4866 participants at study enrollment, 106 lived <150 m, 159 lived 150-299 m, 1161 lived 300-999 m, and 3440 lived ≥1000 m from a major roadway. We did not observe any associations between residential distance to major roads and these markers of cardiac function. Results were similar with additional adjustment for diabetes and hypertension, when considering varying definitions of major roadways, or when limiting analyses to those free from cardiovascular disease at baseline. Overall, we observed little evidence that residential proximity to major roads was associated with cardiac function among African Americans.

21 CFR 868.1890 - Predictive pulmonary-function value calculator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Predictive pulmonary-function value calculator. 868.1890 Section 868.1890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... pulmonary-function value calculator. (a) Identification. A predictive pulmonary-function value calculator is...

21 CFR 868.1890 - Predictive pulmonary-function value calculator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Predictive pulmonary-function value calculator. 868.1890 Section 868.1890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... pulmonary-function value calculator. (a) Identification. A predictive pulmonary-function value calculator is...

The prognostic role of exercise echocardiography in heart failure.

PubMed

Rubiś, Paweł; Drabik, Leszek; Kopeć, Grzegorz; Olszowska, Maria; Płazak, Wojciech; Podolec, Piotr

2011-01-01

Gradual impairment of exercise tolerance is the commonest sign of heart failure (HF). Little is known as to which cardiac contributors of poor exercise capacity carry an independent prognostic information in HF. We investigated the prognostic role of exercise echocardiography (ex-echo) in HF patients. We studied 85 consecutive, symptomatic HF patients (66 males, mean age 62.5 ± 11.8 [range 21-83] years, mean left ventricular ejection fraction [LVEF] 27.2 ± 9.5%). The end-point was all-cause mortality. During the follow-up period (mean 43 ± 21 months) 21 patients died. Resting echocardiography and ex-echo, with the simultaneous measurement of peak oxygen uptake (VO(2peak)), was performed in each patient using a semi-supine ergometer (20 W, 2-min increments). Apart from conventional assessment of systolic and diastolic function (EF, E/A, DT, IVRT) or right ventricular systolic pressure (RVSP), tissue Doppler imaging was used for the assessment of LV and RV peak velocity (IVV) as well as acceleration during isovolumic contraction (IVA), peak velocity during ejection phase (S'), peak early diastolic velocity (E'), peak late diastolic velocity (A'), and ratio of early diastolic mitral/tricuspid velocity to peak early diastolic velocity (E/E'). Patients who died were significantly older, had lower exercise capacity, more advanced HF, greater impairment of baseline systolic function, higher baseline pulmonary artery systolic pressure, and most importantly a lack of improvement in EF, diastolic function, and further increase of RVSP during exercise. Out of all echocardiographic parameters, only peak stress EF (x(2) 6.1; p = 0.01), baseline and peak exercise RVSP (x(2) 12.5 and c(2) 18.7; p 〈 0.001; respectively), and mitral E/E' ratio (x(2) 8.9; p 〈 0.01) were univariate predictors of prognosis and remained independently prognostic when adjusted for age and sex but were eliminated from the model by NT-proBNP. During exercise, more severe systolic and diastolic dysfunction with the elevation of pulmonary arterial pressure is more prevalent in HF patients who have a poorer outcome. The estimation of common parameters such as EF, RVSP and E/E' using ex-echo, provides prognostic information in HF.

Idiopathic pulmonary fibrosis is associated with increased impedance measures of reflux compared to non-fibrotic disease among pre-lung transplant patients.

PubMed

Gavini, S; Finn, R T; Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

2015-09-01

Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF), although the mechanism remains unclear. Gastroesophageal reflux/microaspiration may lead to lung fibrosis, while increased pulmonary workload may also worsen GER. Comparing the GER profile of IPF patients to chronic obstructive pulmonary disease (COPD) patients with similar lung function may help delineate the role of GER in IPF pathogenesis. This was a retrospective cohort study of IPF and COPD patients undergoing pre-lung transplant multichannel intraluminal impedance and pH study (MII-pH) off acid suppression at a tertiary center in 2008-2014. Patients with prior fundoplication were excluded. Baseline demographics, pulmonary function test, and MII-pH results were recorded. Univariate analyses were performed using Fisher's exact (binary variables) and Student's t (continuous variables) tests. Logistic regression was performed to adjust for potential confounders. A total of 90 subjects (54 IPF, 36 COPD) met inclusion criteria. Compared to COPD, IPF patients had increased total reflux episodes (65.9 vs 46.1, p = 0.02), proximal reflux episodes (30.3 vs 20.3, p = 0.04), and prevalence of abnormal total reflux episodes (38.9% vs 16.7%, p = 0.02). On multivariate analyses, abnormal total reflux episodes (OR: 4.9, p = 0.05) and bolus reflux exposure time (OR: 4, p = 0.04) remained significantly associated with IPF. Abnormal reflux was significantly more prevalent among IPF patients after controlling for lung disease severity. Gastroesophageal reflux/microaspiration likely plays a role in fibrosis in IPF. A significant portion of IPF patients had increased non-acid reflux. Therapies aiming to prevent reflux of gastric contents may be more beneficial than antisecretory medications alone in these patients. © 2015 John Wiley & Sons Ltd.

Treatment adherence and health outcomes in patients with bronchiectasis.

PubMed

McCullough, Amanda R; Tunney, Michael M; Quittner, Alexandra L; Elborn, J Stuart; Bradley, Judy M; Hughes, Carmel M

2014-07-01

We aimed to determine adherence to inhaled antibiotics, other respiratory medicines and airway clearance and to determine the association between adherence to these treatments and health outcomes (pulmonary exacerbations, lung function and Quality of Life Questionnaire-Bronchiectasis [QOL-B]) in bronchiectasis after 12 months. Patients with bronchiectasis prescribed inhaled antibiotics for Pseudomonas aeruginosa infection were recruited into a one-year study. Participants were categorised as "adherent" to medication (medication possession ratio ≥80% using prescription data) or airway clearance (score ≥80% in the Modified Self-Reported Medication-Taking Scale). Pulmonary exacerbations were defined as treatment with a new course of oral or intravenous antibiotics over the one-year study. Spirometry and QOL-B were completed at baseline and 12 months. Associations between adherence to treatment and pulmonary exacerbations, lung function and QOL-B were determined by regression analyses. Seventy-five participants were recruited. Thirty-five (53%), 39 (53%) and 31 (41%) participants were adherent to inhaled antibiotics, other respiratory medicines, and airway clearance, respectively. Twelve (16%) participants were adherent to all treatments. Participants who were adherent to inhaled antibiotics had significantly fewer exacerbations compared to non-adherent participants (2.6 vs 4, p = 0.00) and adherence to inhaled antibiotics was independently associated with having fewer pulmonary exacerbations (regression co-efficient = -0.51, 95% CI [-0.81,-0.21], p < 0.001). Adherence to airway clearance was associated with lower QOL-B Treatment Burden (regression co-efficient = -15.46, 95% CI [-26.54, -4.37], p < 0.01) and Respiratory Symptoms domain scores (regression co-efficient = -10.77, 95% CI [-21.45; -0.09], p < 0.05). There were no associations between adherence to other respiratory medicines and any of the outcomes tested. Adherence to treatment was not associated with FEV1 % predicted. Treatment adherence is low in bronchiectasis and affects important health outcomes including pulmonary exacerbations. Adherence should be measured as part of bronchiectasis management and future research should evaluate bronchiectasis-specific adherence strategies.

Bosentan therapy in patients with pulmonary arterial hypertension: the relationship between improvements in 6 minute walk distance and quality of life.

PubMed

Strange, Geoff; Keogh, Anne M; Williams, Trevor J; Wlodarczyk, John; McNeil, Keith D; Gabbay, Eli

2008-09-01

Bosentan, an oral, dual endothelin receptor antagonist, significantly improves functional status, haemodynamic measures and survival in patients with pulmonary arterial hypertension (PAH). However, there are limited data on the effect of bosentan on quality of life (QOL) and its relationship to changes in functional status, as measured by the 6 minute walk distance (6MWD). A retrospective analysis was performed of a large, open-label, multicentre trial (VITAL) of bosentan in patients with PAH. Data for 6MWD were collected at baseline, 3 or 6 months and these results were correlated with QOL measurements collected as part of the assessment of patients enrolled in the trial. Sixty-nine patients with PAH (mean age 52 years) who were enrolled in the trial had valid QOL (SF-36) measurements and 6MWD data that could be retrieved from clinical notes. At 3 and 6 months, bosentan therapy improved 6MWD compared with baseline (49.5 m and 47.2 m, respectively, P < 0.001) as well as QOL domains, with a significant correlation between these two markers on cross-sectional analysis. However, there was a poor relationship when comparing changes in 6MWD with changes in QOL, in response to therapy. Bosentan therapy was associated with improvements in QOL and 6MWD for at least 6 months. At all measured time points, there was a close correlation between 6MWD and most QOL domains. QOL is an important parameter and should be considered as part of the standard assessment for any trial investigating therapy in PAH.

Pulmonary rehabilitation improves cardiovascular response to exercise in COPD.

PubMed

Ramponi, Sara; Tzani, Panagiota; Aiello, Marina; Marangio, Emilio; Clini, Enrico; Chetta, Alfredo

2013-01-01

Pulmonary rehabilitation (PR) has emerged as a recommended standard of care in symptomatic COPD. We now studied whether PR may affect cardiovascular response to exercise in these patients. Twenty-seven patients (9 females aged 69 ± 8 years) with moderate-to-severe airflow obstruction admitted to a 9-week PR course performed a pre-to-post evaluation of lung function test and symptom-limited cardiopulmonary exercise test (CPET). Oxygen uptake (VO2), tidal volume (V(T)), dyspnea and leg fatigue scores were measured during CPET. Cardiovas-cular response was assessed by means of oxygen pulse (O2Pulse), the oxygen uptake efficiency slope and heart rate recovery at the 1st min. A significant increase in peak VO2 and in all cardiovascular parameters (p < 0.05) was found following PR when compared to baseline. Leg fatigue (p < 0.05), but not dyspnea, was significantly reduced after PR. When assessed at metabolic and ventilatory iso levels [% VCO2max and % minute ventilation (VEmax)], O2Pulse and V(T) were significantly higher (p < 0.05) at submaximal exercise (75 and 50% of VCO2max and VEmax) after PR when compared to baseline. V(T) percent changes at 75% VCO2max and 75% VEmax after PR significantly correlated with corresponding changes in O2Pulse (p < 0.01). In COPD patients, a PR training program improved the cardiovascular response during exercise at submaximal exercise independent of the external workload. This change was associated with an enhanced ventilatory function during exercise. Copyright © 2013 S. Karger AG, Basel.

Noninvasive measurement of carboxyhemoglobin levels for adjustment of diffusion capacity measured during pulmonary function testing.

PubMed

Mahoney, Anne M; Stimpson, Claudia L; Scott, Karen L; Hampson, Neil B

2007-12-01

The diffusing capacity of the lungs for carbon monoxide (D(LCO)) is commonly measured during pulmonary function testing (PFT). Although adjustment of the measured D(LCO) for an elevated baseline carboxyhemoglobin level is recommended, carboxyhemoglobin is not routinely measured, which may reduce the accuracy of D(LCO) measurements. We sought to assess the utility of routine carboxyhemoglobin measurement and subsequent D(LCO) correction in patients referred for PFT. We retrospectively reviewed 100 consecutive PFT results, including D(LCO) assessment. We used a pulse CO-oximeter (recently approved by the Food and Drug Administration) to noninvasively measure baseline carboxyhemoglobin (S(pCO)). We used simple descriptive statistics to compare the S(pCO) values. In subjects with elevated S(pCO) (> 2%) we adjusted the percent-of-predicted D(LCO). Interpretation of D(LCO) was categorized according to the American Thoracic Society classification scheme for respiratory impairment. The self-reported smokers had higher average S(pCO) than did self-reported nonsmokers (1.6% vs 3.5%, p < 0.001), although 14% of nonsmokers had an elevated S(pCO) and 26% of smokers had normal S(pCO). When the D(LCO) was corrected for elevated S(pCO), 2 patients moved from a category of moderate impairment to mild impairment. Both were smokers. The noninvasive measurement of carboxyhemoglobin is easy to perform during PFT. When precise measurement of D(LCO) is important, noninvasive measurement of carboxyhemoglobin may be of value. If routine S(pCO) measurement is considered, the highest yield is among current smokers.

Impact of varying physical activity levels on airway sensitivity and bronchodilation in healthy humans.

PubMed

Smith, Joshua R; Kurti, Stephanie P; Johnson, Ariel M; Kolmer, Sarah A; Harms, Craig

2015-12-01

The purpose of this study was to determine if the amount of physical activity influences airway sensitivity and bronchodilation in healthy subjects across a range of physical activity levels. Thirty healthy subjects (age, 21.9 ± 2.6 years; 13 men/17 women) with normal pulmonary function reported to the laboratory on 2 separate occasions where they were randomized to breathe either hypertonic saline (HS) (nebulized hypertonic saline (25%) for 20 min) or HS followed by 5 deep inspirations (DIs), which has been reported to bronchodilate the airways. Pulmonary function tests (PFTs) were performed prior to both conditions and following the HS breathing or 5 DIs. Moderate to vigorous physical activity (MVPA) level was measured via accelerometer worn for 7 days. Following the HS breathing, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) significantly decreased from baseline by -11.8% ± 8.4% and -9.3% ± 6.7%, respectively. A 2-segment linear model determined significant relationships between MVPA and percent change in FEV1 (r = 0.50) and FVC (r = 0.55). MVPA above ∼497 and ∼500 min/week for FEV1 and FVC, respectively, resulted in minor additional improvements (p > 0.05) in PFTs following the HS breathing. Following the DIs, FEV1 and FVC decreased (p < 0.05) by -7.3% ± 8.6% and -5.7% ± 5.7%, respectively, from baseline, but were not related (p > 0.05) to MVPA. In conclusion, these data demonstrate that higher MVPA levels attenuated airway sensitivity but not bronchodilation in healthy subjects.

Maintenance of pulmonary vasculature tone by blood derived from the inferior vena cava in a rabbit model of cavopulmonary shunt.

PubMed

Ikai, Akio; Shirai, Mikiyasu; Nishimura, Kazunobu; Ikeda, Tadashi; Kameyama, Takayuki; Ueyama, Koji; Komeda, Masashi

2005-01-01

After cavopulmonary shunt in which the superior vena cava is anastomosed to the right pulmonary artery, the right lung is in a unique condition without flow pulsatility and hepatic venous effluent. In a previous study, we reported that hypoxic pulmonary vasoconstriction disappeared in the pulmonary circulation after cavopulmonary shunt. In this study, however, to investigate the influence of pulsatility and hepatic venous effluent on hypoxic pulmonary vasoconstriction in the pulmonary circulation, we developed an alternative cavopulmonary shunt rabbit model that included hepatic venous effluent in the pulmonary circulation and reduced the pulsatility of the pulmonary arterial blood flow. We then observed the physiologic characteristics of the peripheral pulmonary artery after cavopulmonary shunt, specifically the disappearance of hypoxic pulmonary vasoconstriction. Sixteen Japanese white rabbits (12-16 weeks old) were used in this study. With general anesthesia, a cavopulmonary shunt was established by anastomosing the right superior vena cava to the right pulmonary artery in an end-to-side fashion. Of the 16 rabbits for the study, the proximal right pulmonary artery was completely ligated in 5 (atresia group) and partially ligated in 6 (stenosis group). Sham operation was performed in the remaining 5 rabbits. Two weeks later, we analyzed the response of the pulmonary artery (which was divided into three categories: segmental, lobular, and acinar level artery) to hypoxia (8% oxygen inhalation) with a specially designed video radiographic system. Morphometric analysis of the resistance pulmonary artery was done in each group after angiography. Mean pressure and pulse pressure in the right pulmonary artery were not significantly different between the atresia and stenosis groups. The mean pulmonary artery pressures in the atresia and stenosis groups were 8 and 11 mm Hg, respectively. However, the pulse pressure was less than 2 mm Hg in both groups. The baseline internal diameter of the resistance pulmonary artery of the atresia group was significantly different from those of the stenosis and sham groups. In the atresia group, the resistance pulmonary arteries did not respond to hypoxia. In contrast, significant constriction (as assessed by percentage change of internal diameter of the resistance pulmonary arteries in the acinar and lobular level arteries) was observed in the pulmonary arteries of the sham and stenosis groups (atresia vs stenosis vs sham 0.4% vs - 19.0% vs - 18.8%, P = .01). In our morphometric study, we observed vasodilation of the resistance pulmonary artery with a thinner medial layer in the atresia group, consistent with the result of microangiography. We developed a cavopulmonary shunt rabbit model in which the inferior vena caval blood was derived from the right ventricle. Hypoxic pulmonary vasoconstriction was maintained in the model with the blood flow from the right ventricle. When the blood flow was not maintained, however, hypoxic pulmonary vasoconstriction disappeared. This phenomenon strongly suggests that a substance in hepatic venous effluent partially regulates the physiological pulmonary vascular function in the rabbit lung.

Relationship of right- to left-sided ventricular filling pressures in advanced heart failure: insights from the ESCAPE trial.

PubMed

Drazner, Mark H; Velez-Martinez, Mariella; Ayers, Colby R; Reimold, Sharon C; Thibodeau, Jennifer T; Mishkin, Joseph D; Mammen, Pradeep P A; Markham, David W; Patel, Chetan B

2013-03-01

Although right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) are correlated in heart failure, in a sizeable minority of patients, the RAP and PCWP are not tightly coupled. The basis of this variability in the RAP/PCWP ratio, and whether it conveys prognostic value, is not known. We analyzed the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial database. Baseline characteristics, including echocardiographic assessment of right ventricular (RV) structure and function, and invasively measured hemodynamic parameters, were compared among tertiles of the RAP/PCWP ratio. Multivariable Cox proportional hazard models assessed the association of RAP/PCWP ratio with the primary ESCAPE outcome (6-month death or hospitalization [days]) adjusting for systolic blood pressure, blood urea nitrogen, 6-minute walk distance, and PCWP. The RAP/PCWP tertiles were 0.27 to 0.4 (tertile 1); 0.41 to 0.615 (tertile 2), and 0.62 to 1.21 (tertile 3). Increasing RAP/PCWP was associated with increasing median right atrial area (23, 26, 29 cm2, respectively; P<0.005), RV area in diastole (21, 27, 27 cm2, respectively; P<0.005), and pulmonary vascular resistance (2.4, 2.9, 3.6 woods units, respectively; P=0.003), and lower RV stroke work index (8.6, 8.4, 5.5 g·m/m2 per beat, respectively; P<0.001). RAP/PCWP ratio was associated with death or hospitalization within 6 months (hazard ratio, 1.16 [1, 1.4]; P<0.05). Increased RAP/PCWP ratio was associated with higher pulmonary vascular resistance, reduced RV function (manifest as a larger right atrium and ventricle and lower RV stroke work index), and an increased risk of adverse outcomes in patients with advanced heart failure.

Proximal pulmonary vascular stiffness as a prognostic factor in children with pulmonary arterial hypertension.

PubMed

Friesen, Richard M; Schäfer, Michal; Ivy, D Dunbar; Abman, Steven H; Stenmark, Kurt; Browne, Lorna P; Barker, Alex J; Hunter, Kendall S; Truong, Uyen

2018-05-16

Main pulmonary artery (MPA) stiffness and abnormal flow haemodynamics in pulmonary arterial hypertension (PAH) are strongly associated with elevated right ventricular (RV) afterload and associated with disease severity and poor clinical outcomes in adults with PAH. However, the long-term effects of MPA stiffness on RV function in children with PAH remain poorly understood. This study is the first comprehensive evaluation of MPA stiffness in children with PAH, delineating the mechanistic relationship between flow haemodynamics and MPA stiffness as well as the prognostic ability of these measures regarding clinical outcomes. Fifty-six children diagnosed with PAH underwent baseline cardiac magnetic resonance (CMR) acquisition and were compared with 23 control subjects. MPA stiffness and wall shear stress (WSS) were evaluated using phase contrast CMR and were evaluated for prognostic potential along with standard RV volumetric and functional indices. Pulse wave velocity (PWV) was significantly increased (2.8 m/s vs. 1.4 m/s, P < 0.0001) and relative area change (RAC) was decreased (25% vs. 37%, P < 0.0001) in the PAH group, correlating with metrics of RV performance. Decreased WSS was associated with a decrease in RAC over time (r = 0.679, P < 0.001). For each unit increase in PWV, there was approximately a 3.2-fold increase in having a moderate clinical event. MPA stiffness assessed by non-invasive CMR was increased in children with PAH and correlated with RV performance, suggesting that MPA stiffness is a major contribution to RV dysfunction. PWV is predictive of moderate clinical outcomes, and may be a useful prognostic marker of disease activity in children with PAH.

Home-based pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a randomized clinical trial

PubMed Central

Dias, Fernanda Dultra; Sampaio, Luciana Maria Malosá; da Silva, Graziela Alves; Gomes, Évelim LF Dantas; do Nascimento, Eloisa Sanches Pereira; Alves, Vera Lucia Santos; Stirbulov, Roberto; Costa, Dirceu

2013-01-01

Introduction Pulmonary rehabilitation (PR) is a multidisciplinary program of care for patients with chronic obstructive pulmonary disease (COPD) with the goal of improving the functional capacity and quality of life, as well as maintaining the clinical stability of COPD sufferers. However, not all patients are available for such a program despite discomfort with their condition. The aim of this study was to evaluate the effects of a home-based PR (HBPR) program on functional ability, quality of life, and respiratory muscle strength and endurance. Patients and methods Patients with COPD according to the Global Initiative of Chronic Obstructive Lung Disease were randomized (double-blind) into two groups. One group performed a protocol at home with aerobic and muscle strength exercises and was called the intervention group; the other group received only instructions to perform breathing and stretching exercises, characterizing it as the control group (CG). We assessed the following variables at baseline and 2 months: exercise tolerance (incremental shuttle walk test and upper limb test), respiratory muscle (strength and endurance test), and health-related quality of life (Airways Questionnaire 20). Results There were no significant changes after the intervention in either of the two groups in exercise tolerance and quality of life. However, the intervention group had improved respiratory endurance compared with the CG, while the CG presented a decrease in the load sustained by the respiratory muscles after the HBPR. Conclusion A program of HBPR with biweekly supervision (although not enough to provide significant improvements in physical capacity or quality of life) played an important role in maintaining the stability of the clinical features of patients with COPD; the patients had no worsening of symptoms during the intervention period according to the daily log. PMID:24235824

Comparison of clinical and laboratory findings between those with pulmonary tuberculosis and those with nontuberculous mycobacterial lung disease.

PubMed

Thanachartwet, Vipa; Desakorn, Varunee; Duangrithi, Duangjai; Chunpongthong, Pongsak; Phojanamongkolkij, Kamol; Jitruckthai, Pasakorn; Kasetjaroen, Yuttichai; Pitisuttithum, Punnee

2014-01-01

In tuberculosis endemic areas, patients with sputum positive for acid-fast bacilli (AFB) are usually diagnosed and treated for pulmonary tuberculosis. The diagnosis of nontuberculous mycobacteria (NTM) lung disease is often ascertained only after lung disease progression occurs, increasing the risk of severe morbidity and mortality. We conducted a matched case-control study among a prospective cohort of 300 patients with newly diagnosed AFB-positive sputum in Thailand during 2010-2012. We compared clinical and laboratory parameters and outcomes among patients with pulmonary tuberculosis, NTM lung disease and NTM colonization. A mycobacterial culture was performed in all patients. Ten patients with NTM lung disease were compared to 50 patients with pulmonary tuberculosis and 10 patients with NTM colonization. The presence of diabetes mellitus or human immunodeficiency virus infection, were associated with NTM lung disease (p = 0.030). Patients with NTM lung disease had a significantly lower body weight prior to treatment (p = 0.021), a higher body weight change from baseline (p = 0.038), and were more likely to have cavitations on chest radiograph (p = 0.033) than those with NTM colonization. In tuberculosis endemic areas, mycobacterial identification should be performed among patients with impaired immune function. NTM lung disease treatment should be considered in patients with NTM sputum isolates who have a history of significant weight loss or cavitations on chest radiography.

Design of the exhale airway stents for emphysema (EASE) trial: an endoscopic procedure for reducing hyperinflation

PubMed Central

2011-01-01

Background Airway Bypass is a catheter-based, bronchoscopic procedure in which new passageways are created that bypass the collapsed airways, enabling trapped air to exit the lungs. The Exhale Airway Stents for Emphysema (EASE) Trial was designed to investigate whether Exhale® Drug-Eluting Stents, placed in new passageways in the lungs, can improve pulmonary function and reduce breathlessness in severely hyperinflated, homogeneous emphysema patients (NCT00391612). Methods/Design The multi-center, randomized, double-blind, sham-controlled trial design was posted on http://www.clinicaltrials.gov in October 2006. Because Bayesian statistics are used for the analysis, the proposed enrollment ranged from 225 up to 450 subjects at up to 45 institutions. Inclusion criteria are: high resolution CT scan with evidence of homogeneous emphysema, post-bronchodilator pulmonary function tests showing: a ratio of FEV1/FVC < 70%, FEV1≤50% of predicted or FEV1 < 1 liter, RV/TLC≥0.65 at screening, marked dyspnea score ≥2 on the modified Medical Research Council scale of 0-4, a smoking history of at least 20 pack years and stopped smoking for at least 8 weeks prior to enrollment. Following 16 to 20 supervised pulmonary rehabilitation sessions, subjects were randomized 2:1 to receive either a treatment (Exhale® Drug-Eluting Stent) or a sham bronchoscopy. A responder analysis will evaluate the co-primary endpoints of an FVC improvement ≥12% of the patient baseline value and modified Medical Research Council dyspnea scale improvement (reduction) ≥1 point at the 6-month follow-up visit. Discussion If through the EASE Trial, Airway Bypass is shown to improve pulmonary function and reduce dyspnea while demonstrating an acceptable safety profile, then homogeneous patients will have a minimally invasive treatment option with meaningful clinical benefit. Trial Registration ClinicalTrials.gov: NCT00391612 PMID:21214899

Low forced vital capacity predicts cytotoxic chemotherapy-associated acute exacerbation of interstitial lung disease in patients with lung cancer.

PubMed

Enomoto, Yasunori; Inui, Naoki; Kato, Terufumi; Baba, Tomohisa; Karayama, Masato; Nakamura, Yutaro; Ogura, Takashi; Suda, Takafumi

2016-06-01

Although acute exacerbation of pre-existing interstitial lung disease (AE-ILD) associated with cytotoxic chemotherapy has been recognized as a severe complication in lung cancer treatment, its risk factors have not been fully studied. Among lung cancer patients receiving cytotoxic chemotherapy, patients with pre-existing ILD were identified based on the pretreatment high-resolution computed tomography (HRCT) findings. Chemotherapy-associated AE-ILD was defined as deterioration or development of dyspnea and HRCT findings of new bilateral ground-glass attenuations with/without non-segmental consolidation superimposed on pre-existing interstitial shadows, without evidence of pulmonary infection, congestion, or pulmonary embolism, within four weeks after the last administration of chemotherapy. Baseline characteristics were reviewed and the risk factors for chemotherapy-associated AE-ILD were evaluated by logistic regression analyses. Among 85 patients identified as having pre-existing ILD, chemotherapy-associated AE-ILD occurred in 26 patients (30.6%); 8 patients died and 11 patients had a severely deteriorated general condition despite intensive treatment. Compared with those without AE-ILD, patients with AE-ILD had significantly lower forced vital capacity (FVC) (median: 91.1% versus 76.6%, P=0.01). Univariate and multivariate logistic regression analyses identified baseline lower FVC and non-small cell lung cancer (NSCLC) as the risk factors for this severe event (odds ratio of FVC: 0.97, 95% confidence interval: 0.94-0.99; odds ratio of NSCLC: 4.65, 95% confidence interval: 1.10-19.76). Chemotherapy-associated AE-ILD was a frequent and lethal complication in lung cancer treatment for patients with pre-existing ILD. Spirometric assessment of pulmonary function may be useful to predict the event. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cause-specific premature death from ambient PM2.5 exposure in India: Estimate adjusted for baseline mortality.

PubMed

Chowdhury, Sourangsu; Dey, Sagnik

2016-05-01

In India, more than a billion population is at risk of exposure to ambient fine particulate matter (PM2.5) concentration exceeding World Health Organization air quality guideline, posing a serious threat to health. Cause-specific premature death from ambient PM2.5 exposure is poorly known for India. Here we develop a non-linear power law (NLP) function to estimate the relative risk associated with ambient PM2.5 exposure using satellite-based PM2.5 concentration (2001-2010) that is bias-corrected against coincident direct measurements. We show that estimate of annual premature death in India is lower by 14.7% (19.2%) using NLP (integrated exposure risk function, IER) for assumption of uniform baseline mortality across India (as considered in the global burden of disease study) relative to the estimate obtained by adjusting for state-specific baseline mortality using GDP as a proxy. 486,100 (811,000) annual premature death in India is estimated using NLP (IER) risk functions after baseline mortality adjustment. 54.5% of premature death estimated using NLP risk function is attributed to chronic obstructive pulmonary disease (COPD), 24.0% to ischemic heart disease (IHD), 18.5% to stroke and the remaining 3.0% to lung cancer (LC). 44,900 (5900-173,300) less premature death is expected annually, if India achieves its present annual air quality target of 40μgm(-3). Our results identify the worst affected districts in terms of ambient PM2.5 exposure and resulting annual premature death and call for initiation of long-term measures through a systematic framework of pollution and health data archive. Copyright © 2016 Elsevier Ltd. All rights reserved.

Longitudinal Pulmonary Function in Newly Hired, Non-World Trade Center-Exposed Fire Department City of New York Firefighters

PubMed Central

Ye, Fen; Hall, Charles B.; Webber, Mayris P.; Cohen, Hillel W.; Dinkels, Michael; Cosenza, Kaitlyn; Weiden, Michael D.; Nolan, Anna; Christodoulou, Vasilios; Kelly, Kerry J.; Prezant, David J.

2013-01-01

Background: Few longitudinal studies characterize firefighters’ pulmonary function. We sought to determine whether firefighters have excessive FEV1 decline rates compared with control subjects. Methods: We examined serial measurements of FEV1 from about 6 months prehire to about 5 years posthire in newly hired male, never smoking, non-Hispanic black and white firefighters, hired between 2003 and 2006, without prior respiratory disease or World Trade Center exposure. Similarly defined Emergency Medical Service (EMS) workers served as control subjects. Results: Through June 30, 2011, 940 firefighters (82%) and 97 EMS workers (72%) who met study criteria had four or more acceptable posthire spirometries. Prehire FEV1% averaged higher for firefighters than EMS workers (99% vs 95%), reflecting more stringent job entry criteria. FEV1 (adjusted for baseline age and height) declined by an average of 45 mL/y both for firefighters and EMS workers, with Fire − EMS decline rate differences averaging 0.2 mL/y (CI, −9.2 to 9.6). Four percent of each group had FEV1 less than the lower limit of normal before hire, increasing to 7% for firefighters and 17.5% for EMS workers, but similar percentages of both groups had adjusted FEV1 decline rates ≥ 10%. Mixed effects modeling showed a significant influence of weight gain but not baseline weight: FEV1 declined by about 8 mL/kg gained for both groups. Adjusting for weight change, FEV1 decline averaged 38 mL/y for firefighters and 34 mL/y for EMS workers. Conclusions: During the first 5 years of duty, firefighters do not show greater longitudinal FEV1 decline than EMS control subjects, and fewer of them develop abnormal lung function. Weight gain is associated with a small loss of lung function, of questionable clinical relevance in this fit and active population. PMID:23188136

Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study.

PubMed

Leeming, Diana J; Byrjalsen, Inger; Sand, Jannie M B; Bihlet, Asger R; Lange, Peter; Thal-Singer, Ruth; Miller, Bruce E; Karsdal, Morten A; Vestbo, Jørgen

2017-12-04

Change in forced expiratory volume in one second (FEV 1 ) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV 1 . One thousand COPD subjects from the observational, multicentre, three-year ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study (NCT00292552, trial registration in February 2006) were included. Matrix metalloproteinase (MMP)-generated fragments of collagen type I, and type VI (C1M and C6M) were assessed in month six serum samples. A random-coefficient model with both a random intercept and a random slope was used to test the ability of the markers to predict post-dose bronchodilator FEV 1 (PD-FEV 1 ) change over two years adjusting for sex, age, BMI, smoking, bronchodilator reversibility, prior exacerbations, emphysema and chronic bronchitis status at baseline. Annual change of PD-FEV 1 was estimated from a linear model for the two-year study period. Serum C1M and C6M were independent predictors of lung function change (p = 0.007/0.005). Smoking, bronchodilator reversibility, plasma hsCRP and emphysema were also significant predictors. The effect estimate between annual change in PD-FEV 1 per one standard deviation (1SD) increase of C1M and C6M was +10.4 mL/yr. and +8.6 mL/yr. C1M, and C6M, had a significant association with baseline FEV 1 . We demonstrated that markers of tissue turnover were significantly associated with lung function change. These markers may function as prognostic biomarkers and possibly as efficacy biomarkers in clinical trials focusing on lung function change in COPD. NCT00292552 , Retrospectively registered, trial registration in February 2006.

Effect of re-expansion after short-period lung collapse on pulmonary capillary permeability and pro-inflammatory cytokine gene expression in isolated rabbit lungs.

PubMed

Funakoshi, T; Ishibe, Y; Okazaki, N; Miura, K; Liu, R; Nagai, S; Minami, Y

2004-04-01

Re-expansion pulmonary oedema is a rare complication caused by rapid re-expansion of a chronically collapsed lung. Several cases of pulmonary oedema associated with one-lung ventilation (OLV) have been reported recently. Elevated levels of pro-inflammatory cytokines in pulmonary oedema fluid are suggested to play important roles in its development. Activation of cytokines after re-expansion of collapsed lung during OLV has not been thoroughly investigated. Here we investigated the effects of re-expansion of the collapsed lung on pulmonary oedema formation and pro-inflammatory cytokine expression. Lungs isolated from female white Japanese rabbits were perfused and divided into a basal (BAS) group (n=7, baseline measurement alone), a control (CONT) group (n=9, ventilated without lung collapse for 120 min) and an atelectasis (ATEL) group (n=9, lung collapsed for 55 min followed by re-expansion and ventilation for 65 min). Pulmonary vascular resistance (PVR) and the coefficient of filtration (Kfc) were measured at baseline and 60 and 120 min. At the end of perfusion, bronchoalveolar lavage fluid/plasma protein ratio (B/P), wet/dry lung weight ratio (W/D) and mRNA expressions of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and myeloperoxidase (MPO) were determined. TNF-alpha and IL-1beta mRNA were significantly up-regulated in lungs of the ATEL group compared with BAS and CONT, though no significant differences were noted in PVR, Kfc, B/P and W/D within and between groups. MPO increased at 120 min in CONT and ATEL groups. Pro-inflammatory cytokines were up-regulated upon re-expansion and ventilation after short-period lung collapse, though no changes were noted in pulmonary capillary permeability.

Intravenous superoxide dismutase as a protective agent to prevent impairment of lung function induced by high tidal volume ventilation.

PubMed

Wu, Nan-Chun; Liao, Fan-Ting; Cheng, Hao-Min; Sung, Shih-Hsien; Yang, Yu-Chun; Wang, Jiun-Jr

2017-07-26

Positive-pressure mechanical ventilation is essential in assisting patients with respiratory failure in the intensive care unit and facilitating oxygenation in the operating room. However, it was also recognized as a primary factor leading to hospital-acquired pulmonary dysfunction, in which pulmonary oxidative stress and lung inflammation had been known to play important roles. Cu/Zn superoxide dismutase (SOD) is an important antioxidant, and possesses anti-inflammatory capacity. In this study, we aimed to study the efficacy of Cu/Zn SOD, administered intravenously during high tidal volume (HTV) ventilation, to prevent impairment of lung function. Thirty-eight male Sprague-Dawley rats were divided into 3 groups: 5 h ventilation with (A) low tidal volume (LTV; 8 mL/kg; n = 10), (B) high tidal volume (HTV; 18 mL/kg; n = 14), or (C) HTV and intravenous treatment of Cu/Zn SOD at a dose of 1000 U/kg/h (HTV + SOD; n = 14). Lung function was evaluated both at baseline and after 5-h ventilation. Lung injury was assessed by histological examination, lung water and protein contents in the bronchoalveolar lavage fluid (BALF). Pulmonary oxidative stress was examined by concentrations of methylguanidine (MG) and malondialdehyde (MDA) in BALF, and antioxidative activity by protein expression of glutathione peroxidase-1 (GPx-1) in the lung. Severity of lung inflammation was evaluated by white blood cell and differential count in BALF, and protein expression of inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and mRNA expression of nuclear factor-κB (NF-κB) in the lung. We also examined protein expression of surfactant protein (SP)-A and D and we measured hourly changes in serum nitric oxide (NO) level. Five hours of LTV ventilation did not induce a major change in lung function, whereas 5 h of HTV ventilation induced apparent combined restrictive and obstructive lung disorder, together with increased pulmonary oxidative stress, decreased anti-oxidative activity and increased lung inflammation (P < 0.05). HTV ventilation also decreased SP-A and SP-D expression and suppressed serum NO level during the time course of ventilation. Cu/Zn SOD administered intravenously during HTV ventilation effectively reversed associated pulmonary oxidative stress and lung inflammation (P < 0.05); moreover, it preserved SP-A and SP-D expressions in the lung and increased serum nitric oxide (NO) level, enhancing vascular NO bioavailability. HTV ventilation can induce combined restrictive and obstructive lung disorders. Intravenous administration of Cu/Zn SOD during HTV ventilation can prevent lung function impairment and lung injury via reducing pulmonary oxidative stress and lung inflammation, preserving pulmonary surfactant expression, and enhancing vascular NO bioavailability.

Effect of heliox- and air-driven nebulized bronchodilator therapy on lung function in patients with asthma.

PubMed

El-Khatib, Mohamad F; Jamaleddine, Ghassan; Kanj, Nadim; Zeineddine, Salah; Chami, Hassan; Bou-Akl, Imad; Husari, Ahmad; Alawieh, Marwan; Bou-Khalil, Pierre

2014-06-01

This study compares the effect of heliox-driven to that of air-driven bronchodilator therapy on the pulmonary function test (PFT) in patients with different levels of asthma severity. One-hundred thirty-two participants were included in the study. Participants underwent spirometry twice with bronchodilator testing on two consecutive days. Air-driven nebulization was used one day and heliox-driven nebulization the other day in random order crossover design. After a baseline PFT, each participant received 2.5 mg of albuterol sulfate nebulized with the randomized driving gas. Post bronchodilator PFT was repeated after 30 min. The next day, the exact same protocol was repeated, except that the other driving gas was used to nebulize the drug. Participants were subgrouped and analyzed according to their baseline FEV(1) on day 1: Group I, FEV(1) ≥80 %; Group II, 80 % > FEV(1) > 50 %; Group III, FEV(1) ≤50 %. The proportion of participants with greater than 12 % and 200-mL increases from their baseline FEV(1) and the changes from baseline in PFT variables were compared between heliox-driven versus air-driven bronchodilation therapy. The proportion of participants with >12 % and 200-mL increases from their baseline FEV(1) with air- or heliox-driven bronchodilation was not different with respect to the proportion of participants with baseline FEV(1) ≥80 % (20 vs. 18 %, respectively) and 80 % > FEV(1) > 50 % (36 vs. 43 %, respectively), but it was significantly greater with heliox-driven bronchodilation in participants with FEV(1) ≤50 % (43 vs. 73 %, respectively; p = 0.01). Changes from baseline FVC, FEV(1), FEV(1)/FVC, FEF(25-75) %, FEF(max), FEF(25) %, FEF(50) %, and FEF(75) % were significantly larger with heliox-driven versus air-driven bronchodilation in participants with baseline FEV(1) ≤50 %. Improvements in PFT variables are more frequent and profound with heliox-driven compared to air-driven bronchodilator therapy only in asthmatic patients with baseline FEV(1) ≤50 %.

Effect of yoga practices on pulmonary function tests including transfer factor of lung for carbon monoxide (TLCO) in asthma patients.

PubMed

Singh, Savita; Soni, Ritu; Singh, K P; Tandon, O P

2012-01-01

Prana is the energy, when the self-energizing force embraces the body with extension and expansion and control, it is pranayama. It may affect the milieu at the bronchioles and the alveoli particularly at the alveolo-capillary membrane to facilitate diffusion and transport of gases. It may also increase oxygenation at tissue level. Aim of our study is to compare pulmonary functions and diffusion capacity in patients of bronchial asthma before and after yogic intervention of 2 months. Sixty stable asthmatic-patients were randomized into two groups i.e group 1 (Yoga training group) and group 2 (control group). Each group included thirty patients. Lung functions were recorded on all patients at baseline, and then after two months. Group 1 subjects showed a statistically significant improvement (P<0.001) in Transfer factor of the lung for carbon monoxide (TLCO), forced vital capacity (FVC), forced expiratory volume in 1st sec (FEV1), peak expiratory flow rate (PEFR), maximum voluntary ventilation (MVV) and slow vital capacity (SVC) after yoga practice. Quality of life also increased significantly. It was concluded that pranayama & yoga breathing and stretching postures are used to increase respiratory stamina, relax the chest muscles, expand the lungs, raise energy levels, and calm the body.

Impact of continuous positive airway pressure (CPAP) on the respiratory capacity of chronic kidney disease patients under hemodialysis treatment.

PubMed

Xavier, Vivian Bertoni; Roxo, Renata Spósito; Miorin, Luiz Antônio; Dos Santos Alves, Vera Lúcia; Dos Santos Sens, Yvoty Alves

2015-06-01

Chronic kidney disease (CKD) patients on long-term dialysis present changes in pulmonary function and respiratory muscle strength, negatively influencing physical capacity. To analyze the impact of a continuous positive airway pressure (CPAP) protocol on the respiratory capacity of CKD patients under hemodialysis. A randomized clinical trial was conducted involving 40 CKD patients 19-83 years old divided into two groups: control (n = 20) and CPAP (n = 20). Subjects were assessed on the respiratory muscle function test, maximal respiratory pressures, peak flow and 6-min walk test, at baseline and again at the 2-month follow-up. CPAP group patients were submitted to CPAP protocol (PEEP: 5 cm H2O, flow: 15 L/min, FiO2: 33 %) three times per week during hemodialysis sessions. The CPAP group showed higher forced vital capacity, forced expiratory volume in one second, peak expiratory flow, maximal inspiratory pressure, peak flow, as well as lower systolic blood pressure, heart rate, respiratory rate and Borg scale, in addition to a longer distance travelled on the 6-min walk test, compared with the control group. The introduction of a CPAP protocol during hemodialysis sessions had a positive impact on pulmonary function and physical capacity in CKD patients.

Aerosolized Red Tide Toxins (Brevetoxins) and Asthma: Continued health effects after 1 hour beach exposure.

PubMed

Kirkpatrick, Barbara; Fleming, Lora E; Bean, Judy A; Nierenberg, Kate; Backer, Lorraine C; Cheng, Yung Sung; Pierce, Richard; Reich, Andrew; Naar, Jerome; Wanner, Adam; Abraham, William M; Zhou, Yue; Hollenbeck, Julie; Baden, Daniel G

2011-01-01

Blooms of the toxic dinoflagellate, Karenia brevis, produce potent neurotoxins in marine aerosols. Recent studies have demonstrated acute changes in both symptoms and pulmonary function in asthmatics after only 1 hour of beach exposure to these aerosols. This study investigated if there were latent and/or sustained effects in asthmatics in the days following the initial beach exposure during periods with and without an active Florida red tide.Symptom data and spirometry data were collected before and after 1 hour of beach exposure. Subjects kept daily symptom diaries and measured their peak flow each morning for 5 days following beach exposure. During non-exposure periods, there were no significant changes in symptoms or pulmonary function either acutely or over 5 days of follow-up. After the beach exposure during an active Florida red tide, subjects had elevated mean symptoms which did not return to the pre-exposure baseline for at least 4 days. The peak flow measurements decreased after the initial beach exposure, decreased further within 24 hours, and continued to be suppressed even after 5 days. Asthmatics may continue to have increased symptoms and delayed respiratory function suppression for several days after 1 hour of exposure to the Florida red tide toxin aerosols.

Aerosolized Red Tide Toxins (Brevetoxins) and Asthma: Continued health effects after 1 hour beach exposure

PubMed Central

Kirkpatrick, Barbara; Fleming, Lora E; Bean, Judy A; Nierenberg, Kate; Backer, Lorraine C; Cheng, Yung Sung; Pierce, Richard; Reich, Andrew; Naar, Jerome; Wanner, Adam; Abraham, William M; Zhou, Yue; Hollenbeck, Julie; Baden, Daniel G

2010-01-01

Blooms of the toxic dinoflagellate, Karenia brevis, produce potent neurotoxins in marine aerosols. Recent studies have demonstrated acute changes in both symptoms and pulmonary function in asthmatics after only 1 hour of beach exposure to these aerosols. This study investigated if there were latent and/or sustained effects in asthmatics in the days following the initial beach exposure during periods with and without an active Florida red tide. Symptom data and spirometry data were collected before and after 1 hour of beach exposure. Subjects kept daily symptom diaries and measured their peak flow each morning for 5 days following beach exposure. During non-exposure periods, there were no significant changes in symptoms or pulmonary function either acutely or over 5 days of follow-up. After the beach exposure during an active Florida red tide, subjects had elevated mean symptoms which did not return to the pre-exposure baseline for at least 4 days. The peak flow measurements decreased after the initial beach exposure, decreased further within 24 hours, and continued to be suppressed even after 5 days. Asthmatics may continue to have increased symptoms and delayed respiratory function suppression for several days after 1 hour of exposure to the Florida red tide toxin aerosols. PMID:21499552

Effects of exercise training in patients with idiopathic pulmonary arterial hypertension.

PubMed

de Man, F S; Handoko, M L; Groepenhoff, H; van 't Hul, A J; Abbink, J; Koppers, R J H; Grotjohan, H P; Twisk, J W R; Bogaard, H-J; Boonstra, A; Postmus, P E; Westerhof, N; van der Laarse, W J; Vonk-Noordegraaf, A

2009-09-01

We determined the physiological effects of exercise training on exercise capacity and quadriceps muscle function in patients with idiopathic pulmonary arterial hypertension (iPAH). In total, 19 clinically stable iPAH patients (New York Heart Association II-III) underwent a supervised exercise training programme for the duration of 12 weeks. Maximal capacity, endurance capacity and quadriceps function were assessed at baseline and after 12 weeks. In 12 patients, serial quadriceps muscle biopsies were obtained. 6-min walk distance and peak exercise capacity did not change after training. However, endurance capacity improved significantly after training, demonstrated by a shift of the anaerobic threshold to a higher workload (from 32+/-5 to 46+/-6 W; p = 0.003) together with an increase in exercise endurance time (p<0.001). Moreover, exercise training increased quadriceps strength by 13% (p = 0.005) and quadriceps endurance by 34% (p = 0.001). Training enhanced aerobic capacity of the quadriceps, by increasing capillarisation (1.36+/-0.10 to 1.78+/-0.13 capillaries per muscle fibre; p<0.001) and oxidative enzyme activity, especially of the type-I (slow) muscle fibres. No changes were found in cross-sectional area and fibre type distribution. Exercise training in iPAH improves exercise endurance and quadriceps muscle function, which is also reflected by structural changes of the quadriceps.

Deletion polymorphisms in the angiotensin converting enzyme gene are associated with pulmonary hypertension evoked by exercise challenge in patients with chronic obstructive pulmonary disease.

PubMed

Kanazawa, H; Okamoto, T; Hirata, K; Yoshikawa, J

2000-10-01

Angiotensin converting enzyme (ACE) plays an important role in the pathogenesis of pulmonary hypertension. In this study we determined whether the deletion (D)/insertion (I) polymorphism in the ACE gene may be associated with pulmonary hypertension evoked by exercise challenge in patients with chronic obstructive pulmonary disease (COPD). ACE genotypes were determined in 19 patients with COPD. All patients underwent right heart catheterization followed by a constant-load exercise test while breathing room air or oxygen. Subgroups were created of seven patients with the II genotype, six with the ID genotype, and six with the DD genotype who were well-matched with respect to age, blood gas data at rest or after exercise, baseline lung function, results of incremental exercise testing, and hemodynamic data at rest. The mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (Rpv) at rest in the three subgrpoups did not differ significantly during breathing of either room air or oxygen. However, the Ppa after exercise challenge in patients with the DD genotype (55.7 +/- 4.9 mm Hg [mean +/- SD]) was significantly higher than in patients with the II genotype (42.6 +/- 7.1 mm Hg, p = 0.008). The Rpv after exercise in patients with the DD genotype was also significantly higher than in patients with the ID and II genotypes. During breathing of oxygen to diminish acute hypoxic pulmonary vasoconstriction, the Ppa in patients with the DD genotype (52.3 +/- 3.1 mm Hg) was higher than in patients with the ID genotype (40.5 +/- 5.9 mm Hg, p = 0.0049) or the II genotype (37.7 +/- 5.9 mm Hg, p = 0.0027). In addition, the Rpv in patients with the DD genotype was higher than in patients with the ID and II genotypes. These results suggest that D-I polymorphism in the ACE gene may be associated with pulmonary hypertension evoked by exercise challenge in patients with COPD. However, the number of patients in this study was very small for a genetic association study, and our results should be examined in larger studies.

Mast cell tryptase changes with Aspergillus fumigatus - Host crosstalk in cystic fibrosis patients.

PubMed

Gomez, Carine; Carsin, Ania; Gouitaa, Marion; Reynaud-Gaubert, Martine; Dubus, Jean-Christophe; Mège, Jean-Louis; Ranque, Stéphane; Vitte, Joana

2018-02-15

Pulmonary and systemic antifungal immunity influences quality of life and survival of people with cystic fibrosis. Aspergillus fumigatus (Af) induces specific IgG and IgE. Mast cells respond to IgE, IgG and direct interactions with Af. Mast cells are the source of the protease tryptase. We aimed at evaluating serum baseline tryptase as a potential biomarker of the Af-host interaction in cystic fibrosis patients. Serum baseline tryptase, IgE and IgG directed to Af extract and Af molecular allergens were measured in 76 cystic fibrosis patients. The main findings were (i) lower levels of serum baseline tryptase in patients displaying specific IgE to Af (p < 0.0001) and (ii) an association between tryptase levels and IgE or IgG responses to Af and ribotoxin (Asp f 1). These findings suggest that serum baseline tryptase is influenced by Af-host interactions and thus might be a marker for mast cell regulation and pulmonary immune defenses. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Molecular Analysis of BMPR2, TBX4, and KCNK3 and Genotype-Phenotype Correlations in Spanish Patients and Families With Idiopathic and Hereditary Pulmonary Arterial Hypertension.

PubMed

Navas, Paula; Tenorio, Jair; Quezada, Carlos Andrés; Barrios, Elvira; Gordo, Gema; Arias, Pedro; López Meseguer, Manuel; Santos-Lozano, Alejandro; Palomino Doza, Julian; Lapunzina, Pablo; Escribano Subías, Pilar

2016-11-01

Recent advances in genetics have led to the discovery of new genes associated with pulmonary arterial hypertension, such as TBX4 and KCNK3. The phenotype and prognosis associated with these new genes have been scarcely described and their role in the Spanish population is unknown. The aim of this study was to characterize the genetics of a Spanish cohort of patients with idiopathic and hereditary pulmonary arterial hypertension and to describe the phenotype and prognostic factors associated with BMPR2 and the new genes (KCNK3 and TBX4). A total of 165 adult patients were screened for BMPR2, KCNK3, and TBX4 mutations, 143 with idiopathic pulmonary arterial hypertension and 22 with hereditary pulmonary arterial hypertension. Baseline characteristics and survival were compared among the different subgroups and predictors of poor outcomes were analyzed. We also performed family screening. The genetic study identified a possibly associated mutation in 11.10% of the idiopathic cases (n = 16) and in 68.18% of the hereditary cases (n = 15). There were 19 mutations in BMPR2, 4 in TBX4, and 3 in KCNK3. The forms associated with TBX4 showed the highest survival rate (P < .01). Advanced functional class at diagnosis was the only factor associated with poor outcomes in the hereditary forms. In the family screening, 37.5% of relatives tested positive. The genetics of pulmonary arterial hypertension in the Spanish population may differ from other populations, with a lower proportion of BMPR2 causative mutations. In our cohort, TBX4-related forms of pulmonary arterial hypertension showed a more benign course and late diagnosis was the only predictor of adverse outcomes in the hereditary forms of the disease. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Two-dimensional knowledge-based volumetric reconstruction of the right ventricle documents short-term improvement in pulmonary hypertension.

PubMed

Schwaiger, Johannes P; Knight, Daniel S; Kaier, Thomas; Gallimore, Adele; Denton, Christopher P; Schreiber, Benjamin E; Handler, Clive; Coghlan, John G

2017-06-01

Data are scarce about short-term right ventricular changes in pulmonary hypertension. Two-dimensional knowledge-based reconstruction of the right ventricle with 2D echocardiography (2DKBR) has been shown to be a valid alternative to Cardiac MRI. In this longitudinal study 25 pulmonary hypertension patients underwent 2DKBR of the right ventricle, assessment of NT-proBNP levels and functional class at baseline and after a mean follow-up of 6.1 months. Patients were followed up clinically for a further mean of 8.2 months. The majority of patients had connective tissue disease (CTD) associated pulmonary arterial hypertension (n=15) or chronic thromboembolic pulmonary hypertension (CTEPH; n=6). A total of 15 patients underwent an intervention, either new targeted therapy, escalation of targeted therapy or pulmonary endarterectomy. A total of 10 clinically stable patients were routinely followed up without any change in therapy. There were significant improvements in the right ventricular end-diastolic volume index (111±29 mL/m² vs 100±36 mL/m²; P=.038), end-systolic volume index (72±23 mL/m² vs 61±25 mL/m²; P=.001), and ejection fraction (35±10% vs 40±9%; P=.030). Changes in NT-proBNP levels correlated strongest with changes in end-systolic volume index (r=-.77; P=<.0001). Four patients experienced clinical worsening during extended follow-up, dilatation of the right ventricle was associated with clinical worsening. In a CTD and CTEPH dominated patient population significant reverse remodeling and improvement of ejection fraction occurred despite a short follow-up and was paralleled by significant changes in NT-proBNP levels. Further right ventricular dilatation was associated with worse clinical outcome. 2DKBR is a feasible substitute for Cardiac MRI to follow-up right ventricular indices in pulmonary hypertension. © 2017, Wiley Periodicals, Inc.

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

PubMed Central

Parvez, Faruque; Chen, Yu; Yunus, Mahbub; Olopade, Christopher; Segers, Stephanie; Slavkovich, Vesna; Argos, Maria; Hasan, Rabiul; Ahmed, Alauddin; Islam, Tariqul; Akter, Mahmud M.; Graziano, Joseph H.

2013-01-01

Rationale: Exposure to arsenic through drinking water has been linked to respiratory symptoms, obstructive lung diseases, and mortality from respiratory diseases. Limited evidence for the deleterious effects on lung function exists among individuals exposed to a high dose of arsenic. Objectives: To determine the deleterious effects on lung function that exist among individuals exposed to a high dose of arsenic. Methods: In 950 individuals who presented with any respiratory symptom among a population-based cohort of 20,033 adults, we evaluated the association between arsenic exposure, measured by well water and urinary arsenic concentrations measured at baseline, and post-bronchodilator–administered pulmonary function assessed during follow-up. Measurements and Main Results: For every one SD increase in baseline water arsenic exposure, we observed a lower level of FEV1 (−46.5 ml; P < 0.0005) and FVC (−53.1 ml; P < 0.01) in regression models adjusted for age, sex, body mass index, smoking, socioeconomic status, betel nut use, and arsenical skin lesions status. Similar inverse relationships were observed between baseline urinary arsenic and FEV1 (−48.3 ml; P < 0.005) and FVC (−55.2 ml; P < 0.01) in adjusted models. Our analyses also demonstrated a dose-related decrease in lung function with increasing levels of baseline water and urinary arsenic. This association remained significant in never-smokers and individuals without skin lesions, and was stronger in male smokers. Among male smokers and individuals with skin lesions, every one SD increase in water arsenic was related to a significant reduction of FEV1 (−74.4 ml, P < 0.01; and −116.1 ml, P < 0.05) and FVC (−72.8 ml, P = 0.02; and −146.9 ml, P = 0.004), respectively. Conclusions: This large population-based study confirms that arsenic exposure is associated with impaired lung function and the deleterious effect is evident at low- to moderate-dose range. PMID:23848239

SERAPHIN haemodynamic substudy: the effect of the dual endothelin receptor antagonist macitentan on haemodynamic parameters and NT-proBNP levels and their association with disease progression in patients with pulmonary arterial hypertension

PubMed Central

Galiè, Nazzareno; Jansa, Pavel; Pulido, Tomás; Channick, Richard N.; Delcroix, Marion; Ghofrani, Hossein-Ardeschir; Le Brun, Franck-Olivier; Mehta, Sanjay; Perchenet, Loïc; Rubin, Lewis J.; Sastry, B.K.S.; Simonneau, Gérald; Sitbon, Olivier; Souza, Rogério; Torbicki, Adam

2017-01-01

Aims The effect of macitentan on haemodynamic parameters and NT-proBNP levels was evaluated in pulmonary arterial hypertension (PAH) patients in the SERAPHIN study. Association between these parameters and disease progression, assessed by the primary endpoint (time to first morbidity/mortality event), was explored. Methods and results Of the 742 randomized patients, 187 with right heart catheterization at baseline and month 6 participated in a haemodynamic sub-study. Prespecified endpoints included change from baseline to month 6 in cardiac index (CI), right atrial pressure (RAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), mixed-venous oxygen saturation, and NT-proBNP. Exploratory analyses examined associations between CI, RAP, and NT-proBNP and disease progression using the Kaplan-Meier method and Cox regression models. Macitentan improved CI, RAP, mPAP, PVR and NT-proBNP vs. placebo at month 6. Absolute levels of CI, RAP and NT-proBNP at baseline and month 6, but not their changes, were associated with morbidity/mortality events. Patients with CI > 2.5 L/min/m2, RAP < 8 mmHg, or NT-proBNP < 750 fmol/ml at month 6 had a lower risk of morbidity/mortality than those not meeting these thresholds (HR 0.49, 95% CL 0.28–0.86; HR 0.72, 95% CL 0.42–1.22; and HR 0.22, 95% CL 0.15–0.33, respectively). Conclusions For all treatment groups, baseline and month 6 values of CI, RAP, and NT-proBNP, but not their changes, were associated with morbidity/mortality events, confirming their relevance in predicting disease progression in patients with PAH. By improving those parameters, macitentan increased the likelihood of reaching threshold values associated with lower risk of morbidity/mortality. PMID:28329315

SERAPHIN haemodynamic substudy: the effect of the dual endothelin receptor antagonist macitentan on haemodynamic parameters and NT-proBNP levels and their association with disease progression in patients with pulmonary arterial hypertension.

PubMed

Galiè, Nazzareno; Jansa, Pavel; Pulido, Tomás; Channick, Richard N; Delcroix, Marion; Ghofrani, Hossein-Ardeschir; Le Brun, Franck-Olivier; Mehta, Sanjay; Perchenet, Loïc; Rubin, Lewis J; Sastry, B K S; Simonneau, Gérald; Sitbon, Olivier; Souza, Rogério; Torbicki, Adam

2017-04-14

The effect of macitentan on haemodynamic parameters and NT-proBNP levels was evaluated in pulmonary arterial hypertension (PAH) patients in the SERAPHIN study. Association between these parameters and disease progression, assessed by the primary endpoint (time to first morbidity/mortality event), was explored. Of the 742 randomized patients, 187 with right heart catheterization at baseline and month 6 participated in a haemodynamic sub-study. Prespecified endpoints included change from baseline to month 6 in cardiac index (CI), right atrial pressure (RAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), mixed-venous oxygen saturation, and NT-proBNP. Exploratory analyses examined associations between CI, RAP, and NT-proBNP and disease progression using the Kaplan-Meier method and Cox regression models. Macitentan improved CI, RAP, mPAP, PVR and NT-proBNP vs. placebo at month 6. Absolute levels of CI, RAP and NT-proBNP at baseline and month 6, but not their changes, were associated with morbidity/mortality events. Patients with CI > 2.5 L/min/m2, RAP < 8 mmHg, or NT-proBNP < 750 fmol/ml at month 6 had a lower risk of morbidity/mortality than those not meeting these thresholds (HR 0.49, 95% CL 0.28-0.86; HR 0.72, 95% CL 0.42-1.22; and HR 0.22, 95% CL 0.15-0.33, respectively). For all treatment groups, baseline and month 6 values of CI, RAP, and NT-proBNP, but not their changes, were associated with morbidity/mortality events, confirming their relevance in predicting disease progression in patients with PAH. By improving those parameters, macitentan increased the likelihood of reaching threshold values associated with lower risk of morbidity/mortality. © The Author 2017. Published on behalf of the European Society of Cardiology

Impact of pulmonary rehabilitation on postoperative complications in patients with lung cancer and chronic obstructive pulmonary disease.

PubMed

Saito, Hajime; Hatakeyama, Kazutoshi; Konno, Hayato; Matsunaga, Toshiki; Shimada, Yoichi; Minamiya, Yoshihiro

2017-09-01

Given the extent of the surgical indications for pulmonary lobectomy in breathless patients, preoperative care and evaluation of pulmonary function are increasingly necessary. The aim of this study was to assess the contribution of preoperative pulmonary rehabilitation (PR) for reducing the incidence of postoperative pulmonary complications in non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD). The records of 116 patients with COPD, including 51 patients who received PR, were retrospectively analyzed. Pulmonary function testing, including slow vital capacity (VC) and forced expiratory volume in one second (FEV 1 ), was obtained preoperatively, after PR, and at one and six months postoperatively. The recovery rate of postoperative pulmonary function was standardized for functional loss associated with the different resected lung volumes. Propensity score analysis generated matched pairs of 31 patients divided into PR and non-PR groups. The PR period was 18.7 ± 12.7 days in COPD patients. Preoperative pulmonary function was significantly improved after PR (VC 5.3%, FEV 1 5.5%; P < 0.05). The FEV 1 recovery rate one month after surgery was significantly better in the PR (101.6%; P < 0.001) than in the non-PR group (93.9%). In logistic regression analysis, predicted postoperative FEV 1 , predicted postoperative %FEV 1 , and PR were independent factors related to postoperative pulmonary complications after pulmonary lobectomy (odds ratio 18.9, 16.1, and 13.9, respectively; P < 0.05). PR improved the recovery rate of pulmonary function after lobectomy in the early period, and may decrease postoperative pulmonary complications. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Longitudinal Lung Function Decrease in Subjects with Spontaneous Healed Pulmonary Tuberculosis.

PubMed

Lee, Seung Heon; Kwon, Amy M; Yang, Hae-Chung; Lee, Seung Ku; Kim, Young; Choi, Jong Hyun; Kim, Je Hyeong; Shin, Chol

2016-01-01

We compared the longitudinal course of post-bronchodilator Forced Expiratory Volume in 1 second (pFEV1) over a 10-year period in subjects with spontaneous healed pulmonary tuberculosis (SHPTB) with that in normal subjects. We prospectively investigated 339 subjects with SHPTB and 3211 normal subjects. pFEV1 values measured biannually over 10 years were analyzed using mixed effects model. At baseline, there were no differences in gender, smoking amount, and mean height, except mean age (50.0 ± 8.1 VS. 48.1 ± 7.3, P< 0.001) between the SHPTB and normal group. 52% of the 339 participants with SHPTB and 56% of the 3211 normal participants participated till the end of study. According to the final model, the SHPTB group showed significantly larger decrease in the average pFEV1 over the time than the normal group (P< 0.001) adjusted for gender, age, height, smoking pack years, and time effects. Especially, the interaction effect between time and group was statistically significant (P = 0.036). The average lung function in terms of pFEV1 decreases faster in subjects with SHPTB than in normal individuals over time.

Comparison of capnovolumetry-derived dead space parameters with pulmonary function test in normal adults using histamine provocation.

PubMed

Sun, Xiaoli; Zhang, Yan; Yang, Wenlan; Liu, Jinming

2015-04-01

This study in healthy adults was conducted to explore the clinical application of capnovolumetric indices as compared to lung function parameters using histamine provocation. Forty healthy subjects received aerosol histamine or salbutamol in an automatic stimulation system with escalating doses of histamine. Dead space volumes of capnovolumetry and lung function parameters were examined with increased concentrations of histamine at a fixed time interval. The doses of histamine were selected from 0.0562 mg-2.2 mg and 0.1 mg salbutamol was inhaled when a maximal dose of histamine was reached. Baseline values in each group were calculated prior to histamine inhalation. Fowler dead space (VDF), Wolff dead space (VDW), threshold dead space (VDT), Bohr dead space (VDB), forced expiratory volume in 1 s (FEV1 ) and peak expiratory flow (PEF) showed a dose-dependent reduction following histamine provocation, but there were no statistical differences in the measurements at baseline and post S6 provocation. The value of dC3/DV at the maximal dose was significantly increased over its baseline value (P < 0.05). VDF, VDT and VDW were significantly increased after bronchodilator use (P < 0.05 or <0.01). The changes in capnovolumetry did not correspond with the results of lung function test. The dC3/DV and airway dead spaces of capnovolumetry in healthy adults are significantly increased compared to lung function parameters before or after bronchodilator use, suggesting that capnovolumetry is feasible in diagnostic evaluation of airway reactivity, especially for persons who are unable to undertake lung function test. © 2014 John Wiley & Sons Ltd.

Interdisciplinary model of care (RADICALS) for early detection and management of chronic obstructive pulmonary disease (COPD) in Australian primary care: study protocol for a cluster randomised controlled trial.

PubMed

Liang, Jenifer; Abramson, Michael J; Zwar, Nicholas; Russell, Grant; Holland, Anne E; Bonevski, Billie; Mahal, Ajay; Hecke, Benjamin van; Phillips, Kirsten; Eustace, Paula; Paul, Eldho; Petrie, Kate; Wilson, Sally; George, Johnson

2017-09-18

Up to half of all smokers develop clinically significant chronic obstructive pulmonary disease (COPD). Gaps exist in the implementation and uptake of evidence-based guidelines for managing COPD in primary care. We describe the methodology of a cluster randomised controlled trial (cRCT) evaluating the efficacy and cost-effectiveness of an interdisciplinary model of care aimed at reducing the burden of smoking and COPD in Australian primary care settings. A cRCT is being undertaken to evaluate an interdisciplinary model of care (RADICALS - Review of Airway Dysfunction and Interdisciplinary Community-based care of Adult Long-term Smokers). General practice clinics across Melbourne, Australia, are identified and randomised to the intervention group (RADICALS) or usual care. Patients who are current or ex-smokers, of at least 10 pack years, including those with an existing diagnosis of COPD, are being recruited to identify 280 participants with a spirometry-confirmed diagnosis of COPD. Handheld lung function devices are being used to facilitate case-finding. RADICALS includes individualised smoking cessation support, home-based pulmonary rehabilitation and home medicines review. Patients at control group sites receive usual care and Quitline referral, as appropriate. Follow-ups occur at 6 and 12 months from baseline to assess changes in quality of life, abstinence rates, health resource utilisation, symptom severity and lung function. The primary outcome is change in St George's Respiratory Questionnaire score of patients with COPD at 6 months from baseline. This project has been approved by the Monash University Human Research Ethics Committee and La Trobe University Human Ethics Committee (CF14/1018 - 2014000433). Results of the study will be disseminated in peer-reviewed journals and research conferences. If the intervention is successful, the RADICALS programme could potentially be integrated into general practices across Australia and sustained over time. ACTRN12614001155684; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Candidate Markers Associated with the Probability of Future Pulmonary Exacerbations in Cystic Fibrosis Patients

PubMed Central

Wojewodka, Gabriella; De Sanctis, Juan B.; Bernier, Joanie; Bérubé, Julie; Ahlgren, Heather G.; Gruber, Jim; Landry, Jennifer; Lands, Larry C.; Nguyen, Dao; Rousseau, Simon; Benedetti, Andrea; Matouk, Elias; Radzioch, Danuta

2014-01-01

Introduction Pulmonary exacerbations (PEs) cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF) lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE. Methods We prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment. Results Out of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation. Conclusion Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation. PMID:24533110

The evidence of benefits of exercise training in interstitial lung disease: a randomised controlled trial.

PubMed

Dowman, Leona M; McDonald, Christine F; Hill, Catherine J; Lee, Annemarie L; Barker, Kathryn; Boote, Claire; Glaspole, Ian; Goh, Nicole S L; Southcott, Anne M; Burge, Angela T; Gillies, Rebecca; Martin, Alicia; Holland, Anne E

2017-07-01

Uncertainty exists regarding the clinical relevance of exercise training across the range of interstitial lung diseases (ILDs). To establish the impact of exercise training in patients with ILDs of differing aetiology and severity. 142 participants with ILD (61 idiopathic pulmonary fibrosis (IPF), 22 asbestosis, 23 connective tissue disease-related ILD (CTD-ILD) and 36 with other aetiologies) were randomised to either 8 weeks of supervised exercise training or usual care. Six-minute walk distance (6MWD), Chronic Respiratory Disease Questionnaire (CRDQ), St George Respiratory Questionnaire IPF-specific version (SGRQ-I) and modified Medical Research Council dyspnoea score were measured at baseline, 9 weeks and 6 months. Exercise training significantly increased 6MWD (25 m, 95% CI 2 to 47 m) and health-related quality of life (CRDQ and SGRQ-I) in people with ILD. Larger improvements in 6MWD, CRDQ, SGRQ-I and dyspnoea occurred in asbestosis and IPF compared with CTD-ILD, but with few significant differences between subgroups. Benefits declined at 6 months except in CTD-ILD. Lower baseline 6MWD and worse baseline symptoms were associated with greater benefit in 6MWD and symptoms following training. Greater gains were seen in those whose exercise prescription was successfully progressed according to the protocol. At 6 months, sustained improvements in 6MWD and symptoms were associated with better baseline lung function and less pulmonary hypertension. Exercise training is effective in patients across the range of ILDs, with clinically meaningful benefits in asbestosis and IPF. Successful exercise progression maximises improvements and sustained treatment effects favour those with milder disease. Results, ACTRN12611000416998. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Intravenous fosfomycin for pulmonary exacerbation of cystic fibrosis: Real life experience of a large adult CF centre.

PubMed

Spoletini, G; Kennedy, M; Flint, L; Graham, T; Etherington, C; Shaw, N; Whitaker, P; Denton, M; Clifton, I; Peckham, D

2018-04-13

The increased prevalence of multi-drug resistant strains of P.aeruginosa and allergic reactions among adult patients with cystic fibrosis (CF) limits the number of antibiotics available to treat pulmonary exacerbations. Fosfomycin, a unique broad spectrum bactericidal antibiotic, might offer an alternative therapeutic option in such cases. To describe the clinical efficacy, safety and tolerability of intravenous fosfomycin in combination with a second anti-pseudomonal antibiotic to treat pulmonary exacerbations in adult patients with CF. A retrospective analysis of data captured prospectively, over a 2-years period, on the Unit electronic medical records for patients who received IV fosfomycin was performed. Baseline characteristics in the 12 months prior treatment, lung function, CRP, renal and liver function and electrolytes at start and end of treatment were retrieved. 54 patients received 128 courses of iv fosfomycin in combination with a second antibiotic, resulting in improved FEV1 (0.94 L vs 1.24 L, p < 0.01) and reduced CRP (65 mg/L vs 19.3 mg/L, p < 0.01). Renal function pre- and post-treatment remained stable. 4% (n = 5) of courses were complicated with AKI at mid treatment, which resolved at the end of the course. Electrolyte supplementation was required in 18% of cases for potassium and magnesium and 7% for phosphate. Nausea was the most common side effects (48%), but was well controlled with anti-emetics. Antibiotic regimens including fosfomycin appear to be clinically effective and safe. Fosfomycin should, therefore, be considered as an add-on therapy in patients who failed to respond to initial treatment and with multiple drug allergies. Copyright © 2018. Published by Elsevier Ltd.

Pulmonary functions in tannery workers--a cross sectional study.

PubMed

Chandrasekaran, Vasanthi; Dilara, K; Padmavathi, R

2014-01-01

Tannery workers are at potential exposure to detrimental agents rendering them vulnerable to respiratory and dermal problems. Thus by performing pulmonary functions among leather tannery workers, we can decipher the effect of chromium and leather dust on lung functions and also the decline of respiratory functions with increasing years of exposure to leather dust. Pulmonary functions were assessed for 130 tannery workers and compared with the 130 unexposed office workers. Pulmonary function measurements namely FVC, FEV1, FEF25-75% and PEFR were measured using portable data logging Spirometer (KOKO Spirometer). The observed pulmonary functions of Tannery-workers in this study showed a reduction in FEV1, FVC, FEV1/FVC ratio, FEF25-75 and PEFR in relation to their predicted values and also compared to the unexposed. Smokers showed a decline in pulmonary functions compared to the non smokers because smoking acts as an additional risk factor in the development of respiratory illnesses. It is worthy to mention that the pulmonary function values correlate negatively with the duration of exposure to leather dust. So this study could provide base line information based upon which legal implementation of preventive measures could be undertaken.

Novel approach to classifying patients with pulmonary arterial hypertension using cluster analysis.

PubMed

Parikh, Kishan S; Rao, Youlan; Ahmad, Tariq; Shen, Kai; Felker, G Michael; Rajagopal, Sudarshan

2017-01-01

Pulmonary arterial hypertension (PAH) patients have distinct disease courses and responses to treatment, but current diagnostic and treatment schemes provide limited insight. We aimed to see if cluster analysis could distinguish clinical phenotypes in PAH. An unbiased cluster analysis was performed on 17 baseline clinical variables of PAH patients from the FREEDOM-M, FREEDOM-C, and FREEDOM-C2 randomized trials of oral treprostinil versus placebo. Participants were either treatment-naïve (FREEDOM-M) or on background therapy (FREEDOM-C, FREEDOM-C2). We tested for association of clusters with outcomes and interaction with respect to treatment. Primary outcome was 6-minute walking distance (6MWD) change. We included 966 participants with 12-week (FREEDOM-M) or 16-week (FREEDOM-C and FREEDOM-C2) follow-up. Four patient clusters were identified. Compared with Clusters 1 (n = 131) and 2 (n = 496), Clusters 3 (n = 246) and 4 (n = 93) patients were older, heavier, had worse baseline functional class, 6MWD, Borg Dyspnea Index, and fewer years since PAH diagnosis. Clusters also differed by PAH etiology and background therapies, but not gender or race. Mean treatment effect of oral treprostinil differed across Clusters 1-4 increased in a monotonic fashion (Cluster 1: 10.9 m; Cluster 2: 13.0 m; Cluster 3: 25.0 m; Cluster 4: 50.9 m; interaction P value = 0.048). We identified four distinct clusters of PAH patients based on common patient characteristics. Patients who were older, diagnosed with PAH for a shorter period, and had worse baseline symptoms and exercise capacity had the greatest response to oral treprostinil treatment.

Pulmonary function tests correlated with thoracic volumes in adolescent idiopathic scoliosis.

PubMed

Ledonio, Charles Gerald T; Rosenstein, Benjamin E; Johnston, Charles E; Regelmann, Warren E; Nuckley, David J; Polly, David W

2017-01-01

Scoliosis deformity has been linked with deleterious changes in the thoracic cavity that affect pulmonary function. The causal relationship between spinal deformity and pulmonary function has yet to be fully defined. It has been hypothesized that deformity correction improves pulmonary function by restoring both respiratory muscle efficiency and increasing the space available to the lungs. This research aims to correlate pulmonary function and thoracic volume before and after scoliosis correction. Retrospective correlational analysis between thoracic volume modeling from plain x-rays and pulmonary function tests was conducted. Adolescent idiopathic scoliosis patients enrolled in a multicenter database were sorted by pre-operative Total Lung Capacities (TLC) % predicted values from their Pulmonary Function Tests (PFT). Ten patients with the best and ten patients with the worst TLC values were included. Modeled thoracic volume and TLC values were compared before and 2 years after surgery. Scoliosis correction resulted in an increase in the thoracic volume for patients with the worst initial TLCs (11.7%) and those with the best initial TLCs (12.5%). The adolescents with the most severe pulmonary restriction prior to surgery strongly correlated with post-operative change in total lung capacity and thoracic volume (r 2  = 0.839; p < 0.001). The mean increase in thoracic volume in this group was 373.1 cm 3 (11.7%) which correlated with a 21.2% improvement in TLC. Scoliosis correction in adolescents was found to increase thoracic volume and is strongly correlated with improved TLC in cases with severe restrictive pulmonary function, but no correlation was found in cases with normal pulmonary function. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:175-182, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Levels of uric acid may predict the future development of pulmonary hypertension in systemic lupus erythematosus: a seven-year follow-up study.

PubMed

Castillo-Martínez, D; Marroquín-Fabián, E; Lozada-Navarro, A C; Mora-Ramírez, M; Juárez, M; Sánchez-Muñoz, F; Vargas-Barrón, J; Sandoval, J; Amezcua-Guerra, L M

2016-01-01

The objective of this paper is to assess whether pulmonary hypertension (PH) may be detected at one point in time or longitudinally predicted by serum uric acid (sUA) levels in systemic lupus erythematosus (SLE). We conducted a post-hoc analysis of a long-term followed cohort of Mexican SLE patients. Echocardiography-based definitions of PH by the ESC/ERS/ISHLT and its associations with clinical and laboratory data on enrollment were studied. Especially, the impact that sUA levels at baseline may have on the future development of PH in patients with normal pulmonary artery systolic pressure (PASP) was explored. Out of the 156 SLE patients originally enrolled in the cohort, 44 met the inclusion criteria for the present study and were grouped as having (n =10) or not having (n = 34) PH. At baseline, sUA levels of 5.83 ± 1.79 and 5.82 ± 1.97 mg/dl (p = ns) were found in patients with and without PH, respectively. No association between PASP and other markers was found. In patients with normal PASP, the presence of sUA ≥ 7 mg/dl at baseline predicted future development of PH (relative risk 8.5, 1.0009 to 72; p = 0.04). In SLE, sUA levels at one point in time are useless to detect PH. However, steady hyperuricemia may predict the future development of PH in patients with normal PASP at baseline. © The Author(s) 2015.

Structural basis for pulmonary functional imaging.

PubMed

Itoh, H; Nakatsu, M; Yoxtheimer, L M; Uematsu, H; Ohno, Y; Hatabu, H

2001-03-01

An understanding of fine normal lung morphology is important for effective pulmonary functional imaging. The lung specimens must be inflated. These include (a) unfixed, inflated lung specimen, (b) formaldehyde fixed lung specimen, (c) fixed, inflated dry lung specimen, and (d) histology specimen. Photography, magnified view, radiograph, computed tomography, and histology of these specimens are demonstrated. From a standpoint of diagnostic imaging, the main normal lung structures consist of airways (bronchi and bronchioles), alveoli, pulmonary vessels, secondary pulmonary lobules, and subpleural pulmonary lymphatic channels. This review summarizes fine radiologic normal lung morphology as an aid to effective pulmonary functional imaging.

Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial.

PubMed

Mehta, Sanjay; Sastry, Bhagavatula Kutumba Srinivasa; Souza, Rogério; Torbicki, Adam; Ghofrani, Hossein-Ardeschir; Channick, Richard N; Delcroix, Marion; Pulido, Tomás; Simonneau, Gérald; Wlodarczyk, John; Rubin, Lewis J; Jansa, Pavel; Hunsche, Elke; Galiè, Nazzareno; Perchenet, Loïc; Sitbon, Olivier

2017-01-01

Pulmonary arterial hypertension (PAH) leads to reduced health-related quality of life (HRQoL). The objectives of this analysis were to evaluate the effect of macitentan on HRQoL in patients with PAH in the Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN) study. The association between baseline HRQoL and long-term outcomes was also investigated. Patients were randomized to placebo, macitentan 3 mg, or macitentan 10 mg once daily. Patients aged 14 years or older completed the 36-Item Short Form Survey (SF-36) at baseline, at month 6 and month 12, and at the end of treatment (EOT). The absolute change from baseline to month 6 in SF-36 scores was calculated. The time to a clinically meaningful deterioration in the SF-36 physical component summary and mental component summary (PCS and MCS) scores and associations between baseline PCS/MCS scores and time to morbidity/mortality events were also assessed. At month 6, macitentan 10 mg significantly improved seven of eight SF-36 domains and the PCS and MCS scores vs placebo. Macitentan 10 mg significantly reduced the risk of a three-point or greater deterioration in PCS (hazard ratio [HR], 0.60; 95% CI, 0.47-0.76; P < .0001) and MCS scores (HR, 0.76; 95% CI, 0.61-0.95; P = .0173) until EOT vs placebo. Patients with a baseline PCS score greater than the median baseline value had a significantly reduced risk of morbidity/mortality compared with patients with a PCS score less than the median; a similar result was observed for the MCS score. Macitentan significantly improved HRQoL in patients with PAH compared with placebo and significantly reduced the risk of a clinically meaningful HRQoL deterioration. An association between better baseline HRQoL and improved long-term outcomes was shown. ClinicalTrials.gov; No.: NCT00660179; URL: clinicaltrials.gov. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Alveolar recruitment manoeuvre is safe in children prone to pulmonary hypertensive crises following open heart surgery: a pilot study.

PubMed

Amorim, Erica de Freitas; Guimaraes, Viviane Assuncao; Carmona, Fabio; Carlotti, Ana Paula de Carvalho Panzeri; Manso, Paulo Henrique; Ferreira, Cesar Augusto; Klamt, Jyrson Guilherme; Vicente, Walter Villela de Andrade

2014-05-01

To test the tolerance and safety of an alveolar recruitment manoeuvre performed in the immediate postoperative period of corrective open heart surgery in children with congenital heart disease associated with excessive pulmonary blood flow and pulmonary arterial hypertension due to left-to-right shunt. Ten infants aged 1-24 months with congenital heart disease associated with excessive pulmonary blood flow and pulmonary artery hypertension (mean pulmonary artery pressure ≥ 25 mmHg) were evaluated. The alveolar recruitment manoeuvre was performed in the operating theatre right after skin closure, and consisted of three successive stages of 30 s each, intercalated by a 1-min interval of baseline ventilation. Positive end-expiratory pressure was set to 10 cmH2O in the first stage and to 15 cmH2O in the two last ones, while the peak inspiratory pressure was kept at to 30 cmH2O in the first stage and at 35 cmH2O in the latter ones. Haemodynamic and respiratory variables were recorded. There was a slight but significant increase in mean pulmonary artery pressure from baseline to Stage 3 (P = 0.0009), as well as between Stages 1 and 2 (P = 0.0001), and 1 and 3 (P = 0.001), with no significant difference between Stages 2 and 3 (P = 0.06). Upon completion of the third stage, there were significant increases in arterial haemoglobin saturation as measured by pulse oximetry (P = 0.0009), arterial blood partial pressure of oxygen (P = 0.04), venous blood oxygen saturation of haemoglobin (P = 0.03) and arterial oxygen partial pressure over inspired oxygen fraction ratio (P = 0.04). A significant reduction in arterial blood partial pressure of carbon dioxide (P = 0.01) and in end tidal carbon dioxide also occurred (P = 0.009). The manoeuvre was well tolerated and besides a slight and transitory elevation in mean pulmonary artery, no other adverse haemodynamic or ventilatory effect was elicited. The alveolar recruitment manoeuvre seemed to be safe and well tolerated immediately after open heart surgery in infants liable to pulmonary hypertensive crises.

21 CFR 868.1880 - Pulmonary-function data calculator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pulmonary-function data calculator. 868.1880 Section 868.1880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-function values based on actual physical data obtained during pulmonary-function testing. (b...

21 CFR 868.1880 - Pulmonary-function data calculator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pulmonary-function data calculator. 868.1880 Section 868.1880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-function values based on actual physical data obtained during pulmonary-function testing. (b...

Cohort Profile: The JS High School study (JSHS): a cohort study of Korean adolescents.

PubMed

Choi, Dong Phil; Lee, Joo Young; Kim, Hyeon Chang

2017-04-01

Major aetiologies of atherosclerotic cardiovascular diseases begin in childhood and atherosclerotic vascular abnormalities can be observed among children and adolescents. Adolescent cohort studies have important advantages because they can observe earlier changes in vascular structure and function. The purpose of the JS High School study (JSHS) is to identify biomarkers predicting or indicating early structural and functional vascular change in adolescents. The JSHS is a prospective cohort study of a Korean adolescent population. The target population of the JSHS was first-graders (aged 14 to17 years) at a high school of South Korea. Enrolment and baseline examinations were conducted in years 2007, 2010, 2011 and 2012. Among the total eligible population of 1115 students, 1071 (96.1%) participated in the study and completed all baseline examinations. Informed consent forms were obtained from each participant and his/her parent or guardian. Baseline examinations include: questionnaires on demographics, health behaviours, medical history, and depression symptoms; fasting blood analysis; anthropometric measurement; body impedance analysis; blood pressure measurement; radial artery tonometry; bone densitometry; pulmonary function tests; and carotid ultrasonography. Participants enrolled from 2007 through 2012 were re-examined after 30 months of follow-up, and those who enrolled in 2012 were re-examined after 24 months of follow-up. The corresponding author may be contacted for potential collaboration and data access. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Massive plasmablast response elicited in the acute phase of hantavirus pulmonary syndrome.

PubMed

García, Marina; Iglesias, Ayelén; Landoni, Verónica I; Bellomo, Carla; Bruno, Agostina; Córdoba, María Teresa; Balboa, Luciana; Fernández, Gabriela C; Sasiain, María Del Carmen; Martínez, Valeria P; Schierloh, Pablo

2017-05-01

Beside its key diagnostic value, the humoral immune response is thought to play a protective role in hantavirus pulmonary syndrome. However, little is known about the cell source of these antibodies during ongoing human infection. Herein we characterized B-cell subsets circulating in Andes-virus-infected patients. A notable potent plasmablast (PB) response that increased 100-fold over the baseline levels was observed around 1 week after the onset of symptoms. These PB present a CD3 neg CD19 low CD20 neg CD38 hi CD27 hi CD138 +/- IgA +/- surface phenotype together with the presence of cytoplasmic functional immunoglobulins. They are large lymphocytes (lymphoblasts) morphologically coincident with the 'immunoblast-like' cells that have been previously described during blood cytology examinations of hantavirus-infected patients. Immunoreactivity analysis of white blood cell lysates suggests that some circulating PB are virus-specific but we also observed a significant increase of reactivity against virus-unrelated antigens, which suggests a possible bystander effect by polyclonal B-cell activation. The presence of this large and transient PB response raises the question as to whether these cells might have a protective or pathological role during the ongoing hantavirus pulmonary syndrome and suggest their practical application as a diagnostic/prognostic biomarker. © 2017 John Wiley & Sons Ltd.

Three-dimensional computed tomographic volumetry precisely predicts the postoperative pulmonary function.

PubMed

Kobayashi, Keisuke; Saeki, Yusuke; Kitazawa, Shinsuke; Kobayashi, Naohiro; Kikuchi, Shinji; Goto, Yukinobu; Sakai, Mitsuaki; Sato, Yukio

2017-11-01

It is important to accurately predict the patient's postoperative pulmonary function. The aim of this study was to compare the accuracy of predictions of the postoperative residual pulmonary function obtained with three-dimensional computed tomographic (3D-CT) volumetry with that of predictions obtained with the conventional segment-counting method. Fifty-three patients scheduled to undergo lung cancer resection, pulmonary function tests, and computed tomography were enrolled in this study. The postoperative residual pulmonary function was predicted based on the segment-counting and 3D-CT volumetry methods. The predicted postoperative values were compared with the results of postoperative pulmonary function tests. Regarding the linear correlation coefficients between the predicted postoperative values and the measured values, those obtained using the 3D-CT volumetry method tended to be higher than those acquired using the segment-counting method. In addition, the variations between the predicted and measured values were smaller with the 3D-CT volumetry method than with the segment-counting method. These results were more obvious in COPD patients than in non-COPD patients. Our findings suggested that the 3D-CT volumetry was able to predict the residual pulmonary function more accurately than the segment-counting method, especially in patients with COPD. This method might lead to the selection of appropriate candidates for surgery among patients with a marginal pulmonary function.

Gut Hormones, Appetite Suppression and Cachexia in Patients with Pulmonary TB

PubMed Central

Chang, Suzanne W.; Pan, William S.; Lozano Beltran, Daniel; Oleyda Baldelomar, Lizet; Solano, Marco Antonio; Tuero, Iskra; Friedland, Jon S.; Torrico, Faustino; Gilman, Robert H.

2013-01-01

Background Cachexia is a hallmark of pulmonary tuberculosis and is associated with poor prognosis. A better understanding of the mechanisms behind such weight loss could reveal targets for therapeutic intervention. The role of appetite-regulatory hormones in tuberculosis is unknown. Methods and Findings 41 subjects with newly-diagnosed pulmonary TB (cases) were compared to 82 healthy controls. We measured appetite, body mass index (BMI), % body fat (BF), plasma peptide YY (PYY), leptin, ghrelin, and resistin for all subjects. Measurements were taken at baseline for controls and at treatment days 0, 30, and 60 for cases. Baseline appetite, BMI, and BF were lower in cases than in controls and improved during treatment. PYY, ghrelin, and resistin were significantly elevated in cases and fell during treatment. Leptin was lower in cases and rose with treatment. Appetite was inversely related to PYY in cases. High pre-treatment PYY predicted reduced gains in appetite and BF. PYY was the strongest independent predictor of appetite in cases across all time points. Conclusions Appetite-regulatory hormones are altered in TB patients. As hormones normalize during treatment, appetite is restored and nutritional status improves. High baseline PYY is an indicator of poor prognosis for improvement in appetite and nutrition during treatment. Wasting in TB patients may partly be mediated by upregulation of PYY with resulting appetite suppression. PMID:23358528

Six-minute-walk distance and accelerometry predict outcomes in chronic obstructive pulmonary disease independent of Global Initiative for Chronic Obstructive Lung Disease 2011 Group.

PubMed

Durheim, Michael T; Smith, Patrick J; Babyak, Michael A; Mabe, Stephanie K; Martinu, Tereza; Welty-Wolf, Karen E; Emery, Charles F; Palmer, Scott M; Blumenthal, James A

2015-03-01

The 2011 combined Global Initiative for Chronic Obstructive Lung Disease (GOLD) assessment incorporates symptoms, exacerbation history, and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and accelerometry also have been used to assess disease severity in COPD. The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown. To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD-related hospitalization or all-cause mortality, independent of GOLD 2011 group. Physical function and medical outcomes were prospectively assessed in 326 patients with moderate to severe COPD in INSPIRE-II, a randomized controlled trial of a coping skills training intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or accelerometry steps were associated with risk of COPD-related hospitalization or all-cause mortality. Physical function declined over time in GOLD group D but remained stable in groups A, B, and C. GOLD classification was associated with time to death or first COPD-related hospitalization. Baseline 6MWD was more strongly associated with time to death or first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval, 0.34, 0.73] per 150 m, P=0.0003) than GOLD 2011 classification. A similar relationship was observed for accelerometry steps (hazard ratio, 0.80 [95% confidence interval, 0.70, 0.92] per 1,000 steps, P=0.002). Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD, independent of GOLD 2011 classification. Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinically meaningful outcomes in COPD.

Quantitative computed tomography for the prediction of pulmonary function after lung cancer surgery: a simple method using simulation software.

PubMed

Ueda, Kazuhiro; Tanaka, Toshiki; Li, Tao-Sheng; Tanaka, Nobuyuki; Hamano, Kimikazu

2009-03-01

The prediction of pulmonary functional reserve is mandatory in therapeutic decision-making for patients with resectable lung cancer, especially those with underlying lung disease. Volumetric analysis in combination with densitometric analysis of the affected lung lobe or segment with quantitative computed tomography (CT) helps to identify residual pulmonary function, although the utility of this modality needs investigation. The subjects of this prospective study were 30 patients with resectable lung cancer. A three-dimensional CT lung model was created with voxels representing normal lung attenuation (-600 to -910 Hounsfield units). Residual pulmonary function was predicted by drawing a boundary line between the lung to be preserved and that to be resected, directly on the lung model. The predicted values were correlated with the postoperative measured values. The predicted and measured values corresponded well (r=0.89, p<0.001). Although the predicted values corresponded with values predicted by simple calculation using a segment-counting method (r=0.98), there were two outliers whose pulmonary functional reserves were predicted more accurately by CT than by segment counting. The measured pulmonary functional reserves were significantly higher than the predicted values in patients with extensive emphysematous areas (<-910 Hounsfield units), but not in patients with chronic obstructive pulmonary disease. Quantitative CT yielded accurate prediction of functional reserve after lung cancer surgery and helped to identify patients whose functional reserves are likely to be underestimated. Hence, this modality should be utilized for patients with marginal pulmonary function.

Iloprost improves ventricular function in the hypertrophic and functionally impaired right heart by direct stimulation.

PubMed

Holmboe, Sarah; Andersen, Asger; Vildbrad, Mads D; Nielsen, Jan M; Ringgaard, Steffen; Nielsen-Kudsk, Jens E

2013-12-01

Right heart function is an important predictor of morbidity and mortality in patients suffering from pulmonary arterial hypertension and congenital heart diseases. We investigated whether the prostacyclin analog iloprost has a direct inotropic effect in the pressure-overloaded hypertrophic and dysfunctional right ventricle (RV). Rats were randomized to monocrotaline injection (60 mg/kg; [Formula: see text]), pulmonary trunk banding (PTB; [Formula: see text]), or a sham operation ([Formula: see text]). RV function was evaluated with magnetic resonance imaging, echocardiography, and invasive pressure measurements at baseline, after intravenous administration of placebo, iloprost 10 ng/kg/min, or iloprost 100 ng/kg/min (Ilo100). Infusion of Ilo100 induced a [Formula: see text] ([Formula: see text]) increase in stroke volume in the sham group and a [Formula: see text] ([Formula: see text]) increase in the PTB group. RV [Formula: see text] was elevated by [Formula: see text] ([Formula: see text]) in the sham group and by [Formula: see text] ([Formula: see text]) in the PTB group. An elevation in cardiac output of [Formula: see text] ([Formula: see text]) and an [Formula: see text] ([Formula: see text]) increase in RV systolic pressure were found in the PTB group. Iloprost caused a decrease in mean arterial blood pressure (MAP) in all groups of animals. An equal reduction in MAP induced by the arterial vasodilator nitroprusside did not improve any of the measured parameters of RV function. We conclude that iloprost has inotropic properties directly improving ventricular function in the hypertrophic and dysfunctional right heart of the rat.

Effects of whole body vibration on pulmonary function, functional exercise capacity and quality of life in people with chronic obstructive pulmonary disease: a systematic review.

PubMed

Yang, Xiaotian; Zhou, Yujing; Wang, Pu; He, Chengqi; He, Hongchen

2016-05-01

To examine the effect of whole-body vibration in enhancing pulmonary function, functional exercise capacity and quality of life in people with chronic obstructive pulmonary disease and examine its safety. Randomized controlled trials examining the effects of whole body vibration among people with chronic obstructive pulmonary disease were identified by two independent researchers. Articles were excluded if they were studies on people with other primary diagnosis, abstracts published in the conferences or books. PEDro scale was used to assess the methodological quality of the selected studies. We evaluated the level of evidence by using the GRADE approach. The results were extracted by two researchers and confirmed by the third researcher if disagreement existed. Sources included Cochrane Central Register of Controlled Trials, PubMed, CINAHL, EMBASE, PEDro, AMED, PsycINFO, ClinicalTrials.gov, Current Controlled Trials and reference lists of all relevant articles. Four studies involving 206 participants were included in this systematic review. Methodological quality was rated as good for two studies. No great benefits on pulmonary function were found in whole body vibration treatment group. Two studies showed that quality of life was improved in people with chronic obstructive pulmonary disease. Whole body vibration led to significant improvements in functional exercise capacity measured with six minutes walking test. Nearly no adverse events were observed. Whole body vibration may improve functional exercise capacity and quality of life in people with chronic obstructive pulmonary disease. There was insufficient evidence to prove the effects of whole body vibration on pulmonary function. © The Author(s) 2015.

21 CFR 868.1900 - Diagnostic pulmonary-function interpretation calculator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Diagnostic pulmonary-function interpretation calculator. 868.1900 Section 868.1900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... pulmonary-function values. (b) Classification. Class II (performance standards). ...

21 CFR 868.1900 - Diagnostic pulmonary-function interpretation calculator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Diagnostic pulmonary-function interpretation calculator. 868.1900 Section 868.1900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... pulmonary-function values. (b) Classification. Class II (performance standards). ...

Pulmonary functions in patients with subclinical hypothyroidism.

PubMed

Cakmak, Gulfidan; Saler, Tayyibe; Saglam, Zuhal Aydan; Yenigun, Mustafa; Ataoglu, Esra; Demir, Tuncalp; Temiz, Levent Umit

2011-10-01

To determine whether alterations in pulmonary function takes place in subclinical hypothyroidism by examining the diffusion lung capacity and muscle strength of such patients. This is a descriptive study conducted in 2009 at Haseki Training and Research Hospital, Istanbul, Turkey. Hundred and twenty-six patients with subclinical hypothyroidism and 58 age and sex matched individuals were recruited. Simple spirometry tests were performed, and pulmonary diffusion capacity (DLco) and muscle strength were measured. ScH patients showed a significant reduciton of the following pulmonary function tests (% predicted value) as compared with control subjects: FVC, FEV1, FEV1%, FEF25-75, FEF25-75%, DLco, DLco/VA, Pimax, Pimax% and Pemax%. These data indicate that pulmonary functions are effected in subclinical hypothyrodism. Therefore patients with or who are at high risk of having subclinical hypothyroidism, should be subjected to evaluation of pulmonary functions with simple spirometry.

The effects of balneotherapy on disease activity, functional status, pulmonary function and quality of life in patients with ankylosing spondylitis.

PubMed

Aydemir, Koray; Tok, Fatih; Peker, Fatma; Safaz, Ismail; Taskaynatan, Mehmet Ali; Ozgul, Ahmet

2010-01-01

This study aimed to determine the effects of balneotherapy on disease activity, functional status, metrology index, pulmonary function and quality of life in patients with ankylosing spondylitis (AS). The study included 28 patients (27 male and 1 female) diagnosed with AS according to modified New York criteria. The patients were treated with balneotherapy for 3 weeks (30 min/day, 5 days/week). The patients were evaluated using the global index, Bath ankylosing spondylitis disease activity index (BASDAI), disease functional index (BASFI), metrology index (BASMI), chest expansion measures, pulmonary function testing, and the medical outcomes study-short form-36 Health Survey (SF-36) (measure of quality of life) before balneotherapy and 1 month after treatment. Post balneotherapy BASDAI and global index decreased, BASMI parameters improved, chest expansion increased, and some SF-36 parameters improved; however, none of these changes were statistically significant (P > 0.05), except for the decrease in BASMI total score (P < 0.05). Before balneotherapy 6 patients had restrictive pulmonary disorder, according to pulmonary function test results. Pulmonary function test results in 3 (50%) patients were normalized following balneotherapy; however, as for the other index, balneotherapy did not significantly affect pulmonary function test results. The AS patients' symptoms, clinical findings, pulmonary function test results, and quality of life showed a trend to improve following balneotherapy, although without reaching significant differences. Comprehensive randomized controlled spa intervention studies with longer follow-up periods may be helpful in further delineating the therapeutic efficacy of balneotherapy in AS patients.

Effects of periodontal treatment on lung function and exacerbation frequency in patients with chronic obstructive pulmonary disease and chronic periodontitis: a 2-year pilot randomized controlled trial.

PubMed

Zhou, Xuan; Han, Jing; Liu, Zhiqiang; Song, Yiqing; Wang, Zuomin; Sun, Zheng

2014-06-01

To evaluate the direct effects of periodontal therapy in Chronic Obstructive Pulmonary Disease (COPD) patients with chronic periodontitis (CP). In a pilot randomized controlled trial, 60 COPD patients with CP were randomly assigned to receive scaling and root planing (SRP) treatment, supragingival scaling treatment, or oral hygiene instructions only with no periodontal treatment. We evaluated their periodontal indexes, respiratory function, and COPD exacerbations at baseline, 6 months, 1, and 2 years. Compared with the control group, measurements of periodontal indexes were significantly improved in patients in two treatment groups at 6-month, 1-year, and 2-year follow-up (all p < 0.05). Overall, the means of forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) and FEV1 were significantly higher in the two therapy groups compared with the control group during the follow-up (p < 0.05). In addition, the frequencies of COPD exacerbation were significantly lower in the two therapy groups than in the control group at 2-year follow-up (p < 0.05). Our preliminary results from this pilot trial suggest that periodontal therapy in COPD patients with CP may improve lung function and decrease the frequency of COPD exacerbation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS cohorts

PubMed Central

2014-01-01

Background Several lung diseases are increasingly recognized as comorbidities with HIV; however, few data exist related to the spectrum of respiratory symptoms, diagnostic testing, and diagnoses in the current HIV era. The objective of the study is to determine the impact of HIV on prevalence and incidence of respiratory disease in the current era of effective antiretroviral treatment. Methods A pulmonary-specific questionnaire was administered yearly for three years to participants in the Multicenter AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS). Adjusted prevalence ratios for respiratory symptoms, testing, or diagnoses and adjusted incidence rate ratios for diagnoses in HIV-infected compared to HIV-uninfected participants were determined. Risk factors for outcomes in HIV-infected individuals were modeled. Results Baseline pulmonary questionnaires were completed by 907 HIV-infected and 989 HIV-uninfected participants in the MACS cohort and by 1405 HIV-infected and 571 HIV-uninfected participants in the WIHS cohort. In MACS, dyspnea, cough, wheezing, sleep apnea, and incident chronic obstructive pulmonary disease (COPD) were more common in HIV-infected participants. In WIHS, wheezing and sleep apnea were more common in HIV-infected participants. Smoking (MACS and WIHS) and greater body mass index (WIHS) were associated with more respiratory symptoms and diagnoses. While sputum studies, bronchoscopies, and chest computed tomography scans were more likely to be performed in HIV-infected participants, pulmonary function tests were no more common in HIV-infected individuals. Respiratory symptoms in HIV-infected individuals were associated with history of pneumonia, cardiovascular disease, or use of HAART. A diagnosis of asthma or COPD was associated with previous pneumonia. Conclusions In these two cohorts, HIV is an independent risk factor for several respiratory symptoms and pulmonary diseases including COPD and sleep apnea. Despite a higher prevalence of chronic respiratory symptoms, testing for non-infectious respiratory diseases may be underutilized in the HIV-infected population. PMID:24884738

Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS cohorts.

PubMed

Gingo, Matthew R; Balasubramani, Goundappa K; Rice, Thomas B; Kingsley, Lawrence; Kleerup, Eric C; Detels, Roger; Seaberg, Eric C; Greenblatt, Ruth M; Holman, Susan; Huang, Laurence; Sutton, Sarah H; Bertolet, Marnie; Morris, Alison

2014-04-30

Several lung diseases are increasingly recognized as comorbidities with HIV; however, few data exist related to the spectrum of respiratory symptoms, diagnostic testing, and diagnoses in the current HIV era. The objective of the study is to determine the impact of HIV on prevalence and incidence of respiratory disease in the current era of effective antiretroviral treatment. A pulmonary-specific questionnaire was administered yearly for three years to participants in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). Adjusted prevalence ratios for respiratory symptoms, testing, or diagnoses and adjusted incidence rate ratios for diagnoses in HIV-infected compared to HIV-uninfected participants were determined. Risk factors for outcomes in HIV-infected individuals were modeled. Baseline pulmonary questionnaires were completed by 907 HIV-infected and 989 HIV-uninfected participants in the MACS cohort and by 1405 HIV-infected and 571 HIV-uninfected participants in the WIHS cohort. In MACS, dyspnea, cough, wheezing, sleep apnea, and incident chronic obstructive pulmonary disease (COPD) were more common in HIV-infected participants. In WIHS, wheezing and sleep apnea were more common in HIV-infected participants. Smoking (MACS and WIHS) and greater body mass index (WIHS) were associated with more respiratory symptoms and diagnoses. While sputum studies, bronchoscopies, and chest computed tomography scans were more likely to be performed in HIV-infected participants, pulmonary function tests were no more common in HIV-infected individuals. Respiratory symptoms in HIV-infected individuals were associated with history of pneumonia, cardiovascular disease, or use of HAART. A diagnosis of asthma or COPD was associated with previous pneumonia. In these two cohorts, HIV is an independent risk factor for several respiratory symptoms and pulmonary diseases including COPD and sleep apnea. Despite a higher prevalence of chronic respiratory symptoms, testing for non-infectious respiratory diseases may be underutilized in the HIV-infected population.

Treatment adherence and health outcomes in patients with bronchiectasis

PubMed Central

2014-01-01

Background We aimed to determine adherence to inhaled antibiotics, other respiratory medicines and airway clearance and to determine the association between adherence to these treatments and health outcomes (pulmonary exacerbations, lung function and Quality of Life Questionnaire-Bronchiectasis [QOL-B]) in bronchiectasis after 12 months. Methods Patients with bronchiectasis prescribed inhaled antibiotics for Pseudomonas aeruginosa infection were recruited into a one-year study. Participants were categorised as “adherent” to medication (medication possession ratio ≥80% using prescription data) or airway clearance (score ≥80% in the Modified Self-Reported Medication-Taking Scale). Pulmonary exacerbations were defined as treatment with a new course of oral or intravenous antibiotics over the one-year study. Spirometry and QOL-B were completed at baseline and 12 months. Associations between adherence to treatment and pulmonary exacerbations, lung function and QOL-B were determined by regression analyses. Results Seventy-five participants were recruited. Thirty-five (53%), 39 (53%) and 31 (41%) participants were adherent to inhaled antibiotics, other respiratory medicines, and airway clearance, respectively. Twelve (16%) participants were adherent to all treatments. Participants who were adherent to inhaled antibiotics had significantly fewer exacerbations compared to non-adherent participants (2.6 vs 4, p = 0.00) and adherence to inhaled antibiotics was independently associated with having fewer pulmonary exacerbations (regression co-efficient = -0.51, 95% CI [-0.81,-0.21], p < 0.001). Adherence to airway clearance was associated with lower QOL-B Treatment Burden (regression co-efficient = -15.46, 95% CI [-26.54, -4.37], p < 0.01) and Respiratory Symptoms domain scores (regression co-efficient = -10.77, 95% CI [-21.45; -0.09], p < 0.05). There were no associations between adherence to other respiratory medicines and any of the outcomes tested. Adherence to treatment was not associated with FEV1 % predicted. Conclusions Treatment adherence is low in bronchiectasis and affects important health outcomes including pulmonary exacerbations. Adherence should be measured as part of bronchiectasis management and future research should evaluate bronchiectasis-specific adherence strategies. PMID:24980161

Effects of exercise training on pulmonary hemodynamics, functional capacity and inflammation in pulmonary hypertension

PubMed Central

Richter, Manuel J.; Grimminger, Jan; Krüger, Britta; Ghofrani, Hossein A.; Mooren, Frank C.; Gall, Henning; Pilat, Christian; Krüger, Karsten

2017-01-01

Pulmonary hypertension (PH) is characterized by severe exercise limitation mainly attributed to the impairment of right ventricular function resulting from a concomitant elevation of pulmonary vascular resistance and pressure. The unquestioned cornerstone in the management of patients with pulmonary arterial hypertension (PAH) is specific vasoactive medical therapy to improve pulmonary hemodynamics and strengthen right ventricular function. Nevertheless, evidence for a beneficial effect of exercise training (ET) on pulmonary hemodynamics and functional capacity in patients with PH has been growing during the past decade. Beneficial effects of ET on regulating factors, inflammation, and metabolism have also been described. Small case-control studies and randomized clinical trials in larger populations of patients with PH demonstrated substantial improvements in functional capacity after ET. These findings were accompanied by several studies that suggested an effect of ET on inflammation, although a direct link between this effect and the therapeutic benefit of ET in PH has not yet been demonstrated. On this background, the aim of the present review is to describe current concepts regarding the effects of exercise on the pulmonary circulation and pathophysiological limitations, as well as the clinical and mechanistic effects of exercise in patients with PH. PMID:28680563

Quality of Life Questionnaire-Bronchiectasis: final psychometric analyses and determination of minimal important difference scores.

PubMed

Quittner, Alexandra L; O'Donnell, Anne E; Salathe, Matthias A; Lewis, Sandra A; Li, Xiaoming; Montgomery, A Bruce; O'Riordan, Thomas G; Barker, Alan F

2015-01-01

The Quality of Life-Bronchiectasis (QOL-B), a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for patients with non-cystic fibrosis (CF) bronchiectasis, contains 37 items on 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden). Psychometric analyses of QOL-B V.3.0 used data from two double-blind, multicentre, randomised, placebo-controlled, phase III trials of aztreonam for inhalation solution (AZLI) in 542 patients with non-CF bronchiectasis and Gram-negative endobronchial infection. Excellent internal consistency (Cronbach's α ≥0.70) and 2-week test-retest reliability (intraclass correlation coefficients ≥0.72) were demonstrated for each scale. Convergent validity with 6 min walk test was observed for Physical and Role Functioning scores. No floor or ceiling effects (baseline scores of 0 or 100) were found for the Respiratory Symptoms scale (primary endpoint of trials). Baseline Respiratory Symptoms scores discriminated between patients based on baseline FEV₁% predicted in only one trial. The minimal important difference score for the Respiratory Symptoms scale was 8.0 points. AZLI did not show efficacy in the two phase III trials. QOL-B responsivity to treatment was assessed by examining changes from baseline QOL-B scores at study visits at which protocol-defined pulmonary exacerbations were reported. Mean Respiratory Symptoms scores decreased 14.0 and 14.2 points from baseline for placebo-treated and AZLI-treated patients with exacerbations, indicating that worsening respiratory symptoms were reflected in clinically meaningful changes in QOL-B scores. Previously established content validity, reliability and responsivity of the QOL-B are confirmed by this final validation study. The QOL-B is available for use in clinical trials and routine clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pulmonary function and fuel use: a population survey.

PubMed

Saha, Asim; Rao, N Mohan; Kulkarni, P K; Majumdar, P K; Saiyed, H N

2005-10-31

In the backdrop of conflicting reports (some studies reported adverse outcomes of biomass fuel use whereas few studies reported absence of any association between adverse health effect and fuel use, may be due to presence of large number of confounding variables) on the respiratory health effects of biomass fuel use, this cross sectional survey was undertaken to understand the role of fuel use on pulmonary function. This study was conducted in a village of western India involving 369 randomly selected adult subjects (165 male and 204 female). All the subjects were interviewed and were subjected to pulmonary function test. Analysis of covariance was performed to compare the levels of different pulmonary function test parameters in relation to different fuel use taking care of the role of possible confounding factors. This study showed that biomass fuel use (especially wood) is an important factor for deterioration of pulmonary function (particularly in female). FEV1 (p < .05), FEV1% (p < .01), PEFR (p < .05) and FEF(25-75) (p < .01) values were significantly lower in biomass fuel using females than nonusers. Comparison of only biomass fuel use vs. only LPG (Liquefied Petroleum Gas) use and only wood vs. only LPG use has showed that LPG is a safer fuel so far as deterioration of pulmonary function is concerned. This study observes some deterioration of pulmonary function in the male subjects also, who came from biomass fuel using families. This study concluded that traditional biomass fuels like wood have adverse effects on pulmonary function.

Methods for measuring right ventricular function and hemodynamic coupling with the pulmonary vasculature.

PubMed

Bellofiore, Alessandro; Chesler, Naomi C

2013-07-01

The right ventricle (RV) is a pulsatile pump, the efficiency of which depends on proper hemodynamic coupling with the compliant pulmonary circulation. The RV and pulmonary circulation exhibit structural and functional differences with the more extensively investigated left ventricle (LV) and systemic circulation. In light of these differences, metrics of LV function and efficiency of coupling to the systemic circulation cannot be used without modification to characterize RV function and efficiency of coupling to the pulmonary circulation. In this article, we review RV physiology and mechanics, established and novel methods for measuring RV function and hemodynamic coupling, and findings from application of these methods to RV function and coupling changes with pulmonary hypertension. We especially focus on non-invasive measurements, as these may represent the future for clinical monitoring of disease progression and the effect of drug therapies.

Toxicodynamics of rigid polystyrene microparticles on pulmonary gas exchange in mice: Implications for microemboli-based drug delivery systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kutscher, H.L.; Gao, D.; Li, S.

The toxicodynamic relationship between the number and size of pulmonary microemboli resulting from uniformly sized, rigid polystyrene microparticles (MPs) administered intravenously and their potential effects on pulmonary gas exchange were investigated. CD-1 male mice (6–8 weeks) were intravenously administered 10, 25 and 45 μm diameter MPs. Oxygen hemoglobin saturation in the blood (SpO{sub 2}) was measured non-invasively using a pulse oximeter while varying inhaled oxygen concentration (F{sub I}O{sub 2}). The resulting data were fit to a physiologically based non-linear mathematical model that estimates 2 parameters: ventilation–perfusion ratio (V{sub A}/Q) and shunt (percentage of deoxygenated blood returning to systemic circulation). Themore » number of MPs administered prior to a statistically significant reduction in normalized V{sub A}/Q was dependent on particle size. MP doses that resulted in a significant reduction in normalized V{sub A}/Q one day post-treatment were 4000, 40,000 and 550,000 MPs/g for 45, 25 and 10 μm MPs, respectively. The model estimated V{sub A}/Q and shunt returned to baseline levels 7 days post-treatment. Measuring SpO{sub 2} alone was not sufficient to observe changes in gas exchange; however, when combined with model-derived V{sub A}/Q and shunt early reversible toxicity from pulmonary microemboli was detected suggesting that the model and physical measurements are both required for assessing toxicity. Moreover, it appears that the MP load required to alter gas exchange in a mouse prior to lethality is significantly higher than the anticipated required MP dose for effective drug delivery. Overall, the current results indicate that the microemboli-based approach for targeted pulmonary drug delivery is potentially safe and should be further explored. -- Highlights: ► Murine pulmonary gas exchange after microembolization was non-invasively studied. ► A physiologically based model quantified impairment of pulmonary gas exchange. ► Number and size of microemboli determine severity of impaired gas exchange. ► Pulmonary gas exchange returns to baseline within 7 days.« less

Mechanical support of total cavopulmonary connection with an axial flow pump.

PubMed

Riemer, R Kirk; Amir, Gabriel; Reichenbach, Steven H; Reinhartz, Olaf

2005-08-01

Even under optimal circumstances, total cavopulmonary connection is associated with a continuous late risk of death. Hemodynamics are distinctly abnormal, with increased systemic venous pressures and frequent low cardiac output. Our study uses a sheep model of total cavopulmonary connection to test the response to axial flow pump (Thoratec HeartMate II; Thoratec Corporation (Pleasanton, Calif)) support of total cavopulmonary connection, which might be suitable to treat patients with failing Fontan circulation. Eight sheep (42-48 kg) were studied. After pilot studies in 3 animals, 5 underwent both pump-supported and nonsupported total cavopulmonary connection in alternating sequence for up to 2 hours. This was achieved with a 12-mm polytetrafluoroethylene graft from the (distally ligated) superior vena cava to the main pulmonary artery and a cannula placed in the inferior vena cava with an attached 16-mm Dacron graft to the main pulmonary artery. Pressures (arterial, inferior vena cava, left atrium, and pulmonary artery) and flows (ascending aorta and inferior vena cava) were recorded over 1 hour both with unsupported total cavopulmonary connection and after placing an axial flow pump (Thoratec HeartMate II) between the inferior vena caval inflow cannula and the main pulmonary artery. Under nonsupported total cavopulmonary connection circulation, inferior vena caval and aortic blood flow decreased by nearly 50%. Inferior vena caval pressure nearly doubled, whereas arterial pressure decreased by one third. Pulmonary artery pressure became nonpulsatile; however, mean pulmonary artery pressure and left atrial pressure did not change significantly. With pump-supported Fontan circulation, cardiac output, inferior vena caval flow, and arterial pressure returned to baseline. Inferior vena caval pressure decreased to below baseline levels. Mean pulmonary artery pressure and left atrial pressure again remained unchanged. Axial flow pump support from the inferior vena cava to the pulmonary artery can prevent the substantial decrease of aortic flow and pressure associated with total cavopulmonary connection and can reverse its poor hemodynamics. This is a simple model that can be used to further evaluate the potential of mechanical support as a treatment option in failing Fontan circulation.

Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial.

PubMed

Raghu, Ganesh; Behr, Juergen; Brown, Kevin K; Egan, Jim J; Kawut, Steven M; Flaherty, Kevin R; Martinez, Fernando J; Nathan, Steven D; Wells, Athol U; Collard, Harold R; Costabel, Ulrich; Richeldi, Luca; de Andrade, Joao; Khalil, Nasreen; Morrison, Lake D; Lederer, David J; Shao, Lixin; Li, Xiaoming; Pedersen, Patty S; Montgomery, A Bruce; Chien, Jason W; O'Riordan, Thomas G

2013-05-07

Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor. To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression. Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300). Academic and private hospitals. Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans. Ambrisentan, 10 mg/d, or placebo. Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function. The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point. The study was terminated early. Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations. Gilead Sciences.

A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV.

PubMed

Triplette, Matthew; Attia, Engi F; Akgün, Kathleen M; Soo Hoo, Guy W; Freiberg, Matthew S; Butt, Adeel A; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T; Graber, Christopher J; Huang, Laurence; Crothers, Kristina

2017-01-01

The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1-39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era.

A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV

PubMed Central

Attia, Engi F.; Akgün, Kathleen M.; Soo Hoo, Guy W.; Freiberg, Matthew S.; Butt, Adeel A.; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T.; Graber, Christopher J.; Huang, Laurence; Crothers, Kristina

2017-01-01

Objectives The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. Methods We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Results Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1–39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). Conclusions A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era. PMID:28122034

Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: a pilot randomized study of high-dose vitamin D3 administration

PubMed Central

Alvarez, Jessica A.; Chong, Elizabeth Y.; Walker, Douglas I.; Chandler, Joshua D.; Michalski, Ellen S.; Grossmann, Ruth E.; Uppal, Karan; Li, Shuzhao; Frediani, Jennifer K.; Tirouvanziam, Rabindra; Tran, ViLinh T.; Tangpricha, Vin; Jones, Dean P.; Ziegler, Thomas R.

2017-01-01

Background Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown. Objective We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D3 administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation. Design Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D3 (250,000 IU vitamin D3 bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D3 supplementation. Results Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P<0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways--predominantly representing amino acid pathways-- differed between the vitamin D3- and placebo-treated CF subjects over time (P<0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D3 treatment. Conclusions Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D3 supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high-dose vitamin D3 in this clinical setting. PMID:28403943

Pulmonary Function in Children with Development Coordination Disorder

ERIC Educational Resources Information Center

Wu, Sheng K.; Cairney, John; Lin, Hsiao-Hui; Li, Yao-Chuen; Song, Tai-Fen

2011-01-01

The purpose of this study was to compare pulmonary function in children with developmental coordination disorder (DCD) with children who are typically developing (TD), and also analyze possible gender differences in pulmonary function between these groups. The Movement ABC test was used to identify the movement coordination ability of children.…

Pirfenidone treatment in idiopathic pulmonary fibrosis: A Saudi experience.

PubMed

Alhamad, Esam H

2015-01-01

Recent trials involving pirfenidone suggest a beneficial effect in the treatment of idiopathic pulmonary fibrosis (IPF). To report on the efficacy and safety of pirfenidone in the treatment of patients with IPF, at a tertiary care hospital in Saudi Arabia. The study included 58 patients with IPF who were evaluated from March 2012 to March 2013. During the study period, 33 patients received pirfenidone, and the remaining patients (n = 25) served as a control group. Baseline clinical characteristics, physiological parameters and the results of a 36-Item Short Form Health Survey (SF-36) were compared between the groups. Furthermore, we compared changes in forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLco), six-minute walk distance (6MWD) and SF-36 for both groups during follow-up. The last follow-up period ended in January 2014. There were no significant differences in baseline clinical characteristics between the groups. Furthermore, we found no differences in FVC, DLco and SF-36 during follow-up (median, 12 months). However, patients receiving pirfenidone treatment were less likely to experience reductions in 6MWD compared with the control group (13% vs. 52%, respectively; P = 0.001). Although adverse events were more frequently reported by the pirfenidone group compared with the control group (85 vs. 56%, respectively; P = 0.015), these patients did not require discontinuation of treatment. Pirfenidone treatment preserves functional capacity, as reflected by the 6MWD. Adverse events associated with pirfenidone treatment were generally well tolerated by the patients.

Expansion of Pathogen-Specific T-Helper 1 and T-Helper 17 Cells in Pulmonary Tuberculosis With Coincident Type 2 Diabetes Mellitus

PubMed Central

Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.; Nutman, Thomas B.; Babu, Subash

2013-01-01

Background. Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, although the immunological mechanisms underlying this interaction remain unexplored. The influence of poorly controlled diabetes on pathogen-specific T-helper 1 (Th1) and T-helper 17 (Th17) responses have not been examined. Methods. To identify the role of Th1 and Th17 cells in tuberculosis with coincident DM, we examined mycobacteria-specific immune responses in the whole blood of individuals who had tuberculosis with DM and compared them to those in individuals who had tuberculosis without DM. Results. Tuberculosis coincident with DM is characterized by elevated frequencies of monofunctional and dual-functional CD4+ Th1 cells following Mycobacterium tuberculosis antigen stimulation and elevated frequencies of Th17 subsets at both baseline and following antigen stimulation. This was associated with increased systemic (plasma) levels of both Th1 and Th17 cytokines and decreased baseline frequencies of natural regulatory T cells but not interleukin 10 or transforming growth factor β. Conclusions. Therefore, our data reveal that tuberculosis in persons with DM is characterized by elevated frequencies of Th1 and Th17 cells, indicating that DM is associated with an alteration in the immune response to tuberculosis, leading to a biased induction of Th1- and Th17-mediated cellular responses and likely contributing to increased immune pathology in M. tuberculosis infection. PMID:23715661

Influence of Anti-TNF and Disease Modifying Antirheumatic Drugs Therapy on Pulmonary Forced Vital Capacity Associated to Ankylosing Spondylitis: A 2-Year Follow-Up Observational Study

PubMed Central

Rocha-Muñoz, Alberto Daniel; Brambila-Tapia, Aniel Jessica Leticia; Zavala-Cerna, María Guadalupe; Vásquez-Jiménez, José Clemente; De la Cerda-Trujillo, Liliana Faviola; Vázquez-Del Mercado, Mónica; Rodriguez-Jimenez, Norma Alejandra; Díaz-Rizo, Valeria; Díaz-González, Viviana; Cardona-Muñoz, Ernesto German; Dávalos-Rodríguez, Ingrid Patricia; Salazar-Paramo, Mario; Gamez-Nava, Jorge Ivan; Nava-Zavala, Arnulfo Hernan; Gonzalez-Lopez, Laura

2015-01-01

Objective. To evaluate the effect of anti-TNF agents plus synthetic disease modifying antirheumatic drugs (DMARDs) versus DMARDs alone for ankylosing spondylitis (AS) with reduced pulmonary function vital capacity (FVC%). Methods. In an observational study, we included AS who had FVC% <80% at baseline. Twenty patients were taking DMARDs and 16 received anti-TNF + DMARDs. Outcome measures: changes in FVC%, BASDAI, BASFI, 6-minute walk test (6MWT), Borg scale after 6MWT, and St. George's Respiratory Questionnaire at 24 months. Results. Both DMARDs and anti-TNF + DMARDs groups had similar baseline values in FVC%. Significant improvement was achieved with anti-TNF + DMARDs in FVC%, at 24 months, when compared to DMARDs alone (P = 0.04). Similarly, patients in anti-TNF + DMARDs group had greater improvement in BASDAI, BASFI, Borg scale, and 6MWT when compared to DMARDs alone. After 2 years of follow-up, 14/16 (87.5%) in the anti-TNF + DMARDs group achieved the primary outcome: FVC% ≥80%, compared with 11/20 (55%) in the DMARDs group (P = 0.04). Conclusions. Patients with anti-TNF + DMARDs had a greater improvement in FVC% and cardiopulmonary scales at 24 months compared with DMARDs. This preliminary study supports the fact that anti-TNF agents may offer additional benefits compared to DMARDs in patients with AS who have reduced FVC%. PMID:26078986

Pre-operative inspiratory muscle training preserves postoperative inspiratory muscle strength following major abdominal surgery - a randomised pilot study.

PubMed

Kulkarni, S R; Fletcher, E; McConnell, A K; Poskitt, K R; Whyman, M R

2010-11-01

The aim of this pilot study was to assess the effect of pre-operative inspiratory muscle training (IMT) on respiratory variables in patients undergoing major abdominal surgery. Respiratory muscle strength (maximum inspiratory [MIP] and expiratory [MEP] mouth pressure) and pulmonary functions were measured at least 2 weeks before surgery in 80 patients awaiting major abdominal surgery. Patients were then allocated randomly to one of four groups (Group A, control; Group B, deep breathing exercises; Group C, incentive spirometry; Group D, specific IMT). Patients in groups B, C and D were asked to train twice daily, each session lasting 15 min, for at least 2 weeks up to the day before surgery. Outcome measurements were made immediately pre-operatively and postoperatively. In groups A, B and C, MIP did not increase from baseline to pre-operative assessments. In group D, MIP increased from 51.5 cmH(2)O (median) pre-training to 68.5 cmH(2)O (median) post-training pre-operatively (P < 0.01). Postoperatively, groups A, B and C showed a fall in MIP from baseline (P < 0.01, P < 0.01) and P = 0.06, respectively). No such significant reduction in postoperative MIP was seen in group D (P = 0.36). Pre-operative specific IMT improves MIP pre-operatively and preserves it postoperatively. Further studies are required to establish if this is associated with reduced pulmonary complications.

Coenzyme Q supplementation in pulmonary arterial hypertension

PubMed Central

Sharp, Jacqueline; Farha, Samar; Park, Margaret M.; Comhair, Suzy A.; Lundgrin, Erika L.; Tang, W.H. Wilson; Bongard, Robert D.; Merker, Marilyn P.; Erzurum, Serpil C.

2014-01-01

Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH). Because coenzyme Q (CoQ) is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8) in comparison to healthy controls (N=7), at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW) decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement. PMID:25180165

Lung function and pulmonary artery blood flow following prenatal maternal retinoic acid and imatinib in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Burgos, Carmen Mesas; Davey, Marcus G; Riley, John S; Jia, Huimin; Flake, Alan W; Peranteau, William H

2017-12-19

Lung and pulmonary vascular maldevelopment in congenital diaphragmatic hernia (CDH) results in significant morbidity and mortality. Retinoic acid (RA) and imatinib have been shown to improve pulmonary morphology following prenatal administration in the rat nitrofen-induced CDH model. It remains unclear if these changes translate into improved function. We evaluated the effect of prenatal RA and imatinib on postnatal lung function, structure, and pulmonary artery (PA) blood flow in the rat CDH model. Olive oil or nitrofen was administered alone or in combination with RA or imatinib to pregnant rats. Pups were assessed for PA blood flow by ultrasound and pulmonary function/morphology following delivery, intubation, and short-term ventilation. Neither RA nor imatinib had a negative effect on lung and body growth. RA accelerated lung maturation indicated by increased alveoli number and thinner interalveolar septa and was associated with decreased PA resistance and improved oxygenation. With the exception of a decreased PA pulsatility index, no significant changes in morphology and pulmonary function were noted following imatinib. Prenatal treatment with RA but not imatinib was associated with improved pulmonary morphology and function, and decreased pulmonary vascular resistance. This study highlights the potential of prenatal pharmacologic therapies, such as RA, for management of CDH. Copyright © 2017 Elsevier Inc. All rights reserved.

Controlled-frequency breath swimming improves swimming performance and running economy.

PubMed

Lavin, K M; Guenette, J A; Smoliga, J M; Zavorsky, G S

2015-02-01

Respiratory muscle fatigue can negatively impact athletic performance, but swimming has beneficial effects on the respiratory system and may reduce susceptibility to fatigue. Limiting breath frequency during swimming further stresses the respiratory system through hypercapnia and mechanical loading and may lead to appreciable improvements in respiratory muscle strength. This study assessed the effects of controlled-frequency breath (CFB) swimming on pulmonary function. Eighteen subjects (10 men), average (standard deviation) age 25 (6) years, body mass index 24.4 (3.7) kg/m(2), underwent baseline testing to assess pulmonary function, running economy, aerobic capacity, and swimming performance. Subjects were then randomized to either CFB or stroke-matched (SM) condition. Subjects completed 12 training sessions, in which CFB subjects took two breaths per length and SM subjects took seven. Post-training, maximum expiratory pressure improved by 11% (15) for all 18 subjects (P < 0.05) while maximum inspiratory pressure was unchanged. Running economy improved by 6 (9)% in CFB following training (P < 0.05). Forced vital capacity increased by 4% (4) in SM (P < 0.05) and was unchanged in CFB. These findings suggest that limiting breath frequency during swimming may improve muscular oxygen utilization during terrestrial exercise in novice swimmers. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Investigation of the efficacy of generic and brand-name tiotropium bromide in the management of chronic obstructive pulmonary disease: A randomized comparative trial.

PubMed

Panahi, Yunes; Ghanei, Mostafa; Behzadi, Mohammad; Salehi, Maryam; Soflaei, Sara Saffar; Sahebkar, Amirhossein

2016-03-01

The beneficial effects of tiotropium bromide, a long acting anticholinergic bronchodilator, in the management of chronic obstructive pulmonary disease have been shown in previous studies. The present study aimed to compare the efficacy and safety of generic (Tiova®) and brand-name (Spiriva®) tiotropium preparations in patients with COPD. In this randomized double-blind parallel-group trial, 79 patients with documented COPD were assigned to Tiova® or Spiriva® for a period of 4 weeks. Assessment of pulmonary function (using spirometry), quality-of-life (using St. George respiratory Questionnaire [SGRQ]) and severity of respiratory symptoms (using breathlessness, cough and sputum scale [BCSS]) was performed at baseline and at the end of treatment period. There were significant increases in FEV1 and reductions in FVC by the end of study in both Tiova® and Spiriva® groups. FEV1/FVC ratio did not change significantly neither in the Tiova® nor in Spiriva® group. Overall SGRQ score as well as subscale scores of symptoms, activity and impacts were improved by both drugs. In the BCSS scale, the frequency and severity of three main symptoms (dyspnea, cough and sputum) was decreased by both drugs. Baseline as well as post-treatment values of spirometric parameters, SGRQ and BCSS scores was comparable between the groups, apart from a lower post-treatment frequency of cough and sputum in the Spiriva® versus Tiova® group. There was no report of adverse events in either of the study groups. The findings of this comparative trial showed equivalent efficacy and safety of Spiriva® and Tiova® in lessening the symptoms as well as improving the quality of life in patients with COPD. This finding has an important translational value given the significantly lower costs of generic versus brand-name products.

Quality Improvement Initiatives to Optimize the Management of Chronic Obstructive Pulmonary Disease in Patients With Lung Cancer.

PubMed

Digby, Geneviève C; Robinson, Andrew

2017-11-01

Patients with lung cancer (LC) frequently have chronic obstructive pulmonary disease (COPD), the optimization of which improves outcomes. A 2014 Queen's University Hospitals audit demonstrated that COPD was underdiagnosed and undertreated in outpatients with LC. We sought to improve the diagnosis and management of COPD in this population. We implemented change using a Define/Measure/Analyze/Improve/Control (DMAIC) improvement cycle. Data were obtained by chart review from the Cancer Care Ontario database and e-Patient System for patients with newly diagnosed LC, including patient characteristics, pulmonary function test (PFT) data, and bronchodilator therapies. Improvement cycle 1 included engaging stakeholders and prioritizing COPD management by respirologists in the Lung Diagnostic Assessment Program. Improvement cycle 2 included physician restructuring and developing a standard work protocol. Data were analyzed monthly and presented on statistical process control P-charts, which assessed differences over time. The χ 2 and McNemar tests assessed for significance between independent and dependent groups, respectively. A total of 477 patients were studied (165 patients at baseline, 166 patients in cycle 1, and 127 patients in cycle 2). There was no change in PFT completion over time, although respirology-managed patients were significantly more likely to undergo a PFT than patients who were not managed by respirology (56.7% v 96.1%; P < .00001). The proportion of respirology-managed patients with LC with airflow obstruction receiving inhaled bronchodilator significantly increased (baseline, 46.3%; cycle 1, 51.0%; and cycle 2, 74.3%). By cycle 2, patients with airflow obstruction were more likely to receive a long-acting bronchodilator if managed by respirology (74.3% v 44.8%; P = .0009). COPD is underdiagnosed and undertreated in outpatients with LC. A DMAIC quality improvement strategy emphasizing COPD treatment during LC evaluation in the Lung Diagnostic Assessment Program significantly improved COPD management.

Classification Models for Pulmonary Function using Motion Analysis from Phone Sensors.

PubMed

Cheng, Qian; Juen, Joshua; Bellam, Shashi; Fulara, Nicholas; Close, Deanna; Silverstein, Jonathan C; Schatz, Bruce

2016-01-01

Smartphones are ubiquitous, but it is unknown what physiological functions can be monitored at clinical quality. Pulmonary function is a standard measure of health status for cardiopulmonary patients. We have shown phone sensors can accurately measure walking patterns. Here we show that improved classification models can accurately measure pulmonary function, with sole inputs being sensor data from carried phones. Twenty-four cardiopulmonary patients performed six minute walk tests in pulmonary rehabilitation at a regional hospital. They carried smartphones running custom software recording phone motion. For every patient, every ten-second interval was correctly computed. The trained model perfectly computed the GOLD level 1/2/3, which is a standard categorization of pulmonary function as measured by spirometry. These results are encouraging towards field trials with passive monitors always running in the background. We expect patients can simply carry their phones during daily living, while supporting automatic computation ofpulmonary function for health monitoring.

Pulmonary function and fuel use: A population survey

PubMed Central

Saha, Asim; Mohan Rao, N; Kulkarni, PK; Majumdar, PK; Saiyed, HN

2005-01-01

Background In the backdrop of conflicting reports (some studies reported adverse outcomes of biomass fuel use whereas few studies reported absence of any association between adverse health effect and fuel use, may be due to presence of large number of confounding variables) on the respiratory health effects of biomass fuel use, this cross sectional survey was undertaken to understand the role of fuel use on pulmonary function. Method This study was conducted in a village of western India involving 369 randomly selected adult subjects (165 male and 204 female). All the subjects were interviewed and were subjected to pulmonary function test. Analysis of covariance was performed to compare the levels of different pulmonary function test parameters in relation to different fuel use taking care of the role of possible confounding factors. Results This study showed that biomass fuel use (especially wood) is an important factor for deterioration of pulmonary function (particularly in female). FEV1 (p < .05), FEV1 % (p < .01), PEFR (p < .05) and FEF25–75 (p < .01) values were significantly lower in biomass fuel using females than nonusers. Comparison of only biomass fuel use vs. only LPG (Liquefied Petroleum Gas) use and only wood vs. only LPG use has showed that LPG is a safer fuel so far as deterioration of pulmonary function is concerned. This study observes some deterioration of pulmonary function in the male subjects also, who came from biomass fuel using families. Conclusion This study concluded that traditional biomass fuels like wood have adverse effects on pulmonary function. PMID:16255784

Clinical and Biological Insights from the University of California San Francisco Prospective and Longitudinal Cohort.

PubMed

Benn, Bryan S; Lehman, Zoe; Kidd, Sharon A; Ho, Melissa; Sun, Sara; Ramstein, Joris; Arger, Nicholas K; Nguyen, Christine P; Su, Robert; Gomez, Antonio; Gelfand, Jeffrey M; Koth, Laura L

2017-10-01

Sarcoidosis is a systemic inflammatory disease characterized by non-necrotizing granulomas in involved organs, most commonly the lung. Description of patient characteristics in the Western United States is limited. Furthermore, blood-based measures that relate to clinical sarcoidosis phenotypes are lacking. We present an analysis of a prospective, longitudinal sarcoidosis cohort at a Northern Californian academic medical center. We enrolled 126 sarcoidosis subjects and 64 healthy controls and recorded baseline demographic and clinical characteristics. We used regression models to identify factors independently associated with pulmonary physiology. We tested whether blood transcript levels at study entry could relate to longitudinal changes in pulmonary physiology. White, non-Hispanics composed ~70% of subjects. Hispanics and Blacks had a diagnostic biopsy at an age ~7 years younger than whites. Obstructive, but not restrictive, physiology characterized Scadding Stage IV patients. Subjects reporting use of immunosuppression had worse FEV1%p, FVC%p, and DLCO%p compared to subjects never treated, regardless of Scadding stage. We defined sarcoidosis disease activity by a drop in pulmonary function over 36 months and found that subjects meeting this definition had significant repression of blood gene transcripts related to T cell receptor signaling pathways, referred to as the "TCR factor." Obstructive pulmonary physiology defined Stage IV patients which were mostly white, non-Hispanics. Genes comprising the composite gene expression score, TCR factor, may represent a blood-derived measure of T-cell activity and an indirect measure of active sarcoidosis inflammation. Validation of this measure could translate into individualized treatment for sarcoidosis patients.

Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum: a population-based, case-control study.

PubMed

Danilenko-Dixon, D R; Heit, J A; Silverstein, M D; Yawn, B P; Petterson, T M; Lohse, C M; Melton, L J

2001-01-01

We sought to determine risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum. We performed a population-based case-control study. All Olmsted County, Minnesota, residents with a first lifetime deep vein thrombosis or pulmonary embolism during pregnancy or post partum from 1966 to 1990 were identified (N = 90). Where possible, a resident without deep vein thrombosis or pulmonary embolism was matched to each patient by date of the first live birth after the patient's child. The medical records of all remaining patients and all control subjects were reviewed for >25 baseline characteristics, which were tested as risk factors for deep vein thrombosis or pulmonary embolism. In multivariate analysis smoking (odds ratio, 2.4) and prior superficial vein thrombosis (odds ratio, 9.4) were independent risk factors for deep vein thrombosis or pulmonary thrombosis during pregnancy or post partum. Venous thromboembolism prophylaxis may be warranted for pregnant women with prior superficial vein thrombosis. Smoking cessation should be recommended, especially during pregnancy and the postpartum period.

Pulmonary function and respiratory symptoms in potash workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graham, B.L.; Dosman, J.A.; Cotton, D.J.

1984-03-01

Over 94% of the workers in each of four Saskatchewan potash mines participated in a respiratory health surveillance program that included a questionnaire and pulmonary function tests. Compared with a nonexposed control group, potash workers had higher prevalences of cough, dyspnea, and chronic bronchitis but better pulmonary function. Prevalences of symptoms and pulmonary function abnormalities were similar among workers at the four mines tested and at the various job locations. Potash dust, diesel fumes, and other air contaminants may have an irritant effect that leads to the increased prevalences of cough and chronic bronchitis. Although no adverse effects of themore » potash mine environment on pulmonary function were found, these findings reflect a healthy worker effect or some selection process that makes the potash workers appear healthier in a cross-sectional study.« less

Pulmonary function and respiratory symptoms in potash workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graham, B.L.; Dosman, J.A.; Cotton, D.J.

1984-03-01

Over 94% of the workers in each of four Saskatchewan potash mines participated in a respiratory health surveillance program that included a questionnaire and pulmonary function tests. Compared with a nonexposed control group, potash workers had higher prevalences of cough, dyspnea, and chronic bronchitis but better pulmonary function. Prevalences of symptoms and pulmonary function abnormalities were similar among workers at the four mines tested and at the various job locations. Potash dust, diesel fumes, and other air contaminants may have an irritant effect that leads to the increased prevalences of cough and chronic bronchitis. Although we found no adverse effectsmore » of the potash mine environment on pulmonary function, these findings reflect a healthy worker effect or some selection process that makes the potash workers appear healthier in a cross-sectional study.« less

The effect of scoliosis surgery on pulmonary function in spinal muscular atrophy type II patients.

PubMed

Chou, Shih-Hsiang; Lin, Gau-Tyan; Shen, Po-Chih; Lue, Yi-Jing; Lu, Cheng-Chang; Tien, Yin-Chun; Lu, Yen-Mou

2017-06-01

Various results of the previous literature related to surgical effect on pulmonary function of spinal muscular atrophy (SMA) patients might be due to different SMA type, different fusion level and technique. The aim of this study was to determine the value of scoliosis surgery for SMA type II patients with regard to pulmonary function, under the same fusion level, fusion technique and average long-term follow-up. Ten SMA II patients who underwent spinal correction procedures from 1993 to 2010 were identified. Data on clinical features and pulmonary function, including forced vital capacity (FVC) and forced expiratory volume in 1st second (FEV 1 ), were collected. The data on pulmonary function were divided into preoperative, postoperative short-term (0-5 years), mid-term (5-10 years), and long-term (>10 years). Statistical comparisons were made using the Wilcoxon test for pulmonary function and body weight analysis. Questions were answered by parents on how surgery influenced the frequency of respiratory infection and the ability to sit at school. The average length of postoperative pulmonary function follow-up was 12.3 years (range 4.9-15.9 years). There was no significant difference in FVC or FEV 1 between preoperative and each postoperative period. However, a significant decline from mid-term to long-term was observed (p = 0.028). Body weight increased significantly in all postoperative periods and was moderately correlated to pulmonary function (r = 0.526 for FVC). The answers to the questionnaire revealed that 80% of the patients had obvious improvement in the frequency of respiratory infection and 100% were tolerable sitting at school. Surgical correction for scoliosis in SMA II patients results in pulmonary function being maintained during long-term follow-up. In addition, the advantages of surgery also include body weight gain, better sitting tolerance, and reduced frequency of respiratory infection.

The Relationship of Welding Fume Exposure, Smoking, and Pulmonary Function in Welders.

PubMed

Roach, Laura L

2018-01-01

The purpose of this study was to explore the relationship between occupational exposure to welding fumes and pulmonary function in an effort to add supportive evidence and clarity to the current body of research. This study utilized a retrospective chart review of pulmonary function testing and pulmonary questionnaires already available in charts from preplacement physicals to the most recent test. When comparing smokers to nonsmokers, utilizing multiple regression and controlling for age and percentage of time using a respirator, years welding was statistically significant at p = .04. Data support that smoking has a synergistic effect when combined with welding fume exposure on pulmonary decline.

Baseline Hemodynamics and Response to Contrast Media During Diagnostic Cardiac Catheterization Predict Adverse Events in Heart Failure Patients.

PubMed

Denardo, Scott J; Vock, David M; Schmalfuss, Carsten M; Young, Gregory D; Tcheng, James E; O'Connor, Christopher M

2016-07-01

Contrast media administered during cardiac catheterization can affect hemodynamic variables. However, little is documented about the effects of contrast on hemodynamics in heart failure patients or the prognostic value of baseline and changes in hemodynamics for predicting subsequent adverse events. In this prospective study of 150 heart failure patients, we measured hemodynamics at baseline and after administration of iodixanol or iopamidol contrast. One-year Kaplan-Meier estimates of adverse event-free survival (death, heart failure hospitalization, and rehospitalization) were generated, grouping patients by baseline measures of pulmonary capillary wedge pressure (PCWP) and cardiac index (CI), and by changes in those measures after contrast administration. We used Cox proportional hazards modeling to assess sequentially adding baseline PCWP and change in CI to 5 validated risk models (Seattle Heart Failure Score, ESCAPE [Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness], CHARM [Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity], CORONA [Controlled Rosuvastatin Multinational Trial in Heart Failure], and MAGGIC [Meta-Analysis Global Group in Chronic Heart Failure]). Median contrast volume was 109 mL. Both contrast media caused similarly small but statistically significant changes in most hemodynamic variables. There were 39 adverse events (26.0%). Adverse event rates increased using the composite metric of baseline PCWP and change in CI (P<0.01); elevated baseline PCWP and decreased CI after contrast correlated with the poorest prognosis. Adding both baseline PCWP and change in CI to the 5 risk models universally improved their predictive value (P≤0.02). In heart failure patients, the administration of contrast causes small but significant changes in hemodynamics. Calculating baseline PCWP with change in CI after contrast predicts adverse events and increases the predictive value of existing models. Patients with elevated baseline PCWP and decreased CI after contrast merit greatest concern. © 2016 American Heart Association, Inc.

High-Resolution Computed Tomography and Pulmonary Function Findings of Occupational Arsenic Exposure in Workers.

PubMed

Ergün, Recai; Evcik, Ender; Ergün, Dilek; Ergan, Begüm; Özkan, Esin; Gündüz, Özge

2017-05-05

The number of studies where non-malignant pulmonary diseases are evaluated after occupational arsenic exposure is very few. To investigate the effects of occupational arsenic exposure on the lung by high-resolution computed tomography and pulmonary function tests. Retrospective cross-sectional study. In this study, 256 workers with suspected respiratory occupational arsenic exposure were included, with an average age of 32.9±7.8 years and an average of 3.5±2.7 working years. Hair and urinary arsenic levels were analysed. High-resolution computed tomography and pulmonary function tests were done. In workers with occupational arsenic exposure, high-resolution computed tomography showed 18.8% pulmonary involvement. In pulmonary involvement, pulmonary nodule was the most frequently seen lesion (64.5%). The other findings of pulmonary involvement were 18.8% diffuse interstitial lung disease, 12.5% bronchiectasis, and 27.1% bullae-emphysema. The mean age of patients with pulmonary involvement was higher and as they smoked more. The pulmonary involvement was 5.2 times higher in patients with skin lesions because of arsenic. Diffusing capacity of lung for carbon monoxide was significantly lower in patients with pulmonary involvement. Besides lung cancer, chronic occupational inhalation of arsenic exposure may cause non-malignant pulmonary findings such as bronchiectasis, pulmonary nodules and diffuse interstitial lung disease. So, in order to detect pulmonary involvement in the early stages, workers who experience occupational arsenic exposure should be followed by diffusion test and high-resolution computed tomography.

Natural history and galsulfase treatment in mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome)--10-year follow-up of patients who previously participated in an MPS VI Survey Study.

PubMed

Giugliani, Roberto; Lampe, Christina; Guffon, Nathalie; Ketteridge, David; Leão-Teles, Elisa; Wraith, James E; Jones, Simon A; Piscia-Nichols, Cheri; Lin, Ping; Quartel, Adrian; Harmatz, Paul

2014-08-01

Mucopolysaccharidosis VI (MPS VI) is a clinically heterogeneous and progressive disorder with multiorgan manifestations caused by deficient N-acetylgalactosamine-4-sulfatase activity. A cross-sectional Survey Study in individuals (n = 121) affected with MPS VI was conducted between 2001 and 2002 to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of disease. We conducted a Resurvey Study (ClinicalTrials.gov: NCT01387854) to obtain 10-year follow-up data, including medical histories and clinical assessments (n = 59), and survival status over 12 years (n = 117). Patients received a mean (SD) of 6.8 (2.2) years of galsulfase ERT between baseline (Survey Study) and follow-up. ERT patients increased in height by 20.4 cm in the 4-7-year-old baseline age group and by 16.8 cm in the 8-12-year-old baseline age group. ERT patients <13 years-old demonstrated improvement in forced vital capacity (FVC) by 68% and forced expiratory volume in 1 sec (FEV1) by 55%, and those ≥13 years-old increased FVC by 12.8% and maintained FEV1. Patients with >200 µg/mg baseline uGAG levels increased FVC by 48% in the <13-year-old baseline age group and by 15% in the ≥13-year-old baseline age group. ERT patients who completed the 6-min walk test demonstrated a mean (SD) increase of 65.7 (100.6) m. Cardiac outcomes did not significantly improve or worsen. Observed mortality rate among naïve patients was 50% (7/14) and 16.5% (17/103) in the ERT group (unadjusted hazard ratio, 0.24; 95% CI, 0.10-0.59). Long-term galsulfase ERT was associated with improvements in pulmonary function and endurance, stabilized cardiac function and increased survival. © 2014 Wiley Periodicals, Inc.

Comparison of Flow and Volume Incentive Spirometry on Pulmonary Function and Exercise Tolerance in Open Abdominal Surgery: A Randomized Clinical Trial.

PubMed

Kumar, Amaravadi Sampath; Alaparthi, Gopala Krishna; Augustine, Alfred Joseph; Pazhyaottayil, Zulfeequer Chundaanveetil; Ramakrishna, Anand; Krishnakumar, Shyam Krishnan

2016-01-01

Surgical procedures in abdominal area lead to changes in pulmonary function, respiratory mechanics and impaired physical capacity leading to postoperative pulmonary complications, which can affect up to 80% of upper abdominal surgery. To evaluate the effects of flow and volume incentive spirometry on pulmonary function and exercise tolerance in patients undergoing open abdominal surgery. A randomized clinical trial was conducted in a hospital of Mangalore city in Southern India. Thirty-seven males and thirteen females who were undergoing abdominal surgeries were included and allocated into flow and volume incentive spirometry groups by block randomization. All subjects underwent evaluations of pulmonary function with measurement of Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Peak Expiratory Flow (PEF). Preoperative and postoperative measurements were taken up to day 5 for both groups. Exercise tolerance measured by Six- Minute Walk Test during preoperative period and measured again at the time of discharge for both groups. Pulmonary function was analysed by post-hoc analysis and carried out using Bonferroni's 't'-test. Exercise tolerance was analysed by Paired 'T'-test. Pulmonary function (FVC, FEV1, and PEFR) was found to be significantly decreased in 1(st), 2(nd) and 3(rd) postoperative day when compared with preoperative day. On 4(th) and 5(th) postoperative day the pulmonary function (FVC, FEV1, and PEFR) was found to be better preserved in both flow and volume incentive spirometry groups. The Six-Minute Walk Test showed a statistically significant improvement in pulmonary function on the day of discharge than in the preoperative period. In terms of distance covered, the volume- incentive spirometry group showed a greater statistically significant improvement from the preoperative period to the time of discharge than was exhibited by the flow incentive spirometry group. Flow and volume incentive spirometry can be safely recommended to patients undergoing open abdominal surgery as there have been no adverse events recorded. Also, these led to a demonstrable improvement in pulmonary function and exercise tolerance.

Comparison of Flow and Volume Incentive Spirometry on Pulmonary Function and Exercise Tolerance in Open Abdominal Surgery: A Randomized Clinical Trial

PubMed Central

Kumar, Amaravadi Sampath; Augustine, Alfred Joseph; Pazhyaottayil, Zulfeequer Chundaanveetil; Ramakrishna, Anand; Krishnakumar, Shyam Krishnan

2016-01-01

Introduction Surgical procedures in abdominal area lead to changes in pulmonary function, respiratory mechanics and impaired physical capacity leading to postoperative pulmonary complications, which can affect up to 80% of upper abdominal surgery. Aim To evaluate the effects of flow and volume incentive spirometry on pulmonary function and exercise tolerance in patients undergoing open abdominal surgery. Materials and Methods A randomized clinical trial was conducted in a hospital of Mangalore city in Southern India. Thirty-seven males and thirteen females who were undergoing abdominal surgeries were included and allocated into flow and volume incentive spirometry groups by block randomization. All subjects underwent evaluations of pulmonary function with measurement of Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Peak Expiratory Flow (PEF). Preoperative and postoperative measurements were taken up to day 5 for both groups. Exercise tolerance measured by Six- Minute Walk Test during preoperative period and measured again at the time of discharge for both groups. Pulmonary function was analysed by post-hoc analysis and carried out using Bonferroni’s ‘t’-test. Exercise tolerance was analysed by Paired ‘T’-test. Results Pulmonary function (FVC, FEV1, and PEFR) was found to be significantly decreased in 1st, 2nd and 3rd postoperative day when compared with preoperative day. On 4th and 5th postoperative day the pulmonary function (FVC, FEV1, and PEFR) was found to be better preserved in both flow and volume incentive spirometry groups. The Six-Minute Walk Test showed a statistically significant improvement in pulmonary function on the day of discharge than in the preoperative period. In terms of distance covered, the volume- incentive spirometry group showed a greater statistically significant improvement from the preoperative period to the time of discharge than was exhibited by the flow incentive spirometry group. Conclusion Flow and volume incentive spirometry can be safely recommended to patients undergoing open abdominal surgery as there have been no adverse events recorded. Also, these led to a demonstrable improvement in pulmonary function and exercise tolerance. PMID:26894090

Pulmonary edema predictive scoring index (PEPSI), a new index to predict risk of reperfusion pulmonary edema and improvement of hemodynamics in percutaneous transluminal pulmonary angioplasty.

PubMed

Inami, Takumi; Kataoka, Masaharu; Shimura, Nobuhiko; Ishiguro, Haruhisa; Yanagisawa, Ryoji; Taguchi, Hiroki; Fukuda, Keiichi; Yoshino, Hideaki; Satoh, Toru

2013-07-01

This study sought to identify useful predictors for hemodynamic improvement and risk of reperfusion pulmonary edema (RPE), a major complication of this procedure. Percutaneous transluminal pulmonary angioplasty (PTPA) has been reported to be effective for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). PTPA has not been widespread because RPE has not been well predicted. We included 140 consecutive procedures in 54 patients with CTEPH. The flow appearance of the target vessels was graded into 4 groups (Pulmonary Flow Grade), and we proposed PEPSI (Pulmonary Edema Predictive Scoring Index) = (sum total change of Pulmonary Flow Grade scores) × (baseline pulmonary vascular resistance). Correlations between occurrence of RPE and 11 variables, including hemodynamic parameters, number of target vessels, and PEPSI, were analyzed. Hemodynamic parameters significantly improved after median observation period of 6.4 months, and the sum total changes in Pulmonary Flow Grade scores were significantly correlated with the improvement in hemodynamics. Multivariate analysis revealed that PEPSI was the strongest factor correlated with the occurrence of RPE (p < 0.0001). Receiver-operating characteristic curve analysis demonstrated PEPSI to be a useful marker of the risk of RPE (cutoff value 35.4, negative predictive value 92.3%). Pulmonary Flow Grade score is useful in determining therapeutic efficacy, and PEPSI is highly supportive to reduce the risk of RPE after PTPA. Using these 2 indexes, PTPA could become a safe and common therapeutic strategy for CTEPH. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Decrease in pulmonary function and oxygenation after lung resection

PubMed Central

Westerdahl, Elisabeth; Langer, Daniel; Souza, Domingos S.R.; Andreasen, Jan Jesper

2018-01-01

Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure) and 6-min walk test (6MWT) were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years). Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity −0.6±0.6 L and forced expiratory volume in 1 s −0.43±0.4 L; both p<0.0001), 6MWT (−37.6±74.8 m; p<0.0001) and oxygenation (−2.9±4.7 units; p<0.001), while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001), whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength. PMID:29362707

Decrease in pulmonary function and oxygenation after lung resection.

PubMed

Brocki, Barbara Cristina; Westerdahl, Elisabeth; Langer, Daniel; Souza, Domingos S R; Andreasen, Jan Jesper

2018-01-01

Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure) and 6-min walk test (6MWT) were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years). Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity -0.6±0.6 L and forced expiratory volume in 1 s -0.43±0.4 L; both p<0.0001), 6MWT (-37.6±74.8 m; p<0.0001) and oxygenation (-2.9±4.7 units; p<0.001), while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001), whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength.

Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis.

PubMed

Elborn, J Stuart; Ramsey, Bonnie W; Boyle, Michael P; Konstan, Michael W; Huang, Xiaohong; Marigowda, Gautham; Waltz, David; Wainwright, Claire E

2016-08-01

Lumacaftor/ivacaftor combination therapy has shown clinical benefits in patients with cystic fibrosis homozygous for the Phe508del CFTR mutation; however, pretreatment lung function is a confounding factor that potentially affects the efficacy and safety of this therapy. We aimed to assess the efficacy and safety of lumacaftor/ivacaftor therapy in these patients, defined by specific categories of lung function. Both trials (TRAFFIC and TRANSPORT) included in this pooled analysis were multinational, randomised, double-blind, placebo-controlled, parallel-group, phase 3 studies. Eligible patients from 187 participating centres in North America, Australia, and the European Union (both trials) were aged 12 years or older with a confirmed diagnosis of cystic fibrosis, homozygous for the Phe508del CFTR mutation, and with a percent predicted FEV1 (ppFEV1) of 40-90 at the time of screening. Patients were randomly assigned with an interactive web response system (1:1:1) to receive placebo, lumacaftor (600 mg once daily) plus ivacaftor (250 mg every 12 h), or lumacaftor (400 mg every 12 h) plus ivacaftor (250 mg every 12 h) for 24 weeks. Prespecified subgroup analyses of pooled efficacy and safety data by lung function, as measured by ppFEV1, were done for patients with baseline ppFEV1 (<40 and ≥40) and screening ppFEV1 (<70 and ≥70). The primary endpoint was the absolute change from baseline in ppFEV1 at week 24 analysed in all randomised patients who received at least one dose of study drug. Both trials are registered with ClinicalTrials.gov (TRAFFIC: NCT01807923; TRANSPORT: NCT01807949). Both trials were done between April, 2013, and April, 2014. Of the 1108 patients included in the efficacy analysis, 81 patients had a ppFEV1 that decreased to lower than 40 between screening and baseline and 1016 had a ppFEV1 of 40 or higher at baseline. At screening, 730 had a ppFEV1 of less than 70, and 342 had a ppFEV1 of 70 or higher. Improvements in the absolute change from baseline at week 24 in ppFEV1 were observed with both lumacaftor/ivacaftor doses in the subgroup with baseline ppFEV1 levels lower than 40 (least-squares mean difference vs placebo was 3·7 percentage points [95% CI 0·5-6·9; p=0·024] in the lumacaftor [600 mg/day]-ivacaftor group and 3·3 percentage points [0·2-6·4; p=0·036] in the lumacaftor [400 mg/12 h]-ivacaftor group). Improvements in ppFEV1 compared with placebo were also reported in the subgroup with baseline ppFEV1 levels of 40 or higher (3·3 percentage points [2·3-4·4; p<0·0001] in the lumacaftor [600 mg per day]-ivacaftor group and 2·8 percentage points [1·7-3·8; p<0·0001] in the lumacaftor [400 mg/12 h]-ivacaftor group). Similar absolute improvements in ppFEV1 compared with placebo were observed in subgroups with screening ppFEV1 levels lower than 70 and ppFEV1 levels of 70 or higher. Increases in body-mass index and reduction in number of pulmonary exacerbation events were observed in both lumacaftor/ivacaftor dose groups compared with placebo across all lung function subgroups. Treatment was generally well tolerated, although the incidence of some respiratory adverse events was higher with lumacaftor/ivacaftor than with placebo in all subgroups. In patients with baseline ppFEV1 levels lower than 40, these adverse events included cough, dyspnoea, and abnormal respiration. These analyses confirm that lumacaftor/ivacaftor combination therapy benefits patients with cystic fibrosis homozygous for Phe508del CFTR who have varying degrees of lung function impairment. Vertex Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Short- and long-term response to corticosteroid therapy in chronic beryllium disease.

PubMed

Marchand-Adam, S; El Khatib, A; Guillon, F; Brauner, M W; Lamberto, C; Lepage, V; Naccache, J-M; Valeyre, D

2008-09-01

Chronic beryllium disease (CBD) is a granulomatous disorder that affects the lung after exposure to beryllium. The present study reports short- and long-term evolution of granulomatous and fibrotic components in eight patients with severe CBD receiving corticosteroid therapy. Eight patients with confirmed CBD were studied at baseline, after initial corticosteroid treatment (4-12 months), at relapse and at the final visit. Beryllium exposure, Glu(69) (HLA-DPB1 genes coding for glutamate at position beta69) polymorphism, symptoms, pulmonary function tests (PFT), serum angiotensin-converting enzyme (SACE) and high-resolution computed tomography (HRCT) quantification of pulmonary lesions were analysed. The CBD patients were observed for a median (range) of 69 (20-180) months. After stopping beryllium exposure, corticosteroids improved symptoms and PFT (vital capacity +26%, diffusing capacity of the lung for carbon monoxide +15%), and decreased SACE level and active lesion HRCT score. In total, 18 clinical relapses occurred after the treatment was tapered and these were associated with SACE and active lesion HRCT score impairment. At the final visit, corticosteroids had completely stabilised all parameters including both HRCT scores of active lesions and fibrotic lesions in six out of eight patients. Corticosteroids were beneficial in chronic beryllium disease. They were effective in suppressing granulomatosis lesions in all cases and in stopping the evolution to pulmonary fibrosis in six out of eight patients.

A comparison of echocardiographic variables of right ventricular function with exercise capacity after bosentan treatment in patients with pulmonary arterial hypertension: Results from a multicenter, prospective, cohort study.

PubMed

Kim, Hyungseop; Bae Lee, Jin; Park, Jae-Hyeong; Yoo, Byung-Su; Son, Jang-Won; Yang, Dong Heon; Lee, Bong-Ryeol

2017-01-01

Bosentan reduces pulmonary arterial pressure and improves exercise capacity in patients with pulmonary arterial hypertension (PAH). However, there are limited data regarding the extent to which the changes in echocardiographic variables reflect improvements in exercise capacity. We aimed to assess the improvement of echocardiographic variables and exercise capacity after 6 months of bosentan treatment for PAH. We performed a prospective study from June 2012 to June 2015 in seven participating medical centers. Echocardiography, including tissue Doppler imaging (TDI) and the 6-minute walk test distance (6MWD), was performed at baseline and after 6 months of bosentan treatment. We analyzed 19 patients with PAH: seven with congenital shunt, six with collagen vascular disease, and six with idiopathic PAH. After bosentan treatment, mean 6MWD increased by 50 meters. Right ventricle (RV) systolic pressure, tricuspid annular plane systolic excursion, myocardial performance index (MPI) derived from TDI (MPI-TDI) of RV and left ventricle (LV), RV fractional area change, and RV ejection fraction were significantly improved. In particular, the magnitude of RV and LV MPI-TDI showed good correlation with changes in the 6MWD. The magnitude of RV and LV MPI-TDI was strongly associated with improvements in exercise capacity. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:28-34, 2017. © 2016 Wiley Periodicals, Inc.

Characteristics of sarcoidosis in Maori and Pacific Islanders.

PubMed

Wilsher, Margaret L; Young, Lisa M; Hopkins, Raewyn; Cornere, Megan

2017-02-01

Ethnicity is strongly associated with variable clinical presentation in sarcoidosis but the association between ethnicity and clinical characteristics has not previously been described in patients of Polynesian ancestry, Maori and Pacific Islander (PI). The objective of this study was to describe the clinical characteristics of sarcoidosis in Maori and PI patients and determine if those were different to European patients. A retrospective review of the medical records of 406 patients (69 Maori/PI) attending a specialist interstitial lung disease (ILD) clinic. The population (207 females, mean age at presentation: 36) reflected the current New Zealand census data (2013) with only people of Indian ethnicity over-represented. Parenchymal lung involvement was uncommon in Maori and PI patients (21% Scadding stage 2, 2% stage 3), and no patient had extensive pulmonary fibrosis (stage 4). Computed tomography (CT) patterns of sarcoid parenchymal lung involvement were less commonly reported for Maori/PI. There were no differences in respect of baseline lung function or requirement for treatment. Ocular and skin involvement occurred more frequently in Maori and PI (P = 0.0045, P = 0.03), and erythema nodosum was more common in Caucasians (P = 0.0008). People of Polynesian ancestry appear to have less pulmonary and more extra-pulmonary manifestations of sarcoidosis. This adds to our knowledge that sarcoidosis heterogeneity is influenced by ethnicity. © 2016 Asian Pacific Society of Respirology.

Colchicine Depolymerizes Microtubules, Increases Junctophilin-2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension.

PubMed

Prins, Kurt W; Tian, Lian; Wu, Danchen; Thenappan, Thenappan; Metzger, Joseph M; Archer, Stephen L

2017-05-31

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by obstructive pulmonary vascular remodeling and right ventricular (RV) dysfunction. Although RV function predicts outcomes in PAH, mechanisms of RV dysfunction are poorly understood, and RV-targeted therapies are lacking. We hypothesized that in PAH, abnormal microtubular structure in RV cardiomyocytes impairs RV function by reducing junctophilin-2 (JPH2) expression, resulting in t-tubule derangements. Conversely, we assessed whether colchicine, a microtubule-depolymerizing agent, could increase JPH2 expression and enhance RV function in monocrotaline-induced PAH. Immunoblots, confocal microscopy, echocardiography, cardiac catheterization, and treadmill testing were used to examine colchicine's (0.5 mg/kg 3 times/week) effects on pulmonary hemodynamics, RV function, and functional capacity. Rats were treated with saline (n=28) or colchicine (n=24) for 3 weeks, beginning 1 week after monocrotaline (60 mg/kg, subcutaneous). In the monocrotaline RV, but not the left ventricle, microtubule density is increased, and JPH2 expression is reduced, with loss of t-tubule localization and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves t-tubule morphology in RV cardiomyocytes. Colchicine therapy diminishes RV hypertrophy, improves RV function, and enhances RV-pulmonary artery coupling. Colchicine reduces small pulmonary arteriolar thickness and improves pulmonary hemodynamics. Finally, colchicine increases exercise capacity. Monocrotaline-induced PAH causes RV-specific derangement of microtubules marked by reduction in JPH2 and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves both t-tubule architecture and RV function. Colchicine also reduces adverse pulmonary vascular remodeling. These results provide biological plausibility for a clinical trial to repurpose colchicine as a RV-directed therapy for PAH. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Prediction of post-operative pulmonary function after lobectomy for primary lung cancer: A comparison among counting method, effective lobar volume, and lobar collapsibility using inspiratory/expiratory CT.

PubMed

Yabuuchi, Hidetake; Kawanami, Satoshi; Kamitani, Takeshi; Yonezawa, Masato; Yamasaki, Yuzo; Yamanouchi, Torahiko; Nagao, Michinobu; Okamoto, Tatsuro; Honda, Hiroshi

2016-11-01

To compare the predictabilities of postoperative pulmonary function after lobectomy for primary lung cancer among counting method, effective lobar volume, and lobar collapsibility. Forty-nine patients who underwent lobectomy for primary lung cancer were enrolled. All patients underwent inspiratory/expiratory CT and pulmonary function tests 2 weeks before surgery and postoperative pulmonary function tests 6-7 months after surgery. Pulmonary function losses (ΔFEV 1.0 and ΔVC) were calculated from the pulmonary function tests. Predictive postoperative pulmonary function losses (ppoΔFEV 1.0 and ppoΔVC) were calculated using counting method, effective volume, and lobar collapsibility. Correlations and agreements between ΔFEV 1.0 and ppoFEV 1.0 and those between ΔVC and ppoΔVC were tested among three methods using Spearman's correlation coefficient and Bland-Altman plots. ΔFEV 1.0 and ppoΔFEV 1.0insp-exp were strongly correlated (r=0.72), whereas ΔFEV 1.0 and ppoΔFEV 1.0count and ΔFEV 1.0 and Pred. ΔFEV 1.0eff.vol. were moderately correlated (r=0.50, 0.56). ΔVC and ppoΔVC eff.vol. (r=0.71) were strongly correlated, whereas ΔVC and ppoΔVC count , and ΔVC and ppoΔVC insp-exp were moderately correlated (r=0.55, 0.42). Volumetry from inspiratory/expiratory CT data could be useful to predict postoperative pulmonary function after lobectomy for primary lung cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pediatric Artificial Lung: A Low-Resistance Pumpless Artificial Lung Alleviates an Acute Lamb Model of Increased Right Ventricle Afterload.

PubMed

Alghanem, Fares; Bryner, Benjamin S; Jahangir, Emilia M; Fernando, Uditha P; Trahanas, John M; Hoffman, Hayley R; Bartlett, Robert H; Rojas-Peña, Alvaro; Hirschl, Ronald B

Lung disease in children often results in pulmonary hypertension and right heart failure. The availability of a pediatric artificial lung (PAL) would open new approaches to the management of these conditions by bridging to recovery in acute disease or transplantation in chronic disease. This study investigates the efficacy of a novel PAL in alleviating an animal model of pulmonary hypertension and increased right ventricle afterload. Five juvenile lambs (20-30 kg) underwent PAL implantation in a pulmonary artery to left atrium configuration. Induction of disease involved temporary, reversible occlusion of the right main pulmonary artery. Hemodynamics, pulmonary vascular input impedance, and right ventricle efficiency were measured under 1) baseline, 2) disease, and 3) disease + PAL conditions. The disease model altered hemodynamics variables in a manner consistent with pulmonary hypertension. Subsequent PAL attachment improved pulmonary artery pressure (p = 0.018), cardiac output (p = 0.050), pulmonary vascular input impedance (Z.0 p = 0.028; Z.1 p = 0.058), and right ventricle efficiency (p = 0.001). The PAL averaged resistance of 2.3 ± 0.8 mm Hg/L/min and blood flow of 1.3 ± 0.6 L/min. This novel low-resistance PAL can alleviate pulmonary hypertension in an acute animal model and demonstrates potential for use as a bridge to lung recovery or transplantation in pediatric patients with significant pulmonary hypertension refractory to medical therapies.

Utility of electrocardiogram in the assessment and monitoring of pulmonary hypertension (idiopathic or secondary to pulmonary developmental abnormalities) in patients≤18 years of age.

PubMed

Lau, Kelvin C; Frank, David B; Hanna, Brian D; Patel, Akash R

2014-07-15

Electrocardiograms have utility in disease stratification and monitoring in adult pulmonary arterial hypertension (PAH). We examined the electrocardiographic findings that are common in pediatric PAH and assessed for correlation with disease severity and progression. We retrospectively identified patients aged≤18 years followed at a single institution from January 2001 to June 2012 with catheterization-confirmed diagnosis of idiopathic PAH and PAH secondary to pulmonary developmental abnormalities. Patients with an electrocardiography performed within 60 days of catheterization were included. Primary and secondary outcomes are the prevalence of abnormal electrocardiographic findings at the time of catheterization and the association between electrocardiographic and hemodynamic findings and electrocardiographic changes with disease progression on follow-up catheterization, respectively. Of the 100 electrocardiography-catheterization pairs derived from the 46 patients identified, 93% had an electrocardiographic abnormality: 78% had right ventricular hypertrophy (RVH) and 52% had right axis deviation (RAD) for age. In patients with idiopathic PAH, the presence of RVH and RAD correlated with pulmonary vascular resistance and transpulmonary gradient. RAD and RVH on baseline electrocardiogram was associated with an increased risk of disease progression on subsequent catheterization (odds ratio 11.0, 95% confidence interval 1.3 to 96.2, p=0.03) after adjusting for PAH subgroup. The sensitivity, specificity, and positive and negative predictive values of RAD and RVH on baseline electrocardiogram for disease progression were 92%, 48%, 33%, and 95%, respectively. In conclusion, electrocardiographic abnormalities are common in pediatric PAH. RAD and RVH on electrocardiogram were associated with worse hemodynamics, whereas their absence is suggestive of a lack of disease progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Impact of Pulmonary Artery Pressure on Exercise Function in Severe COPD

PubMed Central

Sims, Michael W.; Margolis, David J.; Localio, A. Russell; Panettieri, Reynold A.; Kawut, Steven M.; Christie, Jason D.

2009-01-01

Background: Although pulmonary hypertension commonly complicates COPD, the functional consequences of increased pulmonary artery pressures in patients with this condition remain poorly defined. Methods: We conducted a cross-sectional analysis of a cohort of 362 patients with severe COPD who were evaluated for lung transplantation. Patients with pulmonary hemodynamics measured by cardiac catheterization and available 6-min walk test results were included. The association of mean pulmonary artery pressure (mPAP) with pulmonary function, echocardiographic variables, and 6-min walk distance was assessed. Results: The prevalence of pulmonary hypertension (mPAP, > 25 mm Hg; pulmonary artery occlusion pressure [PAOP], < 16 mm Hg) was 23% (95% confidence interval, 19 to 27%). In bivariate analysis, higher mPAP was associated with lower FVC and FEV1, higher Pco2 and lower Po2 in arterial blood, and more right heart dysfunction. Multivariate analysis demonstrated that higher mPAP was associated with shorter distance walked in 6 min, even after adjustment for age, gender, race, height, weight, FEV1, and PAOP (−11 m for every 5 mm Hg rise in mPAP; 95% confidence interval, −21 to −0.7; p = 0.04). Conclusions: Higher pulmonary artery pressures are associated with reduced exercise function in patients with severe COPD, even after controlling for demographics, anthropomorphics, severity of airflow obstruction, and PAOP. Whether treatments aimed at lowering pulmonary artery pressures may improve clinical outcomes in COPD, however, remains unknown. PMID:19318664

Decreased endothelial nitric oxide synthase expression and function contribute to impaired mitochondrial biogenesis and oxidative stress in fetal lambs with persistent pulmonary hypertension.

PubMed

Afolayan, Adeleye J; Eis, Annie; Alexander, Maxwell; Michalkiewicz, Teresa; Teng, Ru-Jeng; Lakshminrusimha, Satyan; Konduri, Girija G

2016-01-01

Impaired vasodilation in persistent pulmonary hypertension of the newborn (PPHN) is characterized by mitochondrial dysfunction. We investigated the hypothesis that a decreased endothelial nitric oxide synthase level leads to impaired mitochondrial biogenesis and function in a lamb model of PPHN induced by prenatal ductus arteriosus constriction. We ventilated PPHN lambs with 100% O2 alone or with inhaled nitric oxide (iNO). We treated pulmonary artery endothelial cells (PAECs) from normal and PPHN lambs with detaNONOate, an NO donor. We observed decreased mitochondrial (mt) DNA copy number, electron transport chain (ETC) complex subunit levels, and ATP levels in PAECs and lung tissue of PPHN fetal lambs at baseline compared with gestation matched controls. Phosphorylation of AMP-activated kinase (AMPK) and levels of peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) and sirtuin-1, which facilitate mitochondrial biogenesis, were decreased in PPHN. Ventilation with 100% O2 was associated with larger decreases in ETC subunits in the lungs of PPHN lambs compared with unventilated PPHN lambs. iNO administration, which facilitated weaning of FiO2 , partly restored mtDNA copy number, ETC subunit levels, and ATP levels. DetaNONOate increased eNOS phosphorylation and its interaction with heat shock protein 90 (HSP90); increased levels of superoxide dismutase 2 (SOD2) mRNA, protein, and activity; and decreased the mitochondrial superoxide levels in PPHN-PAECs. Knockdown of eNOS decreased ETC protein levels in control PAECs. We conclude that ventilation with 100% O2 amplifies oxidative stress and mitochondrial dysfunction in PPHN, which are partly improved by iNO and weaning of oxygen. Copyright © 2016 the American Physiological Society.

Experimental and numeric investigation of Impella pumps as cavopulmonary assistance for a failing Fontan.

PubMed

Haggerty, Christopher M; Fynn-Thompson, Francis; McElhinney, Doff B; Valente, Anne Marie; Saikrishnan, Neelakantan; Del Nido, Pedro J; Yoganathan, Ajit P

2012-09-01

This study sought to evaluate the performance of microaxial ventricular assist devices for the purposes of supporting failing Fontan physiology by decreasing central venous pressure. Three Abiomed Impella pumps (Abiomed, Inc, Danvers, Mass) were evaluated in a mock circulatory system of the Fontan circuit. The local response of pressures and flows to pump function was assessed as a function of pump speed and pulmonary vascular resistance at a high baseline central venous pressure. For one device, subsequent modeling studies were conducted using a lumped parameter model of the single ventricle circuit. The left ventricular devices (Impella 2.5, 5.0) were shown to be suboptimal as single device solutions for cavopulmonary support. The small area of these devices relative to vessel diameter led to significant flow recirculation without an obstructive separator in place. Furthermore, downstream pressure augmentation adversely affected the pressure in the superior vena cava. The use of 2 devices would be mandatory for successful support. The right-sided device (Impella RP), whose outflow was positioned in the left pulmonary artery, demonstrated decreased flow recirculation and did not impede superior caval venous flow. Although static pressure is still required to drive flow through the opposite lung, numeric modeling demonstrated the potential for modest but significant improvements in lowering the central venous pressure (2-8 mm Hg). Left-sided microaxial pumps are not well suited for cavopulmonary support because of severe flow recirculation and the need for multiple devices. The right-ventricular Impella device provides improved performance by directing flow into the pulmonary artery, resulting in modest decreases in central venous pressure. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Rituximab in the Treatment of Interstitial Lung Disease Associated with Antisynthetase Syndrome: A Multicenter Retrospective Case Review.

PubMed

Doyle, Tracy J; Dhillon, Namrata; Madan, Rachna; Cabral, Fernanda; Fletcher, Elaine A; Koontz, Diane C; Aggarwal, Rohit; Osorio, Juan C; Rosas, Ivan O; Oddis, Chester V; Dellaripa, Paul F

2018-06-01

To assess clinical outcomes including imaging findings on computed tomography (CT), pulmonary function testing (PFT), and glucocorticoid (GC) use in patients with the antisynthetase syndrome (AS) and interstitial lung disease (ILD) treated with rituximab (RTX). We retrospectively identified all patients at 2 institutions with AS-ILD who were treated with RTX. Baseline demographics, PFT, and chest CT were assessed before and after RTX. Two radiologists independently evaluated CT using a standardized scoring system. Twenty-five subjects at the Brigham and Women's Hospital (n = 13) and University of Pittsburgh Medical Center (n = 12) were included. Antisynthetase antibodies were identified in all patients (16 Jo1, 6 PL-12, 3 PL-7). In 21 cases (84%), the principal indication for RTX use was recurrent or progressive ILD, owing to failure of other agents. Comparing pre- and post-RTX pulmonary variables at 12 months, CT score and forced vital capacity were stable or improved in 88% and 79% of subjects, respectively. Total lung capacity (%) increased from 56 ± 13 to 64 ± 13 and GC dose decreased from 18 ± 9 to 12 ± 12 mg/day. Although DLCO (%) declined slightly at 1 year, it increased from 42 ± 17 to 70 ± 20 at 3 years. The most common imaging patterns on CT were nonspecific interstitial pneumonia (NSIP; n = 13) and usual interstitial pneumonia/fibrotic NSIP (n = 5), of which 5 had concurrent elements of cryptogenic organizing pneumonia. Stability or improvement in pulmonary function or severity of ILD on CT was seen in most patients. Use of RTX was well tolerated in the majority of patients. RTX may play a therapeutic role in patients with AS-ILD, and further clinical investigation is warranted.

Severity of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension in African Americans

PubMed Central

Blanco, Isabel; Mathai, Stephen; Shafiq, Majid; Boyce, Danielle; M. Kolb, Todd; Chami, Hala; K. Hummers, Laura; Housten, Traci; Chaisson, Neal; L. Zaiman, Ari; M. Wigley, Fredrick; J. Tedford, Ryan; A. Kass, David; Damico, Rachel; E. Girgis, Reda; M. Hassoun, Paul

2014-01-01

Abstract African Americans (AA) with systemic sclerosis (SSc) have a worse prognosis compared to Americans of European descent (EA). We conducted the current study to test the hypothesis that AA patients with SSc have more severe disease and poorer outcomes compared to EA patients when afflicted with pulmonary arterial hypertension (PAH). We studied 160 consecutive SSc patients with PAH diagnosed by right heart catheterization, comparing demographics, hemodynamics, and outcomes between AA and EA patients. The cohort included 29 AA and 131 EA patients with similar baseline characteristics except for increased prevalence of diffuse SSc in AA. AA patients had worse functional class (FC) (80% FC III-IV vs 53%; p = 0.02), higher brain natriuretic peptide (NT-pro-BNP) (5729 ± 9730 pg/mL vs 1892 ± 2417 pg/mL; p = 0.02), more depressed right ventricular function, a trend toward lower 6-minute walk distance (263 ± 111  m vs 333 ± 110  m; p = 0.07), and worse hemodynamics (cardiac index 1.95 ± 0.58 L/min/m2 vs 2.62 ± 0.80 L/min/m2; pulmonary vascular resistance 10.3 ± 6.2 WU vs 7.6 ± 5.0 WU; p  < 0.05) compared with EA patients. Kaplan-Meier survival estimates for AA and EA patients, respectively, were 62% vs 73% at 2 years and 26% vs 44% at 5 years (p  > 0.05). In conclusion, AA patients with SSc-PAH are more likely to have diffuse SSc and to present with significantly more severe PAH compared with EA patients. AA patients also appear to have poorer survival, though larger studies are needed to investigate this association definitively. PMID:25181310

Role of Vascular and Lymphatic Endothelial Cells in Hantavirus Pulmonary Syndrome Suggests Targeted Therapeutic Approaches

PubMed Central

Gorbunova, Elena E.; Dalrymple, Nadine A.; Gavrilovskaya, Irina N.

2013-01-01

Abstract Background Hantaviruses in the Americas cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). Hantaviruses nonlytically infect microvascular and lymphatic endothelial cells and cause dramatic changes in barrier functions without disrupting the endothelium. Hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions. The endothelium of arteries, veins, and lymphatic vessels are unique and central to the function of vast pulmonary capillary beds that regulate pulmonary fluid accumulation. Results We have found that HPS-causing hantaviruses alter vascular barrier functions of microvascular and lymphatic endothelial cells by altering receptor and signaling pathway responses that serve to permit fluid tissue influx and clear tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to cause acute pulmonary edema, as well as potential therapeutic targets for reducing the severity of HPS disease. Conclusions Here we discuss interactions of HPS-causing hantaviruses with the endothelium, roles for unique lymphatic endothelial responses in HPS, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease. PMID:24024573

Role of vascular and lymphatic endothelial cells in hantavirus pulmonary syndrome suggests targeted therapeutic approaches.

PubMed

Mackow, Erich R; Gorbunova, Elena E; Dalrymple, Nadine A; Gavrilovskaya, Irina N

2013-09-01

Hantaviruses in the Americas cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). Hantaviruses nonlytically infect microvascular and lymphatic endothelial cells and cause dramatic changes in barrier functions without disrupting the endothelium. Hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions. The endothelium of arteries, veins, and lymphatic vessels are unique and central to the function of vast pulmonary capillary beds that regulate pulmonary fluid accumulation. We have found that HPS-causing hantaviruses alter vascular barrier functions of microvascular and lymphatic endothelial cells by altering receptor and signaling pathway responses that serve to permit fluid tissue influx and clear tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to cause acute pulmonary edema, as well as potential therapeutic targets for reducing the severity of HPS disease. Here we discuss interactions of HPS-causing hantaviruses with the endothelium, roles for unique lymphatic endothelial responses in HPS, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease.

Effect of medical conditions on improvement in self-reported and observed functional performance of elders.

PubMed

Miller, Ram R; Zhang, Yuqing; Silliman, Rebecca A; Hayes, Margaret Kelly; Leveille, Suzanne G; Murabito, Joanne M; Kiel, Douglas; O'Connor, George T; Felson, David T

2004-02-01

To evaluate the effect of nine disabling medical conditions upon recovery from functional limitations by elders. Retrospective analysis of prospective longitudinal cohort. Community. Persons aged 65 and older in Framingham Heart Study. Change in function in elders from biennial Examinations 18 (1983-85; baseline) through 23 (1994-96). At each examination, subjects reported limitations in heavy household work, walking up and down stairs, walking half a mile, bathing, toileting, and continence. They were also directly observed for performance of transferring in and out of a chair, dressing, walking 50 feet, and carrying a 10-pound object 10 feet. The prevalence of functional limitations and the incidence of recovery from functional limitation by the subsequent examination for each task were calculated. The effects of congestive heart failure, cognitive impairment, diabetes mellitus, stroke, depressive symptoms, hip fracture, knee pain, claudication, and chronic obstructive pulmonary disease were evaluated. The relationship between the total number of comorbid conditions present (0, 1, 2, 3 or more), the presence of each individual condition at the start of each examination cycle, and the incidence of recovery from functional limitations were examined using generalized estimating equations. One thousand eight hundred twenty-five subjects were studied at baseline; 1,026 were available 10 years later. Mean age of subjects at baseline was 73.5 (range 61-95); 60.7% were women. The prevalence of functional limitations ranged from 3.1% to 29.8% at biennial Examination 18 and increased to 15.1% to 32.4% at Examination 23. The incidence of recovery ranged from 3.2% to 78.4% depending upon the task and the examination cycle. Increasing disease burden, as measured by the number of comorbidities, was associated with a decreased likelihood of recovery from functional limitations. Diabetes mellitus, stroke, depressive symptoms, hip fracture, and knee pain had the strongest adverse effect upon recovery from functional limitations. In these community-dwelling elders, recovery from prevalent functional limitations was frequent. Increasing disease burden was associated with a decreased incidence of recovery. Diabetes mellitus, stroke, depressive symptoms, hip fracture, and knee pain had the strongest adverse effect on recovery from functional limitations.

Impaired pulmonary function after treatment for tuberculosis: the end of the disease?

PubMed

Chushkin, Mikhail Ivanovich; Ots, Oleg Nikolayevich

2017-01-01

To evaluate the prevalence of pulmonary function abnormalities and to investigate the factors affecting lung function in patients treated for pulmonary tuberculosis. A total of 214 consecutive patients (132 men and 82 women; 20-82 years of age), treated for pulmonary tuberculosis and followed at a local dispensary, underwent spirometry and plethysmography at least one year after treatment. Pulmonary impairment was present in 102 (47.7%) of the 214 patients evaluated. The most common functional alteration was obstructive lung disease (seen in 34.6%). Of the 214 patients, 60 (28.0%) showed reduced pulmonary function (FEV1 below the lower limit of normal). Risk factors for reduced pulmonary function were having had culture-positive pulmonary tuberculosis in the past, being over 50 years of age, having recurrent tuberculosis, and having a lower level of education. Nearly half of all tuberculosis patients evolve to impaired pulmonary function. That underscores the need for pulmonary function testing after the end of treatment. Avaliar a prevalência de alterações da função pulmonar e investigar os fatores que afetam a função pulmonar em pacientes tratados para tuberculose pulmonar. Um total de 214 pacientes consecutivos (132 homens e 82 mulheres; 20-82 anos de idade), tratados para tuberculose pulmonar e acompanhados em um dispensário local, foi submetido a espirometria e pletismografia pelo menos um ano após o tratamento. O comprometimento pulmonar estava presente em 102 (47,7%) dos 214 pacientes avaliados. A alteração funcional mais comum foi o distúrbio ventilatório obstrutivo (observado em 34,6%). Dos 214 pacientes, 60 (28,0%) apresentaram função pulmonar reduzida (VEF1 abaixo do limite inferior de normalidade). Os fatores de risco para função pulmonar reduzida foram tuberculose pulmonar com cultura positiva no passado, idade acima de 50 anos, recidiva de tuberculose e menor nível de escolaridade. Quase metade de todos os pacientes com tuberculose evolui com comprometimento da função pulmonar. Isso reforça a necessidade de testes de função pulmonar após o término do tratamento.

[Clinical, hemodynamic and angiographic results of total cavo-pulmonary connection].

PubMed

Jimenez, A C; Neville, P; Chamboux, C; Crenn, R; Vaillant, M C; Marchand, M; Chantepie, A

1998-05-01

The aim of the study was to assess the short and medium term results of total cavo-pulmonary connection based on analysis of the functional status, the cavo-pulmonary circulation and the surgical techniques, and the hepatic consequences. Fifteen patients with congenital defects beyond repair were treated by total cavo-pulmonary connection at Tours between March 1st 1992 and July 30th 1996. There were 12 children (mean age: 6.3 years) and 3 adults aged 25 to 28. Results were assessed by clinical examination, hepatic function tests and cardiovascular investigations including right heart catheterisation with angiography in 14 patients. There were no fatalities. Seven patients were in functional Class I and 8 in Class II at medium term (average follow-up of 33 months). Hepatic function was mildly abnormal in all patients with an increase in serum bilirubin and gamma GT, and a decrease in the coagulation factors. The mean pressures in the atrial channel were 12 mmHg (9-16 mmHg), in the superior vena 13.2 mmHg (10-18 mmHg), in the right pulmonary artery 9.5 mmHg (7-15 mmHg) and 11.6 mmHg (8-16 mmHg) in the left pulmonary artery. Significant residual stenosis of a pulmonary branch was observed in 2 cases. The cavo-pulmonary anastomoses were out of line, one from the other, in all cases. The atrial channel was tubular in 9 cases and dilated with slight stagnation of the contrast medium in its inferior region in 5 cases. Total cavo-pulmonary connection transformed the clinical status of these patients but was associated with minor abnormalities of liver function. The quality of the cavo-pulmonary circulation and the surgical anastomoses was estimated to be satisfactory in the majority of cases.

Pulmonary Morbidity in Infancy after Exposure to Chorioamnionitis in Late Preterm Infants.

PubMed

McDowell, Karen M; Jobe, Alan H; Fenchel, Matthew; Hardie, William D; Gisslen, Tate; Young, Lisa R; Chougnet, Claire A; Davis, Stephanie D; Kallapur, Suhas G

2016-06-01

Chorioamnionitis is an important cause of preterm birth, but its impact on postnatal outcomes is understudied. To evaluate whether fetal exposure to inflammation is associated with adverse pulmonary outcomes at 6 to 12 months' chronological age in infants born moderate to late preterm. Infants born between 32 and 36 weeks' gestational age were prospectively recruited (N = 184). Chorioamnionitis was diagnosed by placenta and umbilical cord histology. Select cytokines were measured in samples of cord blood. Validated pulmonary questionnaires were administered (n = 184), and infant pulmonary function testing was performed (n = 69) between 6 and 12 months' chronological age by the raised volume rapid thoracoabdominal compression technique. A total of 25% of participants had chorioamnionitis. Although infant pulmonary function testing variables were lower in infants born preterm compared with historical normative data for term infants, there were no differences between infants with chorioamnionitis (n = 20) and those without (n = 49). Boys and black infants had lower infant pulmonary function testing measurements than girls and white infants, respectively. Chorioamnionitis exposure was associated independently with wheeze (odds ratio [OR], 2.08) and respiratory-related physician visits (OR, 3.18) in the first year of life. Infants exposed to severe chorioamnionitis had increased levels of cord blood IL-6 and greater pulmonary morbidity at age 6 to 12 months than those exposed to mild chorioamnionitis. Elevated IL-6 was associated with significantly more respiratory problems (OR, 3.23). In infants born moderate or late preterm, elevated cord blood IL-6 and exposure to histologically identified chorioamnionitis was associated with respiratory morbidity during infancy without significant changes in infant pulmonary function testing measurements. Black compared with white and boy compared with girl infants had lower infant pulmonary function testing measurements and worse pulmonary outcomes.

Occult pulmonary embolism: a common occurrence in deep venous thrombosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dorfman, G.S.; Cronan, J.J.; Tupper, T.B.

1987-02-01

Ventilation-perfusion scans were used in a prospective study to determine the prevalence of occult pulmonary embolus in proven deep venous thrombosis. Fifty-eight patients without symptoms of pulmonary embolism, but with venographically proven deep venous thrombosis, were subjected to chest radiographs, /sup 99m/Tc macroaggregated-albumin perfusion scans, and /sup 133/Xe ventilation scans. Of the 49 patients with deep venous thrombosis proximal to the calf veins, 17 (35%) had high-probability scans. Of all 58 patients, only 12 (21%) had normal scans. When the study population was compared with a group of 430 patients described in reports of pulmonary perfusion in asymptomatic persons, amore » significantly higher percentage of high-probability scans was found in the study population with deep venous thrombosis. Baseline ventilation-perfusion lung scanning is valuable for patients with proven above-knee deep venous thrombosis.« less

Pulmonary functions in plastic factory workers: a preliminary study.

PubMed

Khaliq, Farah; Singh, Pawan; Chandra, Prakash; Gupta, Keshav; Vaney, Neelam

2011-01-01

Exposure to long term air pollution in the work environment may result in decreased lung functions and various other health problems. A significant occupational hazard to lung functions is experienced by plastic factory workers. The present study is planned to assess the pulmonary functions of workers in the plastic factory where recycling of pastic material was done. These workers were constantly exposed to fumes of various chemicals throughout the day. Thirty one workers of plastic factory were assessed for their pulmonary functions. Parameters were compared with 31 age and sex matched controls not exposed to the same environment. The pulmonary function tests were done using Sibelmed Datospir 120 B portable spirometer. A significant decrease in most of the flow rates (MEF 25%, MEF 50%, MEF 75% and FEF 25-75%) and most of the lung volumes and capacities (FVC, FEV1, VC, TV, ERV, MVV) were observed in the workers. Smoking and duration of exposure were not affecting the lung functions as the non smokers also showed a similar decrement in pulmonary functions. Similarly the workers working for less than 5 years also had decrement in pulmonary functions indicating that their lungs are being affected even if they have worked for one year. Exposure to the organic dust in the work environment should be controlled by adequate engineering measures, complemented by effective personal respiratory protection.

Characteristics of Alpha-1 Antitrypsin-Deficient Individuals in the Long-term Oxygen Treatment Trial and Comparison with Other Subjects with Chronic Obstructive Pulmonary Disease.

PubMed

Stoller, James K; Aboussouan, Loutfi S; Kanner, Richard E; Wilson, Laura A; Diaz, Phil; Wise, Robert

2015-12-01

Alpha-1 antitrypsin deficiency (AATD) predisposes to chronic obstructive pulmonary disease, but is underrecognized. Oxygenation and exercise desaturation in individuals with AATD-associated chronic obstructive pulmonary disease has been sparsely studied. The Long-term Oxygen Treatment Trial (LOTT) permits comparing these features of individuals with AATD with alpha-1 antitrypsin-replete (called "usual chronic obstructive pulmonary disease") LOTT participants. Compare demographic, clinical, baseline oxygenation, and exercise desaturation features in participating AATD subjects with those of other LOTT subjects. LOTT is a multicenter randomized controlled trial comparing use of supplemental oxygen versus not in subjects with chronic obstructive pulmonary disease and moderate hypoxemia (resting oxygen saturation as measured by pulse oximetry, 89-93%) or normal oxygen saturation at rest and significant exercise desaturation. Among the 597 LOTT participants with nonmissing alpha-1 antitrypsin levels, 11 (1.8%) had severe AATD and 44 (7.4%) had mild/moderate AATD. Comparison of the 11 severely AAT-deficient individuals with the 542 LOTT participants with usual chronic obstructive pulmonary disease showed that the AATD subjects were younger and despite less smoking, had lower FEV1/FVC (mean post-bronchodilator FEV1/FVC, 0.38 ± 0.06 vs. 0.46 ± 0.13; P = 0.002). Comparison with 27 age-, sex-, and FEV1-matched alpha-1 antitrypsin-normal LOTT participants showed no baseline difference in resting room air pulse oximetry saturation (AATD, 93.6% ± 2.3% vs. 92.7% ± 2.2%; P = 0.64). Exercise-related desaturation was more severe in the individuals with AATD based on desaturation to 88% or less sooner during a 6-minute-walk test, having a higher percentage of desaturation points (e.g., <90%) during exercise, and having a higher distance-saturation product (defined as the distance walked in 6 min multiplied by the nadir saturation achieved during the 6-minute-walk test). These data suggest that individuals with AATD experience more profound desaturation with exercise than age-, sex-, race-, and FEV1-matched control subjects with usual chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00692198).

Antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease: protocol of a randomised controlled proof-of-concept trial (APPLE COPD-ICON 2).

PubMed

Kunadian, Vijay; Chan, Danny; Ali, Hani; Wilkinson, Nina; Howe, Nicola; McColl, Elaine; Thornton, Jared; von Wilamowitz-Moellendorff, Alexander; Holstein, Eva-Maria; Burns, Graham; Fisher, Andrew; Stocken, Deborah; De Soyza, Anthony

2018-05-26

The antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease (APPLE COPD-ICON2) trial is a prospective 2×2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) at high risk of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the required response in platelet function measured using the Multiplate test in patients with COPD. Patients with COPD are screened for eligibility using inclusion and exclusion criteria. Eligible patients are randomised and allocated into one of four groups to receive aspirin plus placebo, ticagrelor plus placebo, aspirin plus ticagrelor or placebo only. Markers of systemic inflammation, platelet reactivity, arterial stiffness, carotid intima-media thickness (CIMT), lung function and quality of life questionnaires are assessed. The primary outcome consists of inhibition (binary response) of aspirin and ADP-induced platelet function at 6 months. Secondary outcomes include changes in inflammatory markers, CIMT, non-invasive measures of vascular stiffness, quality of life using questionnaires (EuroQol-five dimensions-five levels of perceived problems (EQ5D-5L), St. George's COPD questionnaire) and to record occurrence of repeat hospitalisation, angina, myocardial infarction or death from baseline to 6 months. Safety outcomes will be rates of major and minor bleeding, forced expiratory volume in 1 s, forced vital capacity and Medical Research Council dyspnoea scale. The study was approved by the North East-Tyne and Wear South Research Ethics Committee (15/NE/0155). Findings of the study will be presented in scientific sessions and published in peer-reviewed journals. ISRCTN43245574; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sleep and pulmonary outcomes for clinical trials of airway plexiform neurofibromas in NF1.

PubMed

Plotkin, Scott R; Davis, Stephanie D; Robertson, Kent A; Akshintala, Srivandana; Allen, Julian; Fisher, Michael J; Blakeley, Jaishri O; Widemann, Brigitte C; Ferner, Rosalie E; Marcus, Carole L

2016-08-16

Plexiform neurofibromas (PNs) are complex, benign nerve sheath tumors that occur in approximately 25%-50% of individuals with neurofibromatosis type 1 (NF1). PNs that cause airway compromise or pulmonary dysfunction are uncommon but clinically important. Because improvement in sleep quality or airway function represents direct clinical benefit, measures of sleep and pulmonary function may be more meaningful than tumor size as endpoints in therapeutic clinical trials targeting airway PN. The Response Evaluation in Neurofibromatosis and Schwannomatosis functional outcomes group reviewed currently available endpoints for sleep and pulmonary outcomes and developed consensus recommendations for response evaluation in NF clinical trials. For patients with airway PNs, polysomnography, impulse oscillometry, and spirometry should be performed to identify abnormal function that will be targeted by the agent under clinical investigation. The functional group endorsed the use of the apnea hypopnea index (AHI) as the primary sleep endpoint, and pulmonary resistance at 10 Hz (R10) or forced expiratory volume in 1 or 0.75 seconds (FEV1 or FEV0.75) as primary pulmonary endpoints. The group defined minimum changes in AHI, R10, and FEV1 or FEV0.75 for response criteria. Secondary sleep outcomes include desaturation and hypercapnia during sleep and arousal index. Secondary pulmonary outcomes include pulmonary resistance and reactance measurements at 5, 10, and 20 Hz; forced vital capacity; peak expiratory flow; and forced expiratory flows. These recommended sleep and pulmonary evaluations are intended to provide researchers with a standardized set of clinically meaningful endpoints for response evaluation in trials of NF1-related airway PNs. © 2016 American Academy of Neurology.

Pulmonary MR imaging with ultra-short TEs: utility for disease severity assessment of connective tissue disease patients.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Takenaka, Daisuke; Takahashi, Masaya; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Obara, Makoto; van Cauteren, Marc; Sugimura, Kazuro

2013-08-01

To evaluate the utility of pulmonary magnetic resonance (MR) imaging with ultra-short echo times (UTEs) at a 3.0 T MR system for pulmonary functional loss and disease severity assessments of connective tissue disease (CTD) patients with interstitial lung disease (ILD). This prospective study was approved by the institutional review board, and written informed consent was obtained from 18 CTD patients (eight men and ten women) and eight normal subjects with suspected chest disease (three men and five women). All subjects underwent thin-section MDCT, pulmonary MR imaging with UTEs, pulmonary function test and serum KL-6. Regional T2 maps were generated from each MR data set, and mean T2 values were determined from ROI measurements. From each thin-section MDCT data set, CT-based disease severity was evaluated with a visual scoring system. Mean T2 values for normal and CTD subjects were statistically compared by using Student's t-test. To assess capability for pulmonary functional loss and disease severity assessments, mean T2 values were statistically correlated with pulmonary functional parameters, serum KL-6 and CT-based disease severity. Mean T2 values for normal and CTD subjects were significantly different (p=0.0019) and showed significant correlations with %VC, %DLCO, serum KL-6 and CT-based disease severity of CTD patients (p<0.05). Pulmonary MR imaging with UTEs is useful for pulmonary functional loss and disease severity assessments of CTD patients with ILD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Correlation between pulmonary function and brain volume in healthy elderly subjects.

PubMed

Taki, Yasuyuki; Kinomura, Shigeo; Ebihara, Satoru; Thyreau, Benjamin; Sato, Kazunori; Goto, Ryoi; Kakizaki, Masako; Tsuji, Ichiro; Kawashima, Ryuta; Fukuda, Hiroshi

2013-06-01

Cigarette smoking decreases brain regional gray matter volume and is related to chronic obstructive lung disease (COPD). COPD leads to decreased pulmonary function, which is represented by forced expiratory volume in one second percentage (FEV1.0 %); however, it is unclear if decreased pulmonary function is directly related to brain gray matter volume decline. Because there is a link between COPD and cognitive decline, revealing a direct relationship between pulmonary function and brain structure is important to better understand how pulmonary function affects brain structure and cognitive function. Therefore, the purpose of this study was to analyze whether there were significant correlations between FEV1.0 % and brain regional gray and white matter volumes using brain magnetic resonance (MR) image data from 109 community-dwelling healthy elderly individuals. Brain MR images were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. We found a significant positive correlation between the regional white matter volume of the cerebellum and FEV1.0 % after adjusting for age, sex, and intracranial volume. Our results suggest that elderly individuals who have a lower FEV1.0 % have decreased regional white matter volume in the cerebellum. Therefore, preventing decreased pulmonary function is important for cerebellar white matter volume in the healthy elderly population.

Association between high-density lipoprotein cholesterol level and pulmonary function in healthy Korean adolescents: the JS high school study.

PubMed

Park, Ji Hye; Mun, Seyeon; Choi, Dong Phil; Lee, Joo Young; Kim, Hyeon Chang

2017-12-11

Accumulating evidence suggests that high-density lipoprotein (HDL) cholesterol is associated with pulmonary function and pulmonary disorders. The aim of this study was to evaluate the association between HDL cholesterol and pulmonary function in healthy adolescents. This cross-sectional study was based on data collected for the JS High School study. The analysis included 644 adolescents (318 male and 326 female) aged 15-16 years old and free from asthma or chronic obstructive pulmonary disease. Fasting blood samples were collected for hematologic and biochemical assessment. Forced vital capacity volume (FVC) and forced expiratory volume in the 1 s (FEV1) were measured using dry-rolling-seal spirometry. The associations between HDL cholesterol and pulmonary function were analyzed using multiple linear regression models. Among male adolescents, an increase of 1.0 mg/dL in HDL cholesterol was associated with 10 mL decrease in FVC (p = 0.013) and FEV1 (p = 0.013) after adjusting for age, height, weight, alcohol drinking, smoking, physical activity, systolic blood pressure, total cholesterol, triglyceride, and monthly household income. Percent predicted values of FVC (p = 0.036) and FEV1 (p = 0.017) were also inversely associated with HDL cholesterol. However, among female adolescents, HDL cholesterol level was not significantly associated with absolute or percent predictive value of FVC and FEV1. Higher HDL cholesterol level may be associated with decreased pulmonary function among healthy male adolescents. The sex differences observed in the association between HDL cholesterol and pulmonary function need further investigation.

Regulation of pulmonary inflammation by mesenchymal cells.

PubMed

Alkhouri, Hatem; Poppinga, Wilfred Jelco; Tania, Navessa Padma; Ammit, Alaina; Schuliga, Michael

2014-12-01

Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue remodelling, but also have an important role in pulmonary inflammation. This review will describe the immunomodulatory functions of pulmonary mesenchymal cells, such as airway smooth muscle (ASM) cells and lung fibroblasts, in chronic respiratory disease. An important theme of the review is that pulmonary mesenchymal cells not only respond to inflammatory mediators, but also produce their own mediators, whether pro-inflammatory or pro-resolving, which influence the quantity and quality of the lung immune response. The notion that defective pro-inflammatory or pro-resolving signalling in these cells potentially contributes to disease progression is also discussed. Finally, the concept of specifically targeting pulmonary mesenchymal cell immunomodulatory function to improve therapeutic control of chronic respiratory disease is considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

Right ventricular morphology and function in chronic obstructive pulmonary disease patients living at high altitude.

PubMed

Güvenç, Tolga Sinan; Erer, Hatice Betül; Kul, Seref; Perinçek, Gökhan; Ilhan, Sami; Sayar, Nurten; Yıldırım, Binnaz Zeynep; Doğan, Coşkun; Karabağ, Yavuz; Balcı, Bahattin; Eren, Mehmet

2013-01-01

Pulmonary vasculature is affected in patients with chronic pulmonary obstructive disease (COPD). As a result of increased pulmonary resistance, right ventricular morphology and function are altered in COPD patients. High altitude and related hypoxia causes pulmonary vasoconstriction, thereby affecting the right ventricle. We aimed to investigate the combined effects of COPD and altitude-related chronic hypoxia on right ventricular morphology and function. Forty COPD patients living at high altitude (1768 m) and 41 COPD patients living at sea level were enrolled in the study. All participants were diagnosed as COPD by a pulmonary diseases specialist depending on symptoms, radiologic findings and pulmonary function test results. Detailed two-dimensional echocardiography was performed by a cardiologist at both study locations. Oxygen saturation and mean pulmonary artery pressure were higher in the high altitude group. Right ventricular end diastolic diameter, end systolic diameter, height and end systolic area were significantly higher in the high altitude group compared to the sea level group. Parameters of systolic function, including tricuspid annular systolic excursion, systolic velocity of tricuspid annulus and right ventricular isovolumic acceleration were similar between groups, while fractional area change was significantly higher in the sea level groups compared to the high altitude group. Indices of diastolic function and myocardial performance index were similar between groups. An increase in mean pulmonary artery pressure and right ventricular dimensions are observed in COPD patients living at high altitude. Despite this increase, systolic and diastolic functions of the right ventricle, as well as global right ventricular performance are similar in COPD patients living at high altitude and sea level. Altitude-related adaptation to chronic hypoxia could explain these findings. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Pulmonary Function in Middle-Aged Patients With Idiopathic Scoliosis With Onset Before the Age of 10 Years.

PubMed

Danielsson, Aina J; Ekerljung, Linda; Hallerman, Kerstin Lofdahl

2015-09-01

Consecutive patients with idiopathic scoliosis diagnosed before age 10 attended a clinical follow-up at least 10 years after treatment. To evaluate the pulmonary function in adulthood after treatment with brace or surgery before maturity. Long-term studies of these patients have not been published. One hundred twenty-four patients (69% of the original group) underwent radiography, spirometry, and answered symptom questionnaires. A total of 73 patients had spirometries before treatment enabling longitudinal evaluation. Overall, 68 braced only (BT) and 56 surgically treated (ST) were analyzed in detail. A population-based control group was used. At follow-up, the mean age was 41.5 years and the mean curve size 36 degrees (26% of the curves >45 degrees). The full patient group had a significantly reduced pulmonary function (as measured by the forced vital capacity [FVC], percentage of predicted) compared with the control group, mean 85% versus 102% (p < .0001). Both subgroups of BT and ST patients showed a significant reduction, more in the ST than the BT group (means 79% and 90%, respectively, p = .0003). The most important risk factor for a low lung function at follow-up was a low initial FVC value. Initial curve size correlated with pulmonary function both before treatment and at follow-up. Most surgically treated patients, who had larger curves before treatment, did not improve their pulmonary function after surgery. Both braced and surgically treated patients had reduced pulmonary function at the age of around 40 years. The pulmonary function did not worsen over time in most patients. There was no difference in terms of symptoms between patient groups and controls. Initial curve size was found to be of great importance for pulmonary function. Initial spirometry and follow-up in selected patients is important. III. Copyright © 2015 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Skeletal muscle power and fatigue at the tolerable limit of ramp-incremental exercise in COPD.

PubMed

Cannon, Daniel T; Coelho, Ana Claudia; Cao, Robert; Cheng, Andrew; Porszasz, Janos; Casaburi, Richard; Rossiter, Harry B

2016-12-01

Muscle fatigue (a reduced power for a given activation) is common following exercise in chronic obstructive pulmonary disease (COPD). Whether muscle fatigue, and reduced maximal voluntary locomotor power, are sufficient to limit whole body exercise in COPD is unknown. We hypothesized in COPD: 1) exercise is terminated with a locomotor muscle power reserve; 2) reduction in maximal locomotor power is related to ventilatory limitation; and 3) muscle fatigue at intolerance is less than age-matched controls. We used a rapid switch from hyperbolic to isokinetic cycling to measure the decline in peak isokinetic power at the limit of incremental exercise ("performance fatigue") in 13 COPD patients (FEV 1 49 ± 17%pred) and 12 controls. By establishing the baseline relationship between muscle activity and isokinetic power, we apportioned performance fatigue into the reduction in muscle activation and muscle fatigue. Peak isokinetic power at intolerance was ~130% of peak incremental power in controls (274 ± 73 vs. 212 ± 84 W, P < 0.05), but ~260% in COPD patients (187 ± 141 vs. 72 ± 34 W, P < 0.05), greater than controls (P < 0.05). Muscle fatigue as a fraction of baseline peak isokinetic power was not different in COPD patients vs. controls (0.11 ± 0.20 vs. 0.19 ± 0.11). Baseline to intolerance, the median frequency of maximal isokinetic muscle activity, was unchanged in COPD patients but reduced in controls (+4.3 ± 11.6 vs. -5.5 ± 7.6%, P < 0.05). Performance fatigue as a fraction of peak incremental power was greater in COPD vs. controls and related to resting (FEV 1 /FVC) and peak exercise (V̇ E /maximal voluntary ventilation) pulmonary function (r 2 = 0.47 and 0.55, P < 0.05). COPD patients are more fatigable than controls, but this fatigue is insufficient to constrain locomotor power and define exercise intolerance. Copyright © 2016 the American Physiological Society.

Heat shock protein 70 secretion by neonatal tracheal tissue during mechanical ventilation: association with indices of tissue function and modeling.

PubMed

Chong, Euming; Dysart, Kevin C; Chidekel, Aaron; Locke, Robert; Shaffer, Thomas H; Miller, Thomas L

2009-04-01

Mechanical ventilation (MV) of the neonatal airway alters mechanical properties and activates tissue-modeling pathways. Heat shock protein (HSP70) is a marker of tissue injury and modulates inflammation, which may influence subsequent pulmonary tissue modeling by matrix metalloproteinases (MMPs). HSP70 secretion is up-regulated in MV airway tissues and associated with changes in airway elasticity and secretion of MMPs. Proximal tracheal segments were isolated in 13 newborn lambs and were either MV for 4 h or SHAM. At baseline and hourly, tracheal segments were flushed and tracheal elasticity was determined. Tracheal wash fluid was assayed for HSP70 by ELISA and for MMPs by substrate zymography. HSP70 secretion increased from baseline to a peak at 1 h in both groups (p < 0.01), greater in the MV group (p < 0.05), and returned to baseline values by 2 h. This response was in contrast to the progressive decrease in tracheal elasticity (p < 0.05). The HSP70 elevation pattern was noted in MMP-2, but beyond 1 h, MMP-2 returned to baseline values in MV group but remained elevated in SHAM (p < 0.05). HSP70 secretion is associated with the degree of biophysical tracheal injury as well as the time course of MMP-2 secretion by tracheal tissues.

International spinal cord injury pulmonary function basic data set.

PubMed

Biering-Sørensen, F; Krassioukov, A; Alexander, M S; Donovan, W; Karlsson, A-K; Mueller, G; Perkash, I; Sheel, A William; Wecht, J; Schilero, G J

2012-06-01

To develop the International Spinal Cord Injury (SCI) Pulmonary Function Basic Data Set within the framework of the International SCI Data Sets in order to facilitate consistent collection and reporting of basic bronchopulmonary findings in the SCI population. International. The SCI Pulmonary Function Data Set was developed by an international working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. The final International SCI Pulmonary Function Data Set contains questions on the pulmonary conditions diagnosed before spinal cord lesion,if available, to be obtained only once; smoking history; pulmonary complications and conditions after the spinal cord lesion, which may be collected at any time. These data include information on pneumonia, asthma, chronic obstructive pulmonary disease and sleep apnea. Current utilization of ventilator assistance including mechanical ventilation, diaphragmatic pacing, phrenic nerve stimulation and Bi-level positive airway pressure can be reported, as well as results from pulmonary function testing includes: forced vital capacity, forced expiratory volume in one second and peak expiratory flow. The complete instructions for data collection and the data sheet itself are freely available on the website of ISCoS (http://www.iscos.org.uk).

Optical techniques in pulmonary medicine. SPIE photonics West.

PubMed

Suter, Melissa J; Lam, Stephen; Brenner, Matthew

2012-04-01

There is ongoing interest in the emerging field of pulmonary photonic-based diagnostics. Potential clinical need areas that are being actively investigated at this time include airway and peripheral lung cancer diagnostics, pulmonary parenchymal and interstitial disorders, alveolar structure function, inhalation injury, ciliary function analysis, asthma and obstructive lung diseases.

Leaving Moderate Tricuspid Valve Regurgitation Alone at the Time of Pulmonary Valve Replacement: A Worthwhile Approach.

PubMed

Kogon, Brian; Mori, Makoto; Alsoufi, Bahaaldin; Kanter, Kirk; Oster, Matt

2015-06-01

Pulmonary valve disruption in patients with tetralogy of Fallot and congenital pulmonary stenosis often results in pulmonary insufficiency, right ventricular dilation, and tricuspid valve regurgitation. Management of functional tricuspid regurgitation at the time of subsequent pulmonary valve replacement remains controversial. Our aims were to (1) analyze tricuspid valve function after pulmonary valve replacement through midterm follow-up and (2) determine the benefits, if any, of concomitant tricuspid annuloplasty. Thirty-five patients with tetralogy of Fallot or congenital pulmonary stenosis were analyzed. All patients had been palliated in childhood by disrupting the pulmonary valve, and all patients had at least moderate tricuspid valve regurgitation at the time of subsequent pulmonary valve replacement. Preoperative and serial postoperative echocardiograms were analyzed. Pulmonary and tricuspid regurgitation, along with right ventricular dilation and dysfunction were scored as 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Right ventricular volume and area were also calculated. Comparisons were made between patients who underwent pulmonary valve replacement alone and those who underwent concomitant tricuspid valve annuloplasty. At 1 month after pulmonary valve replacement, there were significant reductions in pulmonary valve regurgitation (mean 3 vs 0.39, p < 0.0001), tricuspid valve regurgitation (mean 2.33 vs 1.3, p < 0.0001), and in right ventricular dilation, volume, and area. There was no difference in the degree of tricuspid regurgitation 1 month postoperatively between patients who underwent concomitant tricuspid annuloplasty and those who underwent pulmonary valve replacement alone (mean 1.31 vs 1.29, p = 0.81). However, at latest follow-up (mean 7.0 ± 2.8 years), the degree of tricuspid regurgitation was significantly higher in the concomitant annuloplasty group (mean 1.87 vs 1.12, p = 0.005). In patients with at least moderate tricuspid valve regurgitation, significant improvement in tricuspid valve function and right ventricular size occurs in the first postoperative month after pulmonary valve replacement, irrespective of concomitant tricuspid valve annuloplasty. The tricuspid valve appears to function better over the midterm if annuloplasty is not performed. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Angiotensin-converting enzyme DD genotype in patients with primary pulmonary hypertension: increased frequency and association with preserved haemodynamics.

PubMed

Abraham, William T; Raynolds, Mary V; Badesch, David B; Wynne, Kristine M; Groves, Bertron M; Roden, Robert L; Robertson, Alastair D; Lowes, Brian D; Zisman, Lawrence S; Voelkel, Norbert F; Bristow, Michael R; Perryman, M Benjamin

2003-03-01

HYPOTHESIS/INTRODUCTION: A polymorphic marker within the angiotensin- converting enzyme (ACE) gene has been associated with circulating and tissue ACE activity and with a variety of forms of cardiovascular disease. Since angiotensin II (Ang II) causes pulmonary vasoconstriction and vascular and myocardial remodelling, we postulated a role for the renin-angiotensin system and the ACE DD genotype in the pathophysiology of primary pulmonary hypertension (PPH) and in the right ventricular response to pressure overload in these patients. The incidence of the ACE DD genotype was evaluated in 60 patients with severe PPH compared with two normal control populations, a group of healthy population-based controls (n=158) and subjects found suitable for cardiac organ donation (n=79). Genomic DNA extracted from peripheral leukocytes was amplified using the polymerase chain reaction to detect polymorphic markers. Haemodynamics were determined by right heart catheterisation in a subset of the PPH patients. The frequency of the ACE DD genotype was 45% in the patients with PPH, compared with 24% in the organ donors, and 28% in population-based healthy controls (p=0.01 for chi-square test). Of the 32 PPH patients with baseline haemodynamics, 12 exhibited the ACE DD genotype and 20 were non-DD. While the mean pulmonary artery pressure and the duration of symptoms attributable to pulmonary hypertension was not different between the DD and non-DD groups, cardiac output was significantly lower (3.29+0.27 vs. 5.07+0.37 L/minute, p=0.002) and the mean right atrial pressure tended to be higher (8.85+1.29 vs. 4.92+1.27 mmHg, p=0.08) in the non-DD group. The reduction in cardiac output seen in the non-DD group was not due to a difference in heart rate, but to a significant reduction in stroke volume, consistent with a decreased contractile state. In addition, non-DD patients exhibited a significantly worse functional capacity (NYHA Class 3.14+0.12 vs. 2.40+0.28, p=0.02). 1) The ACE DD genotype is significantly increased in patients with severe PPH compared with normal controls, suggesting that certain individuals may be genetically predisposed to developing pulmonary hypertension. 2) The ACE DD genotype is associated with preserved right ventricular function in PPH patients, supporting a compensatory myocardial or inotropic role for Ang II in the pressure overloaded right ventricle.

Exercise training in pulmonary arterial hypertension associated with connective tissue diseases

PubMed Central

2012-01-01

Introduction The objective of this prospective study was to assess short- and long-term efficacy of exercise training (ET) as add-on to medical therapy in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH). Methods Patients with invasively confirmed CTD-APAH received ET in-hospital for 3 weeks and continued at home for 12 weeks. Efficacy parameters have been evaluated at baseline and after 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of 2.9 ± 1.9 years. Results Twenty-one consecutive patients were included and assessed at baseline, and after 3 weeks, 14 after 15 weeks. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 67 ± 52 meters after 3 weeks (p < 0.001) and by 71 ± 35 meters after 15 weeks (p = 0.003), scores of quality of life (p < 0.05), heart rate at rest, peak oxygen consumption, oxygen saturation and maximal workload. Systolic pulmonary artery pressure and diastolic systemic blood pressure improved significantly after 3 weeks of ET. The 1- and 2-year overall-survival rates were 100%, the 3-year survival 73%. In one patient lung transplantation was performed 6 months after ET. Conclusion ET as add-on to medical therapy is highly effective in patients with CTD-APAH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further randomized controlled studies are needed to confirm these results. Trial registration ClinicalTrials.gov: NCT00491309. PMID:22709477

One-year glargine treatment can improve the course of lung disease in children and adolescents with cystic fibrosis and early glucose derangements.

PubMed

Mozzillo, Enza; Franzese, Adriana; Valerio, Giuliana; Sepe, Angela; De Simone, Ilaria; Mazzarella, Gianfranco; Ferri, Pasqualina; Raia, Valeria

2009-05-01

Diabetes increases morbidity and mortality in cystic fibrosis (CF) patients, but several studies indicate that also prediabetic status may have a potential impact on both nutrition and lung function. To evaluate the effect of glargine on the clinical course in CF patients with early glucose derangements. CF population was screened for glucose tolerance. CF patients with age >10 yr were screened with fasting hyperglycemia (FH). CF patients with age >10 yr without FH and those with age <10 yr with occasional FH were evaluated for glucose abnormalities on the basis of oral glucose tolerance test and/or continuous glucose monitoring system. All CF patients with glucose derangements were enrolled in an open clinical trial with glargine. Body mass index (BMI) z-score, forced expiratory volume in the first second (FEV(1)), number of acute pulmonary exacerbations and hemoglobin A1c, were as outcome measures at baseline and after 1 yr of treatment. After 12 months of therapy, BMI z-score improved only in patients with baseline BMI z-score less than -1 (p = 0.017). An 8.8% increase in FEV(1) (p = 0.01) and 42% decrease in the number of pulmonary exacerbations (p = 0.003) were found in the whole group compared with previous 12 months of therapy. Glargine could represent an innovative strategy to prevent lung disease progression in CF patients with early glucose derangements. Larger controlled trials are needed to better clarify the effects of insulin on clinical status in CF patients with early glucose derangements.

Health-related quality of life in a national cohort of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.

PubMed

Roman, Antonio; Barbera, Joan Albert; Castillo, Maria Jesús; Muñoz, Rocío; Escribano, Pilar

2013-05-01

Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) experience impaired health-related quality of life (HRQL). The objective of this study was to evaluate HRQL in a nation-wide sample. This is a prospective, multicenter, non-interventional study of HRQL including 139 (89%) PAH and 17 (11%) CTEPH patients (women 70.5%; mean age, 52.2) recruited from 21 Spanish hospitals. 55% had idiopathic PAH, 34% other PAH and 11% CTEPH. HRQL was measured using the Short Form 36 Health Survey (SF-36) and EuroQoL-5D (baseline and after 6 months). HRQL in the patients with PAH or CTEPH was impaired. The physical component of SF-36 and the EuroQol-5D correlated with the functional class (FC). Mean EuroQol-5D visual analogical scale (EQ-5D VAS) scores were 73.5±18.4, 62.9±20.7 and 51.3±16.0 (P<.0001) in patients with FC I, II and III, respectively. Every increase of one FC represented a loss of 4.0 on the PCS SF-36 and a loss of 9.5 on the EQ-5D VAS. Eight patients who died or received a transplant during the study period presented poorer initial HRQL compared with the rest of the population. No significant changes in HRQL were observed in survivors after 6 months of follow-up. HRQL is impaired in this population, especially in PAH/CTEPH patients near death. HRQL measurements could help predict the prognosis in PAH and CTPH and provide additional information in these patients. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

Pulmonary Right Ventricular Resynchronization in Congenital Heart Disease: Acute Improvement in Right Ventricular Mechanics and Contraction Efficiency.

PubMed

Janoušek, Jan; Kovanda, Jan; Ložek, Miroslav; Tomek, Viktor; Vojtovič, Pavel; Gebauer, Roman; Kubuš, Peter; Krejčíř, Miroslav; Lumens, Joost; Delhaas, Tammo; Prinzen, Frits

2017-09-01

Electromechanical discoordination may contribute to long-term pulmonary right ventricular (RV) dysfunction in patients after surgery for congenital heart disease. We sought to evaluate changes in RV function after temporary RV cardiac resynchronization therapy. Twenty-five patients aged median 12.0 years after repair of tetralogy of Fallot and similar lesions were studied echocardiographically (n=23) and by cardiac catheterization (n=5) after primary repair (n=4) or after surgical RV revalvulation for significant pulmonary regurgitation (n=21). Temporary RV cardiac resynchronization therapy was applied in the presence of complete right bundle branch block by atrial-synchronized RV free wall pacing in complete fusion with spontaneous ventricular depolarization using temporary electrodes. The q-RV interval at the RV free wall pacing site (mean 77.2% of baseline QRS duration) confirmed pacing from a late activated RV area. RV cardiac resynchronization therapy carried significant decrease in QRS duration ( P <0.001) along with elimination of the right bundle branch block QRS morphology, increase in RV filling time ( P =0.002), pulmonary artery velocity time integral ( P =0.006), and RV maximum +dP/dt ( P <0.001), and decrease in RV index of myocardial performance ( P =0.006). RV mechanical synchrony improved: septal-to-lateral RV mechanical delay decreased ( P <0.001) and signs of RV dyssynchrony pattern were significantly abolished. RV systolic stretch fraction reflecting the ratio of myocardial stretching and contraction during systole diminished ( P =0.001). In patients with congenital heart disease and right bundle branch block, RV cardiac resynchronization therapy carried multiple positive effects on RV mechanics, synchrony, and contraction efficiency. © 2017 American Heart Association, Inc.

Dose-Response Head-to-Head Comparison of Inodilators Dobutamine, Milrinone, and Levosimendan in Chronic Experimental Pulmonary Hypertension.

PubMed

Tavares-Silva, Marta; Alaa, Mohamed; Leite, Sara; Oliveira-Pinto, José; Lopes, Lucas; Leite-Moreira, Adelino F; Lourenço, André P

2017-09-01

The choice of inodilator drug in the acute management of patients with pulmonary hypertension (PH) having right ventricular (RV) failure remains unsettled and challenging. Comprehensive experimental evaluations may provide further insight and fundamental translational research clues to support inodilator selection and clinical trial design. Our aim was to compare acute dose-response hemodynamic effects of inodilators dobutamine (DOB), milrinone (MIL), and levosimendan (LEV) in chronic experimental PH. Seven-week-old male Wistar rats were randomly injected with 60 mg·kg -1 monocrotaline (MCT) or vehicle (Ctrl, n = 7) and underwent systemic and pulmonary artery (PA) pressure and RV pressure-volume (PV) hemodynamic evaluation under halogenate anesthesia 24 to 30 days after injection. The MCT-injected animals (n = 7 each) randomly received dose-response infusions of DOB (1, 3, 6 and 12 μg·kg -1 ·min -1 ), MIL (MIL: 1, 3, 6 and 12 μg·kg -1 ·min -1 ), or LEV (0.3, 0.6, 1.2 and 2.4 μg·kg -1 ·min -1 ). Load-independent indexes were obtained by inferior vena cava occlusion at baseline and after the last dose. All inodilators increased RV ejection fraction, preload recruitable stroke work, and ventricular-vascular coupling without jeopardizing perfusion pressure. Dobutamine raised heart rate and PA pressure. Only LEV increased cardiac index and decreased PA elastance and pulmonary vascular resistance (PVR). Moreover, only LEV downward-shifted the end-diastolic PV relationship, thereby improving RV compliance. Adding sildenafil to LEV further decreased PVR. Levosimendan had beneficial acute systolic and diastolic functional effects in experimental chronic PH and RV afterload compared to DOB and MIL. It should be further tested in clinical trials enrolling patients with PH in the perioperative and critical care settings.

C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury.

PubMed

Shah, Dilip; Romero, Freddy; Zhu, Ying; Duong, Michelle; Sun, Jianxin; Walsh, Kenneth; Summer, Ross

2015-12-04

The collectin proteins are innate immune molecules found in high concentrations on the epithelial and endothelial surfaces of the lung. While these proteins are known to have important anti-inflammatory actions in the airways of the lung little is known of their functional importance in the pulmonary circulation. We recently demonstrated that the circulating collectin protein adiponectin has potent anti-inflammatory effects on the lung endothelium, leading us to reason that other structurally related proteins might have similar effects. To test this hypothesis, we investigated the anti-inflammatory actions of C1q in lung endothelial homeostasis and the pulmonary vascular response to LPS or HCl injury. We show that lung endothelium from C1q-deficient (C1q(-/-)) mice expresses higher baseline levels of the vascular adhesion markers ICAM-1, VCAM-1, and E-selectin when compared with wild-type mice. Further, we demonstrate that these changes are associated with enhanced susceptibility of the lung to injury as evident by increased expression of adhesion markers, enhanced production of pro-inflammatory cytokines, and augmented neutrophil recruitment. Additionally, we found that C1q(-/-) mice also exhibited enhanced endothelial barrier dysfunction after injury as manifested by decreased expression of junctional adherens proteins and enhanced vascular leakage. Mechanistically, C1q appears to mediate its effects by inhibiting phosphorylation of p38 mitogen-activated protein kinase (MAPK) and blocking nuclear translocation of the P65 subunit of nuclear factor (NF)-κB. In summary, our findings indicate a previously unrecognized role for C1q in pulmonary vascular homeostasis and provide added support for the hypothesis that circulating collectin proteins have protective effects on the lung endothelium. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury*

PubMed Central

Shah, Dilip; Romero, Freddy; Zhu, Ying; Duong, Michelle; Sun, Jianxin; Walsh, Kenneth; Summer, Ross

2015-01-01

The collectin proteins are innate immune molecules found in high concentrations on the epithelial and endothelial surfaces of the lung. While these proteins are known to have important anti-inflammatory actions in the airways of the lung little is known of their functional importance in the pulmonary circulation. We recently demonstrated that the circulating collectin protein adiponectin has potent anti-inflammatory effects on the lung endothelium, leading us to reason that other structurally related proteins might have similar effects. To test this hypothesis, we investigated the anti-inflammatory actions of C1q in lung endothelial homeostasis and the pulmonary vascular response to LPS or HCl injury. We show that lung endothelium from C1q-deficient (C1q−/−) mice expresses higher baseline levels of the vascular adhesion markers ICAM-1, VCAM-1, and E-selectin when compared with wild-type mice. Further, we demonstrate that these changes are associated with enhanced susceptibility of the lung to injury as evident by increased expression of adhesion markers, enhanced production of pro-inflammatory cytokines, and augmented neutrophil recruitment. Additionally, we found that C1q−/− mice also exhibited enhanced endothelial barrier dysfunction after injury as manifested by decreased expression of junctional adherens proteins and enhanced vascular leakage. Mechanistically, C1q appears to mediate its effects by inhibiting phosphorylation of p38 mitogen-activated protein kinase (MAPK) and blocking nuclear translocation of the P65 subunit of nuclear factor (NF)-κB. In summary, our findings indicate a previously unrecognized role for C1q in pulmonary vascular homeostasis and provide added support for the hypothesis that circulating collectin proteins have protective effects on the lung endothelium. PMID:26487714

Antacid Therapy and Disease Progression in Patients with Idiopathic Pulmonary Fibrosis Who Received Pirfenidone.

PubMed

Kreuter, Michael; Spagnolo, Paolo; Wuyts, Wim; Renzoni, Elisabetta; Koschel, Dirk; Bonella, Francesco; Maher, Toby M; Kolb, Martin; Weycker, Derek; Kirchgässler, Klaus-Uwe; Costabel, Ulrich

2017-01-01

Gastroesophageal reflux disease is a potential risk factor for idiopathic pulmonary fibrosis (IPF) progression; however, the impact of antacid therapy (AAT) is under debate. To evaluate the effect of AAT on IPF progression in pirfenidone-treated patients. This post hoc analysis included patients with IPF who received pirfenidone in 3 trials (CAPACITY [PIPF-004/PIPF-006] and ASCEND [PIPF-016]). Pulmonary function, exercise tolerance, survival, hospitalizations, and adverse events (AEs) over 52 weeks were analyzed by baseline AAT use. Disease progression was defined as a decrease in forced vital capacity (FVC) of ≥10%, a decrease in 6-min walking distance of ≥50 m, or death over 1 year. Of 623 patients, 44% received AAT. No significant differences were found at 52 weeks (AAT versus non-AAT, respectively) in disease progression (24.9 vs. 30.6%; p = 0.12), all-cause mortality rate (2.9 vs. 4.0%; p = 0.47), IPF-related mortality rate (1.1 vs. 2.0%; p = 0.37), all-cause hospitalization rate (16.1 vs. 18.3%; p = 0.48), or mean change in percent FVC (-2.7 vs. -3.1%; p = 0.44). A relative, but not absolute, FVC decline of ≥10% favored AAT (15 vs. 22%; p = 0.03). Severe gastrointestinal AEs (3.7 vs. 0.9%; p = 0.015) and severe pulmonary infections (3.7 vs. 1.1%; p = 0.035) were more frequent with AAT. AAT and pirfenidone had outcomes comparable to those of pirfenidone alone in patients with IPF, underscoring the need for prospective trials to elucidate the role of AAT with or without antifibrotic drugs as a treatment for IPF. © 2017 The Author(s) Published by S. Karger AG, Basel.

Lack of efficacy of Lactobacillus GG in reducing pulmonary exacerbations and hospital admissions in children with cystic fibrosis: A randomised placebo controlled trial.

PubMed

Bruzzese, Eugenia; Raia, Valeria; Ruberto, Eliana; Scotto, Riccardo; Giannattasio, Antonietta; Bruzzese, Dario; Cavicchi, Maria Cristina; Francalanci, Michela; Colombo, Carla; Faelli, Nadia; Daccò, Valeria; Magazzù, Giuseppe; Costa, Stefano; Lucidi, Vincenzina; Majo, Fabio; Guarino, Alfredo

2017-11-08

Intestinal dysbiosis has been described in Cystic Fibrosis (CF) and probiotics have been proposed to restore microbial composition. Aim of the study was to investigate the effects of Lactobacillus rhamnosus GG (LGG) on clinical outcomes in children with cystic fibrosis (CF). A multicentre, randomised double-blind, clinical trial was conducted in children with CF. After 6months of baseline assessment, enrolled children (2 to 16years of age) received Lactobacillus GG (6×10 9 CFU/day) or placebo for 12months. Primary outcomes were proportion of subjects with at least one pulmonary exacerbation and hospitalisation over 12months. Secondary endpoints were total number of exacerbations and hospitalisations, pulmonary function, and nutritional status. Ninety-five patients were enrolled (51/95 female; median age of 103±50months). In a multivariate GEE logistic analysis, the odds of experiencing at least one exacerbation was not significantly different between the two groups, also after adjusting for the presence of different microbial organisms and for the number of pulmonary exacerbations within 6months before randomisation (OR 0.83; 95% CI 0.38 to 1.82, p=0.643). Similarly, LGG supplementation did not significantly affect the odds of hospitalisations (OR 1.67; 95% CI 0.75 to 3.72, p=0.211). No significant difference was found for body mass index and FEV1. LGG supplementation had no effect on respiratory and nutritional outcomes in this large study population of children with CF under stringent randomised clinical trial conditions. Whether earlier interventions, larger doses, or different strains of probiotics may be effective is unknown. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Differences in change in coping styles between good responders, moderate responders and non-responders to pulmonary rehabilitation.

PubMed

Stoilkova-Hartmann, Ana; Janssen, Daisy J A; Franssen, Frits M E; Wouters, Emiel F M

2015-12-01

Pulmonary rehabilitation (PR) improves exercise tolerance and health status in patients with chronic obstructive pulmonary disease (COPD). Data on the effects of PR on coping styles are limited. Aim of the present study was to compare changes in coping styles between patients who had a good, moderate and no improvement in either exercise tolerance or health status after PR. Coping styles of 439 COPD patients undergoing PR were assessed by the Utrecht Coping List (UCL) at baseline and after PR. Patients' pulmonary function, six-minute walking distance (6MWD), St. George's Respiratory Questionnaire (SGRQ) and Hospital Anxiety and Depression Scale (HADS-A and HADS-D) were recorded. Good, moderate and non-responders were defined on the basis of minimally clinically important difference (MCID) for SGRQ total score and/or 6MWD. Overall, 54.0% of the patients fulfilled the criteria for good responders, while 22.1% were moderate responders. Change in passive reaction pattern coping style differed significantly between good responders and non-responders following PR (p < 0.001). Moreover, within the groups, changes in coping styles after PR occurred among the good responders, whereas the majority of moderate responders' and non-responders' coping styles were not significantly influenced by PR. Good responders decreased their passive reaction pattern coping style in contrast to non-responders after PR. In general, PR did not change the coping among moderate and non-responders. Further research is warranted to determine whether including interventions targeting coping styles may modify coping behaviour of COPD patients, as well as improvement in exercise tolerance or health status after PR. Copyright © 2015 Elsevier Ltd. All rights reserved.

Long-term effects of a 12-week exercise training program on clinical outcomes in idiopathic pulmonary fibrosis.

PubMed

Vainshelboim, Baruch; Oliveira, Jose; Fox, Benjamin Daniel; Soreck, Yafit; Fruchter, Oren; Kramer, Mordechai Reuven

2015-06-01

Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, lung disease, with few therapeutic options. Data are limited with respect to the long-term effect of exercise training (ET) in IPF. This study sought to evaluate the long-term effects of a 12-week ET program on clinical outcomes in IPF patients. Thirty-four IPF patients were randomly allocated to ET or control groups. ET group participated in a 12-week supervised exercise program, while the control group continued with regular medical treatment alone. Exercise capacity, 30 s-chair-stand test for leg strength, dyspnea, and Saint George's Respiratory Questionnaire (SGRQ) for quality of life (QOL) were assessed at baseline and re-evaluated at 11 months from baseline. In addition, at 30-month time point from baseline, the impact of the 12-week intervention was analyzed with respect to survival and cardio-respiratory-related hospitalizations. Thirty-two patients completed the 12-week intervention and 28 patients (14 in each group) were re-evaluated. At 11-month follow-up, no significant differences between the groups and time effect were demonstrated for most outcomes. ET group showed preserved values at the baseline level while the control group showed a trend of deterioration. Only the 30 s-chair-stand test (mean difference 3 stands, p = 0.01) and SGRQ (mean difference -6 units, p = 0.037) were significantly different between the groups. At 30 months, the survival analysis showed three deaths, eight hospitalizations occurred in the control group versus one death, one lung transplantation and seven hospitalizations in the ET group, with no significant differences between groups. At 11-month follow-up, the 12-week ET program showed clinical outcomes were preserved at baseline levels with some maintenance of improvements in leg strength and QOL in the ET group. The control group showed a trend of deterioration in the outcomes. At 30 months, the 12-week ET program did not show benefits in prognosis although the study was underpowered to detect such differences. We suggest including ET as a long-term continued treatment and as a core component of pulmonary rehabilitation programs for IPF patients.

Baseline predictors of sputum culture conversion in pulmonary tuberculosis: importance of cavities, smoking, time to detection and W-Beijing genotype.

PubMed

Visser, Marianne E; Stead, Michael C; Walzl, Gerhard; Warren, Rob; Schomaker, Michael; Grewal, Harleen M S; Swart, Elizabeth C; Maartens, Gary

2012-01-01

Time to detection (TTD) on automated liquid mycobacterial cultures is an emerging biomarker of tuberculosis outcomes. The M. tuberculosis W-Beijing genotype is spreading globally, indicating a selective advantage. There is a paucity of data on the association between baseline TTD and W-Beijing genotype and tuberculosis outcomes. To assess baseline predictors of failure of sputum culture conversion, within the first 2 months of antitubercular therapy, in participants with pulmonary tuberculosis. Between May 2005 and August 2008 we conducted a prospective cohort study of time to sputum culture conversion in ambulatory participants with first episodes of smear and culture positive pulmonary tuberculosis attending two primary care clinics in Cape Town, South Africa. Rifampicin resistance (diagnosed on phenotypic susceptibility testing) was an exclusion criterion. Sputum was collected weekly for 8 weeks for mycobacterial culture on liquid media (BACTEC MGIT 960). Due to missing data, multiple imputation was performed. Time to sputum culture conversion was analysed using a Cox-proportional hazards model. Bayesian model averaging determined the posterior effect probability for each variable. 113 participants were enrolled (30.1% female, 10.5% HIV-infected, 44.2% W-Beijing genotype, and 89% cavities). On Kaplan Meier analysis 50.4% of participants underwent sputum culture conversion by 8 weeks. The following baseline factors were associated with slower sputum culture conversion: TTD (adjusted hazard ratio (aHR) = 1.11, 95% CI 1.02; 1.2), lung cavities (aHR = 0.13, 95% CI 0.02; 0.95), ever smoking (aHR = 0.32, 95% CI 0.1; 1.02) and the W-Beijing genotype (aHR = 0.51, 95% CI 0.25; 1.07). On Bayesian model averaging, posterior probability effects were strong for TTD, lung cavitation and smoking and moderate for W-Beijing genotype. We found that baseline TTD, smoking, cavities and W-Beijing genotype were associated with delayed 2 month sputum culture. Larger studies are needed to confirm the relationship between the W-Beijing genotype and sputum culture conversion.

Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial

PubMed Central

McGarvey, Lorcan; Pavord, Ian D.; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S.

2017-01-01

Background To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. Methods This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. Results At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (−12.2±23.28 in BC1036 group and −11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. Conclusions This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. Clinical trial registration ClinicalTrials.gov: NCT01656668. PMID:28839984

GPCRs in pulmonary arterial hypertension: tipping the balance.

PubMed

Iyinikkel, Jean; Murray, Fiona

2018-02-21

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease characterised by increased pulmonary vascular resistance and excessive proliferation of pulmonary artery smooth muscle cells (PASMC). GPCRs, which are attractive pharmacological targets, are important regulators of pulmonary vascular tone and PASMC phenotype. PAH is associated with the altered expression and function of a number of GPCRs in the pulmonary circulation, which leads to the vasoconstriction and proliferation of PASMC and thereby contributes to the imbalance of pulmonary vascular tone associated with PAH; drugs targeting GPCRs are currently used clinically to treat PAH and extensive preclinical work supports the utility of a number of additional GPCRs. Here we review how GPCR expression and function changes with PAH and discuss why GPCRs continue to be relevant drug targets for the disease. © 2018 The British Pharmacological Society.

Pulmonary function and respiratory symptoms of school children exposed to ambient air pollution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Yoon Shin; Ko, Ung Ring

1996-12-31

This study was undertaken to evaluate the health effect of air pollution on pulmonary function and respiratory symptoms of Korean school children between 7 and 10 years of age during November 1995-January 1996. A standard respiratory symptom questionnaire was administered and spirometry was performed to examine pulmonary function of 121 children in an urban polluted area, Seoul, and of 119 children in non-polluted area, Sokcho, respectively. There was significant difference in the level of pulmonary function [forced expiratory volume in second (FEV{sub 1.0}) and forced vital capacity (FVC)] between exposed groups to polluted area and non-polluted area. Parental smoking wasmore » significantly related to respiratory symptoms of cough, phlegm, and the level of pulmonary function. The observed changes in FEV{sub 1.0} and FVC seemed to relate to home cooking fuel, not to respiratory symptoms. The additional longitudinal work that carefully monitors ambient and indoor air pollution and health effects data should be conducted to confirm these results.« less

Pulmonary function outcomes for assessing cystic fibrosis care.

PubMed

Wagener, Jeffrey S; Elkin, Eric P; Pasta, David J; Schechter, Michael S; Konstan, Michael W; Morgan, Wayne J

2015-05-01

Assessing cystic fibrosis (CF) patient quality of care requires the choice of an appropriate outcome measure. We looked systematically and in detail at pulmonary function outcomes that potentially reflect clinical practice patterns. Epidemiologic Study of Cystic Fibrosis data were used to evaluate six potential outcome variables (2002 best FVC, FEV(1), and FEF(25-75) and rate of decline for each from 2000 to 2002). We ranked CF care sites by outcome measure and then assessed any association with practice patterns and follow-up pulmonary function. Sites ranked in the top quartile had more frequent monitoring, treatment of exacerbations, and use of chronic therapies and oral corticosteroids. The follow-up rate of pulmonary function decline was not predicted by site ranking. Different pulmonary function outcomes associate slightly differently with practice patterns, although annual FEV(1) is at least as good as any other measure. Current site ranking only moderately predicts future ranking. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Hyperpolarized Gas MRI: Technique and Applications

PubMed Central

McAdams, Holman P.; Kaushik, S. Sivaram; Driehuys, Bastiaan

2015-01-01

Synopsis Functional imaging today offers a rich world of information that is more sensitive to changes in lung structure and function than traditionally obtained pulmonary function tests. Hyperpolarized helium (3He) and xenon (129Xe) MR imaging of the lungs provided new sensitive contrast mechanisms to probe changes in pulmonary ventilation, microstructure and gas exchange. With the recent scarcity in the supply of 3He the field of hyperpolarized gas imaging shifted to the use of cheaper and naturally available 129Xe. Xenon is well tolerated and recent technical advances have ensured that the 129Xe image quality is on par with that of 3He. The added advantage of 129Xe is its solubility in pulmonary tissue, which allows exploring specific lung function characteristics involved in gas exchange and alveolar oxygenation. With a plethora of contrast mechanisms, hyperpolarized gases and 129Xe in particular, stands to be an excellent probe of pulmonary structure and function, and provide sensitive and non-invasive biomarkers for a wide variety of pulmonary diseases. PMID:25952516

[Clinical analysis of nasal resistance and pulmonary function testing in patients with chronic nasal-sinusitis and nasal polyps].

PubMed

Liao, Hua; Shen, Ying; Wang, Pengjun

2015-05-01

To study the pulmonary function and nasal resistance characteristics of patients with chronic nose-sinusitis and nasal polyps (CRSwNP), to explore the evaluation role of nasal resistance in nasal ventilation function and the effect of endoscopic sinus surgery on pulmonary function in patients with CRSwNP. Fifty CRSwNP patients that met the study criteria were selected . The patients were performed endoscopic surgeries according to Messerklinger surgical procedures under general anesthesia. Extent of surgery was based on preoperative CT showing the range of the lesion of disease and endoscopic findings. Perioperative treatments contained intranasal corticosteroids, cephalosporin or penicillin antibiotics, nasal irrigation and other treatments. Main outcome measures included visual analog scale (VAS), endoscopic Lind-Kennedy scores, nasal resistence, pulmonary function in patientsone week before and after surgery, three months and six months after surgery. Pulmonary function includes forced expiratory volume in one second (FEV1), forced vital capacity FEV1/FVC and peak expiratory flow (PEF). The study found that there were significantly positive correlations among VAS score, Lund-Kennedy score and nasal resistance (P < 0.05) in CRSwNP patients, but there is a significantly negative correlation between VAS score, Lund-Kennedy score, nasal resistance and pulmonary function indexes of FEV1, FVC and PEF (P < 0.05). The VAS score, Lund-Kennedy score and nasal resistance values of CRSwNP patients were decreased significantly after comprehensive treatments with nasal endoscopic operation as the major one, the difference was statistically different (P < 0.05). And the pulmonary function indexs (FEV1, FVC, PEF) were significantly increased after surgery in CRSwNP patients. The nasal resistance can objectively and reliably reflect the degree of nasal congestion and the recovery of nasal function in CRSwNP patients after endoscopic sinus surgery. The detection method of nasal resistance is simple. Functional endoscopic sinus surgery can effectively improve the pulmonary ventilation function in CRSwNP patients, providing some clinical references about the prevention and treatment of CRS related lower respiratory disease.

Mediating pathways from central obesity to childhood asthma: a population-based longitudinal study.

PubMed

Chih, An-Hsuan; Chen, Yang-Ching; Tu, Yu-Kang; Huang, Kuo-Chin; Chiu, Tai-Yuan; Lee, Yungling Leo

2016-09-01

The mediating pathways linking obesity and asthma are largely unknown. We aimed to investigate the mediating pathways and to search for the most prominent pathological mechanism between central obesity and childhood asthma.In the Taiwan Children Health Study, we collected data on an open cohort of children aged 9-13 years. Children's respiratory outcomes, atopic conditions, obesity measures and pulmonary function were surveyed annually between 2010 and 2012. Exhaled nitric oxide fraction concentrations were recorded in 2012. Generalised estimating equations and general linear models were used to examine the associations between central obesity, possible mediators and asthma. Structural equation models were applied to investigate the pathways that mediate the link between central obesity and asthma.Central obesity (waist-to-hip ratio) most accurately predicted childhood asthma. In the active asthma model, the percentage of mediation was 28.6% for pulmonary function, 18.1% for atopy and 5.7% for airway inflammation. The percentage of mediation for pulmonary function was 40.2% in the lifetime wheeze model. Pulmonary function was responsible for the greatest percentage of mediation among the three mediators in both models.Decline in pulmonary function is the most important pathway in central obesity related asthma. Pulmonary function screening should be applied to obese children for asthma risk prediction. Copyright ©ERS 2016.

Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function.

PubMed

Severgnini, Paolo; Selmo, Gabriele; Lanza, Christian; Chiesa, Alessandro; Frigerio, Alice; Bacuzzi, Alessandro; Dionigi, Gianlorenzo; Novario, Raffaele; Gregoretti, Cesare; de Abreu, Marcelo Gama; Schultz, Marcus J; Jaber, Samir; Futier, Emmanuel; Chiaranda, Maurizio; Pelosi, Paolo

2013-06-01

The impact of intraoperative ventilation on postoperative pulmonary complications is not defined. The authors aimed at determining the effectiveness of protective mechanical ventilation during open abdominal surgery on a modified Clinical Pulmonary Infection Score as primary outcome and postoperative pulmonary function. Prospective randomized, open-label, clinical trial performed in 56 patients scheduled to undergo elective open abdominal surgery lasting more than 2 h. Patients were assigned by envelopes to mechanical ventilation with tidal volume of 9 ml/kg ideal body weight and zero-positive end-expiratory pressure (standard ventilation strategy) or tidal volumes of 7 ml/kg ideal body weight, 10 cm H2O positive end-expiratory pressure, and recruitment maneuvers (protective ventilation strategy). Modified Clinical Pulmonary Infection Score, gas exchange, and pulmonary functional tests were measured preoperatively, as well as at days 1, 3, and 5 after surgery. Patients ventilated protectively showed better pulmonary functional tests up to day 5, fewer alterations on chest x-ray up to day 3 and higher arterial oxygenation in air at days 1, 3, and 5 (mmHg; mean ± SD): 77.1 ± 13.0 versus 64.9 ± 11.3 (P = 0.0006), 80.5 ± 10.1 versus 69.7 ± 9.3 (P = 0.0002), and 82.1 ± 10.7 versus 78.5 ± 21.7 (P = 0.44) respectively. The modified Clinical Pulmonary Infection Score was lower in the protective ventilation strategy at days 1 and 3. The percentage of patients in hospital at day 28 after surgery was not different between groups (7 vs. 15% respectively, P = 0.42). A protective ventilation strategy during abdominal surgery lasting more than 2 h improved respiratory function and reduced the modified Clinical Pulmonary Infection Score without affecting length of hospital stay.

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

PubMed

McGeachie, M J; Yates, K P; Zhou, X; Guo, F; Sternberg, A L; Van Natta, M L; Wise, R A; Szefler, S J; Sharma, S; Kho, A T; Cho, M H; Croteau-Chonka, D C; Castaldi, P J; Jain, G; Sanyal, A; Zhan, Y; Lajoie, B R; Dekker, J; Stamatoyannopoulos, J; Covar, R A; Zeiger, R S; Adkinson, N F; Williams, P V; Kelly, H W; Grasemann, H; Vonk, J M; Koppelman, G H; Postma, D S; Raby, B A; Houston, I; Lu, Q; Fuhlbrigge, A L; Tantisira, K G; Silverman, E K; Tonascia, J; Weiss, S T; Strunk, R C

2016-05-12

Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Pulmonary 3 T MRI with ultrashort TEs: influence of ultrashort echo time interval on pulmonary functional and clinical stage assessments of smokers.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Seki, Shinichiro; Obara, Makoto; van Cauteren, Marc; Takahashi, Masaya; Sugimura, Kazuro

2014-04-01

To assess the influence of ultrashort TE (UTE) intervals on pulmonary magnetic resonance imaging (MRI) with UTEs (UTE-MRI) for pulmonary functional loss assessment and clinical stage classification of smokers. A total 60 consecutive smokers (43 men and 17 women; mean age 70 years) with and without COPD underwent thin-section multidetector row computed tomography (MDCT), UTE-MRI, and pulmonary functional measurements. For each smoker, UTE-MRI was performed with three different UTE intervals (UTE-MRI A: 0.5 msec, UTE-MRI B: 1.0 msec, UTE-MRI C: 1.5 msec). By using the GOLD guidelines, the subjects were classified as: "smokers without COPD," "mild COPD," "moderate COPD," and "severe or very severe COPD." Then the mean T2* value from each UTE-MRI and CT-based functional lung volume (FLV) were correlated with pulmonary function test. Finally, Fisher's PLSD test was used to evaluate differences in each index among the four clinical stages. Each index correlated significantly with pulmonary function test results (P < 0.05). CT-based FLV and mean T2* values obtained from UTE-MRI A and B showed significant differences among all groups except between "smokers without COPD" and "mild COPD" groups (P < 0.05). UTE-MRI has a potential for management of smokers and the UTE interval is suggested as an important parameter in this setting. Copyright © 2013 Wiley Periodicals, Inc.

Six-Minute-Walk Distance and Accelerometry Predict Outcomes in Chronic Obstructive Pulmonary Disease Independent of Global Initiative for Chronic Obstructive Lung Disease 2011 Group

PubMed Central

Smith, Patrick J.; Babyak, Michael A.; Mabe, Stephanie K.; Martinu, Tereza; Welty-Wolf, Karen E.; Emery, Charles F.; Palmer, Scott M.; Blumenthal, James A.

2015-01-01

Rationale: The 2011 combined Global Initiative for Chronic Obstructive Lung Disease (GOLD) assessment incorporates symptoms, exacerbation history, and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and accelerometry also have been used to assess disease severity in COPD. The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown. Objectives: To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD-related hospitalization or all-cause mortality, independent of GOLD 2011 group. Methods: Physical function and medical outcomes were prospectively assessed in 326 patients with moderate to severe COPD in INSPIRE-II, a randomized controlled trial of a coping skills training intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or accelerometry steps were associated with risk of COPD-related hospitalization or all-cause mortality. Measurements and Main Results: Physical function declined over time in GOLD group D but remained stable in groups A, B, and C. GOLD classification was associated with time to death or first COPD-related hospitalization. Baseline 6MWD was more strongly associated with time to death or first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval, 0.34, 0.73] per 150 m, P = 0.0003) than GOLD 2011 classification. A similar relationship was observed for accelerometry steps (hazard ratio, 0.80 [95% confidence interval, 0.70, 0.92] per 1,000 steps, P = 0.002). Conclusions: Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD, independent of GOLD 2011 classification. Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinically meaningful outcomes in COPD. PMID:25568929

Update on diagnosis and treatment of idiopathic pulmonary fibrosis

PubMed Central

Baddini-Martinez, José; Baldi, Bruno Guedes; da Costa, Cláudia Henrique; Jezler, Sérgio; Lima, Mariana Silva; Rufino, Rogério

2015-01-01

Idiopathic pulmonary fibrosis is a type of chronic fibrosing interstitial pneumonia, of unknown etiology, which is associated with a progressive decrease in pulmonary function and with high mortality rates. Interest in and knowledge of this disorder have grown substantially in recent years. In this review article, we broadly discuss distinct aspects related to the diagnosis and treatment of idiopathic pulmonary fibrosis. We list the current diagnostic criteria and describe the therapeutic approaches currently available, symptomatic treatments, the action of new drugs that are effective in slowing the decline in pulmonary function, and indications for lung transplantation. PMID:26578138

PREOPERATIVE PREDICTION OF LUNG FUNCTION IN PNEUMONECTOMY BY SPIROMETRY AND LUNG PERFUSION SCINTIGRAPHY

PubMed Central

Cukic, Vesna

2012-01-01

Introduction: Nowadays an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused by common etiologic factor - smoking cigarettes. Loss of lung tissue in such patients can worsen much the postoperative pulmonary function. So it is necessary to asses the postoperative pulmonary function especially after maximal resection, i.e. pneumonectomy. Objective: To check over the accuracy of preoperative prognosis of postoperative lung function after pneumonectomy using spirometry and lung perfusion scinigraphy. Material and methods: The study was done on 17 patients operated at the Clinic for thoracic surgery, who were treated previously at the Clinic for Pulmonary Diseases “Podhrastovi” in the period from 01. 12. 2008. to 01. 06. 2011. Postoperative pulmonary function expressed as ppoFEV1 (predicted postoperative forced expiratory volume in one second) was prognosticated preoperatively using spirometry, i.e.. simple calculation according to the number of the pulmonary segments to be removed and perfusion lung scintigraphy. Results: There is no significant deviation of postoperative achieved values of FEV1 from predicted ones obtained by both methods, and there is no significant differences between predicted values (ppoFEV1) obtained by spirometry and perfusion scintigraphy. Conclusion: It is necessary to asses the postoperative pulmonary function before lung resection to avoid postoperative respiratory failure and other cardiopulmonary complications. It is absolutely necessary for pneumonectomy, i.e.. maximal pulmonary resection. It can be done with great possibility using spirometry or perfusion lung scintigraphy. PMID:23378687

Pulmonary adverse effects of welding fume in automobile assembly welders.

PubMed

Sharifian, Seyed Akbar; Loukzadeh, Ziba; Shojaoddiny-Ardekani, Ahmad; Aminian, Omid

2011-01-01

Welding is one of the key components of numerous manufacturing industries, which has potential physical and chemical health hazards. Many components of welding fumes can potentially affect the lung function. This study investigates the effects of welding fumes on lung function and respiratory symptoms among welders of an automobile manufacturing plant in Iran. This historical cohort study assesses 43 male welders and 129 office workers by a questionnaire to record demographic data, smoking habits, work history and respiratory symptoms as well as lung function status by spirometry. The average pulmonary function values of welders were lower relative to controls with dose-effect relationship between work duration and pulmonary function impairment. The prevalence of chronic bronchitis was higher in welders than controls. Our findings suggest that welders are at risk for pulmonary disease.

Idiopathic Pulmonary Fibrosis: The Association between the Adaptive Multiple Features Method and Fibrosis Outcomes.

PubMed

Salisbury, Margaret L; Lynch, David A; van Beek, Edwin J R; Kazerooni, Ella A; Guo, Junfeng; Xia, Meng; Murray, Susan; Anstrom, Kevin J; Yow, Eric; Martinez, Fernando J; Hoffman, Eric A; Flaherty, Kevin R

2017-04-01

Adaptive multiple features method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns. To evaluate AMFM and visual quantification of HRCT patterns and their relationship with disease progression in idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish. Proportion of lung occupied by ground glass, ground glass-reticular (GGR), honeycombing, emphysema, and normal lung densities were measured by AMFM and three radiologists, documenting baseline disease extent and postbaseline change. Disease progression includes composite mortality, hospitalization, and 10% FVC decline. Agreement between visual and AMFM measurements was moderate for GGR (Pearson's correlation r = 0.60, P < 0.0001; mean difference = -0.03 with 95% limits of agreement of -0.19 to 0.14). Baseline extent of GGR was independently associated with disease progression when adjusting for baseline Gender-Age-Physiology stage and smoking status (hazard ratio per 10% visual GGR increase = 1.98, 95% confidence interval [CI] = 1.20-3.28, P = 0.008; and hazard ratio per 10% AMFM GGR increase = 1.36, 95% CI = 1.01-1.84, P = 0.04). Postbaseline visual and AMFM GGR trajectories were correlated with postbaseline FVC trajectory (r = -0.30, 95% CI = -0.46 to -0.11, P = 0.002; and r = -0.25, 95% CI = -0.42 to -0.06, P = 0.01, respectively). More extensive baseline visual and AMFM fibrosis (as measured by GGR densities) is independently associated with elevated hazard for disease progression. Postbaseline change in AMFM-measured and visually measured GGR densities are modestly correlated with change in FVC. AMFM-measured fibrosis is an automated adjunct to existing prognostic markers and may allow for study enrichment with subjects at increased disease progression risk.

Airway and Pulmonary β2-Adrenergic Vasodilatory Function in Current Smokers and Never Smokers.

PubMed

Hurwitz, Barry E; Mendes, Eliana S; Schmid, Andreas; Parker, Meela; Arana, Johana; Gonzalez, Alex; Wanner, Adam

2017-03-01

Cigarette smoking has been associated with diminished vasodilatory function in the airway circulation. It is possible that cigarette smoking similarly affects the pulmonary circulation before resting pulmonary circulatory abnormalities become manifested. The aim of this study was to compare the acute effect of inhaled albuterol on airway and pulmonary hemodynamic function as an index of β 2 -adrenoceptor-mediated vasodilation in smokers and never smokers. In 30 adults, airway and pulmonary vascular function was assessed before and 15 min after albuterol inhalation (270 μg). From mean systemic arterial pressure, cardiac output, airway blood flow, and mean pulmonary arterial pressure, airway vascular resistance (AVR) and pulmonary vascular resistance (PVR) were derived. Albuterol induced a substantial drop in mean (± SE) PVR (-67.2% ± 5%), with no difference between groups. In contrast, the albuterol-induced decrease in AVR was significantly greater in never smokers than in smokers (-28.6% ± 3% vs -3.1% ± 6%; P < .02). These results are consistent with a dysfunction in a β 2 -adrenergic signaling pathway mediating vasorelaxation in the airway circulation of current smokers. The vasodilatory deficit in the airway circulation but not in the pulmonary circulation could be related to local differences in the impact of cigarette smoke on the vascular endothelium. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Occupational PAH exposures during prescribed pile burns.

PubMed

Robinson, M S; Anthony, T R; Littau, S R; Herckes, P; Nelson, X; Poplin, G S; Burgess, J L

2008-08-01

Wildland firefighters are exposed to particulate matter and gases containing polycyclic aromatic hydrocarbons (PAHs), many of which are known carcinogens. Our objective was to evaluate the extent of firefighter exposure to particulate and PAHs during prescribed pile burns of mainly ponderosa pine slash and determine whether these exposures were correlated with changes in urinary 1-hydroxypyrene (1-HP), a PAH metabolite. Personal and area sampling for particulate and PAH exposures were conducted on the White Mountain Apache Tribe reservation, working with 21 Bureau of Indian Affairs/Fort Apache Agency wildland firefighters during the fall of 2006. Urine samples were collected pre- and post-exposure and pulmonary function was measured. Personal PAH exposures were detectable for only 3 of 16 PAHs analyzed: naphthalene, phenanthrene, and fluorene, all of which were identified only in vapor-phase samples. Condensed-phase PAHs were detected in PM2.5 area samples (20 of 21 PAHs analyzed were detected, all but naphthalene) at concentrations below 1 microg m(-3). The total PAH/PM2.5 mass fractions were roughly a factor of two higher during smoldering (1.06 +/- 0.15) than ignition (0.55 +/- 0.04 microg mg(-1)). There were no significant changes in urinary 1-HP or pulmonary function following exposure to pile burning. In summary, PAH exposures were low in pile burns, and urinary testing for a PAH metabolite failed to show a significant difference between baseline and post-exposure measurements.

Identifying a susceptible subgroup: effects of the Pittsburgh air pollution episode upon schoolchildren.

PubMed

Stebbings, J H; Fogleman, D G

1979-07-01

Pulmonary function test results on 224 parochial schoolchildren collected during and after the Pittsburgh air pollution episode of November 1975 were reanalyzed to determine whether a small subgroup of susceptible children could be defined. Individual regressions of three-quarter second forced expiratory volumes (FEV.75) and forced vital capacities (FVC) on time over the six-day study period were calculated, and the distributions of individual slopes for the four exposed and two control schools were compared. Excesses of strong upward trends in the exposed areas would suggest effects of suspended particulate air pollution by indicating significant improvement following the episode. A highly statistically significant excess of strong upward trends in the FVC among exposed students was observed, and was consistent by sex and by school within sex. Approximately 10--15% of the students appear susceptible to an average impairment of about 20% of the FVC. The findings are limited by the small number of subjects with strong post-episode upward trends in the FVC, and by lack of validation by replication of the study design, but do suggest that episode levels of suspended particulates induce lung damage, and that this may occur only in a small susceptible subgroup. Children with low baseline pulmonary function values, histories of asthma, or with acute respiratory symptoms immediately following the episode were not found to be especially susceptible to these effects of suspended particulates.

The effect of habitual waterpipe tobacco smoking on pulmonary function and exercise capacity in young healthy males: A pilot study.

PubMed

Hawari, F I; Obeidat, N A; Ghonimat, I M; Ayub, H S; Dawahreh, S S

2017-01-01

Evidence regarding the health effects of habitual waterpipe smoking is limited, particularly in young smokers. Respiratory health and cardiopulmonary exercise tests were compared in young male habitual waterpipe smokers (WPS) versus non-smokers. 69 WPS (≥3 times/week for three years) and 69 non-smokers were studied. Respiratory health was assessed through the American Thoracic Society and the Division of Lung Diseases (ATS-DLD-78) adult questionnaire. Pulmonary function and cardiopulmonary exercise tests were performed. Self-reported respiratory symptoms, forced expiratory volume in first second (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC ratio, forced expiratory flow between 25 and 75% of FVC (FEF 25-75% ), peak expiratory flow (PEF), exercise time, peak end-tidal CO 2 tension (PetCO 2 ), subject-reported leg fatigue and dyspnea; peak O 2 uptake (VO 2 max), and end-expiratory lung volume (EELV) change from baseline (at peak exercise) were measured. WPS were more likely than non-smokers to report respiratory symptoms. WPS also demonstrated: shorter exercise time; lower peak VO 2 ; higher perceived dyspnea at mid-exercise; lower values of the following: FEV 1 , FVC, PEF, and EELV change. Habitual waterpipe tobacco smoking in young seemingly healthy individuals is associated with a greater burden of respiratory symptoms and impaired exercise capacity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of sulfur dioxide exposure on African-American and Caucasian asthmatics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heath, S.K.; Koenig, J.Q.; Morgan, M.S.

1994-07-01

There is concern that air pollution may be causing increases in asthma morbidity and mortality, especially among African-Americans. It is possible that there may be ethnic differences in susceptibility. To evaluate this speculation, a comparative pilot study of respiratory function in 10 African American and 12 Caucasian methacholine positive asthmatic males was conducted. Subjects were exposed to pure air or 1 ppm SO[sub 2] while breathing inside a polycarbonate head dome, for 10 min of rest and 10 min of exercise. Baseline and postexposure pulmonary function measurements were recorded, and nasal lavage fluid samples were collected and processed for epithelialmore » and white blood counts. Although significant increases were seen in total respiratory resistance following SO[sub 2] exposure in both groups (P = 0.04), no ethnic-based difference in response was seen. No significant differences were found in pulmonary or nasal measurements after exposure to SO[sub 2] between African-American and Caucasian subjects. No significant changes in epithelial or white blood cell count were found either when data were analyzed from the entire group or separately from the two subject groups. Even though there were no significant group changes, some individuals were particularly responsive to SO[sub 2]. Three Caucasian and 5 African-American subjects showed greater than 20% increases in respiratory resistance. 26 refs., 2 figs., 3 tabs.« less

Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension.

PubMed

Voswinckel, Robert; Reichenberger, Frank; Enke, Beate; Kreckel, Andre; Krick, Stefanie; Gall, Henning; Schermuly, Ralph Theo; Grimminger, Friedrich; Rubin, Lewis J; Olschewski, Horst; Seeger, Werner; Ghofrani, Hossein A

2008-10-01

Inhaled treprostinil was recently developed for the treatment of pulmonary arterial hypertension (PAH). We investigated the safety and acute haemodynamic effects of the combination oral sildenafil and inhaled treprostinil in an open label study in patients with precapillary pulmonary hypertension. Inhaled nitric oxide (20ppm; n=50), sildenafil (50mg; n=50) and inhaled treprostinil (15microg; n=25 or 30microg; n=25) were applied in subsequent order during right heart catheter investigation to consecutive patients with pulmonary arterial hypertension (PAH; n=28), non-operable chronic thromboembolic pulmonary hypertension (CTEPH; n=17) and pulmonary fibrosis associated pulmonary hypertension (n=5). Inhaled nitric oxide reduced pulmonary vascular resistance (PVR) to 87.3+/-5.1% of baseline values, reduced mean pulmonary arterial pressure (PAP) to 89.7+/-3.5% and increased cardiac output (CO) to 102.4+/-2.9%. Sildenafil reduced PVR to 80.1+/-5.0%, mPAP to 86.5+/-2.9% and increased CO to 103.8+/-3.2%. Treprostinil, inhaled 1h after sildenafil, reduced PVR to 66.3+/-3.8%, mPAP to 77.8+/-3.3%, and increased CO to 107.1+/-3.3% (mean+/-95% confidence interval). Subgroup analysis showed similar acute haemodynamic effects in PAH and CTEPH patients. Ventilation/perfusion distribution measurement in six patients with pre-existing gas exchange limitations was not changed by sildenafil and treprostinil. Relevant side effects were not observed. The combination of sildenafil and inhaled treprostinil was well tolerated and induced additive, pulmonary selective vasodilatation in pulmonary hypertension patients. This could be of relevance also for long-term treatment of PAH and CTEPH patients.

[Analysis of clinical features in patients with pneumoconiosis complicated with pulmonary emphysema].

PubMed

Li, X; Dai, W R; Li, L; Liu, W F; Yang, Z X; Xie, L

2017-11-20

Objective: To investigate the clinical features of pneumoconiosis complicated with pulmo-nary emphysema. Methods: selected 868 patients with pneumoconiosis were selected from December 2015 to December 2016 in Hunan occupational disease prevention and treatment hospital. Collected the results of high-resolution spiral CT, arterial blood gas, ECG, pulmonary function and MRC score. The subjects were divided into pneumoconiosis complicated with pulmonary emphysema group and simple pneumoconiosis group accord-ing to the results of HRCT. The smoking, MRC score, pulmonary function, blood gas and complications were compared. Results: A total of 868 patients were enrolled in the study. Emphysema 232 people, accounting for 26.73%. The incidence of emphysema in the first phase of pneumoconiosis was 12.69%, and the incidence rate of emphysema in pneumoconiosis was 17.03%, The incidence of three Stage pneumoconiosis was highest, up to 60.76%, the incidence of emphysema increased with the increase of stages of pneumoconiosis ( P =0.000) .The smoking index of pneumoconiosis combined with emphysema group was significantly higher than that of simple pneumoconiosis group ( P <0.01) . The MRC score of pneumoconiosis complicated with pulmonary em-physema group was higher than that of simple pneumoconiosis group ( P =0.000) . In pneumoconiosis complicat-ed with pulmonary emphysema group the FEV(1.0)%, FVC%, FEV(1.0)/FVC, DLCO%, oxygen partial pressure were significantly lower than that of simple pneumoconiosis group ( P ≤0.05) . The combined rate of Bullae of lung in pneumoconiosis complicated with pulmonary emphysema group was higher than that of simple pneumo-coniosis group ( P <0.01) . Conclusion: pneumoconiosis stage and smoking. Patients with pneumoconiosis com-plicated with pulmonary emphysema had heavier breathing difficulties, more serious pulmonary function and active endurance, the degree of hypoxia is more serious, and had a higher incidence of complications. The pul-monary function of pneumoconiosis complicated with pulmonary emphysema is not consistent with the typical CPFE.

Usefulness of QuantiFERON®-TB Gold test in psoriatic patients under treatment with tumour necrosis factor blockers.

PubMed

Saraceno, Rosita; Specchio, Francesca; Chiricozzi, Andrea; Sarmati, Loredana; Amicosante, Massimo; Chimenti, Maria Sole; Chimenti, Sergio

2014-02-01

Infliximab is a human/mouse chimeric anti-tumour necrosis factor (TNF)-α antibody that is effective in the management of psoriasis. Anti-TNF treatments may reactivate latent tuberculosis infection (LTBI); therefore, screening for LTBI is mandatory before starting any anti-TNF-α therapy. The aim of this study is to evaluate the usefulness of the QuantiFERON®-TB Gold (QFT-G) test in psoriatic patients under treatment with infliximab. A retrospective study had been performed on patients affected by psoriasis who had been treated with infliximab from 2003 to 2012 at a single centre. QFT-G was tested by a standard TB enzyme-linked immunosorbent assay, based on detection of interferon-γ release from sensitized leucocytes exposed to the synthetic Mycobacterium tuberculosis antigens at baseline and every 6 months until the end of treatment. A total of 140 patients were included. At baseline, 7 QFT-G tests were positive and 133 tests were negative. Of the 133 patients, 11 (8%) who were negative at baseline became QFT-G test positive during treatment. Of those 11 patients, 5 had a reversion during treatment. Of the 133 patients, 122 (92%) who were negative at baseline remained negative. It was found that the development of positive QFT-G tests, observed in 8% treated with infliximab, was not associated with pulmonary or extra-pulmonary tuberculosis.

[Usefulness of tricuspid annular displacement (TAD) to identify right ventricular dysfunction in normotensive patients with acute pulmonary embolism].

PubMed

Hugues, T; Yaici, K; Latcu, D-G; Rinaldi, J-P; Zarqane, N; Saoudi, N; Gibelin, P

2011-02-01

Echocardiographic criteria of right ventricular dysfunction (RVD) in acute pulmonary embolism (PE) differ among published studies. Assessment of RV systolic function remains difficult because of the RV's complex shape. We aimed to evaluate RV systolic function with TAD in patients (pts) with acute PE. TAD (QLAB, Philips Medical Imaging) was based on a tissue-tracking algorithm that is ultrasound beam angle independent for automated detection of tricuspid annular displacement. Prospective and observational study. All adults' pts who were diagnosed with PE from December 2008 to December 2009 at Princess Grace Hospital, Monaco were eligible for this study after exclusion of history of heart failure. We evaluated 36 consecutive pts with PE (18 male, mean age 62.7 years), which underwent echocardiography, plasma BNP titration during the first day after admission, and a second echocardiography obtained within 48 hours before discharge. TAD value were significantly lower in pts with abnormal RV function by echocardiogram (15.9 ± 0.3 vs. 12.7 ± 0.2 ; P = 0.026). Pts with a normal BNP (<80 pg/ml) had an elevated TAD (16.4 ± 0.2 vs. 11.2 ± 0.3 mm ; P < 0.0001). At discharge, echocardiographic data were obtained from 33 pts (mean: 8.3 ± 3.5 days). RV end diastolic diameter, RV to LV diameter, pulmonary arterial systolic pressure, mean pulmonic valve acceleration time, RV FAC, Sa and TAD were significantly improved. There was no difference between TAD among pts with echocardiographic RVD at baseline vs. pts without RVD (14.9 ± 3.7 vs. 16.1 ± 2.9 mm ; P = 0.3). Four pts who deteriorated during short-term observation had substantially lower TAD values than those with uncomplicated courses (7.7 ± 0.4mm vs. 14.6 ± 0.2 mm ; P = 0.001). In conclusion, impaired TAD was associated with decreased RV systolic function in pts with acute PE. To identify the clinical meaning of decreased TAD, larger trials with longer follow-up periods are needed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Two-year home-based nocturnal noninvasive ventilation added to rehabilitation in chronic obstructive pulmonary disease patients: A randomized controlled trial

PubMed Central

2011-01-01

Background The use of noninvasive intermittent positive pressure ventilation (NIPPV) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure remains controversial as long-term data are almost lacking. The aim was to compare the outcome of 2-year home-based nocturnal NIPPV in addition to rehabilitation (NIPPV + PR) with rehabilitation alone (PR) in COPD patients with chronic hypercapnic respiratory failure. Methods Sixty-six patients could be analyzed for the two-year home-based follow-up period. Differences in change between the NIPPV + PR and PR group were assessed by a linear mixed effects model with a random effect on the intercept, and adjustment for baseline values. The primary outcome was health-related quality of life (HRQoL); secondary outcomes were mood state, dyspnea, gas exchange, functional status, pulmonary function, and exacerbation frequency. Results Although the addition of NIPPV did not significantly improve the Chronic Respiratory Questionnaire compared to rehabilitation alone (mean difference in change between groups -1.3 points (95% CI: -9.7 to 7.4)), the addition of NIPPV did improve HRQoL assessed with the Maugeri Respiratory Failure questionnaire (-13.4% (-22.7 to -4.2; p = 0.005)), mood state (Hospital Anxiety and Depression scale -4.0 points (-7.8 to 0.0; p = 0.05)), dyspnea (Medical Research Council -0.4 points (-0.8 to -0.0; p = 0.05)), daytime arterial blood gases (PaCO2 -0.4 kPa (-0.8 to -0.2; p = 0.01); PaO2 0.8 kPa (0.0 to 1.5; p = 0.03)), 6-minute walking distance (77.3 m (46.4 to 108.0; p < 0.001)), Groningen Activity and Restriction scale (-3.8 points (-7.4 to -0.4; p = 0.03)), and forced expiratory volume in 1 second (115 ml (19 to 211; p = 0.019)). Exacerbation frequency was not changed. Conclusions The addition of NIPPV to pulmonary rehabilitation for 2 years in severe COPD patients with chronic hypercapnic respiratory failure improves HRQoL, mood, dyspnea, gas exchange, exercise tolerance and lung function decline. The benefits increase further with time. Trial registration ClinicalTrials.Gov (ID NCT00135538). PMID:21861914

Correlation of 68Ga Ventilation-Perfusion PET/CT with Pulmonary Function Test Indices for Assessing Lung Function.

PubMed

Le Roux, Pierre-Yves; Siva, Shankar; Steinfort, Daniel P; Callahan, Jason; Eu, Peter; Irving, Lou B; Hicks, Rodney J; Hofman, Michael S

2015-11-01

Pulmonary function tests (PFTs) are routinely used to assess lung function, but they do not provide information about regional pulmonary dysfunction. We aimed to assess correlation of quantitative ventilation-perfusion (V/Q) PET/CT with PFT indices. Thirty patients underwent V/Q PET/CT and PFT. Respiration-gated images were acquired after inhalation of (68)Ga-carbon nanoparticles and administration of (68)Ga-macroaggregated albumin. Functional volumes were calculated by dividing the volume of normal ventilated and perfused (%NVQ), unmatched and matched defects by the total lung volume. These functional volumes were correlated with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and diffusing capacity for carbon monoxide (DLCO). All functional volumes were significantly different in patients with chronic obstructive pulmonary disease (P < 0.05). FEV1/FVC and %NVQ had the highest correlation (r = 0.82). FEV1 was also best correlated with %NVQ (r = 0.64). DLCO was best correlated with the volume of unmatched defects (r = -0.55). Considering %NVQ only, a cutoff value of 90% correctly categorized 28 of 30 patients with or without significant pulmonary function impairment. Our study demonstrates strong correlations between V/Q PET/CT functional volumes and PFT parameters. Because V/Q PET/CT is able to assess regional lung function, these data support the feasibility of its use in radiation therapy and preoperative planning and assessing pulmonary dysfunction in a variety of respiratory diseases. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Respiratory motor training and neuromuscular plasticity in patients with chronic obstructive pulmonary disease: A pilot study.

PubMed

Ovechkin, Alexander V; Sayenko, Dimitry G; Ovechkina, Elena N; Aslan, Sevda C; Pitts, Teresa; Folz, Rodney J

2016-07-15

The objective of this study was to examine the feasibility of a full-scale investigation of the neurophysiological mechanisms of COPD-induced respiratory neuromuscular control deficits. Characterization of respiratory single- and multi-muscle activation patterns using surface electromyography (sEMG) were assessed along with functional measures at baseline and following 21±2 (mean±SD) sessions of respiratory motor training (RMT) performed during a one-month period in four patients with GOLD stage II or III COPD. Pre-training, the individuals with COPD showed significantly increased (p<0.05) overall respiratory muscle activity and disorganized multi-muscle activation patterns in association with lowered spirometrical measures and decreased fast- and slow-twitch fiber activity as compared to healthy controls (N=4). Following RMT, functional and respiratory sEMG activation outcomes during quite breathing and forced expiratory efforts were improved suggesting that functional improvements, induced by task-specific RMT, are evidence respiratory neuromuscular networks re-organization. Published by Elsevier B.V.

[The repercussions of pulmonary congestion on ventilatory volumes, capacities and flows].

PubMed

Carmo, M M; Ferreira, T; Lousada, N; Bárbara, C; Neves, P R; Correia, J M; Rendas, A B

1994-10-01

To evaluate the effects of pulmonary congestion on pulmonary function. Prospective study performed in patients with left ventricular failure or mitral stenosis. Forty-eight hospitalized patients were included suffering from pulmonary congestion either from left ventricular failure or mitral stenosis. While in hospital all patients were submitted to right heart catheterization by the Swan-Ganz method and also to an echocardiographic examination. Within 48 hours after the patients were submitted to the following lung function studies: lung volumes and capacities by the multi-breath helium dilution method and airway flows by pneumotachography. Respiratory symptoms were evaluated by the Medical Research Council Questionnaire and the functional class classified according to the NYHA. Correlations were made between the functional and clinical data. Regarding the cardiac evaluation patients presented with a mean pulmonary wedge pressure of 19.9 +/- 8.6 mmHg, a cardiac index of 2.5 +/- 0.8 l/min/m2, an end diastolic dimension of the left ventricle of 65.9 +/- 10.1 mm, and end systolic dimension of 51.2 +/- 12.2 mm, with a shortening fraction of 21.8 +/- 9.5%. The pulmonary evaluation showed a restrictive syndrome with a reduction in the mean values of the following parameters: total pulmonary capacity 71 +/- 14.4% of the predicted value (pv), forced vital capacity (FVC) 69.8 +/- 20.5% pv, and forced expiratory volume (FEV1) of 64 +/- 21.8% vp. The index FEV1/FVC was within the normal value of 72.7 +/- 9.7%. These lung function results did not correlate significantly with either the clinical, the hemodynamic or echocardiographic findings. In these group of patients pulmonary congestion led to the development of a restrictive syndrome which failed to correlate in severity with the duration of the disease, the pulmonary wedge pressure and the left ventricular function.

Pulmonary Morbidity in Infancy after Exposure to Chorioamnionitis in Late Preterm Infants

PubMed Central

McDowell, Karen M.; Jobe, Alan H.; Fenchel, Matthew; Hardie, William D.; Gisslen, Tate; Young, Lisa R.; Chougnet, Claire A.; Davis, Stephanie D.

2016-01-01

Rationale: Chorioamnionitis is an important cause of preterm birth, but its impact on postnatal outcomes is understudied. Objectives: To evaluate whether fetal exposure to inflammation is associated with adverse pulmonary outcomes at 6 to 12 months’ chronological age in infants born moderate to late preterm. Methods: Infants born between 32 and 36 weeks’ gestational age were prospectively recruited (N = 184). Chorioamnionitis was diagnosed by placenta and umbilical cord histology. Select cytokines were measured in samples of cord blood. Validated pulmonary questionnaires were administered (n = 184), and infant pulmonary function testing was performed (n = 69) between 6 and 12 months’ chronological age by the raised volume rapid thoracoabdominal compression technique. Measurements and Main Results: A total of 25% of participants had chorioamnionitis. Although infant pulmonary function testing variables were lower in infants born preterm compared with historical normative data for term infants, there were no differences between infants with chorioamnionitis (n = 20) and those without (n = 49). Boys and black infants had lower infant pulmonary function testing measurements than girls and white infants, respectively. Chorioamnionitis exposure was associated independently with wheeze (odds ratio [OR], 2.08) and respiratory-related physician visits (OR, 3.18) in the first year of life. Infants exposed to severe chorioamnionitis had increased levels of cord blood IL-6 and greater pulmonary morbidity at age 6 to 12 months than those exposed to mild chorioamnionitis. Elevated IL-6 was associated with significantly more respiratory problems (OR, 3.23). Conclusions: In infants born moderate or late preterm, elevated cord blood IL-6 and exposure to histologically identified chorioamnionitis was associated with respiratory morbidity during infancy without significant changes in infant pulmonary function testing measurements. Black compared with white and boy compared with girl infants had lower infant pulmonary function testing measurements and worse pulmonary outcomes. PMID:27015030

Machine Learning Algorithms Utilizing Quantitative CT Features May Predict Eventual Onset of Bronchiolitis Obliterans Syndrome After Lung Transplantation.

PubMed

Barbosa, Eduardo J Mortani; Lanclus, Maarten; Vos, Wim; Van Holsbeke, Cedric; De Backer, William; De Backer, Jan; Lee, James

2018-02-19

Long-term survival after lung transplantation (LTx) is limited by bronchiolitis obliterans syndrome (BOS), defined as a sustained decline in forced expiratory volume in the first second (FEV 1 ) not explained by other causes. We assessed whether machine learning (ML) utilizing quantitative computed tomography (qCT) metrics can predict eventual development of BOS. Paired inspiratory-expiratory CT scans of 71 patients who underwent LTx were analyzed retrospectively (BOS [n = 41] versus non-BOS [n = 30]), using at least two different time points. The BOS cohort experienced a reduction in FEV 1 of >10% compared to baseline FEV 1 post LTx. Multifactor analysis correlated declining FEV 1 with qCT features linked to acute inflammation or BOS onset. Student t test and ML were applied on baseline qCT features to identify lung transplant patients at baseline that eventually developed BOS. The FEV 1 decline in the BOS cohort correlated with an increase in the lung volume (P = .027) and in the central airway volume at functional residual capacity (P = .018), not observed in non-BOS patients, whereas the non-BOS cohort experienced a decrease in the central airway volume at total lung capacity with declining FEV 1 (P = .039). Twenty-three baseline qCT parameters could significantly distinguish between non-BOS patients and eventual BOS developers (P < .05), whereas no pulmonary function testing parameters could. Using ML methods (support vector machine), we could identify BOS developers at baseline with an accuracy of 85%, using only three qCT parameters. ML utilizing qCT could discern distinct mechanisms driving FEV 1 decline in BOS and non-BOS LTx patients and predict eventual onset of BOS. This approach may become useful to optimize management of LTx patients. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Chronic obstructive pulmonary disease self-management activation research trial (COPD-SMART): results of recruitment and baseline patient characteristics.

PubMed

Russo, Rennie; Coultas, David; Ashmore, Jamile; Peoples, Jennifer; Sloan, John; Jackson, Bradford E; Uhm, Minyong; Singh, Karan P; Blair, Steven N; Bae, Sejong

2015-03-01

To describe the recruitment methods, study participation rate, and baseline characteristics of a representative sample of outpatients with COPD eligible for pulmonary rehabilitation participating in a trial of a lifestyle behavioral intervention to increase physical activity. A patient registry was developed for recruitment using an administrative database from primary care and specialty clinics of an academic medical center in northeast Texas for a parallel group randomized trial. The registry was comprised of 5582 patients and over the course of the 30 month recruitment period 325 patients were enrolled for an overall study participation rate of 35.1%. After a 6-week COPD self-management education period provided to all enrolled patients, 305 patients were randomized into either usual care (UC; n=156) or the physical activity self-management intervention (PASM; n=149). There were no clinically significant differences in demographics, clinical characteristics, or health status indicators between the randomized groups. The results of this recruitment process demonstrate the successful use of a patient registry for enrolling a representative sample of outpatients eligible for pulmonary rehabilitation with COPD from primary and specialty care. Moreover, this approach to patient recruitment provides a model for future studies utilizing administrative databases and electronic health records. Published by Elsevier Inc.

Computer laboratory notification system via short message service to reduce health care delays in management of tuberculosis in Taiwan.

PubMed

Chen, Tun-Chieh; Lin, Wei-Ru; Lu, Po-Liang; Lin, Chun-Yu; Lin, Shu-Hui; Lin, Chuen-Ju; Feng, Ming-Chu; Chiang, Horn-Che; Chen, Yen-Hsu; Huang, Ming-Shyan

2011-06-01

We investigated the impacts of introducing an expedited acid-fast bacilli (AFB) smear laboratory procedure and an automatic, real-time laboratory notification system by short message with mobile phones on delays in prompt isolation of patients with pulmonary tuberculosis (TB). We analyzed the data for all patients with active pulmonary tuberculosis at a hospital in Kaohsiung, Taiwan, a 1,600-bed medical center, during baseline (January 2004 to February 2005) and intervention (July 2005 to August 2006) phases. A total of 96 and 127 patients with AFB-positive TB was reported during the baseline and intervention phases, respectively. There were significant decreases in health care system delays (ie, laboratory delays: reception of sputum to reporting, P < .001; response delays: reporting to patient isolation, P = .045; and interval from admission to patient isolation, P < .001) during the intervention phase. Significantly fewer nurses were exposed to each patient with active pulmonary TB during the intervention phase (P = .039). Implementation of expedited AFB smear laboratory procedures and an automatic, real-time laboratory mobile notification system significantly decreased delays in the diagnosis and isolation of patients with active TB. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Bolus versus continuous low dose of enalaprilat in congestive heart failure with acute refractory decompensation.

PubMed

Podbregar, M; Voga, G; Horvat, M; Zuran, I; Krivec, B; Skale, R; Pareznik, R

1999-01-01

The first dose of angiotensin-converting enzyme (ACE) inhibitors may trigger a considerable fall of blood pressure in chronic heart failure. The response may be dose-related. To determine hemodynamic and systemic oxygenation effects of low-dose enalaprilat, we administered intravenous enalaprilat (0.004 mg/kg) as bolus (group B) or continuous 1-hour infusion (group C) in 20 patients with congestive heart failure due to ischemic heart disease with acute decompensation refractory to inotropic, vasodilator and diuretic therapy. Hemodynamic and systemic oxygenation variables were recorded at baseline (+0 min), +30, +60, +120, +180, and +360 min after the start of intervention. Mean arterial pressure (MAP) (p < 0. 001), mean pulmonary artery pressure (MPAP) (p < 0.001), pulmonary artery occlusion pressure (PAOP) (p < 0.001), oxygen extraction ratio (ER) (p < 0.026) decreased regardless of enalaprilat application. Compared to group B, there was in group C prolonged decrease of MAP, MPAP, PAOP, ER and increase of pulmonary artery oxyhemoglobin saturation in regard to baseline values. Cardiac index, heart rate, central venous pressure and oxygen consumption index did not change. A low dose of intravenous enalaprilat (0.004 mg/kg) can be used to safely improve hemodynamics and systemic oxygenation in congestive heart failure due to ischemic heart disease with acute refractory decompensation.

[Functional respiratory evolution in two patients with emphysema and pulmonary fibrosis].

PubMed

Arce, Santiago C; Molinari, Luciana; De Vito, Eduardo L

2009-01-01

Combined pulmonary fibrosis and emphysema (CPFE) is a frequently under-diagnosed condition. Isolated pulmonary function tests (PFT) can give rise to misinterpretations. We have found no reports on these patients' spirometric progression. We describe two cases of CPFE, showing long-term functional evolution to have a more accurate understanding of current spirometric values. The most relevant findings are: 1) spirometry with discrete functional alterations in the presence of a marked dyspnea and the need, in one patient, for chronic oxygen therapy; and 2) functional evolution reflecting "pseudonormalisation" of the initial obstructive spirometric pattern, possibly as a result of fibrosis development. A mild obstructive defect in a patient with chronic airflow limitation and marked impairment of his/her clinical status and functional class should alert on the possibility of associated pulmonary fibrosis. A computed tomography (CT) and previous PFTs will allow a better understanding of this condition.

Modification of hemi-Fontan operation for patients with functional single ventricle and anomalous pulmonary venous connection to the superior vena cava: mid-term results†

PubMed Central

Ito, Hiroki; Murata, Masaya; Ide, Yujiro; Sugano, Mikio; Kanno, Kazuyoshi; Imai, Kenta; Ishido, Motonori; Fukuba, Ryohei; Sakamoto, Kisaburo

2016-01-01

OBJECTIVES Fontan candidates with mixed totally anomalous pulmonary venous connection often have postoperative pulmonary venous obstruction after cavopulmonary anastomosis. Because some pulmonary venous obstructions have no intimal hypertrophy at reoperation, we considered such pulmonary venous obstructions to be caused by 3D deformities arising from dissection or mobilization of the vessels, and hypothesized that keeping the pulmonary venous branches in a natural position could avoid such obstruction. Here, we evaluated a modified hemi-Fontan strategy consisting of minimal dissection with no division of vessels and patch separation between systemic and pulmonary venous flow. METHODS We retrospectively reviewed clinical records of infants with a functional single ventricle and supracardiac anomalous pulmonary venous connection who had undergone this procedure between 2002 and 2012. RESULTS Nine infants underwent this procedure (median age, 5.6 months; range 3.2–30), all with right atrial isomerism and several pulmonary venous branches directly and separately connecting to the superior vena cava. In 5 patients, all pulmonary veins drained into the superior vena cava; in 1, the right pulmonary veins drained into the superior vena cava and in 3, a pulmonary venous branch drained into the superior vena cava. The median follow-up was 6.9 years (0.8–13 years). Three patients underwent reoperation for postoperative pulmonary venous obstruction caused by intimal hypertrophy; however, we confirmed no pulmonary venous obstruction caused by 3D deformities on the pulmonary venous branches connecting separately to the superior vena cava. Although 2 patients were effectively relieved from pulmonary venous obstruction, 1 died due to recurrent pulmonary venous obstruction. There was no late death and no sinus-node dysfunction. Eight patients underwent successful Fontan operation and catheterization. The median interval from the Fontan operation to the latest catheterization was 3.7 years (0.9–3.7 years). The median arterial oxygen saturation was 94% (91–97%) and the central venous pressure was 12 mmHg (8–14 mmHg); no deficiency of pulmonary arteries and veins was noted. CONCLUSIONS For patients with functional single ventricle and anomalous pulmonary venous connections to the superior vena cava, our novel strategy of second-stage palliation could avoid postoperative pulmonary venous obstruction caused by 3D deformities, but may not eliminate pulmonary venous obstruction caused by intimal hypertrophy. PMID:26860898

Effect of Monthly, High-Dose, Long-Term Vitamin D on Lung Function: A Randomized Controlled Trial.

PubMed

Sluyter, John D; Camargo, Carlos A; Waayer, Debbie; Lawes, Carlene M M; Toop, Les; Khaw, Kay-Tee; Scragg, Robert

2017-12-13

Although observational studies suggest positive vitamin D-lung function associations, randomized trials are inconsistent. We examined effects of vitamin D supplementation on lung function. We recruited 442 adults (50-84 years, 58% male) into a randomized, double-blinded, placebo-controlled trial. Participants received, for 1.1 years (median; range = 0.9-1.5 years), either (1) vitamin D₃ 200,000 IU, followed by monthly 100,000 IU doses ( n = 226); or (2) placebo monthly ( n = 216). At baseline and follow-up, spirometry yielded forced expiratory volume in 1 s (FEV1; primary outcome). Mean (standard deviation) 25-hydroxyvitamin D increased from 61 (24) nmol/L at baseline to 119 (45) nmol/L at follow-up in the vitamin D group, but was unchanged in the placebo group. There were no significant lung function improvements (vitamin D versus placebo) in the total sample, vitamin D-deficient participants or asthma/chronic obstructive pulmonary disease (COPD) participants. However, among ever-smokers ( n = 217), the mean (95% confidence interval) FEV1 increase in the vitamin D versus placebo was 57 (4, 109) mL ( p = 0.03). FEV1 increases were larger among vitamin D-deficient ever-smokers ( n = 54): 122 (8, 236) mL ( p = 0.04). FEV1 improvements were largest among ever-smokers with asthma/COPD ( n = 60): 160 (53, 268) mL ( p = 0.004). Thus, vitamin D supplementation did not improve lung function among everyone, but benefited ever-smokers, especially those with vitamin D deficiency or asthma/COPD.

Normal Physiological Values for Conscious Pigs Used in Biomedical Research

DTIC Science & Technology

1989-05-01

6. Cardiovascular and Pulmonary Functions........... 18 TABLE 7. Bioenergetics..................................... 19 TABLE 8. Renal Function...procedure developed in our laboratory. Plasma concentrations of aldosterone, cortisol, total T3, total T4, free T4, insulin and glucagon were...pulmonary vascular resistance , alveolar ventilation, alveolar ventilation/perfusion ratio, arterial 02 transport, tissue 02 extraction ratio, pulmonary

Effect of change in symptoms, respiratory status, nutritional profile and quality of life on response to treatment for advanced non-small cell lung cancer.

PubMed

Mohan, Anant; Singh, P; Kumar, S; Mohan, C; Pathak, A K; Pandey, R M; Guleria, R

2008-01-01

Quality of life (QOL), and pulmonary and nutritional parameters are important outcome measures during treatment of lung cancer; however, the effect of chemotherapy on these factors and their relationship with clinical response is unclear. Patients with non-small cell lung cancer (NSCLC) were evaluated for symptom profile, nutritional status (using anthropometry), pulmonary functions by spirometry and six minute walk distance (6 MWD), and QOL using the WHO-QOL Bref 26 questionnaire, before and after chemotherapy. Forty-four patients were studied (mean (SD) age, 55 (10) years, 75% males). The majority (98%) had stage III or IV disease and 72% were current / ex-smokers with median pack-years of 27.0 (range, 0.5-90). Some 61% had a Karnofsky Performance Scale (KPS) 70 or 80. The commonest symptoms were coughing, dyspnea, chest pain, anorexia and fever (79%, 72%, 68%, 57% and 40%, respectively). The mean (SD) 6 MWD was 322.5 (132.6) meters. The mean (SD) percentage forced vital capacity (FVC %), and forced expiratory volume in one second (FEV1 %) were 64.7 (18.8) and 57.8 (19.4), respectively. The mean (SD) QOL scores for the physical, psychological, social, and environmental domains were 52.9 (20.5), 56.1 (17.9), 64.5 (21.8), 57.1 (16.6), respectively. Fourteen patients (32%) responded to chemotherapy. Non-responders had significantly higher baseline occurrence of fever, anorexia, and weight loss, higher pack-years of smoking and poorer KPS compared to responders. Overall, chemotherapy caused significant decline in the frequency of coughing, dyspnea, chest pain, fever, anorexia, weight loss, and improvement in hemoglobin and albumin levels. There was no significant improvement in pulmonary functions, nutritional status, or QOL scores after treatment. Lung cancer patients have a poor QOL. Although chemotherapy provides significant symptomatic benefit, this does not translate into similar benefit in respiratory and nutritional status or QOL. Patients with constitutional symptoms, higher smoking burden, and poor KPS are less likely to respond to chemotherapy. Management of NSCLC must include strategies to improve various aspects of QOL, nutritional status and pulmonary reserve to achieve comprehensive benefit.

Lung clearance index to monitor treatment response in pulmonary exacerbations in preschool children with cystic fibrosis.

PubMed

Rayment, Jonathan H; Stanojevic, Sanja; Davis, Stephanie D; Retsch-Bogart, George; Ratjen, Felix

2018-05-01

Antibiotic treatment for pulmonary symptoms in preschool children with cystic fibrosis (CF) varies among clinicians. The lung clearance index (LCI) is sensitive to early CF lung disease, but its utility to monitor pulmonary exacerbations in young children has not been assessed. We aim to (1) understand how LCI changes during lower respiratory tract symptoms relative to a recent clinically stable measurement, (2) determine whether LCI can identify antibiotic treatment response and (3) compare LCI changes to changes in spirometric indices. LCI and spirometry were measured at quarterly clinic visits over a 12-month period in preschool children with CF. Symptomatic visits were identified and classified as treated or untreated. Treatment response was estimated using propensity score matching methods. 104 symptomatic visits were identified in 78 participants. LCI increased from baseline in both treated (mean relative change +23.8% (95% CI 16.2 to 31.4)) and untreated symptomatic visits (mean relative change +11.2% (95% CI 2.4 to 19.9)). A significant antibiotic treatment effect was observed when LCI was used as the outcome measure (average treatment effect -15.5% (95% CI -25.4 to -5.6)) but not for z-score FEV 1 . LCI significantly deteriorated with pulmonary symptoms relative to baseline and improved with antibiotic treatment. These data suggest that LCI may have a role in the routine clinical care of preschool children with CF. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pulmonary function studies in young healthy Malaysians of Kelantan, Malaysia.

PubMed

Bandyopadhyay, Amit

2011-11-01

Pulmonary function tests have been evolved as clinical tools in diagnosis, management and follow up of respiratory diseases as it provides objective information about the status of an individual's respiratory system. The present study was aimed to evaluate pulmonary function among the male and female young Kelantanese Malaysians of Kota Bharu, Malaysia, and to compare the data with other populations. A total of 128 (64 males, 64 females) non-smoking healthy young subjects were randomly sampled for the study from the Kelantanese students' population of the University Sains Malaysia, Kota Bharu Campus, Kelantan, Malaysia. The study population (20-25 yr age group) had similar socio-economic background. Each subject filled up the ATS (1978) questionnaire to record their personal demographic data, health status and consent to participate in the study. Subjects with any history of pulmonary diseases were excluded from the study. The pulmonary function measurements exhibited significantly higher values among males than the females. FEV 1% did not show any significant inter-group variation probably because the parameter expresses FEV 1 as a percentage of FVC. FVC and FEV 1 exhibited significant correlations with body height and body mass among males whereas in the females exhibited significant correlation with body mass, body weight and also with age. FEV 1% exhibited significant correlation with body height and body mass among males and with body height in females. FEF 25-75% did not show any significant correlation except with body height among females. However, PEFR exhibited significant positive correlation with all the physical parameters except with age among the females. On the basis of the existence of significant correlation between different physical parameters and pulmonary function variables, simple and multiple regression norms have been computed. From the present investigation it can be concluded that Kelantanese Malaysian youths have normal range of pulmonary function in both the sexes and the computed regression norms may be used to predict the pulmonary function values in the studied population.

Pulmonary function studies in young healthy Malaysians of Kelantan, Malaysia

PubMed Central

Bandyopadhyay, Amit

2011-01-01

Background & objectives: Pulmonary function tests have been evolved as clinical tools in diagnosis, management and follow up of respiratory diseases as it provides objective information about the status of an individual's respiratory system. The present study was aimed to evaluate pulmonary function among the male and female young Kelantanese Malaysians of Kota Bharu, Malaysia, and to compare the data with other populations. Methods: A total of 128 (64 males, 64 females) non-smoking healthy young subjects were randomly sampled for the study from the Kelantanese students’ population of the University Sains Malaysia, Kota Bharu Campus, Kelantan, Malaysia. The study population (20-25 yr age group) had similar socio-economic background. Each subject filled up the ATS (1978) questionnaire to record their personal demographic data, health status and consent to participate in the study. Subjects with any history of pulmonary diseases were excluded from the study. Results: The pulmonary function measurements exhibited significantly higher values among males than the females. FEV1% did not show any significant inter-group variation probably because the parameter expresses FEV1 as a percentage of FVC. FVC and FEV1 exhibited significant correlations with body height and body mass among males whereas in the females exhibited significant correlation with body mass, body weight and also with age. FEV1% exhibited significant correlation with body height and body mass among males and with body height in females. FEF25-75% did not show any significant correlation except with body height among females. However, PEFR exhibited significant positive correlation with all the physical parameters except with age among the females. On the basis of the existence of significant correlation between different physical parameters and pulmonary function variables, simple and multiple regression norms have been computed. Interpretation & conclusions: From the present investigation it can be concluded that Kelantanese Malaysian youths have normal range of pulmonary function in both the sexes and the computed regression norms may be used to predict the pulmonary function values in the studied population. PMID:22199104

Baseline regional perfusion impacts exercise response to endobronchial valve therapy in advanced pulmonary emphysema.

PubMed

Argula, Rahul G; Strange, Charlie; Ramakrishnan, Viswanathan; Goldin, Jonathan

2013-11-01

Advanced heterogeneous emphysema with hyperinflation impacts exercise tolerance in COPD. Bronchoscopic lung volume reduction using Zephyr endobronchial valves (EBVs) has been shown to improve lung function in patients with heterogeneous emphysema. It is unclear whether the target lobe perfusion of patients receiving EBV therapy impacts exercise tolerance as measured by the 6-min walk test distance (6MWTD). We performed a retrospective analysis on the treatment group of the Endobronchial Valve for Emphysema Palliation Trial (VENT) to evaluate the impact of perfusion, measured by 99mTc-MAA-perfusion scintigraphy, on the 6-month improvement in 6MWTD. A mixed-model analysis was performed for the treatment outcome, adjusting for other variables such as age, target lobe position, fissure integrity, BMI, sex, destruction score, and lobar exclusion. Dichotomized at the median, of the 169 patients who received EBV therapy, 88 had a low target lobe regional perfusion and 81 had high target lobe regional perfusion at baseline. Patients with a low target lobe regional perfusion had a significant improvement in 6MWTD when compared with those with a high baseline target lobe regional perfusion (30.24 m vs 3.72 m, P = .03). Shifts in perfusion after EBV therapy occurred only in patients with high baseline perfusion and did not correlate with improved 6MWTD. Patients having heterogeneous emphysema with a low baseline target lobe regional perfusion benefit from EBV therapy, independent of the degree of target lobe destruction. This effect is attenuated if the EBV therapy is not occlusive. Characterization of baseline perfusion may enhance clinical results of patients with emphysema undergoing EBV therapy. ClinicalTrials.gov; No.: NCT00000606; URL: www.clincialtrials.gov.

Intravenous injection of pharmaceutical tablets presenting as multiple pulmonary nodules and declining pulmonary function in an adolescent with cystic fibrosis.

PubMed

Smith, Kelly J; Elidemir, Okan; Dishop, Megan K; Eldin, Karen W; Tatevian, Nina; Moore, Robert H

2006-09-01

Here we present the unusual case of an adolescent with cystic fibrosis presenting with declining pulmonary function and diffuse micronodular pulmonary disease. This case illustrates the radiographic and pathologic findings associated with the intravenous injection and pulmonary arterial embolization of insoluble pharmaceutical-tablet constituents. The number of first-time users reporting nonmedical use of prescription pain relievers is increasing dramatically, especially in adolescents. Recognition of both the diagnostic imaging features and histologic features on lung biopsy are critical steps for early diagnosis, intervention, and potential prevention of sudden death in these at-risk patients.

Pulmonary artery pressure increases during commercial air travel in healthy passengers.

PubMed

Smith, Thomas G; Talbot, Nick P; Chang, Rae W; Wilkinson, Elizabeth; Nickol, Annabel H; Newman, David G; Robbins, Peter A; Dorrington, Keith L

2012-07-01

It is not known whether the mild hypoxia experienced by passengers during commercial air travel triggers hypoxic pulmonary vasoconstriction and increases pulmonary artery pressure in flight. Insidious pulmonary hypertensive responses could endanger susceptible passengers who have cardiopulmonary disease or increased hypoxic pulmonary vascular sensitivity. Understanding these effects may improve pre-flight assessment of fitness-to-fly and reduce in-flight morbidity and mortality. Eight healthy volunteers were studied during a scheduled commercial airline flight from London, UK, to Denver, CO. The aircraft was a Boeing 777 and the duration of the flight was 9 h. Systolic pulmonary artery pressure (sPAP) was assessed by portable Doppler echocardiography during the flight and over the following week in Denver, where the altitude (5280 ft/1610 m) simulates a commercial airliner environment. Cruising cabin altitude ranged between 5840 and 7170 ft (1780 to 2185 m), and mean arterial oxygen saturation was 95 +/- 0.6% during the flight. Mean sPAP increased significantly in flight by 6 +/- 1 mmHg to 33 +/- 1 mmHg, an increase of approximately 20%. After landing in Denver, sPAP was still 3 +/- 1 mmHg higher than baseline and remained elevated at 30 +/- 1 mmHg for a further 12 h. Pulmonary artery pressure increases during commercial air travel in healthy passengers, raising the possibility that hypoxic pulmonary hypertension could develop in susceptible individuals. A hypoxia altitude simulation test with simultaneous echocardiography ('HAST-echo') may be beneficial in assessing fitness to fly in vulnerable patients.

Comparison of Diaphragmatic Breathing Exercise, Volume and Flow Incentive Spirometry, on Diaphragm Excursion and Pulmonary Function in Patients Undergoing Laparoscopic Surgery: A Randomized Controlled Trial

PubMed Central

Anand, R.

2016-01-01

Objective. To evaluate the effects of diaphragmatic breathing exercises and flow and volume-oriented incentive spirometry on pulmonary function and diaphragm excursion in patients undergoing laparoscopic abdominal surgery. Methodology. We selected 260 patients posted for laparoscopic abdominal surgery and they were block randomization as follows: 65 patients performed diaphragmatic breathing exercises, 65 patients performed flow incentive spirometry, 65 patients performed volume incentive spirometry, and 65 patients participated as a control group. All of them underwent evaluation of pulmonary function with measurement of Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Peak Expiratory Flow Rate (PEFR), and diaphragm excursion measurement by ultrasonography before the operation and on the first and second postoperative days. With the level of significance set at p < 0.05. Results. Pulmonary function and diaphragm excursion showed a significant decrease on the first postoperative day in all four groups (p < 0.001) but was evident more in the control group than in the experimental groups. On the second postoperative day pulmonary function (Forced Vital Capacity) and diaphragm excursion were found to be better preserved in volume incentive spirometry and diaphragmatic breathing exercise group than in the flow incentive spirometry group and the control group. Pulmonary function (Forced Vital Capacity) and diaphragm excursion showed statistically significant differences between volume incentive spirometry and diaphragmatic breathing exercise group (p < 0.05) as compared to that flow incentive spirometry group and the control group. Conclusion. Volume incentive spirometry and diaphragmatic breathing exercise can be recommended as an intervention for all patients pre- and postoperatively, over flow-oriented incentive spirometry for the generation and sustenance of pulmonary function and diaphragm excursion in the management of laparoscopic abdominal surgery. PMID:27525116

Comparison of Diaphragmatic Breathing Exercise, Volume and Flow Incentive Spirometry, on Diaphragm Excursion and Pulmonary Function in Patients Undergoing Laparoscopic Surgery: A Randomized Controlled Trial.

PubMed

Alaparthi, Gopala Krishna; Augustine, Alfred Joseph; Anand, R; Mahale, Ajith

2016-01-01

Objective. To evaluate the effects of diaphragmatic breathing exercises and flow and volume-oriented incentive spirometry on pulmonary function and diaphragm excursion in patients undergoing laparoscopic abdominal surgery. Methodology. We selected 260 patients posted for laparoscopic abdominal surgery and they were block randomization as follows: 65 patients performed diaphragmatic breathing exercises, 65 patients performed flow incentive spirometry, 65 patients performed volume incentive spirometry, and 65 patients participated as a control group. All of them underwent evaluation of pulmonary function with measurement of Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Peak Expiratory Flow Rate (PEFR), and diaphragm excursion measurement by ultrasonography before the operation and on the first and second postoperative days. With the level of significance set at p < 0.05. Results. Pulmonary function and diaphragm excursion showed a significant decrease on the first postoperative day in all four groups (p < 0.001) but was evident more in the control group than in the experimental groups. On the second postoperative day pulmonary function (Forced Vital Capacity) and diaphragm excursion were found to be better preserved in volume incentive spirometry and diaphragmatic breathing exercise group than in the flow incentive spirometry group and the control group. Pulmonary function (Forced Vital Capacity) and diaphragm excursion showed statistically significant differences between volume incentive spirometry and diaphragmatic breathing exercise group (p < 0.05) as compared to that flow incentive spirometry group and the control group. Conclusion. Volume incentive spirometry and diaphragmatic breathing exercise can be recommended as an intervention for all patients pre- and postoperatively, over flow-oriented incentive spirometry for the generation and sustenance of pulmonary function and diaphragm excursion in the management of laparoscopic abdominal surgery.

Inapparent pulmonary vascular disease in an ex-heroin user

DOE Office of Scientific and Technical Information (OSTI.GOV)

Antonelli Incalzi, R.; Ludovico Maini, C.; Giuliano Bonetti, M.

1986-04-01

A severe pulmonary vascular derangement, usually reported in drug addicts, was diagnosed in a 28-year-old asymptomatic ex-heroin user by means of fortuitously performed pulmonary perfusion imaging. Neither physical findings nor pulmonary function tests, aroused suspicion of the diagnosis. A search for asymptomatic pulmonary vascular disease probably should be undertaken in drug addicts.

Roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction.

PubMed

Liu, Jia-Ming; Shen, Jian-Xiong; Zhang, Jian-Guo; Zhao, Hong; Li, Shu-Gang; Zhao, Yu; Qiu, Giu-Xing

2012-01-01

It has been stated that preoperative pulmonary function tests are essential to assess the surgical risk in patients with scoliosis. Arterial blood gas tests have also been used to evaluate pulmonary function before scoliotic surgery. However, few studies have been reported. The aim of this study was to investigate the roles of preoperative arterial blood gas tests in the surgical treatment of scoliosis with moderate or severe pulmonary dysfunction. This study involved scoliotic patients with moderate or severe pulmonary dysfunction (forced vital capacity < 60%) who underwent surgical treatment between January 2002 and April 2010. A total of 73 scoliotic patients (23 males and 50 females) with moderate or severe pulmonary dysfunction were included. The average age of the patients was 16.53 years (ranged 10 - 44). The demographic distribution, medical records, and radiographs of all patients were collected. All patients received arterial blood gas tests and pulmonary function tests before surgery. The arterial blood gas tests included five parameters: partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, alveolar-arterial oxygen tension gradient, pH, and standard bases excess. The pulmonary function tests included three parameters: forced expiratory volume in 1 second ratio, forced vital capacity ratio, and peak expiratory flow ratio. All five parameters of the arterial blood gas tests were compared between the two groups with or without postoperative pulmonary complications by variance analysis. Similarly, all three parameters of the pulmonary function tests were compared. The average coronal Cobb angle before surgery was 97.42° (range, 50° - 180°). A total of 15 (20.5%) patients had postoperative pulmonary complications, including hypoxemia in 5 cases (33.3%), increased requirement for postoperative ventilatory support in 4 (26.7%), pneumonia in 2 (13.3%), atelectasis in 2 (13.3%), pneumothorax in 1 (6.7%), and hydrothorax in 1 (6.7%). No significant differences in demographic characteristics or perioperative factors (P > 0.05) existed between the two groups with or without postoperative pulmonary complications. According to the variance analysis, there were no statistically significant differences in any parameter of the arterial blood gas tests between the two groups. No significant correlation between the results of the preoperative arterial blood gas tests and postoperative pulmonary complications existed in scoliotic patients with moderate or severe pulmonary dysfunction. However, the postoperative complications tended to increase with the decrease of partial pressure of arterial oxygen in the arterial blood gas tests.

Quantitative computed tomography of pulmonary emphysema and ventricular function in chronic obstructive pulmonary disease patients with pulmonary hypertension.

PubMed

Huang, Yu-Sen; Hsu, Hsao-Hsun; Chen, Jo-Yu; Tai, Mei-Hwa; Jaw, Fu-Shan; Chang, Yeun-Chung

2014-01-01

This study strived to evaluate the relationship between degree of pulmonary emphysema and cardiac ventricular function in chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH) using electrocardiographic-gated multidetector computed tomography (CT). Lung transplantation candidates with the diagnosis of COPD and PH were chosen for the study population, and a total of 15 patients were included. The extent of emphysema is defined as the percentage of voxels below -910 Hounsfield units in the lung windows in whole lung CT without intravenous contrast. Heart function parameters were measured by electrocardiographic-gated CT angiography. Linear regression analysis was conducted to examine the associations between percent emphysema and heart function indicators. Significant correlations were found between percent emphysema and right ventricular (RV) measurements, including RV end-diastolic volume (R(2) = 0.340, p = 0.023), RV stroke volume (R(2) = 0.406, p = 0.011), and RV cardiac output (R(2) = 0.382, p = 0.014); the correlations between percent emphysema and left ventricular function indicators were not observed. The study revealed that percent emphysema is correlated with RV dysfunction among COPD patients with PH. Based on our findings, percent emphysema can be considered for use as an indicator to predict the severity of right ventricular dysfunction among COPD patients.

Lung volumes, ventricular function and pulmonary arterial flow in children operated on for left-sided congenital diaphragmatic hernia: long-term results.

PubMed

Abolmaali, Nasreddin; Koch, Arne; Götzelt, Knut; Hahn, Gabriele; Fitze, Guido; Vogelberg, Christian

2010-07-01

To compare MRI-based functional pulmonary and cardiac measurements in the long-term follow-up of children operated on for left-sided congenital diaphragmatic hernia (CDH) with age- and body size-matched healthy controls. Twelve children who received immediate postnatal surgery for closure of isolated left-sided CDH were included and received basic medical examinations, pulmonary function testing and echocardiography. MRI included measurement of lung volume, ventricular function assessment and velocity-encoded imaging of the pulmonary arteries and was compared with the data for 12 healthy children matched for age and body size. While patients' clinical test results were not suspicious, comparison between the MRI data for patients and those for healthy controls revealed significant differences. In patients, the volumes of the left lungs were increased and the tidal volume was larger on the right side. While the stroke volumes of both ventricles were reduced, heart rate and ejection fraction were increased. Flow, acceleration time and cross-sectional area of the left pulmonary artery were reduced. Functional MRI detected pulmonary and cardiac findings in the late follow-up of CDH children which may be missed by standard clinical methods and might be relevant for decisions regarding late outcome and treatment.

Travelers' Health: Deep Vein Thrombosis and Pulmonary Embolism

MedlinePlus

... risk factors for VTE. The risk decreases with time after air travel and returns to baseline by 8 weeks; most ... are at increased risk be evaluated with enough time prior to departure so ... travel health provider has prescribed. PREVENTIVE MEASURES FOR LONG- ...

Effects of exercise training on pulmonary vessel muscularization and right ventricular function in an animal model of COPD.

PubMed

Hassel, Erlend; Berre, Anne Marie; Skjulsvik, Anne Jarstein; Steinshamn, Sigurd

2014-09-28

Right ventricular dysfunction in COPD is common, even in the absence of pulmonary hypertension. The aim of the present study was to examine the effects of high intensity interval training (HIIT) on right ventricular (RV) function, as well as pulmonary blood vessel remodeling in a mouse model of COPD. 42 female A/JOlaHsd mice were randomized to exposure to either cigarette smoke or air for 6 hours/day, 5 days/week for 14 weeks. Mice from both groups were further randomized to sedentariness or HIIT for 4 weeks. Cardiac function was evaluated by echocardiography and muscularization of pulmonary vessel walls by immunohistochemistry. Smoke exposure induced RV systolic dysfunction demonstrated by reduced tricuspid annular plane systolic excursion. HIIT in smoke-exposed mice reversed RV dysfunction. There were no significant effects on the left ventricle of neither smoke exposure nor HIIT. Muscularization of the pulmonary vessels was reduced after exercise intervention, but no significant effects on muscularization were observed from smoke exposure. RV function was reduced in mice exposed to cigarette smoke. No Increase in pulmonary vessel muscularization was observed in these mice, implying that other mechanisms caused the RV dysfunction. HIIT attenuated the RV dysfunction in the smoke exposed mice. Reduced muscularization of the pulmonary vessels due to HIIT suggests that exercise training not only affects the heart muscle, but also has important effects on the pulmonary vasculature.

Relationship of respiratory symptoms and pulmonary function to tar, nicotine, and carbon monoxide yield of cigarettes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krzyzanowski, M.; Sherrill, D.L.; Paoletti, P.

The data from consecutive surveys of the Tucson Epidemiologic Study (1981-1988) were used to evaluate the relationship in cigarette smokers of respiratory symptoms and pulmonary function to tar, nicotine, and carbon monoxide (CO) yields of the cigarette. There were 690 subjects who reported smoking regularly in at least one survey, over age 15. After adjustment for intensity and duration of smoking and for depth of inhalation, the risk of chronic phlegm, cough, and dyspnea were not related to the tar and nicotine yields. In 414 subjects with pulmonary function tested in at least one of the three surveys the spirometricmore » indices used were significantly related to the daily dose of tar, nicotine, and CO (product of the cigarette yield and daily number of cigarettes smoked). The effects were more pronounced for past than for current doses. However, the differentiation of pulmonary function due to various yields of cigarettes was small in comparison to the difference in pulmonary function between smokers and nonsmokers.« less

The optimization of iloprost inhalation under moderate flow of oxygen therapy in severe pulmonary arterial hypertension.

PubMed

Nakayama, Kazuhiko; Emoto, Noriaki; Tamada, Naoki; Okano, Mitsumasa; Shinkura, Yuto; Yanaka, Kenichi; Onishi, Hiroyuki; Hiraishi, Mana; Yamada, Shinichiro; Tanaka, Hidekazu; Shinke, Toshiro; Hirata, Ken-Ichi

2018-01-01

Inhaled iloprost efficiently improves pulmonary hemodynamics, exercise capacity, and quality of life in patients with pulmonary arterial hypertension (PAH). However, the process of inhalation is laborious for patients suffering from resting dyspnea. We describe a 75-year-old man with idiopathic PAH and a low gas transfer. Investigations excluded significant parenchymal lung disease and airflow obstruction (presuming FEV1/FVC ration > 70%). The patient struggled to complete iloprost inhalation due to severe dyspnea and hypoxemia. As such, we optimized the methods of oxygen supply from the nasal cannula to the trans-inhalator during the inhalation. We successfully shortened the inhalation duration that effectively reduced the laborious efforts required of patients. We also recorded pulmonary hemodynamics during inhalation of nebulized iloprost. This revealed significant hemodynamic improvement immediately following inhalation but hemodynamics returned to baseline within 2 hours. We hope that this optimization will enable patients with severe PAH to undergo iloprost inhalation.

Pulse oximetry in the pulmonary tissue for the non-invasive measurement of mixed venous oxygen saturation.

PubMed

Nitzan, Meir; Nitzan, Itamar

2013-08-01

The oxygen saturation of the systemic arterial blood is associated with the adequacy of respiration, and can be measured non-invasively by pulse oximetry in the systemic tissue. The oxygen saturation of the blood in the pulmonary artery, the mixed venous blood, reflects the balance between oxygen supply to the systemic tissues and their oxygen demand. The mixed venous oxygen saturation has also clinical significance because it is used in Fick equation for the quantitative measurement of cardiac output. At present the measurement of the mixed venous oxygen saturation is invasive and requires insertion of a Swan-Ganz catheter into the pulmonary artery. We suggest a noninvasive method for the measurement of the mixed venous oxygen saturation in infants, pulmonary pulse oximetry. The method is similar to the systemic pulse oximetry, which is based on the different light absorption curves of oxygenated and deoxygenated hemoglobin and on the analysis of photoplethysmographic curves in two wavelengths. The proposed pulmonary pulse oximeter includes light-sources of two wavelengths in the infrared, which illuminate the pulmonary tissue through the thoracic wall. Part of the light which is scattered back from the pulmonary tissue and passes through the thoracic wall is detected, and for each wavelength a pulmonary photoplethysmographic curve is obtained. The pulmonary photoplethysmographic curves reflect blood volume increase during systole in the pulmonary arteries in the lung tissue, which contain mixed venous blood. The ratio R of the amplitude-to-baseline ratio for the two wavelengths is related to the mixed venous oxygen saturation through equations derived for the systemic pulse oximetry. The method requires the use of extinction coefficients values for oxygenated and deoxygenated hemoglobin, which can be found in the literature. Copyright © 2013 Elsevier Ltd. All rights reserved.

Short and long term response to pulmonary exacerbation treatment in cystic fibrosis

PubMed Central

Heltshe, Sonya L.; Goss, Christopher H.; Thompson, Valeria; Sagel, Scott D.; Sanders, Don B.; Marshall, Bruce C.; Flume, Patrick A.

2016-01-01

Background Treatment of pulmonary exacerbations (PEx) in cystic fibrosis (CF) varies widely with no consensus on management practices or best indicators of therapeutic success. To design trials evaluating PEx treatment factors, we characterize the heterogeneity of PEx care in adults and pediatrics, and correlate it with measures of clinical response including short and long term lung function changes, change in symptom severity score, and time to next intravenous (IV) antibiotic therapy. Methods Data were used from a prospective observational study of CF patients ≥10 years of age enrolled at six sites between 2007 and 2010. All were started on IV antibiotics for a clinically diagnosed PEx. ANOVA, logistic and Cox regression were used to examine the association of treatment factors with short and long term clinical response. Results Of 123 CF patients (60% female, aged 23.1±10.2 years), 33% experienced <10% relative improvement in FEV1 during treatment which was associated with failing to recover baseline lung function three months after treatment (OR=7.8, 95% CI=(1.9, 31.6), p=0.004) and a longer time to next IV antibiotic (HR=0.48, 95% CI=(0.27, 0.85), p=0.011). Symptom improvement was observed but was not associated with subsequent lung function or time to next antibiotic therapy which had a median recurrence time of 143 days. Conclusions Immediate symptomatic or respiratory response to PEx treatment did not have a clear relationship with subsequent outcomes such as lung function or IV antibiotic-free interval. These results can inform future research of treatment regimens for PEx in terms of interventions and outcome measures. PMID:25911223

Mortality in Advanced Chronic Obstructive Pulmonary Disease and Heart Failure Following Cardiopulmonary Rehabilitation.

PubMed

Kang, Youjeong; Steele, Bonnie G; Burr, Robert L; Dougherty, Cynthia M

2018-07-01

Cardiopulmonary rehabilitation (CR) improves physical function and quality of life (QoL) in chronic obstructive pulmonary disease (COPD) and heart failure (HF), but it is unknown if CR improves outcomes in very severe disease. This study's purpose was to describe functional capacity (6-min walk distance [6MWD], steps/day), symptoms (dyspnea, depression), QoL (Short-Form Health Survey-Veterans [SF-36 V]) and cardiopulmonary function ( N-terminal pro-brain natriuretic peptide [NT-proBNP], forced expiratory volume in 1 s [FEV 1 ]), and derive predictors of mortality among patients with severe COPD and HF who participated in CR. In this secondary analysis of a randomized controlled trial comparing two CR methods in severe COPD and HF, 90 (COPD = 63, HF = 27) male veterans, mean age 66 ± 9.24 years, 79% Caucasian, and body mass index 31 kg/m 2 , were followed for 12 months after CR. The COPD group had greater functional decline than the HF group (6MWD, p = .006). Dyspnea was lower ( p = .001) and QoL higher ( p = .006) in the HF group. Mean NT-proBNP was higher in the HF group at all time points. FEV 1 improved over 12 months in both groups ( p = .01). Mortality was 8.9%, 16.7%, and 37.8% at 12, 24, and 60 months, respectively. One-year predictors of mortality were baseline total steps (<3,000/day), 6MWD (<229 meters), and NT-proBNP level (>2,000 mg/pg). In very severe COPD and HF, risks of mortality over 12 months can predict patients unlikely to benefit from CR and should be considered at initial referral.

Serum insulin-like growth factor-1 (IGF-1) during CF pulmonary exacerbation: trends and biomarker correlations.

PubMed

Gifford, A H; Nymon, A B; Ashare, A

2014-04-01

Cystic fibrosis (CF) is characterized by low circulating levels of insulin-like growth factor-1 (IGF-1), a hormone produced by the liver that governs anabolism and influences immune cell function. Because treatment of CF pulmonary exacerbation (CFPE) often improves body weight and lung function, we questioned whether serum IGF-1 trends were emblematic of these responses. Initially, we compared serum levels between healthy adults with CF and controls of similar age. We then measured serum IGF-1 throughout the CFPE cycle. We also investigated correlations among IGF-1 and other serum biomarkers during CFPE. Anthopometric, spirometric, and demographic data were collected. Serum IGF-1 concentrations were measured by ELISA. CF subjects in their usual state of health had lower serum IGF-1 levels than controls. Serum IGF-1 concentrations fell significantly from baseline at the beginning of CFPE. Treatment with intravenous antibiotics was associated with significant improvement in serum IGF-1 levels, body mass index (BMI), and percent-predicted forced expiratory volume in 1 sec (FEV1 %). At early and late CFPE, serum IGF-1 was directly correlated with FEV1 %, serum iron, hemoglobin concentration, and transferrin saturation (TSAT) and indirectly correlated with alpha-1-antitrypsin. This study not only supports the paradigm that CF is characterized by IGF-1 deficiency but also that trends in lung function, nutritional status, and serum IGF-1 are related. Improvements in all three parameters after antibiotics for CFPE likely highlight the connection between lung function and nutritional status in CF. Close correlations among IGF-1 and iron-related hematologic parameters suggest that IGF-1 may participate in CF iron homeostasis, another process that is known to be influenced by CFPE. © 2013 Wiley Periodicals, Inc.

Do sanitary ceramic workers have a worse presentation of chest radiographs or pulmonary function tests than other ceramic workers?

PubMed

Tsao, Yu-Chung; Liu, Su-Hsun; Tzeng, I-Shiang; Hsieh, Tsung-Han; Chen, Jau-Yuan; Luo, Jiin-Chyuan John

2017-03-01

Silicosis remains the most prevalent occupational disease worldwide. There have been no specific studies focusing on the association between exposure settings at work and the clinical severity in silicosis patients. In this study, we describe and compare the clinical characteristics and silicosis-associated exposure history at work among workers from several types of ceramic production facilities in Taiwan. We reviewed the medical records of 221 patients who were first diagnosed with silicosis at the Occupational Medicine Clinic of Northern Taiwan in 2012. For each patient, we collected data on demographic characteristics, smoking habits, working history, duration of exposure, and years on the first relevant job. We also retrieved clinical reports of the pulmonary function test and the baseline chest radiography used for silicosis staging. As compared to other ceramic workers, sanitary ceramic workers had a worse X-ray type (p=0.044), more advanced age (p<0.001), longer working duration (p=0.029), and a higher proportion of starting the first relevant job prior to the year 1975 (p=0.003). However, after adjusting for age, work duration, and an initial occupational exposure prior to 1975, sanitary ceramic workers showed a comparable risk for worse X-ray findings to other ceramic workers (adjusted odds ratio=1.18, p=0.704). Results of multivariable regression models on individual lung function parameter also suggested comparably impaired lung function tests between sanitary and other ceramic workers (p>0.05). In this study, we found that sanitary ceramic workers were at a similar risk to other ceramic workers for moderate to severe silicosis when older age and longer working duration were accounted for. Copyright © 2016. Published by Elsevier B.V.

IDENTIFICATION AND CHARACTERIZATION OF DISEASE USING PULMONARY FUNCTION TESTS

EPA Science Inventory

Abstract
Pulmonary function testing is used routinely in human medicine to objectively define functional deficits in individuals with respiratory disease. Despite the fact that respiratory disease is a common problem in veterinary medicine, evaluation of the small animal pa...

Incidence of Pneumothorax in Patients With Lymphangioleiomyomatosis Undergoing Pulmonary Function and Exercise Testing.

PubMed

Taveira-DaSilva, Angelo M; Julien-Williams, Patricia; Jones, Amanda M; Moss, Joel

2016-07-01

Because pneumothorax is frequent in lymphangioleiomyomatosis, patients have expressed concerns regarding the risk of pneumothorax associated with pulmonary function or exercise testing. Indeed, pneumothorax has been reported in patients with lung disease after both of these tests. The aim of this study was to determine the incidence of pneumothorax in patients with lymphangioleiomyomatosis during admissions to the National Institutes of Health Clinical Research Center between 1995 and 2015. Medical records were reviewed to identify patients who had a pneumothorax during their stay at the National Institutes of Health. A total of 691 patients underwent 4,523 pulmonary function tests and 1,900 exercise tests. Three patients developed pneumothorax after pulmonary function tests and/or exercise tests. The incidence of pneumothorax associated with lung function testing was 0.14 to 0.29 of 100 patients or 0.02 to 0.04 of 100 tests. The incidence of pneumothorax in patients undergoing exercise testing was 0.14 to 0.28 of 100 patients or 0.05 to 0.10 of 100 tests. The risk of pneumothorax associated with pulmonary function or exercise testing in patients with lymphangioleiomyomatosis is low. Published by Elsevier Inc.

Healthcare Resource Uses and Out-of-Pocket Expenses Associated with Pulmonary TB Treatment in Thailand.

PubMed

Tanvejsilp, Pimwara; Loeb, Mark; Dushoff, Jonathan; Xie, Feng

2017-08-22

In Thailand, pharmaceutical care has been recently introduced to a tertiary hospital as an approach to improve adherence to tuberculosis (TB) treatment in addition to home visit and modified directly observed therapy (DOT). However, the economic impact of pharmaceutical care is not known. The aim of this study was to estimate healthcare resource uses and costs associated with pharmaceutical care compared with home visit and modified DOT in pulmonary TB patients in Thailand from a healthcare sector perspective inclusive of out-of-pocket expenditures. We conducted a retrospective study using data abstracted from the hospital billing database associated with pulmonary TB patients who began treatment between 2010 and 2013 in three hospitals in Thailand. We used generalized linear models to compare the costs by accounting for baseline characteristics. All costs were converted to international dollars (Intl$) RESULTS: The mean direct healthcare costs to the public payer were $519.96 (95%confidence interval [CI] 437.31-625.58) associated with pharmaceutical care, $1020.39 (95% CI 911.13-1154.11) for home visit, and $887.79 (95% CI 824.28-955.91) for modified DOT. The mean costs to patients were $175.45 (95% CI 130.26-230.48) for those receiving pharmaceutical care, $53.77 (95% CI 33.25-79.44) for home visit, and $49.33 (95% CI 34.03-69.30) for modified DOT. After adjustment for baseline characteristics, pharmaceutical care was associated with lower total direct costs compared with home visit (-$354.95; 95% CI -285.67 to -424.23) and modified DOT (-$264.61; 95% CI -198.76 to -330.46). After adjustment for baseline characteristics, pharmaceutical care was associated with lower direct costs compared with home visit and modified DOT.

Alteration of serum inflammatory cytokines in active pulmonary tuberculosis following anti-tuberculosis drug therapy.

PubMed

Chowdhury, Imran Hussain; Ahmed, Albin Mostaque; Choudhuri, Subhadip; Sen, Aditi; Hazra, Avijit; Pal, Nishith Kumar; Bhattacharya, Basudev; Bahar, Bojlul

2014-11-01

Active pulmonary tuberculosis (APTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis (Mtb). The objective of this study was to quantify and assess the role of serum inflammatory cytokines in active pulmonary tuberculosis patients following anti-tuberculosis drug (ATD) therapy. Blood samples were collected from APTB patients and normal healthy subjects (NHS) (total n=204) at baseline and 2, 4 and 6 months post-therapy and the abundance of serum inflammatory cytokines were measured by cytokine specific ELISA. Compared to NHS, APTB patients at baseline had higher levels of serum pro-inflammatory cytokines IL-12p40 (P<0.001), IFN-γ (P<0.001), TNF-α (P<0.01), IL-1β (P<0.001) and IL-6 (P<0.001) and anti-inflammatory cytokines IL-10 (P<0.001) and TGF-β1 (P<0.001) while there was no change in the level of IL-4. In APTB patients, the serum levels of IFN-γ, TNF-α, IL-6 and TGF-β1 directly relate to the bacterial load while the TNF-α, IL-1β, IL-6 and TGF-β1 relate to radiological severity. At baseline, the IL-6 level in NHS and APTB patients differed most and following ATD therapy, this level rapidly decreased and stabilized by 4-month in APTB patients. It is concluded that a subtle reduction in the serum level of IL-6 of the APTB patients following ATD therapy might play a vital role in immune-protection of the host against Mtb infection and hence the serum IL-6 level can be a useful marker to diagnose the effectiveness of therapy in the patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Factors for Predicting Outcomes among Non-HIV Patients with Pulmonary Tuberculosis

PubMed Central

Tsukahara, Toshinori; Horita, Nobuyuki; Tashiro, Ken; Nagai, Kenjiro; Shinkai, Masaharu; Yamamoto, Masaki; Sato, Takashi; Hara, Yu; Nagakura, Hideyuki; Shibata, Yuji; Watanabe, Hiroki; Nakashima, Kentaro; Ushio, Ryota; Nagashima, Akimichi; Ikeda, Misako; Narita, Atsuya; Sasaki, Katsuhito; Kobayashi, Nobuaki; Kudo, Makoto; Kaneko, Takeshi

2017-01-01

Objective Onodera's Prognostic Nutritional Index (PNI), determined as “10× albumin (g/dL) + 0.005× lymphocyte count (/μL),” was originally designed to determine the risk of complications following gastrointestinal surgery. This single-center, retrospective observational study was designed to investigate whether or not the PNI can predict the treatment outcome. Methods We consecutively reviewed HIV-negative pulmonary tuberculosis adults in an isolation ward. Most patients were being treated with standard three- or four-drug regimens. Patients were discharged after consecutive negative smears/cultures were confirmed. The risk of all-cause death was assessed using a multivariable Cox proportional hazard model and a log-rank trend test. Results During the observation period, we observed 371 consecutive patients with a median age of 72 (interquartile range [IQR]: 54-82) years. In our cohort, 295 (79.5%) patients were discharged alive, and 76 (20.5%) died in-hospital. Patients who died in-hospital had a lower PNI [median 21.2 (IQR: 18.5-25.9)] than those who were discharged alive [median 35.1 (IQR: 28.0-43.3); p<0.001]. The area under the receiver operating characteristic curve was 0.87. After dividing the patients based on the baseline PNI quartile, those patients with a lower PNI showed a poorer survival than those with a higher PNI (log-rank trend p<0.001). After adjusting for other baseline variables, the baseline PNI was still associated with in-hospital death with a hazard ratio of 0.86 (95% confidence interval: 0.82-0.91, p<0.001). Conclusion Our results showed that a low PNI was clearly related to a poor survival prognosis in smear-positive HIV-negative pulmonary tuberculosis inpatients. PMID:29021438

Inhaled nitric oxide pretreatment but not posttreatment attenuates ischemia-reperfusion-induced pulmonary microvascular leak.

PubMed

Chetham, P M; Sefton, W D; Bridges, J P; Stevens, T; McMurtry, I F

1997-04-01

Ischemia-reperfusion (I/R) pulmonary edema probably reflects a leukocyte-dependent, oxidant-mediated mechanism. Nitric oxide (NO) attenuates leukocyte-endothelial cell interactions and I/R-induced microvascular leak. Cyclic adenosine monophosphate (cAMP) agonists reverse and prevent I/R-induced microvascular leak, but reversal by inhaled NO (INO) has not been tested. In addition, the role of soluble guanylyl cyclase (sGC) activation in the NO protection effect is unknown. Rat lungs perfused with salt solution were grouped as either I/R, I/R with INO (10 or 50 ppm) on reperfusion, or time control. Capillary filtration coefficients (Kfc) were estimated 25 min before ischemia (baseline) and after 30 and 75 min of reperfusion. Perfusate cell counts and lung homogenate myeloperoxidase activity were determined in selected groups. Additional groups were treated with either INO (50 ppm) or isoproterenol (ISO-10 microM) after 30 min of reperfusion. Guanylyl cyclase was inhibited with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ-15 microM), and Kfc was estimated at baseline and after 30 min of reperfusion. (1) Inhaled NO attenuated I/R-induced increases in Kfc. (2) Cell counts were similar at baseline. After 75 min of reperfusion, lung neutrophil retention (myeloperoxidase activity) and decreased perfusate neutrophil counts were similar in all groups. (3) In contrast to ISO, INO did not reverse microvascular leak. (4) 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) prevented I/R-induced microvascular leak in ODQ-treated lungs, but INO was no longer effective. Inhaled NO attenuates I/R-induced pulmonary microvascular leak, which requires sGC activation and may involve a mechanism independent of inhibition of leukocyte-endothelial cell interactions. In addition, INO is ineffective in reversing I/R-induced microvascular leak.

Factors for Predicting Outcomes among Non-HIV Patients with Pulmonary Tuberculosis.

PubMed

Tsukahara, Toshinori; Horita, Nobuyuki; Tashiro, Ken; Nagai, Kenjiro; Shinkai, Masaharu; Yamamoto, Masaki; Sato, Takashi; Hara, Yu; Nagakura, Hideyuki; Shibata, Yuji; Watanabe, Hiroki; Nakashima, Kentaro; Ushio, Ryota; Nagashima, Akimichi; Ikeda, Misako; Narita, Atsuya; Sasaki, Katsuhito; Kobayashi, Nobuaki; Kudo, Makoto; Kaneko, Takeshi

2017-12-15

Objective Onodera's Prognostic Nutritional Index (PNI), determined as "10× albumin (g/dL) + 0.005× lymphocyte count (/μL)," was originally designed to determine the risk of complications following gastrointestinal surgery. This single-center, retrospective observational study was designed to investigate whether or not the PNI can predict the treatment outcome. Methods We consecutively reviewed HIV-negative pulmonary tuberculosis adults in an isolation ward. Most patients were being treated with standard three- or four-drug regimens. Patients were discharged after consecutive negative smears/cultures were confirmed. The risk of all-cause death was assessed using a multivariable Cox proportional hazard model and a log-rank trend test. Results During the observation period, we observed 371 consecutive patients with a median age of 72 (interquartile range [IQR]: 54-82) years. In our cohort, 295 (79.5%) patients were discharged alive, and 76 (20.5%) died in-hospital. Patients who died in-hospital had a lower PNI [median 21.2 (IQR: 18.5-25.9)] than those who were discharged alive [median 35.1 (IQR: 28.0-43.3); p<0.001]. The area under the receiver operating characteristic curve was 0.87. After dividing the patients based on the baseline PNI quartile, those patients with a lower PNI showed a poorer survival than those with a higher PNI (log-rank trend p<0.001). After adjusting for other baseline variables, the baseline PNI was still associated with in-hospital death with a hazard ratio of 0.86 (95% confidence interval: 0.82-0.91, p<0.001). Conclusion Our results showed that a low PNI was clearly related to a poor survival prognosis in smear-positive HIV-negative pulmonary tuberculosis inpatients.

Protocol for a mixed-methods study of supplemental oxygen in pulmonary fibrosis.

PubMed

Belkin, Amanda; Fier, Kaitlin; Albright, Karen; Baird, Susan; Crowe, Brenda; Eres, Linda; Korn, Marjorie; Maginn, Leslie; McCormick, Mark; Root, Elisabeth D; Vierzba, Thomas; Wamboldt, Frederick S; Swigris, Jeffrey J

2014-11-01

Little is known about whether or how supplemental oxygen affects patients with pulmonary fibrosis. A mixed-methods study is described. Patients with pulmonary fibrosis, informal caregivers of pulmonary fibrosis patients and practitioners who prescribe supplemental oxygen will be interviewed to gather data on perceptions of how supplemental oxygen impacts patients. In addition, three hundred pulmonary fibrosis patients who do not use daytime supplemental oxygen will be recruited to participate in a longitudinal, pre-/post- study in which patient-reported outcome (PRO) and activity data will be collected at baseline, immediately before daytime supplemental oxygen is initiated, and then once and again 9-12 months later. Activity data will be collected using accelerometers and portable GPS data recorders. The primary outcome is change in dyspnea from before to one month after supplemental oxygen is initiated. Secondary outcomes include scores from PROs to assess cough, fatigue and quality of life as well as the activity data. In exploratory analyses, we will use longitudinal data analytic techniques to assess the trajectories of outcomes over time while controlling for potentially influential variables. Throughout the study and at its completion, results will be posted on the website for our research program (the Participation Program for Pulmonary Fibrosis or P3F) at http://www.pulmonaryfibrosisresearch.org.

INTERPRETATIONS AND LIMITATION OF PULMONARY FUNCTION TESTING IN SMALL LABORATORY ANIMALS

EPA Science Inventory

Pulmonary function tests are tools available to the researcher and clinician to evaluate the ability of the lung to perform its essential function of gas exchange. o meet this principal function, the lung needs to operate efficiently with minimal mechanical work as well as provid...

Longitudinal follow-up of fibrosing interstitial pneumonia: relationship between physiologic testing, computed tomography changes, and survival rate.

PubMed

Hwang, Jeong-Hwa; Misumi, Shigeki; Curran-Everett, Douglas; Brown, Kevin K; Sahin, Hakan; Lynch, David A

2011-08-01

The aim of this study was to evaluate the prognostic implications of computed tomography (CT) and physiologic variables at baseline and on sequential evaluation in patients with fibrosing interstitial pneumonia. We identified 72 patients with fibrosing interstitial pneumonia (42 with idiopathic disease, 30 with collagen vascular disease). Pulmonary function tests and CT were performed at the time of diagnosis and at a median follow-up of 12 months, respectively. Two chest radiologists scored the extent of specific abnormalities and overall disease on baseline and follow-up CT. Rate of survival was estimated using the Kaplan-Meier method. Three Cox proportional hazards models were constructed to evaluate the relationship between CT and physiologic variables and rate of survival: model 1 included only baseline variables, model 2 included only serial change variables, and model 3 included both baseline and serial change variables. On follow-up CT, the extent of mixed ground-glass and reticular opacities (P<0.001), pure reticular opacity (P=0.04), honeycombing (P=0.02), and overall extent of disease (P<0.001) was increased in the idiopathic group, whereas these variables remained unchanged in the collagen vascular disease group. Patients with idiopathic disease had a shorter rate of survival than those with collagen vascular disease (P=0.03). In model 1, the extent of honeycombing on baseline CT was the only independent predictor of mortality (P=0.02). In model 2, progression in honeycombing was the only predictor of mortality (P=0.005). In model 3, baseline extent of honeycombing and progression of honeycombing were the only independent predictors of mortality (P=0.001 and 0.002, respectively). Neither baseline nor serial change physiologic variables, nor the presence of collagen vascular disease, was predictive of rate of survival. The extent of honeycombing at baseline and its progression on follow-up CT are important determinants of rate of survival in patients with fibrosing interstitial pneumonia.

Dynamic chest radiography: flat-panel detector (FPD) based functional X-ray imaging.

PubMed

Tanaka, Rie

2016-07-01

Dynamic chest radiography is a flat-panel detector (FPD)-based functional X-ray imaging, which is performed as an additional examination in chest radiography. The large field of view (FOV) of FPDs permits real-time observation of the entire lungs and simultaneous right-and-left evaluation of diaphragm kinetics. Most importantly, dynamic chest radiography provides pulmonary ventilation and circulation findings as slight changes in pixel value even without the use of contrast media; the interpretation is challenging and crucial for a better understanding of pulmonary function. The basic concept was proposed in the 1980s; however, it was not realized until the 2010s because of technical limitations. Dynamic FPDs and advanced digital image processing played a key role for clinical application of dynamic chest radiography. Pulmonary ventilation and circulation can be quantified and visualized for the diagnosis of pulmonary diseases. Dynamic chest radiography can be deployed as a simple and rapid means of functional imaging in both routine and emergency medicine. Here, we focus on the evaluation of pulmonary ventilation and circulation. This review article describes the basic mechanism of imaging findings according to pulmonary/circulation physiology, followed by imaging procedures, analysis method, and diagnostic performance of dynamic chest radiography.

Endothelial and Smooth Muscle Cell Ion Channels in Pulmonary Vasoconstriction and Vascular Remodeling

PubMed Central

Makino, Ayako; Firth, Amy L.; Yuan, Jason X.-J.

2017-01-01

The pulmonary circulation is a low resistance and low pressure system. Sustained pulmonary vasoconstriction and excessive vascular remodeling often occur under pathophysiological conditions such as in patients with pulmonary hypertension. Pulmonary vasoconstriction is a consequence of smooth muscle contraction. Many factors released from the endothelium contribute to regulating pulmonary vascular tone, while the extracellular matrix in the adventitia is the major determinant of vascular wall compliance. Pulmonary vascular remodeling is characterized by adventitial and medial hypertrophy due to fibroblast and smooth muscle cell proliferation, neointimal proliferation, intimal, and plexiform lesions that obliterate the lumen, muscularization of precapillary arterioles, and in situ thrombosis. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction, while increased release of mitogenic factors, upregulation (or downregulation) of ion channels and transporters, and abnormalities in intracellular signaling cascades are key to the remodeling of the pulmonary vasculature. Changes in the expression, function, and regulation of ion channels in PASMC and pulmonary arterial endothelial cells play an important role in the regulation of vascular tone and development of vascular remodeling. This article will focus on describing the ion channels and transporters that are involved in the regulation of pulmonary vascular function and structure and illustrating the potential pathogenic role of ion channels and transporters in the development of pulmonary vascular disease. PMID:23733654

Chronic respiratory disfunction due to diffuse alveolar hemorrhage in patients with systemic lupus erythematosus and primary vasculitis.

PubMed

Pérez Aceves, Eva; Pérez Cristóbal, Mario; Espinola Reyna, Gerardo A; Ariza Andraca, Raul; Xibille Fridmann, Daniel; Barile Fabris, Leonor A

2013-01-01

Pulmonary hemorrhage (PH) occurs in 2-5% of SLE patients, and is associated with a high mortality rate (79-90%). Diagnostic criteria for this complication include: 1) Pulmonary infiltrates, with at least ¾ of lung tissue involved in a chest x ray, 2) Acute respiratory failure, 3) A decrease of 3g/dL or more in hemoglobin levels. PH might lead to organized pneumonia, collagen deposition, and pulmonary fibrosis which in time might cause changes in pulmonary function tests with either restrictive or obstructive patterns. To evaluate the existence of abnormalities in pulmonary function tests after a PH episode. We included patients with SLE and primary vasculitis that developed PH. During the acute episode, we measured SLEDAI in SLE patients, five factor score in microscopic polyangiitis (MPA) and Birmingham Vasculitis Activity Store (BVAS) in granulomatosis with polyangiitis (GPA) (Wegener). We determined the number of PH events, treatment, and ventilator assistance requirements and correlated its association with abnormal pulmonary function tests. We included 10 patients, 7 with SLE, 2 with MPA and 1 with GPA (Wegener). The mean activity measures were: SLEDAI 20.4 ± 7.5, FFS 2, and BVAS 36. Treatment consisted in methylprednisolone (MPD) in 3 patients, MPD plus cyclophosphamide (CY) in 6 patients, and MPD, CY, IV immunoglobulin, and plasmapheresis in one patient. Five patients required ventilatory support. We found abnormalities in pulmonary function tests in 8 patients, three had an obstructive pattern and five a restrictive pattern; 2 patients did not show any change. We did not find a significant association with any of the studied variables. PH might cause abnormalities in pulmonary function tests and prolonged immunosuppressive treatment could be required. Copyright © 2012 Elsevier España, S.L. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunil, Vasanthi R., E-mail: sunilvr@eohsi.rutgers.edu; Patel, Kinal J., E-mail: kinalv5@gmail.com; Shen, Jianliang, E-mail: jianliangs@gmail.com

Nitrogen mustard is a vesicant that causes damage to the respiratory tract. In these studies, we characterized the acute effects of nitrogen mustard on lung structure, inflammatory mediator expression, and pulmonary function, with the goal of identifying mediators potentially involved in toxicity. Treatment of rats (male Wistar, 200-225 g) with nitrogen mustard (mechlorethamine hydrochloride, i.t., 0.25 mg/kg) resulted in marked histological changes in the respiratory tract, including necrotizing bronchiolitis, thickening of alveolar septa, and inflammation which was evident within 24 h. This was associated with increases in bronchoalveolar lavage protein and cells, confirming injury to alveolar epithelial regions of themore » lung. Nitrogen mustard administration also resulted in increased expression of inducible nitric oxide synthase and cyclooxygenase-2, pro-inflammatory proteins implicated in lung injury, in alveolar macrophages and alveolar and bronchial epithelial cells. Expression of connective tissue growth factor and matrix metalloproteinase-9, mediators regulating extracellular matrix turnover was also increased, suggesting that pathways leading to chronic lung disease are initiated early in the pathogenic process. Following nitrogen mustard exposure, alterations in lung mechanics and function were also observed. These included decreases in baseline static compliance, end-tidal volume and airway resistance, and a pronounced loss of methacholine responsiveness in resistance, tissue damping and elastance. Taken together, these data demonstrate that nitrogen mustard induces rapid structural and inflammatory changes in the lung which are associated with altered lung functioning. Understanding the nature of the injury induced by nitrogen mustard and related analogs may aid in the development of efficacious therapies for treatment of pulmonary injury resulting from exposure to vesicants.« less

Doxycycline use in patients with lymphangioleiomyomatosis: biomarkers and pulmonary function response *, **

PubMed Central

Pimenta, Suzana Pinheiro; Baldi, Bruno Guedes; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

2013-01-01

OBJECTIVE: To assess blockade of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the variation in FEV1, in patients with lymphangioleiomyomatosis (LAM) treated with doxycycline (a known MMP inhibitor) for 12 months. METHODS: An open-label, single-arm, interventional clinical trial in which LAM patients received doxycycline (100 mg/day) for 12 months. Patients underwent full pulmonary function testing, a six-minute walk test, and quality of life assessment, as well as blood and urine sampling for quantification of MMP-2, MMP-9, and VEGF-D levels-at baseline, as well as at 6 and 12 months after the initiation of doxycycline. RESULTS: Thirty-one LAM patients received doxycycline for 12 months. Although there was effective blockade of urinary MMP-9 and serum MMP-2 after treatment, there were no significant differences between pre and post-doxycycline serum levels of MMP-9 and VEGF-D. On the basis of their response to doxycycline (as determined by the variation in FEV1), the patients were divided into two groups: the doxycycline-responder (doxy-R) group (n = 13); and the doxycycline-nonresponder (doxy-NR) group (n = 18). The patients with mild spirometric abnormalities responded better to doxycycline. The most common side effects were mild epigastric pain, nausea, and diarrhea. CONCLUSIONS: In patients with LAM, doxycycline treatment results in effective MMP blockade, as well as in improved lung function and quality of life in those with less severe disease. However, these benefits do not seem to be related to the MMP blockade, raising the hypothesis that there is a different mechanism of action. PMID:23503480

The UCSD Shortness of Breath Questionnaire has Longitudinal Construct Validity in Idiopathic Pulmonary Fibrosis

PubMed Central

Swigris, Jeffrey J.; Han, Meilan; Vij, Rekha; Noth, Imre; Eisenstein, Eric L.; Anstrom, Kevin J.; Brown, Kevin K.; Fairclough, Diane

2012-01-01

Background Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that often causes disabling dyspnea. In IPF and other lung diseases, patient-reported outcomes (PROs)—questionnaires designed to gather information from the patient's perspective—can determine whether therapies affect dyspnea or other outcomes meaningful to patients. Before a PRO can be used confidently as an outcome measure in a longitudinal trial, studies must demonstrate the PRO's ability to capture change over time in the target population. Our goal in this study was to examine whether the UCSD Shortness of Breath Questionnaire does so in patients with IPF. Methods We used data from the Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (STEP-IPF) to perform analyses that examined associations between UCSD scores and five external measures (anchors) at baseline and over time. Anchors included the Activity domain from St. George's Respiratory Questionnaire (SGRQ-A), the Physical Functioning domain from the SF-36 (SF36-PF), forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and distance walked during a timed walk test (6MWD). Linear regression models were used to examine relationships between UCSD scores and anchors over time. Results At baseline, UCSD scores were weakly correlated with percent predicted FVC (−0.21, p=0.005) and percent predicted DLCO (−0.20, p=0.008), moderately correlated with 6MWD (−0.39, p<0.0001) and strongly correlated with SGRQ-A (0.79, p<0.0001) and SF36-PF (−0.72, p<0.0001). Change over time in UCSD scores was associated with change in FVC (estimate=2.54, standard error [SE]=1.23, p=0.04), SGRQ-A (estimate=7.94, SE=1.11, p<0.0001), SF36-PF (estimate=6.00, SE=1.13, p<0.0001), and 6MWD (estimate=4.23, SE=1.18, p=0.0004) but not DLCO (estimate=0.33, SE=1.33, p=0.80). Conclusions These results support the validity of the UCSD to assess change in dyspnea over time in patients with IPF. PMID:22801586

The effect of pollutional haze on pulmonary function

PubMed Central

Liu, Shao-Kun; Cai, Shan; Chen, Yan; Xiao, Bing; Chen, Ping

2016-01-01

Detrimental health effects of atmospheric exposure to ambient particulate matter (PM) have been investigated in numerous studies. Exposure to pollutional haze, the carrier of air pollutants such as PM and nitrogen dioxide (NO2) has been linked to lung and cardiovascular disease, resulting increases in both hospital admissions and mortality. This review focuses on the constituents of pollutional haze and its effects on pulmonary function. The article presents the available information and seeks to correlate pollutional haze and pulmonary function. PMID:26904252

Genome-wide association and large scale follow-up identifies 16 new loci influencing lung function

PubMed Central

Artigas, María Soler; Loth, Daan W; Wain, Louise V; Gharib, Sina A; Obeidat, Ma’en; Tang, Wenbo; Zhai, Guangju; Zhao, Jing Hua; Smith, Albert Vernon; Huffman, Jennifer E; Albrecht, Eva; Jackson, Catherine M; Evans, David M; Cadby, Gemma; Fornage, Myriam; Manichaikul, Ani; Lopez, Lorna M; Johnson, Toby; Aldrich, Melinda C; Aspelund, Thor; Barroso, Inês; Campbell, Harry; Cassano, Patricia A; Couper, David J; Eiriksdottir, Gudny; Franceschini, Nora; Garcia, Melissa; Gieger, Christian; Gislason, Gauti Kjartan; Grkovic, Ivica; Hammond, Christopher J; Hancock, Dana B; Harris, Tamara B; Ramasamy, Adaikalavan; Heckbert, Susan R; Heliövaara, Markku; Homuth, Georg; Hysi, Pirro G; James, Alan L; Jankovic, Stipan; Joubert, Bonnie R; Karrasch, Stefan; Klopp, Norman; Koch, Beate; Kritchevsky, Stephen B; Launer, Lenore J; Liu, Yongmei; Loehr, Laura R; Lohman, Kurt; Loos, Ruth JF; Lumley, Thomas; Al Balushi, Khalid A; Ang, Wei Q; Barr, R Graham; Beilby, John; Blakey, John D; Boban, Mladen; Boraska, Vesna; Brisman, Jonas; Britton, John R; Brusselle, Guy G; Cooper, Cyrus; Curjuric, Ivan; Dahgam, Santosh; Deary, Ian J; Ebrahim, Shah; Eijgelsheim, Mark; Francks, Clyde; Gaysina, Darya; Granell, Raquel; Gu, Xiangjun; Hankinson, John L; Hardy, Rebecca; Harris, Sarah E; Henderson, John; Henry, Amanda; Hingorani, Aroon D; Hofman, Albert; Holt, Patrick G; Hui, Jennie; Hunter, Michael L; Imboden, Medea; Jameson, Karen A; Kerr, Shona M; Kolcic, Ivana; Kronenberg, Florian; Liu, Jason Z; Marchini, Jonathan; McKeever, Tricia; Morris, Andrew D; Olin, Anna-Carin; Porteous, David J; Postma, Dirkje S; Rich, Stephen S; Ring, Susan M; Rivadeneira, Fernando; Rochat, Thierry; Sayer, Avan Aihie; Sayers, Ian; Sly, Peter D; Smith, George Davey; Sood, Akshay; Starr, John M; Uitterlinden, André G; Vonk, Judith M; Wannamethee, S Goya; Whincup, Peter H; Wijmenga, Cisca; Williams, O Dale; Wong, Andrew; Mangino, Massimo; Marciante, Kristin D; McArdle, Wendy L; Meibohm, Bernd; Morrison, Alanna C; North, Kari E; Omenaas, Ernst; Palmer, Lyle J; Pietiläinen, Kirsi H; Pin, Isabelle; Polašek, Ozren; Pouta, Anneli; Psaty, Bruce M; Hartikainen, Anna-Liisa; Rantanen, Taina; Ripatti, Samuli; Rotter, Jerome I; Rudan, Igor; Rudnicka, Alicja R; Schulz, Holger; Shin, So-Youn; Spector, Tim D; Surakka, Ida; Vitart, Veronique; Völzke, Henry; Wareham, Nicholas J; Warrington, Nicole M; Wichmann, H-Erich; Wild, Sarah H; Wilk, Jemma B; Wjst, Matthias; Wright, Alan F; Zgaga, Lina; Zemunik, Tatijana; Pennell, Craig E; Nyberg, Fredrik; Kuh, Diana; Holloway, John W; Boezen, H Marike; Lawlor, Debbie A; Morris, Richard W; Probst-Hensch, Nicole; Kaprio, Jaakko; Wilson, James F; Hayward, Caroline; Kähönen, Mika; Heinrich, Joachim; Musk, Arthur W; Jarvis, Deborah L; Gläser, Sven; Järvelin, Marjo-Riitta; Stricker, Bruno H Ch; Elliott, Paul; O’Connor, George T; Strachan, David P; London, Stephanie J; Hall, Ian P; Gudnason, Vilmundur; Tobin, Martin D

2011-01-01

Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD). We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function. PMID:21946350

Net atrioventricular compliance is an independent predictor of cardiovascular death in mitral stenosis.

PubMed

Nunes, Maria Carmo Pereira; Tan, Timothy C; Elmariah, Sammy; Lodi-Junqueira, Lucas; Nascimento, Bruno Ramos; do Lago, Rodrigo; Padilha da Silva, Jose Luiz; Reis, Rodrigo Citton Padilha; Zeng, Xin; Palacios, Igor F; Hung, Judy; Levine, Robert A

2017-12-01

Rheumatic mitral stenosis (MS) is a progressive disease, and risk of death may persist despite relief of the obstruction. Net atrioventricular compliance (C n ) modulates the overall haemodynamic burden of the MS and may be useful in predicting cardiovascular death after percutaneous mitral valvuloplasty (PMV). A total of 427 patients (mean age 50±16 years, 84% female) with severe MS undergoing PMV were enrolled. Doppler-derived C n was estimated at baseline using a previously validated equation. The primary endpoint was late cardiovascular death, and the secondary endpoint was a composite of all-cause mortality, mitral valve (MV) replacement or repeat PMV over a median follow-up of 31 months (IQR: 7.8-49.2 months). At baseline, 209 patients (49%) were in New York Heart Association (NYHA) functional class III or IV. During follow-up, 49 patients died (41 cardiovascular deaths), 50 underwent MV replacement and 12 required repeat PMV, with an overall incidence of cardiac mortality and adverse events of 4.1 deaths and 11.1 events per 100 patient-years, respectively. Low baseline C n was a strong predictor of both cardiac death (adjusted HR 0.70, 95% CI 0.49 to 0.86) and composite endpoint (adjusted HR 0.81, 95% CI 0.67 to 0.91) after adjusting for clinical factors, baseline pulmonary artery pressure, tricuspid regurgitation severity, right ventricular function and immediate procedural haemodynamic data. The inclusion of C n in a model with conventional parameters resulted in improvement in 5-year cardiovascular mortality risk prediction. Baseline C n is a strong predictor of cardiovascular death in patients with MS undergoing PMV, independent of other prognostic markers of decreased survival in MS, including baseline patient characteristics and postprocedural data. C n assessment therefore has potential value in evaluation of cardiovascular mortality risk in the setting of MS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Three-Dimensional Right Ventricular Strain Versus Volume Quantification in Heart Transplant Recipients in Relation to Pulmonary Artery Pressure.

PubMed

Sade, Leyla Elif; Kozan, Hatice; Eroglu, Serpil; Pirat, Bahar; Aydinalp, Alp; Sezgin, Atilla; Muderrisoglu, Haldun

2017-02-01

Residual pulmonary hypertension challenges the right ventricular function and worsens the prognosis in heart transplant recipients. The complex geometry of the right ventricle complicates estimation of its function with conventional transthoracic echocardiography. We evaluated right ventricular function in heart transplant recipients with the use of 3-dimensional echocardiography in relation to systolic pulmonary artery pressure. We performed 32 studies in 26 heart transplant patients, with 6 patients having 2 studies at different time points with different pressures and thus included. Right atrial volume, tricuspid annular plane systolic excursion, peak systolic annular velocity, fractional area change, and 2-dimensional speckle tracking longitudinal strain were obtained by 2-dimensional and tissue Doppler imaging. Three-dimensional right ventricular volumes, ejection fraction, and 3-dimensional right ventricular strain were obtained from the 3-dimensional data set by echocardiographers. Systolic pulmonary artery pressure was obtained during right heart catheterization. Overall mean systolic pulmonary artery pressure was 26 ± 7 mm Hg (range, 14-44 mmHg). Three-dimensional end-diastolic (r = 0.75; P < .001) and end-systolic volumes (r = 0.55; P = .001)correlated well with systolic pulmonary artery pressure. Right ventricular ejection fraction and right atrium volume also significantly correlated with systolic pulmonary artery pressure (r = 0.49 and P = .01 for both). However, right ventricular 2- and 3-dimensional strain, tricuspid annular plane systolic excursion, and tricuspid annular velocity did not. The effects of pulmonary hemodynamic burden on right ventricular function are better estimated by a 3-dimensional volume evaluation than with 3-dimensional longitudinal strain and other 2-dimensional and tissue Doppler measurements. These results suggest that the peculiar anatomy of the right ventricle necessitates 3-dimensional volume quantification in heart transplant recipients in relation to residual pulmonary hypertension.

Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension.

PubMed

Beghetti, Maurice; Rudzinski, Andrzej; Zhang, Min

2017-07-04

Despite the increased risk for pulmonary hypertension in children with Down syndrome, the response to treatment with targeted therapies for pulmonary hypertension in these patients is not well characterized. The Sildenafil in Treatment-naive children, Aged 1-17 years, with pulmonary arterial hypertension (STARTS-1) trial was a dose-ranging study of the short-term efficacy and safety of oral sildenafil in children with pulmonary arterial hypertension. We assessed the safety and efficacy of oral sildenafil in children with Down syndrome and pulmonary arterial hypertension. This was a post-hoc analysis of children with Down syndrome and pulmonary arterial hypertension enrolled in the STARTS-1 trial. Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), and cardiac index (CI) were assessed at baseline and following 16 weeks of treatment with sildenafil. Of 234 patients randomized and treated in the STARTS-1 trial, 48 (20.5%) had Down syndrome. Although sildenafil produced dose-related reductions in PVRI and mPAP, compared with placebo, in non-Down syndrome patients and children developmentally able to exercise, this was not satisfactorily marked in patients with Down syndrome. The dose-related reductions in PVRI, compared with placebo, occurred in all subgroups, with the exception of the Down syndrome subgroup. Sildenafil appeared to be well tolerated in the Down syndrome subpopulation and the most frequently reported AEs were similar to those reported for the entire STARTS-1 population. Sildenafil treatment for 16 weeks had no effect on PVRI or mPAP in children with Down syndrome and pulmonary arterial hypertension. The results suggest that children with Down syndrome may be less responsive to sildenafil for pulmonary arterial hypertension, but the incomplete work-up for the etiology of pulmonary arterial hypertension may have introduced a potential bias. Study received, September 8, 2005 (retrospectively registered); Study start, August 2003; ClinicalTrials.gov identifier, NCT00159913 .

The Effect of Airway Pressure Release Ventilation on Pulmonary Catheter Readings: Specifically Pulmonary Capillary Wedge Pressure in a Swine Model

DTIC Science & Technology

2011-01-01

pressure (PEEP) of 5 cm H2O was initiated. Ventilator mode was changed to APRV with incremental elevations of CPAP -high from 10 to 35 cm H2O. After a...Results. Increasing CPAP caused increased PCWP and LAPmeasurements above their baseline values. Mean PCWP and LAP were linearly related (LAP = 0.66...PCWP + 4.5 cmH2O, R2 = 0.674, and P < .001) over a wide range of high and low CPAP values during APRV. With return to conventional ventilation, PCWP

Nitric oxide alterations following acute ductal constriction in the fetal lamb: a role for superoxide

PubMed Central

Hsu, Jong-Hau; Oishi, Peter; Wiseman, Dean A.; Hou, Yali; Chikovani, Omar; Datar, Sanjeev; Sajti, Eniko; Johengen, Michael J.; Harmon, Cynthia; Black, Stephen M.

2010-01-01

Acute partial compression of the fetal ductus arteriosus (DA) results in an initial abrupt increase in pulmonary blood flow (PBF), which is followed by a significant reduction in PBF to baseline values over the ensuing 2–4 h. We have previously demonstrated that this potent vasoconstricting response is due, in part, to an endothelin-1 (ET-1)-mediated decrease in nitric oxide synthase (NOS) activity. In addition, in vitro data demonstrate that ET-1 increases superoxide levels in pulmonary arterial smooth muscle cells and that oxidative stress alters NOS activity. Therefore, the objectives of this study were to determine the potential role of superoxide in the alterations of hemodynamics and NOS activity following acute ductal constriction in the late-gestation fetal lamb. Eighteen anesthetized near-term fetal lambs were instrumented, and a lung biopsy was performed. After a 48-h recovery, acute constriction of the DA was performed by inflating a vascular occluder. Polyethylene glycol-superoxide dismutase (PEG-SOD; 1,000–1,500 units/kg, n = 7) or PEG-alone (vehicle control group, n = 5) was injected into the pulmonary artery before ductal constriction. Six animals had a sham operation. In PEG-alone-treated lambs, acute ductal constriction rapidly decreased pulmonary vascular resistance (PVR) by 88%. However, by 4 h, PVR returned to preconstriction baseline. This vasoconstriction was associated with an increase in lung superoxide levels (82%), a decrease in total NOS activity (50%), and an increase in P-eNOS-Thr495 (52%) (P < 0.05). PEG-SOD prevented the increase of superoxide after ductal constriction, attenuated the vasoconstriction, preserved NOS activity, and increased P-eNOS Ser1177 (307%, P < 0.05). Sham procedure induced no changes. These data suggest that an acute decrease in NOS activity that is mediated, in part, by increased superoxide levels, and alterations in the phosphorylation status of the endothelial NOS isoform, underlie the pulmonary vascular response to acute ductal constriction. PMID:20363848

[MRI methods for pulmonary ventilation and perfusion imaging].

PubMed

Sommer, G; Bauman, G

2016-02-01

Separate assessment of respiratory mechanics, gas exchange and pulmonary circulation is essential for the diagnosis and therapy of pulmonary diseases. Due to the global character of the information obtained clinical lung function tests are often not sufficiently specific in the differential diagnosis or have a limited sensitivity in the detection of early pathological changes. The standard procedures of pulmonary imaging are computed tomography (CT) for depiction of the morphology as well as perfusion/ventilation scintigraphy and single photon emission computed tomography (SPECT) for functional assessment. Magnetic resonance imaging (MRI) with hyperpolarized gases, O2-enhanced MRI, MRI with fluorinated gases and Fourier decomposition MRI (FD-MRI) are available for assessment of pulmonary ventilation. For assessment of pulmonary perfusion dynamic contrast-enhanced MRI (DCE-MRI), arterial spin labeling (ASL) and FD-MRI can be used. Imaging provides a more precise insight into the pathophysiology of pulmonary function on a regional level. The advantages of MRI are a lack of ionizing radiation, which allows a protective acquisition of dynamic data as well as the high number of available contrasts and therefore accessible lung function parameters. Sufficient clinical data exist only for certain applications of DCE-MRI. For the other techniques, only feasibility studies and case series of different sizes are available. The clinical applicability of hyperpolarized gases is limited for technical reasons. The clinical application of the techniques described, except for DCE-MRI, should be restricted to scientific studies.

Novel Assessment of Interstitial Lung Disease Using the "Computer-Aided Lung Informatics for Pathology Evaluation and Rating" (CALIPER) Software System in Idiopathic Inflammatory Myopathies.

PubMed

Ungprasert, Patompong; Wilton, Katelynn M; Ernste, Floranne C; Kalra, Sanjay; Crowson, Cynthia S; Rajagopalan, Srinivasan; Bartholmai, Brian J

2017-10-01

To evaluate the correlation between measurements from quantitative thoracic high-resolution CT (HRCT) analysis with "Computer-Aided Lung Informatics for Pathology Evaluation and Rating" (CALIPER) software and measurements from pulmonary function tests (PFTs) in patients with idiopathic inflammatory myopathies (IIM)-associated interstitial lung disease (ILD). A cohort of patients with IIM-associated ILD seen at Mayo Clinic was identified from medical record review. Retrospective analysis of HRCT data and PFTs at baseline and 1 year was performed. The abnormalities in HRCT were quantified using CALIPER software. A total of 110 patients were identified. At baseline, total interstitial abnormalities as measured by CALIPER, both by absolute volume and by percentage of total lung volume, had a significant negative correlation with diffusing capacity for carbon monoxide (DLCO), total lung capacity (TLC), and oxygen saturation. Analysis by subtype of interstitial abnormality revealed significant negative correlations between ground glass opacities (GGO) and reticular density (RD) with DLCO and TLC. At one year, changes of total interstitial abnormalities compared with baseline had a significant negative correlation with changes of TLC and oxygen saturation. A negative correlation between changes of total interstitial abnormalities and DLCO was also observed, but it was not statistically significant. Analysis by subtype of interstitial abnormality revealed negative correlations between changes of GGO and RD and changes of DLCO, TLC, and oxygen saturation, but most of the correlations did not achieve statistical significance. CALIPER measurements correlate well with functional measurements in patients with IIM-associated ILD.

Cardiovascular function in pulmonary emphysema.

PubMed

Visca, Dina; Aiello, Marina; Chetta, Alfredo

2013-01-01

Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them. On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well. Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage. We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema. Patients with emphysema may differ among COPD population even in terms of cardiovascular function.

Advanced Techniques in Pulmonary Function Test Analysis Interpretation and Diagnosis

PubMed Central

Gildea, T.J.; Bell, C. William

1980-01-01

The Pulmonary Functions Analysis and Diagnostic System is an advanced clinical processing system developed for use at the Pulmonary Division, Department of Medicine at the University of Nebraska Medical Center. The system generates comparative results and diagnostic impressions for a variety of routine and specialized pulmonary functions test data. Routine evaluation deals with static lung volumes, breathing mechanics, diffusing capacity, and blood gases while specialized tests include lung compliance studies, small airways dysfunction studies and dead space to tidal volume ratios. Output includes tabular results of normal vs. observed values, clinical impressions and commentary and, where indicated, a diagnostic impression. A number of pulmonary physiological and state variables are entered or sampled (A to D) with periodic status reports generated for the test supervisor. Among the various physiological variables sampled are respiratory frequency, minute ventilation, oxygen consumption, carbon dioxide production, and arterial oxygen saturation.

Evidence of functional declining and global comorbidity measured at baseline proved to be the strongest predictors for long-term death in elderly community residents aged 85 years: a 5-year follow-up evaluation, the OCTABAIX study

PubMed Central

Formiga, Francesc; Ferrer, Assumpta; Padros, Gloria; Montero, Abelardo; Gimenez-Argente, Carme; Corbella, Xavier

2016-01-01

Objective To investigate the predictive value of functional impairment, chronic conditions, and laboratory biomarkers of aging for predicting 5-year mortality in the elderly aged 85 years. Methods Predictive value for mortality of different geriatric assessments carried out during the OCTABAIX study was evaluated after 5 years of follow-up in 328 subjects aged 85 years. Measurements included assessment of functional status comorbidity, along with laboratory tests on vitamin D, cholesterol, CD4/CD8 ratio, hemoglobin, and serum thyrotropin. Results Overall, the mortality rate after 5 years of follow-up was 42.07%. Bivariate analysis showed that patients who survived were predominantly female (P=0.02), and they showed a significantly better baseline functional status for both basic (P<0.001) and instrumental (P<0.001) activities of daily living (Barthel and Lawton index), better cognitive performance (Spanish version of the Mini-Mental State Examination) (P<0.001), lower comorbidity conditions (Charlson) (P<0.001), lower nutritional risk (Mini Nutritional Assessment) (P<0.001), lower risk of falls (Tinetti gait scale) (P<0.001), less percentage of heart failure (P=0.03) and chronic obstructive pulmonary disease (P=0.03), and took less chronic prescription drugs (P=0.002) than nonsurvivors. Multivariate Cox regression analysis identified a decreased score in the Lawton index (hazard ratio 0.86, 95% confidence interval: 0.78–0.91) and higher comorbidity conditions (hazard ratio 1.20, 95% confidence interval: 1.08–1.33) as independent predictors of mortality at 5 years in the studied population. Conclusion The ability to perform instrumental activities of daily living and the global comorbidity assessed at baseline were the predictors of death, identified in our 85-year-old community-dwelling subjects after 5 years of follow-up. PMID:27143867

The effect of cisatracurium and rocuronium on lung function in anesthetized children.

PubMed

Yang, Charles I; Fine, Gavin F; Jooste, Edmund H; Mutich, Rebecca; Walczak, Stephen A; Motoyama, Etsuro K

2013-12-01

Neuromuscular blocking drugs have been implicated in intraoperative bronchoconstrictive episodes. We examined the effects of clinically relevant doses of cisatracurium and rocuronium on the lung mechanics of pediatric subjects. We hypothesized that cisatracurium and rocuronium would have bronchoconstrictive effects. We studied ASA physical status I and II pediatric subjects having elective dental or urological procedures, requiring general anesthesia with endotracheal intubations with either cisatracurium or rocuronium. Pulmonary function tests were performed before and after neuromuscular blocking drug dosing and again after albuterol administration. Using forced deflation and passive deflation techniques, forced vital capacity (FVC) and maximum expiratory flow rate at 10% (MEF10) of FVC were obtained. Fractional changes from the baseline were used to compare subjects. Changes in MEF10 of >30% were considered clinically significant. A Shapiro-Wilk test, paired t test, and Wilcoxon rank sum test were used to analyze the data. Twenty-five subjects (median age = 5.25 years; range = 9 months-9.9 years) were studied; 12 subjects received cisatracurium and 13 subjects received rocuronium. Data are shown as mean proportional change ± SD or, in the case of not normally distributed, median proportional change (first, third quartile) with P values. In the cisatracurium group, there were no differences between baseline and postneuromuscular blocker administration in the fractional change from the baselines of FVC (1.00 ± 0.04, P = 0.5), but there was a significant decrease in MEF10 (0.80 ± 0.18, P = 0.002). In the rocuronium group, there were small yet significant decreases of FVC (0.99 [first quartile 0.97, third quartile 1], P = 0.02) and significant decreases in MEF10 (0.78 ± 0.26, P = 0.008). After administration of albuterol in the cisatracurium group, FVC increased slightly but significantly from baseline values (1.02 ± 0.02, P = 0.005). MEF10 increased significantly beyond baseline values (1.24 ± 0.43, P =0.04). In the rocuronium group, there were also significant differences between baseline and postalbuterol administration from the baseline value of FVC (1.02 ± 0.02, P = 0.004) and MEF10 (1.23 ± 0.29, P = 0.01). At clinically relevant doses, both cisatracurium and rocuronium caused changes in lung function, indicating constriction of smaller airways. In general, these changes were mild and not clinically detectable. However, in the rocuronium group, 3 of 13 patients showed more noticeable decreases in MEF10 (≤50%), demonstrating the potential for significant broncho-bronchiolar constriction in susceptible patients.

Recovery of pulmonary functions, exercise capacity, and quality of life after pulmonary rehabilitation in survivors of ARDS due to severe influenza A (H1N1) pneumonitis.

PubMed

Hsieh, Meng-Jer; Lee, Wei-Chun; Cho, Hsiu-Ying; Wu, Meng-Fang; Hu, Han-Chung; Kao, Kuo-Chin; Chen, Ning-Hung; Tsai, Ying-Huang; Huang, Chung-Chi

2018-04-20

Acute respiratory distress syndrome (ARDS) due to severe influenza A H1N1 pneumonitis would result in impaired pulmonary functions and health-related quality of life (HRQoL) after hospital discharge. The recovery of pulmonary functions, exercise capacity, and HRQoL in the survivors of ARDS due to 2009 pandemic influenza A H1N1 pneumonitis (H1N1-ARDS) was evaluated in a tertiary teaching hospital in northern Taiwan between May 2010 and June 2011. Data of spirometry, total lung capacity (TLC), diffusing capacity of carbon monoxide (DL CO ), and 6-minute walk distance (6MWD) in the patients survived from H1N1-ARDS were collected 1, 3, and 6 months post-hospital discharge. HRQoL was evaluated with St. George respiratory questionnaire (SGRQ). Nine survivors of H1N1-ARDS in the study period were included. All these patients received 2 months' pulmonary rehabilitation program. Pulmonary functions and exercise capacity included TLC, forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1 ), DL CO , and 6MWD improved from 1 to 3 months post-hospital discharge. Only TLC had further significant improvement from 3 to 6 months. HRQoL represented as the total score of SGRQ had no significant improvement in the first 3 months but improved significantly from 3 to 6 months post-discharge. The impaired pulmonary functions and exercise capacity in the survivors of H1N1-ARDS improved soon at 3 months after hospital discharge. Their quality of life had keeping improved at 6 months even though there was no further improvement of their pulmonary functions and exercise capacity. © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

An integrated programme after pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: effect on emotional and functional dimensions of quality of life.

PubMed

Moullec, G; Ninot, G

2010-02-01

To assess whether a maintenance integrated health care programme is effective in improving functional and emotional dimensions of quality of life in patients with chronic obstructive pulmonary disease (COPD) after a first pulmonary rehabilitation. Prospective controlled trial. Three rehabilitation centres and three patient self-help associations within a health care network in France. Forty patients with moderate to severe COPD. After a first four-week inpatient pulmonary rehabilitation programme, patients took part in a maintenance integrated health care programme or usual care for 12 months. The primary outcomes were the change in functional and emotional dimensions of quality of life measured by the St George's Respiratory Questionnaire (SGRQ), the brief World Health Organization Quality of Life questionnaire (Brief-WHOQOL) and six specific questions using a 10-cm visual analogue scale. Secondary outcomes were change in exercise tolerance measured by six-minute walking test and cycle exercise. At one year, the maintenance intervention (n = 11) produced improvements in functional and emotional dimensions scores of quality of life and exercise tolerance. Patients in the usual aftercare group (n = 16) exhibited maintenance of functional dimension scores of quality of life, but a clinically relevant decline in emotional scores of quality of life and in six-minute walking distance one year after the pulmonary rehabilitation. Patient self-help association seems to be an innovative and efficient organizational structure to support patients with COPD after pulmonary rehabilitation in real-life settings. A distinction between emotional and functional dimensions of quality of life may improve the design and evaluation of integrated health care programmes in patients with COPD.

Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

PubMed Central

Astorga, Cristian R.; González-Candia, Alejandro; Candia, Alejandro A.; Figueroa, Esteban G.; Cañas, Daniel; Ebensperger, Germán; Reyes, Roberto V.; Llanos, Aníbal J.; Herrera, Emilio A.

2018-01-01

Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs (Ovis aries) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle) and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1) during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations. Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05). This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05) and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05). Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05). Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05). Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia. PMID:29559926

Parenchymal preserving anatomic resections result in less pulmonary function loss in patients with Stage I non-small cell lung cancer.

PubMed

Macke, Ryan A; Schuchert, Matthew J; Odell, David D; Wilson, David O; Luketich, James D; Landreneau, Rodney J

2015-04-01

A suggested benefit of sublobar resection for stage I non-small cell lung cancer (NSCLC) compared to lobectomy is a relative preservation of pulmonary function. Very little objective data exist, however, supporting this supposition. We sought to evaluate the relative impact of both anatomic segmental and lobar resection on pulmonary function in patients with resected clinical stage I NSCLC. The records of 159 disease-free patients who underwent anatomic segmentectomy (n = 89) and lobectomy (n = 70) for the treatment of stage I NSCLC with pre- and postoperative pulmonary function tests performed between 6 to 36 months after resection were retrospectively reviewed. Changes in forced expiratory volume in one second (FEV1) and diffusion capacity of carbon monoxide (DLCO) were analyzed based upon the number of anatomic pulmonary segments removed: 1-2 segments (n = 77) or 3-5 segments (n = 82). Preoperative pulmonary function was worse in the lesser resection cohort (1-2 segments) compared to the greater resection group (3-5 segments) (FEV1(%predicted): 79% vs. 85%, p = 0.038; DLCO(%predicted): 63% vs. 73%, p = 0.010). A greater decline in FEV1 was noted in patients undergoing resection of 3-5 segments (FEV1 (observed): 0.1 L vs. 0.3 L, p = 0.003; and FEV1 (% predicted): 4.3% vs. 8.2%, p = 0.055). Changes in DLCO followed this same trend (DLCO(observed): 1.3 vs. 2.4 mL/min/mmHg, p = 0.015; and DLCO(% predicted): 3.6% vs. 5.9%, p = 0.280). Parenchymal-sparing resections resulted in better preservation of pulmonary function at a median of one year, suggesting a long-term functional benefit with small anatomic segmental resections (1-2 segments). Prospective studies to evaluate measurable functional changes, as well as quality of life, between segmentectomy and lobectomy with a larger patient cohort appear justified.

Inhaled nitric oxide therapy increases blood nitrite, nitrate, and s-nitrosohemoglobin concentrations in infants with pulmonary hypertension.

PubMed

Ibrahim, Yomna I; Ninnis, Janet R; Hopper, Andrew O; Deming, Douglas D; Zhang, Amy X; Herring, Jason L; Sowers, Lawrence C; McMahon, Timothy J; Power, Gordon G; Blood, Arlin B

2012-02-01

To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity after inhaled NO (iNO) therapy in infants with pulmonary hypertension. In this single center study, 5 sequential blood samples were collected from infants with pulmonary hypertension before, during, and after therapy with iNO (n = 17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n = 16) and from healthy adults for comparison (n = 12). After beginning iNO (20 ppm) whole blood nitrite levels increased approximately two-fold within 2 hours (P<.01). Whole blood nitrate levels increased to 4-fold higher than baseline during treatment with 20 ppm iNO (P<.01). S-nitrosohemoglobin increased measurably after beginning iNO (P<.01), whereas iron nitrosyl hemoglobin and total hemoglobin-bound NO-species compounds did not change. Treatment of pulmonary hypertensive infants with iNO results in increases in levels of nitrite, nitrate, and S-nitrosohemoglobin in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart, and other organs. Copyright © 2012 Mosby, Inc. All rights reserved.

Inhaled NO therapy increases blood nitrite, nitrate and S-nitrosohemoglobin concentrations in infants with pulmonary hypertension

PubMed Central

Ibrahim, Yomna I.; Ninnis, Janet R.; Hopper, Andrew O.; Deming, Douglas D.; Zhang, Amy X.; Herring, Jason L.; Sowers, Lawrence C.; McMahon, Timothy J.; Power, Gordon G.; Blood, Arlin B.

2011-01-01

Objective To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity following inhaled NO therapy in infants with pulmonary hypertension. Study design In this single center study five sequential blood samples were collected from infants with pulmonary hypertension before, during and after therapy with iNO (n=17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n=16) and from healthy adults for comparison (n=12). Results After beginning iNO (20 ppm) whole blood nitrite increased about two-fold within two hours (P<0.01). Whole blood nitrate increased to four-fold higher than baseline during treatment with 20ppm iNO (P<0.01). S-nitrosohemoglobin (SNO-Hb) increased measurably after beginning iNO (P<0.01) whereas iron nitrosyl hemoglobin and total Hb-bound NO-species compounds did not change. Conclusion Treatment of pulmonary hypertensive infants with iNO results in increases in nitrite, nitrate, and SNO-Hb in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart and other organs. PMID:21907348

Hemodynamic responses to etomidate on induction of anesthesia in pediatric patients.

PubMed

Sarkar, Molly; Laussen, Peter C; Zurakowski, David; Shukla, Avinash; Kussman, Barry; Odegard, Kirsten C

2005-09-01

Etomidate is often used for inducing anesthesia in patients who have limited hemodynamic reserve. Using invasive hemodynamic monitoring, we studied the acute effects of a bolus of etomidate during induction of anesthesia in children. Twelve children undergoing cardiac catheterization were studied (mean age, 9.2 +/- 4.8 yr; mean weight, 33.4 +/- 15.4 kg); catheterization procedures included device closure of secundum atrial septal defects (n = 7) and radiofrequency catheter ablation procedures for supraventricular tachycardia (n = 5). Using IV sedation, a balloon-tipped pulmonary artery catheter was placed to measure intracardiac and pulmonary artery pressures and oxygen saturations. Baseline measurements were recorded and then repeated after a bolus of IV etomidate (0.3 mg/kg). For the entire group, no significant changes in right atrial, aortic, or pulmonary artery pressure, oxygen saturations, calculated Qp:Qs ratio or systemic or pulmonary vascular resistance were detected after the bolus dose of etomidate. The lack of clinically significant hemodynamic changes after etomidate administration supports the clinical impression that etomidate is safe in children. Further research is needed to determine the hemodynamic profile of etomidate in neonates and in pediatric patients with severe ventricular dysfunction and pulmonary hypertension.

Computational Modeling of Airway and Pulmonary Vascular Structure and Function: Development of a “Lung Physiome”

PubMed Central

Tawhai, M. H.; Clark, A. R.; Donovan, G. M.; Burrowes, K. S.

2011-01-01

Computational models of lung structure and function necessarily span multiple spatial and temporal scales, i.e., dynamic molecular interactions give rise to whole organ function, and the link between these scales cannot be fully understood if only molecular or organ-level function is considered. Here, we review progress in constructing multiscale finite element models of lung structure and function that are aimed at providing a computational framework for bridging the spatial scales from molecular to whole organ. These include structural models of the intact lung, embedded models of the pulmonary airways that couple to model lung tissue, and models of the pulmonary vasculature that account for distinct structural differences at the extra- and intra-acinar levels. Biophysically based functional models for tissue deformation, pulmonary blood flow, and airway bronchoconstriction are also described. The development of these advanced multiscale models has led to a better understanding of complex physiological mechanisms that govern regional lung perfusion and emergent heterogeneity during bronchoconstriction. PMID:22011236

Sputum microbiome temporal variability and dysbiosis in chronic obstructive pulmonary disease exacerbations: an analysis of the COPDMAP study.

PubMed

Wang, Zhang; Singh, Richa; Miller, Bruce E; Tal-Singer, Ruth; Van Horn, Stephanie; Tomsho, Lynn; Mackay, Alexander; Allinson, James P; Webb, Adam J; Brookes, Anthony J; George, Leena M; Barker, Bethan; Kolsum, Umme; Donnelly, Louise E; Belchamber, Kylie; Barnes, Peter J; Singh, Dave; Brightling, Christopher E; Donaldson, Gavin C; Wedzicha, Jadwiga A; Brown, James R

2018-04-01

Recent studies suggest that lung microbiome dysbiosis, the disease associated disruption of the lung microbial community, might play a key role in chronic obstructive pulmonary disease (COPD) exacerbations. However, characterising temporal variability of the microbiome from large longitudinal COPD cohorts is needed to better understand this phenomenon. We performed a 16S ribosomal RNA survey of microbiome on 716 sputum samples collected longitudinally at baseline and exacerbations from 281 subjects with COPD at three UK clinical centres as part of the COPDMAP consortium. The microbiome composition was similar among centres and between stable and exacerbations except for a small significant decrease of Veillonella at exacerbations. The abundance of Moraxella was negatively associated with bacterial alpha diversity. Microbiomes were distinct between exacerbations associated with bacteria versus eosinophilic airway inflammation. Dysbiosis at exacerbations, measured as significant within subject deviation of microbial composition relative to baseline, was present in 41% of exacerbations. Dysbiosis was associated with increased exacerbation severity indicated by a greater fall in forced expiratory volume in one second, forced vital capacity and a greater increase in CAT score, particularly in exacerbations with concurrent eosinophilic inflammation. There was a significant difference of temporal variability of microbial alpha and beta diversity among centres. The variation of beta diversity significantly decreased in those subjects with frequent historical exacerbations. Microbial dysbiosis is a feature of some exacerbations and its presence, especially in concert with eosinophilic inflammation, is associated with more severe exacerbations indicated by a greater fall in lung function. Results, NCT01620645. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Economic evaluation of exercise training in patients with pulmonary hypertension.

PubMed

Ehlken, Nicola; Verduyn, Cora; Tiede, Henning; Staehler, Gerd; Karger, Gabriele; Nechwatal, Robert; Opitz, Christian F; Klose, Hans; Wilkens, Heinrike; Rosenkranz, Stephan; Halank, Michael; Grünig, Ekkehard

2014-06-01

Exercise training as an add-on to medical therapy has been shown to improve exercise capacity, quality of life, and possibly prognosis in patients with pulmonary hypertension (PH). The purpose of this study was to analyze the impact of exercise training on healthcare costs in PH. Estimated healthcare costs have been compared between patients with severe PH under optimized medical therapy only (control group) versus patients who received exercise training as an add-on to medical therapy (training group). Cost-analysis included a cost-estimation model of costs for baseline and follow-up visits and all PH-related healthcare events that occurred within the follow-up period. Time to clinical worsening and survival were assessed by clinical records, phone, and/or control visits. At baseline, the training (n = 58) and control group (n = 48) did not differ in age, gender, WHO-functional class, 6-min walking distance, hemodynamic parameters, or PH-targeted medication. During a follow-up of 24 ± 12 months, the training group had significantly better survival rates at 1 and 3 years and less worsening events (death, lung transplantation, hospitalization due to PH, new PAH-targeted medication) than the control group (15 vs. 25 events, p < 0.05), which also led to lower estimated healthcare costs of 657 within a period of 2 years. This is the first study to investigate the cost-effectiveness of exercise training in PH. Due to less worsening events within 2 years, healthcare costs were lower in patients performing exercise training as add-on to medical therapy than in patients with medical treatment only. Further prospective, randomized studies are needed to confirm these findings.

One-year treatment with mometasone furoate in chronic obstructive pulmonary disease

PubMed Central

Calverley, Peter MA; Rennard, Stephen; Nelson, Harold S; Karpel, Jill P; Abbate, Eduardo H; Stryszak, Paul; Staudinger, Heribert

2008-01-01

Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS). This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing. In a 52-week, randomized, double-blind, placebo-controlled study, 911 subjects with moderate-to-severe COPD managed without ICS received MF-DPI 800 μg QD PM, MF-DPI 400 μg BID, or placebo. The change from baseline in postbronchodilator forced expiratory volume in 1 second (FEV1), total COPD symptom scores, and health status as well as the percentage of subjects with a COPD exacerbation were assessed. Adverse events were recorded. Mometasone furoate administered via a dry powder inhaler 800 μg QD PM and 400 μg BID significantly increased postbronchodilator FEV1 from baseline (50 mL and 53 mL, respectively, versus a 19 mL decrease for placebo; P < 0.001). The percentage of subjects exacerbating was significantly lower in the pooled MF-DPI groups than in the placebo group (P = 0.043). Subjects receiving MF-DPI 400 μg BID reported a statistically significant (19%) reduction in COPD symptom scores compared with placebo (P < 0.001). Health status as measured with St. George's Respiratory Questionnaire (SGRQ) improved significantly in all domains (Total, Activity, Impacts, and Symptoms) in the pooled MF-DPI groups versus placebo (P ≤ 0.031). MF-DPI treatment was well tolerated. Once-daily MF-DPI improved lung function and health status in subjects with moderate-to-severe COPD and was comparable to BID MF-DPI. PMID:19014549

Tiotropium Respimat Soft Mist Inhaler versus HandiHaler to improve sleeping oxygen saturation and sleep quality in COPD.

PubMed

Bouloukaki, Izolde; Tzanakis, Nikolaos; Mermigkis, Charalampos; Giannadaki, Katerina; Moniaki, Violeta; Mauroudi, Eleni; Michelakis, Stylianos; Schiza, Sophia E

2016-05-01

Patients with chronic obstructive pulmonary disease (COPD) have poor sleep quality as a result of various alterations in oxygenation parameters and sleep macro- and micro-architecture. There is a shortage of data to support the efficacy of long-acting inhaled anticholinergic agents in improving these adverse effects, which are known to have a negative impact on clinical outcomes. We aimed to compare the tiotropium Respimat Soft Mist Inhaler and the HandiHaler in terms of their effects on sleeping oxygen saturation (SaO2) and sleep quality in patients with COPD. In a randomized, open-label, parallel-group trial involving 200 patients with mild to moderate COPD (resting arterial oxygen tension >60 mmHg while awake), we compared the effects of 6 months' treatment with the two devices on sleeping SaO2 and sleep quality. Overnight polysomnography and pulmonary function testing were performed at baseline and after 6 months' treatment. A total of 188 patients completed the trial. Both groups showed significant improvement in minimum sleep SaO2 and time of sleep spent with SaO2 below 90 (TST90) compared to baseline. The patients using the Respimat had significantly better TST90 than did those using the HandiHaler. Sleep disturbance was highly variable in these patients, but the sleep stage durations were significantly better in the Respimat group. Sleeping SaO2 can be improved by tiotropium delivered using either the HandiHaler device or the Respimat Soft Mist Inhaler. However, the patients who used the Respimat device had significantly better TST90 and sleep architecture parameters.

Growth in children with pulmonary arterial hypertension: a longitudinal retrospective multiregistry study.

PubMed

Ploegstra, Mark-Jan; Ivy, D Dunbar; Wheeler, Jeremy G; Brand, Monika; Beghetti, Maurice; Rosenzweig, Erika B; Humpl, Tilman; Iriart, Xavier; Rouzic, Erwan Muros-Le; Bonnet, Damien; Berger, Rolf M F

2016-04-01

To enable adequate interpretation of growth measurements in the management of children with pulmonary arterial hypertension (PAH), we assessed growth and its associated determinants in children with PAH. We did a retrospective longitudinal study of height and body-mass index in reference to WHO growth standards by pooling data from four contemporary prospective registries of paediatric PAH representing 53 centres in 19 countries. The main outcome measures were median height for age and body-mass index for age percentiles and longitudinal deviation of height for age and body-mass index for age Z scores from WHO standards. 601 children were followed up for a median of 2·9 years (IQR 1·5-4·4). Baseline median height for age percentile was 26 (IQR 4-54) and baseline median body-mass index for age percentile was 41 (IQR 12-79). Mean height for age Z score was significantly lower than the reference (-0·81, 95% CI -0·93 to -0·69; p<0·0001), as was body-mass index for age Z score (-0·12, -0·25 to -0·01; p=0·047). Height for age Z score was particularly decreased in young patients (aged ≤5 years) with idiopathic or hereditary PAH and in all patients with PAH associated with congenital heart disease. Although Z scores increased in some patients and decreased in others, we detected no significant trend in height for age Z score (p=0·57) or body-mass index for age Z score (p=0·48) before taking account of covariates. Multivariable linear mixed effects modelling showed that age, cause of PAH, ex-prematurity, WHO functional class, trisomy 21, and time since diagnosis were associated with height for age Z score, whereas age, ethnicity, and trisomy 21 were associated with body-mass index for age Z score. A favourable WHO functional class course was independently associated with increases in height for age Z score. PAH is associated with impaired growth, especially in younger children and those with pulmonary arterial hypertension associated with congenital heart disease. The degree of impairment is independently associated with cause of PAH and comorbidities, but also with disease severity and duration. Because a favourable clinical course was associated with catch-up growth, height for age could serve as an additional and globally available clinical parameter to monitor patients' clinical condition. Actelion Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Mid-Term Changes of Pulmonary Function Tests After Phrenic Nerve Transfer.

PubMed

Yavari, Masoud; Hassanpour, Seyed Esmail; Khodayari, Mohammad

2016-03-01

In the restoration of elbow flexion, the phrenic nerve has proven to be a good donor, but considering the role of the phrenic nerve in respiratory function, we cannot disregard the potential dangers of this method. In the current study, we reviewed the results of pulmonary function tests (PFT) in four patients who underwent phrenic nerve transfer. We reviewed the results of serial spirometry tests, which were performed before and after phrenic nerve transfer surgery. All patients regained Biceps power to M3 strength or above. None of our patients experienced pulmonary problems or respiratory complaints, but a significant reduction of spirometric parameters occurred after surgery. This study highlights the close link between the role of the phrenic nerve and pulmonary function, such that the use of this nerve as a transfer donor leads to spirometric impairments.

[Study on the correlation between the severity of chronic rhinosinusitis and bronchial asthma and pulmonary function].

PubMed

Liu, Yonggang

2015-07-01

To explore the correlation between the severity of patients with rhinitis-nasosinusitis and the bronchial asthma and the pulmonary function. Sixty-four cases of patients with rhinitis-nasosinusitis and 53 cases of patients with chronic sinusitis from June 2012 to September 2013 were randomly selected, and the patients were divided into group of rhinitis-nasosinusitis with nasal polyps and group of chronic sinusitis according to disease species, and analyzed the correlation between the severity of the deseases and the changes of the pulmonary function respectively for the patients of two groups by using Spearman method. The incidence of asthma for patients with different levels of sinusitis and nasal polyps seemed no significant difference (P > 0.05); the incidence of allergic rhinitis also seemed no significant difference (P > 0.05); the incidence of asthma for patients with different lesion range of sinusitis and nasal polyps seemed no significant difference (P > 0.05); the incidence of allergic rhinitis also seemed no significant different (P < 0.05). The conditions of the patients with different levels of sinusitis and nasal polyps were directly related to the reduction of pulmonary function (r = 2.431, P < 0.05); The conditions of the patients with different lesion range of sinusitis were directly related to the reduction of pulmonary function (r = 2.641, P < 0.05). There was some correlation between the severity of patients with rhinitis-nasosinusitis and the bronchial asthma and the condition of pulmonary function of patients.

Amount of smoking, pulmonary function, and bone mineral density in middle-aged Korean men: KNHANES 2008-2011.

PubMed

Lee, Ji Hyun; Hong, A Ram; Kim, Jung Hee; Kim, Kyoung Min; Koo, Bo Kyung; Shin, Chan Soo; Kim, Sang Wan

2018-01-01

Smoking induces bone loss; however, data on the relationship between smoking history and bone mineral density (BMD) are lacking. Age and pulmonary function can affect BMD. We investigated the relationships among pack-years (PYs) of smoking, pulmonary function, and BMD in middle-aged Korean men (50-64 years old). This cross-sectional study used data from the Korean National Health and Nutrition Examination Survey, 2008-2011. All participants underwent BMD measurements using dual energy X-ray absorptiometry and pulmonary function tests using standardized spirometry. In total, 388 never-smokers and 1088 ever-smokers were analyzed. The number of PYs of smoking was negatively correlated with total hip BMD (r = -0.088; P = 0.004) after adjusting for age, height, and weight. Ever-smokers were classified into 3 groups according to PYs of smoking. The highest tertile (n = 482) exhibited significantly lower total hip bone mass than the lowest tertile (n = 214) after adjusting for confounding factors (age, height, weight, forced expiratory volume in 1 s (FEV 1 ), alcohol consumption, physical activity, and vitamin D levels) that could affect bone metabolism (P = 0.003). In conclusion, smoking for >30 PYs was significantly associated with low hip BMD after adjusting for pulmonary function in middle-aged Korean men. Long-term smoking may be a risk factor for bone loss in middle-aged men independent of age, height, weight, and pulmonary function.

[A rare form of obstructive pulmonary disease].

PubMed

van Loenhout, C J; den Bakker, M A; van Wijsenbeek, M S; Hoek, R A S; van Hal, P Th W

2016-01-01

Lymphangioleiomyomatosis (LAM) is characterised by progressive dyspnoea, spontaneous pneumothorax and cystic pulmonary destruction. The disease may show similarities with emphysema clinically, radiologically and on lung function tests. A 44-year-old woman was referred for lung transplantation because of a 6-year history of dyspnoea and severe obstructive pulmonary function disorder with decreased diffusion capacity. Both her relatively young age and the fact that she had never smoked made us doubt the diagnosis 'COPD'. The pulmonary cysts seen on high-resolution CT (HRCT) suggested LAM. This was confirmed when we revised a pulmonary biopsy that had previously been performed. CT investigation should be carried out in patients with severe obstructive pulmonary disease without a risk profile appropriate for COPD. Diffuse, homogenous cysts on CT scan can indicate LAM, particularly in women. Conflict of interest and financial support: none declared.

In smokers, Sonic hedgehog modulates pulmonary endothelial function through vascular endothelial growth factor.

PubMed

Henno, Priscilla; Grassin-Delyle, Stanislas; Belle, Emeline; Brollo, Marion; Naline, Emmanuel; Sage, Edouard; Devillier, Philippe; Israël-Biet, Dominique

2017-05-23

Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The Sonic hedgehog (SHH) pathway is involved in vascular physiology. We sought to establish whether the SHH pathway has a role in pulmonary endothelial dysfunction in smokers. The ex vivo endothelium-dependent relaxation of pulmonary artery rings in response to acetylcholine (Ach) was compared in 34 current or ex-smokers and 8 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine. We tested the effects of SHH inhibitors (GANT61 and cyclopamine), an SHH activator (SAG) and recombinant VEGF on the Ach-induced relaxation. The level of VEGF protein in the pulmonary artery ring was measured in an ELISA. SHH pathway gene expression was quantified in reverse transcriptase-quantitative polymerase chain reactions. Ach-induced relaxation was much less intense in smokers than in never-smokers (respectively 24 ± 6% and 50 ± 7% with 10 -4 M Ach; p = 0.028). All SHH pathway genes were expressed in pulmonary artery rings from smokers. SHH inhibition by GANT61 reduced Ach-induced relaxation and VEGF gene expression in the pulmonary artery ring. Recombinant VEGF restored the ring's endothelial function. VEGF gene and protein expression levels in the pulmonary artery rings were positively correlated with the degree of Ach-induced relaxation and negatively correlated with the number of pack-years. SHH pathway genes and proteins are expressed in pulmonary artery rings from smokers, where they modulate endothelial function through VEGF.

The effect of perioperative beta-blockade on the pulmonary function of patients undergoing major arterial surgery.

PubMed

Kieran, S M; Cahill, R A; Browne, I; Sheehan, S J; Mehigan, D; Barry, M C

2006-09-01

Concern about the potential detrimental side-effects of beta-blockade on pulmonary function often dissuades against their perioperative use in patients undergoing major arterial surgery (especially in those with chronic obstructive pulmonary disease (COPD)). In this study we aimed to establish prospectively the clinical relevance of these concerns. After ethics committee approval and individual informed consent, the pulmonary function of twenty patients (mean age 68.7 years (range 43-82), 11 males) scheduled to undergo non-emergency major vascular surgery was studied by recording symptoms and spirometry before and after institution of effective beta-blockade. Fifteen patients (75%) had significant smoking histories (mean pack years/patient=50), while 12 (60%) had COPD. All patients tolerated effective beta-blockade satisfactorily without developing either subjective deterioration in symptoms or significant change on spirometry. The mean change in FEV1 following adequate beta-blockade was 0.05+/-0.24 liters (95% CI -0.06 to +1.61), p=0.35, giving a mean percentage change of 3.18%+/-11.66 (95% CI -2.26 to 8.62). Previously held concerns about worsening pulmonary function through the short-term use of beta-blockers should not dissuade their perioperative usage in patients with peripheral vascular disease. Furthermore, the accuracy of pulmonary function tests in preoperative assessment and risk stratification also appears unaffected by this therapy.

Lung function declines in patients with pulmonary sarcoidosis and increased respiratory epithelial permeability to sup 99m Tc-DTPA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chinet, T.; Dusser, D.; Labrune, S.

1990-02-01

Respiratory epithelial clearance of {sup 99m}Tc-DTPA (RC-Tc-DTPA) and pulmonary function tests (PFT) were determined at intervals of 6 or 12 months in 37 untreated, nonsmoking patients with sarcoidosis over a period of 6 to 36 months. PFT included the measurements of total lung capacity (TLC), vital capacity (VC), FEV1, and diffusing capacity for carbon monoxide. No difference was found between the respiratory clearance of {sup 113m}In-DTPA (2.25 +/- 1.00%/min) and RC-Tc-DTPA (2.29 +/- 1.11%/min) in eight patients with pulmonary sarcoidosis. Pulmonary function decreased 15% or more in at least 2 function tests during 11 follow-up periods, but it remained stablemore » during 47 follow-up periods. In patients whose lung function deteriorated, RC-Tc-DTPA increased to 3.51 +/- 1.55%/min; in contrast, in patients whose lung function remained stable, regardless of the initial values, RC-Tc-DTPA was normal (1.00 +/- 0.50%/min; p less than 0.001). In eight patients who were treated with corticosteroids, RC-Tc-DTPA decreased from 3.48 +/- 1.31%/min to 1.56 +/- 0.64%/min (p less than 0.001), and PFT improved. We conclude that in nonsmokers with pulmonary sarcoidosis, increased RC-Tc-DTPA is not related to dissociation of 99mTc from DTPA, RC-Tc-DTPA is increased when pulmonary function decreases, and, when increased, RC-Tc-DTPA decreases with corticosteroid therapy.« less

Differences in coagulation among Asians and Caucasians and the implication for reconstructive microsurgery.

PubMed

Singhal, Dhruv; Smorodinsky, Emmanuil; Guo, Lifei

2011-01-01

Microvascular reconstructive surgery has seen a revival with the introduction of muscle-sparing perforator flaps. Recognition of potential ethnic differences in coagulation profiles would be important to a microvascular surgeon. Based on clinical observations, we hypothesize that Asian patients have a less thrombogenic coagulation profile than Caucasians. An extensive retrospective review was performed. The annual incidence of venous thromboembolism in the United States is generally accepted to range from 70 to 120 events per 100,000 people versus 16 to 17 events per 100,000 persons in Asia. Autopsy analysis of pulmonary embolism incidence was noted to be 15% in North Americans and less than 1% in Asian populations. Thromboelastography analysis of Asian and Caucasian patients undergoing cholecystectomy revealed different hemostatic mechanisms. Comparison of Asians and Caucasians undergoing the Fontan procedure revealed significantly lower postoperative factor levels in Asians than Caucasians. Baseline comparison of factor and serum levels revealed Asians with the least thrombogenic profiles compared with other ethnic groups. Asians and Caucasians demonstrate different baseline rates of deep vein thrombosis and pulmonary embolism, different hemostatic responses to surgery, and different baseline levels of clotting factors. Further study may lead to better pre-, intra-, and postoperative care of the free flap patient based on their ethnic coagulation profile. © Thieme Medical Publishers.

Pulmonary Impairment in Tuberculosis Survivors: The Korean National Health and Nutrition Examination Survey 2008-2012.

PubMed

Jung, Jae-Woo; Choi, Jae-Chol; Shin, Jong-Wook; Kim, Jae-Yeol; Choi, Byoung-Whui; Park, In-Won

2015-01-01

Pulmonary tuberculosis (TB) can affect lung function, but studies regarding long-term follow-up in patients with no sequelae on chest X-ray (CXR) have not been performed. We evaluated lung functional impairment and persistent respiratory symptoms in those with prior pulmonary TB and those with prior pulmonary TB with no residual sequelae on CXR, and determined risk factors for airflow obstruction. We used data from adults aged ≥ 40 years from the annual Korean National Health and Nutrition Examination Surveys conducted between 2008 and 2012. P values for comparisons were adjusted for age, sex, and smoking status. In total of 14,967 adults, 822 subjects (5.5%) had diagnosed and treated pulmonary TB (mean 29.0 years ago). The FVC% (84.9 vs. 92.6), FEV1% (83.4 vs. 92.4), and FEV1/FVC% (73.4 vs. 77.9) were significantly decreased in subjects with prior pulmonary TB compared to those without (p < 0.001, each). In 12,885 subjects with no sequalae on CXR, those with prior pulmonary TB (296, 2.3%) had significantly lower FEV1% (90.9 vs. 93.4, p = 0.001) and FEV1/FVC% (76.6 vs. 78.4, p < 0.001) than those without. Subjects with prior pulmonary TB as well as subjects with no sequalae on CXR were more likely to experience cough and physical activity limitations due to pulmonary symptoms than those without prior pulmonary TB (p < 0.001, each). In total subjects, prior pulmonary TB (OR, 2.314; 95% CI, 1.922-2.785), along with age, male, asthma, and smoking mount was risk factor for airflow obstruction. In subjects with prior pulmonary tuberculosis, inactive TB lesion on chest x-ray (OR, 2.300; 95% CI, 1.606-3.294) were risk factors of airflow obstruction. In addition to subjects with inactive TB lesion on CXR, subjects with no sequelae on CXR can show impaired pulmonary function and respiratory symptoms. Prior TB is a risk factor for airflow obstruction and that the risk is more important when they have inactive lesions on chest X-ray. Hence, the patients with treated TB should need to have regular follow-up of lung function and stop smoking for early detection and prevention of the chronic airway disease.

Assessment and prevalence of pulmonary oedema in contemporary acute heart failure trials: a systematic review.

PubMed

Platz, Elke; Jhund, Pardeep S; Campbell, Ross T; McMurray, John J

2015-09-01

Pulmonary oedema is a common and important finding in acute heart failure (AHF). We conducted a systematic review to describe the methods used to assess pulmonary oedema in recent randomized AHF trials and report its prevalence in these trials. Of 23 AHF trials published between 2002 and 2013, six were excluded because they were very small or not randomized, or missing full-length publications. Of the remaining 17 (n = 200-7141) trials, six enrolled patients with HF and reduced ejection fraction (HF-REF) and 11, patients with both HF-REF and HF with preserved ejection fraction (HF-PEF). Pulmonary oedema was an essential inclusion criterion, in most trials, based upon findings on physical examination ('rales'), radiographic criteria ('signs of congestion'), or both. The prevalence of pulmonary oedema in HF-REF trials ranged from 75% to 83% and in combined HF-REF and HF-PEF trials from 51% to 100%. Five trials did not report the prevalence or extent of pulmonary oedema assessed by either clinical examination or chest x-ray. Improvement of pulmonary congestion with treatment was inconsistently reported and commonly grouped with other signs of congestion into a score. One trial suggested that patients with rales over >2/3 of the lung fields on admission were at higher risk of adverse outcomes than those without. Although pulmonary oedema is a common finding in AHF, represents a therapeutic target, and may be of prognostic importance, recent trials used inconsistent criteria to define it, and did not consistently report its severity at baseline or its response to treatment. Consistent and ideally quantitative, methods for the assessment of pulmonary oedema in AHF trials are needed. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Echocardiographic Assessment of the Alterations in Pulmonary Blood Flow Associated with Ketamine and Etomidate Administration in Children with Tetralogy of Fallot.

PubMed

Jha, Ajay K; Gharde, Parag; Chauhan, Sandeep; Kiran, Usha; Malhotra Kapoor, Poonam

2016-02-01

Despite widespread uses of ketamine, the clinical studies determining its effect on pulmonary blood flow in children with tetralogy of Fallot (TOF) are lacking. Furthermore, the quantification of pulmonary blood flow is not possible in these patients, because pulmonary artery catheter is contraindicated. Therefore, the purpose of this study was to evaluate the changes in pulmonary blood flow by intra-operative transesophageal echocardiography after ketamine or etomidate administration in children with TOF. Eleven children each in the two clinical variants of TOF (group A-moderate to severe cyanosis; group B-mild to minimal cyanosis) undergoing intracardiac repair were prospectively studied after endotracheal intubation. A single bolus dose of ketamine (2 mg/kg) and etomidate (0.3 mg/kg) was administered in a random order after 15 minute interval. Hemodynamic, arterial blood gas, and echocardiographic measurements were obtained at 7 consecutive times (T) points (baseline, 1, 2, 4, 6, 8, and 15 minutes after drug administration). Ketamine produced a significant reduction in VTI-T (velocity time integrals total of left upper pulmonary vein), RVOT-PG (right ventricular outflow tract peak gradient), and MG (mean gradient) in group A while those in group B had a significant increase in VTI-T, RVOT-PG, and RVOT-MG at time (T1, T2, T4, and T6; P = 0.00). This divergent behavior, however, was not observed with etomidate. Etomidate does not change pulmonary blood flow. However, ketamine produces divergent effects; it increases pulmonary blood flow in children with minimal cyanosis and decreases pulmonary blood flow in children with moderate to severe cyanosis. © 2015, Wiley Periodicals, Inc.

Yoga respiratory training improves respiratory function and cardiac sympathovagal balance in elderly subjects: a randomised controlled trial

PubMed Central

Santaella, Danilo F; Devesa, Cesar R S; Rojo, Marcos R; Amato, Marcelo B P; Drager, Luciano F; Casali, Karina R; Montano, Nicola

2011-01-01

Objectives Since ageing is associated with a decline in pulmonary function, heart rate variability and spontaneous baroreflex, and recent studies suggest that yoga respiratory exercises may improve respiratory and cardiovascular function, we hypothesised that yoga respiratory training may improve respiratory function and cardiac autonomic modulation in healthy elderly subjects. Design 76 healthy elderly subjects were enrolled in a randomised control trial in Brazil and 29 completed the study (age 68±6 years, 34% males, body mass index 25±3 kg/m2). Subjects were randomised into a 4-month training program (2 classes/week plus home exercises) of either stretching (control, n=14) or respiratory exercises (yoga, n=15). Yoga respiratory exercises (Bhastrika) consisted of rapid forced expirations followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril. Pulmonary function, maximum expiratory and inspiratory pressures (PEmax and PImax, respectively), heart rate variability and blood pressure variability for spontaneous baroreflex determination were determined at baseline and after 4 months. Results Subjects in both groups had similar demographic parameters. Physiological variables did not change after 4 months in the control group. However, in the yoga group, there were significant increases in PEmax (34%, p<0.0001) and PImax (26%, p<0.0001) and a significant decrease in the low frequency component (a marker of cardiac sympathetic modulation) and low frequency/high frequency ratio (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex did not change, and quality of life only marginally increased in the yoga group. Conclusion Respiratory yoga training may be beneficial for the elderly healthy population by improving respiratory function and sympathovagal balance. Trial Registration CinicalTrials.gov identifier: NCT00969345; trial registry name: Effects of respiratory yoga training (Bhastrika) on heart rate variability and baroreflex, and quality of life of healthy elderly subjects. PMID:22021757

Pulmonary Function, Muscle Strength and Mortality in Old Age

PubMed Central

Buchman, A. S.; Boyle, P. A.; Wilson, R.S.; Gu, Liping; Bienias, Julia L.; Bennett, D. A.

2009-01-01

Numerous reports have linked extremity muscle strength with mortality but the mechanism underlying this association is not known. We used data from 960 older persons without dementia participating in the Rush Memory and Aging Project to test two sequential hypotheses: first, that extremity muscle strength is a surrogate for respiratory muscle strength, and second, that the association of respiratory muscle strength with mortality is mediated by pulmonary function. In a series of proportional hazards models, we first demonstrated that the association of extremity muscle strength with mortality was no longer significant after including a term for respiratory muscle strength, controlling for age, sex, education, and body mass index. Next, the association of respiratory muscle strength with mortality was attenuated by more than 50% and no longer significant after including a term for pulmonary function. The findings were unchanged after controlling for cognitive function, parkinsonian signs, physical frailty, balance, physical activity, possible COPD, use of pulmonary medications, vascular risk factors including smoking, chronic vascular diseases, musculoskeletal joint pain, and history of falls. Overall, these findings suggest that pulmonary function may partially account for the association of muscle strength and mortality. PMID:18755207

Analysis of responses to valerian root extract in the feline pulmonary vascular bed.

PubMed

Fields, Aaron M; Richards, Todd A; Felton, Jason A; Felton, Shaili K; Bayer, Erin Z; Ibrahim, Ikhlass N; Kaye, Alan David

2003-12-01

This study was undertaken to investigate pulmonary vascular response to valerian (Valeriana officinalis) in the feline pulmonary vasculature under constant flow conditions. In separate experiments, the effects of NG-L-nitro-L-arginine methyl ester (L-NIO), a nitric oxide synthase inhibitor, glibenclamide, an adenosine triphosphate (ATP)-sensitive potassium (K+) channel blocker, meclofenamate, a nonselective cyclooxygenase (COX) inhibitor, bicuculline, a GABA(A) receptor antagonist, and saclofen, a GABA(B) antagonist, were investigated on pulmonary arterial responses to various agonists in the feline pulmonary vascular bed. These agonists included valerian, muscimol, a GABA(A) agonist, SKF-97541 a GABA(B) agonist, acetylcholine (ACh), and bradykinin, both inducers of nitric oxide synthase, arachidonic acid, a COX substrate, and pinacidil, an ATP-sensitive K+ channel activator, during increased tone conditions induced by the thromboxane A2 mimic, U46619. Laboratory investigation. Mongrel cats of either gender. Injections of the abovementioned agonists and antagonists were given. Baseline pulmonary tone, responses to the agonists, and responses to the agonists after injections of antagonists were all measured via a pulmonary catheter transducer and recorded. Valerian root extract is a potent smooth muscle dilator in the feline pulmonary vascular bed. The vasodilatory effects of valerian root extract were unchanged after the administration of L-NIO, glibenclamide, and meclofenamate. These effects were ablated, however, by both saclofen and bicuculline. The ability of saclofen and bicuculline to modulate the dilatory effects of valerian root extract was not statistically different. The vasodilatory effects of valerian root extract are mediated by a nonselective GABA mechanism.

Effectiveness of a group opt-in session on uptake and graduation rates for pulmonary rehabilitation.

PubMed

Graves, J; Sandrey, V; Graves, T; Smith, D L

2010-08-01

Pulmonary rehabilitation (PR) is an effective intervention in the treatment of patients with chronic obstructive pulmonary disease (COPD). Unfortunately some patients offered this treatment either fail to take up the offer or fail to complete the course. Studies have indicated a number of factors influencing uptake and completion rates. We describe the introduction of an intervention, the group opt-in session (GOIS), prior to individualised baseline assessment and entry to the PR course, with the intention being to improve uptake and completion rates. A 1.5-hour-long GOIS was offered as the first face-to-face contact to all patients referred for PR. Drop-out rates at all stages of the pathway from referral to graduation were collected on 200 patients prior to the introduction of the GOIS (non-GOIS group) and compared to the first 400 patients following introduction (the GOIS group). Possible independent predictors of course uptake and completion were examined in the GOIS group. The proportion of referred patients taking up the offer of individualised baseline assessment or a GOIS was similar (75% vs. 72.2%, p value not significant [ns]). However, since in the GOIS group the opt-in session preceded the individualised baseline assessment and some patients opted-out, a smaller proportion of referred patients underwent this assessment than in the non-GOIS group (58.7% vs. 75%, p < 0.001). In addition, dropouts following individualised baseline assessments were also reduced (7% vs. 22%, p < 0.001). Both of these factors reduced 'wasted' assessments. Similar proportions of patients referred began the PR course in both groups (53% vs. 51.7%, ns), but a higher proportion of patients graduated in the GOIS group (87.9% vs. 76.4%, p < 0.05). Drop-out rates due to illness were similar in both groups (8.5% pre vs. 6.8% post, ns). However, drop-out rates not due to illness were much higher in the non-GOIS group (15.1% vs. 5.3%, p < 0.001). In the GOIS group, patients who did not attend the GOIS were, on average, younger (64.6 years vs. 69.7 years, p < 0.001) and had a higher mean percent predicted Forced Expiratory Volume (50.6% vs. 43.8%, p < 0.05) than those that did attend. A greater proportion of patients who opted in to the GOIS and attended the PR course lived less than 25 minutes from the PR centre than either those who did not attend the GOIS or who attended and then opted out (77.4% vs. 63%, p<0.005). The GOIS improved the graduation rates at The North Bristol Lung Centre PR Course and reduced wasted assessments. There was no effect on initial uptake. Analysis of the behaviour of patients invited to a GOIS suggested that age, lung function and travel distance were important factors influencing patient choice.

[Pulmonary function in patients with infiltrative pulmonary tuberculosis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2007-01-01

Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, pulmonary residual volume (PRV), R(aw), R(in),, R(ex), DLCO-SB, DLCO-SS, PaO2, and PaCO2 were determined in 103 patients with infiltrative pulmonary tuberculosis. Pulmonary dysfunction was detected in 83.5% of the patients. Changes were found in lung volumes and capacities in 63.1%, impaired bronchial patency and pulmonary gas exchange dysfunction were in 60.2 and 41.7%, respectively. The changes in pulmonary volumes and capacities appeared as increased PRV, decreased VC and FVC, and decreased and increased TGV and TLC; impaired bronchial patency presented as decreased PEF, MEF25, MEF50, MEF75, FEV1/VC% and increased R(aw) R(in), and R(ex); pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SB, DLCO-SS, and PaO2 and decreased and increased PaCO2. The magnitude of the observed functional changes was generally slight. Significant disorders were observed rarely and very pronounced ones were exceptional.

[Pulmonary function in patients with disseminated pulmonary tuberculosis].

PubMed

Nefedov, V B; Shergina, E A; Popova, L A

2007-01-01

Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/VC%, PEF, MEF25%, MEF50%, MEF75%, TLS, TGV, pulmonary residual volume (PRV), Raw, Rin, Rex, DLCO-SB, DLCO-SS, PaO2, and PaCO2 were determined in 29 patients with disseminated pulmonary tuberculosis. Pulmonary dysfunction was detected in 93.1% of the patients. Changes were found in lung volumes and capacities in 65.5%, impaired bronchial patency and pulmonary gas exchange dysfunction were in 79.3 and 37.9%, respectively. The changes in pulmonary volumes and capacities appeared as increased PRV, decreased VC, FVC, and TLS, decreased and increased TGV; impaired bronchial patency presented as decreased PEF, MEF25%, MEF50%, MEF75%, and FEV1/VC% and increased Raw, Rin, and Rex; pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SS and PaO2 and decreased and increased PaCO2. The observed functional changes varied from slight to significant and pronounced with a preponderance of small disorders, a lower detection rate of significant disorders, and rare detection of very pronounced ones.

Recommendations for a Standardized Pulmonary Function Report. An Official American Thoracic Society Technical Statement.

PubMed

Culver, Bruce H; Graham, Brian L; Coates, Allan L; Wanger, Jack; Berry, Cristine E; Clarke, Patricia K; Hallstrand, Teal S; Hankinson, John L; Kaminsky, David A; MacIntyre, Neil R; McCormack, Meredith C; Rosenfeld, Margaret; Stanojevic, Sanja; Weiner, Daniel J

2017-12-01

The American Thoracic Society committee on Proficiency Standards for Pulmonary Function Laboratories has recognized the need for a standardized reporting format for pulmonary function tests. Although prior documents have offered guidance on the reporting of test data, there is considerable variability in how these results are presented to end users, leading to potential confusion and miscommunication. A project task force, consisting of the committee as a whole, was approved to develop a new Technical Standard on reporting pulmonary function test results. Three working groups addressed the presentation format, the reference data supporting interpretation of results, and a system for grading quality of test efforts. Each group reviewed relevant literature and wrote drafts that were merged into the final document. This document presents a reporting format in test-specific units for spirometry, lung volumes, and diffusing capacity that can be assembled into a report appropriate for a laboratory's practice. Recommended reference sources are updated with data for spirometry and diffusing capacity published since prior documents. A grading system is presented to encourage uniformity in the important function of test quality assessment. The committee believes that wide adoption of these formats and their underlying principles by equipment manufacturers and pulmonary function laboratories can improve the interpretation, communication, and understanding of test results.

Morphologic Response of the Pulmonary Vasculature to Endoscopic Lung Volume Reduction.

PubMed

Rahaghi, Farbod N; Come, Carolyn E; Ross, James; Harmouche, Rola; Diaz, Alejandro A; Estepar, Raul San Jose; Washko, George

Endoscopic Lung Volume Reduction has been used to reduce lung hyperinflation in selected patients with severe emphysema. Little is known about the effect of this procedure on the intraparenchymal pulmonary vasculature. In this study we used CT based vascular reconstruction to quantify the effect of the procedure on the pulmonary vasculature. Intraparenchymal vasculature was reconstructed and quantified in 12 patients with CT scans at baseline and 12 weeks following bilateral introduction of sealants in the upper lobes. The volume of each lung and each lobe was measured, and the vascular volume profile was calculated for both lower lobes. The detected vasculature was further labeled manually as arterial or venous in the right lower lobe. There was an increase in the volume of the lower lobes (3.14L to 3.25L, p=0.0005). There was an increase in BV5, defined as the volume of blood vessels with cross sectional area of less than 5mm 2 , (53.2ml to 57.9ml, p=0.03). This was found to be correlated with the increase in lower lobe volumes (R=0.65, p=0.02). The changes appear to be symmetric for veins and arteries with a correlation coefficient of 0.87 and a slope of near identity. In the subjects studied, there was an increase, from baseline, in BV5 in the lower lobes that correlated with the change in the volume of the lower lobes. The change appeared to be symmetric for both arteries and veins. The study illustrates the use of intraparenchymal pulmonary vascular reconstruction to study morphologic changes in response to interventions.

Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: Tolerability and adverse drug reactions.

PubMed

Galli, Jonathan A; Pandya, Aloknath; Vega-Olivo, Michelle; Dass, Chandra; Zhao, Huaqing; Criner, Gerard J

2017-08-01

The real-world tolerability of pirfenidone and nintedanib in non-clinical trial patients is unknown. Many patients with pulmonary fibrosis have significant medical co-morbidities or baseline characteristics that exclude them from clinical trial participation. We conducted a retrospective chart review study on subjects prescribed nintedanib or pirfenidone for pulmonary fibrosis treatment (any aetiology) from September 2014 to February 2016. A total of 186 subjects were included: 129 received pirfenidone and 57 were prescribed nintedanib and followed up for mean observation periods of 52 ± 17 weeks for pirfenidone and 41 ± 15 weeks for nintedanib. The primary outcome was drug discontinuation as a result of an adverse event. Subjects had significant respiratory impairment at baseline, 63% required home oxygen therapy and mean diffusion capacity of carbon monoxide (DLCO) was 36 ± 14% predicted. Drug discontinuation as a result of an adverse event occurred in 20.9% of subjects on pirfenidone and 26.3% on nintedanib. Drug discontinuation rates for both pirfenidone and nintedanib did not significantly differ from corresponding large clinical trials (ASCEND/CAPACITY and INPULSIS 1 and 2, respectively). Adverse events that occurred with highest frequency on pirfenidone were nausea (26.4%), rash/photosensitivity (14.7%) and dyspepsia/gastroesophageal reflux disease (GERD) (12.4%). Diarrhoea (52.6%) and nausea (29.8%) were reported most often with nintedanib therapy. Patients with pulmonary fibrosis treated with nintedanib or pirfenidone in routine clinical practice had drug tolerability and adverse event profiles comparable with subjects enrolled in clinical trials despite having a greater degree of respiratory impairment and a high prevalence of co-morbid medical conditions. © 2017 Asian Pacific Society of Respirology.

High Oxygen Delivery to Preserve Exercise Capacity in Patients with Idiopathic Pulmonary Fibrosis Treated with Nintedanib. Methodology of the HOPE-IPF Study.

PubMed

Ryerson, Christopher J; Camp, Pat G; Eves, Neil D; Schaeffer, Michele; Syed, Nafeez; Dhillon, Satvir; Jensen, Dennis; Maltais, Francois; O'Donnell, Denis E; Raghavan, Natya; Roman, Michael; Stickland, Michael K; Assayag, Deborah; Bourbeau, Jean; Dion, Genevieve; Fell, Charlene D; Hambly, Nathan; Johannson, Kerri A; Kalluri, Meena; Khalil, Nasreen; Kolb, Martin; Manganas, Helene; Morán-Mendoza, Onofre; Provencher, Steve; Ramesh, Warren; Rolf, J Douglass; Wilcox, Pearce G; Guenette, Jordan A

2016-09-01

Pulmonary rehabilitation improves dyspnea and exercise capacity in idiopathic pulmonary fibrosis (IPF); however, it is unknown whether breathing high amounts of oxygen during exercise training leads to further benefits. Herein, we describe the design of the High Oxygen Delivery to Preserve Exercise Capacity in IPF Patients Treated with Nintedanib study (the HOPE-IPF study). The primary objective of this study is to determine the physiological and perceptual impact of breathing high levels of oxygen during exercise training in patients with IPF who are receiving antifibrotic therapy. HOPE-IPF is a two-arm double-blind multicenter randomized placebo-controlled trial of 88 patients with IPF treated with nintedanib. Patients will undergo 8 weeks of three times weekly aerobic cycle exercise training, breathing a hyperoxic gas mixture with a constant fraction of 60% inhaled oxygen, or breathing up to 40% oxygen as required to maintain an oxygen saturation level of at least 88%. End points will be assessed at baseline, postintervention (Week 8), and follow-up (Week 26). The primary analysis will compare the between-group baseline with post-training change in endurance time during constant work rate cycle exercise tests. Additional analyses will evaluate the impact of training with high oxygen delivery on 6-minute walk distance, dyspnea, physical activity, and quality of life. The HOPE-IPF study will lead to a comprehensive understanding of IPF exercise physiology, with the potential to change clinical practice by indicating the need for increased delivery of supplemental oxygen during pulmonary rehabilitation in patients with IPF. Clinical trial registered with www.clinicaltrials.gov (NCT02551068).

Lyophilized allografts without pre-treatment with glutaraldehyde are more suitable than cryopreserved allografts for pulmonary artery reconstruction

PubMed Central

Olmos-Zúãiga, J.R.; Jasso-Victoria, R.; Díaz-Martínez, N.E.; Gaxiola-Gaxiola, M.O.; Sotres-Vega, A.; Heras-Romero, Y.; Baltazares-Lipp, M.; Baltazares-Lipp, M.E.; Santillán-Doherty, P.; Hernández-Jiménez, C.

2015-01-01

Various methods are available for preservation of vascular grafts for pulmonary artery (PA) replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA) grafts and cryopreserved (CryoPA) grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP) in group III increased significantly at the end of the study compared with baseline (P=0.02) and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA)] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA). Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising. PMID:26648092

The Ratio of Angiopoietin-2 to Angiopoietin-1 as a Predictor of Mortality in Acute Lung Injury Patients

PubMed Central

Ong, Thida; McClintock, Dana E.; Kallet, Richard H.; Ware, Lorraine B.; Matthay, Michael A.; Liu, Kathleen D.

2014-01-01

Objective To test the hypothesis that the concentration of angiopoietin-2 relative to angiopoietin-1 (Ang-2/Ang-1) may be a useful biologic marker of mortality in acute lung injury (ALI) patients. We also tested the association of Ang-2/Ang-1 with physiologic and biologic markers of activated endothelium. Design Prospective observational cohort study. Setting Intensive care units in a tertiary care university hospital and a university-affiliated city hospital. Patients Fifty-six mechanically ventilated patients with ALI. Interventions Baseline plasma samples and pulmonary dead space fraction measurements were collected within 48 hours of ALI diagnosis. Measurements and Main Results Plasma levels of Ang-1 and Ang-2 and of biomarkers of endothelial activation were measured by ELISA. Baseline Ang-2/Ang-1 was significantly higher in patients who died [median 58 (IQR 17–117) vs. 14 (IQR 6–35), p=0.01]. In a multivariable analysis stratified by dead space fraction, Ang-2/Ang-1 was an independent predictor of death with an adjusted odds ratio of 4.3 (95% CI 1.3–13.5, p=0.01) in those with an elevated pulmonary dead space fraction (p=0.03 for interaction between pulmonary dead space fraction and Ang-2/Ang-1). Moderate to weak correlation was found with biologic markers of endothelial activation. Conclusions The ratio of Ang-2/Ang-1 may be a prognostic biomarker of endothelial activation in ALI patients and, along with pulmonary dead space fraction, may be useful for risk stratification of ALI patients, particularly in identifying subgroups for future research and therapeutic trials. PMID:20581666

Comparison of TST and IGRA in Diagnosis of Latent Tuberculosis Infection in a High TB-Burden Setting.

PubMed

Sharma, Surendra K; Vashishtha, Richa; Chauhan, L S; Sreenivas, V; Seth, Divya

2017-01-01

There are currently two tests for diagnosing latent tuberculosis infection (LTBI); TST and IGRA. However, it is still unclear that which one of these tests performs better in high TB-burden settings. 1511 household contacts of pulmonary TB patients were enrolled to compare the performance of TST and IGRA for LTBI. At baseline all participant underwent testing for IGRA [QuantiFERON-TB® Gold In-tube (QFT-GIT) assay] and TST [2 tuberculin unit (TU), purified protein derivative (PPD), RT23, Staten Serum Institute (SSI), Copenhagen, Denmark]. All the household contacts were followed-up for two years for incident TB cases. Active TB was diagnosed in 76 household contacts at an incidence rate of 2.14 per 1000 person-years. Both, TST [Hazard Ratio (HR): 1.14, 95% confidence interval (CI): 0.72-1.79, p = 0.57], as well as QFT-GIT assay (HR: 1.66, 95% CI: 0.97-2.84, p = 0.06) results at baseline were not significantly associated with subsequent development of active TB among household contacts of pulmonary TB patients. Neither TST nor IGRA predicted subsequent development of active TB among household contacts of pulmonary TB patients during follow-up. However, keeping in view the cost, and other logistics, TST remains the most preferred method for LTBI diagnosis in resource-limited, high TB-burden settings.

Functional classification of pulmonary hypertension in children: Report from the PVRI pediatric taskforce, Panama 2011.

PubMed

Lammers, Astrid E; Adatia, Ian; Cerro, Maria Jesus Del; Diaz, Gabriel; Freudenthal, Alexandra Heath; Freudenthal, Franz; Harikrishnan, S; Ivy, Dunbar; Lopes, Antonio A; Raj, J Usha; Sandoval, Julio; Stenmark, Kurt; Haworth, Sheila G

2011-08-02

The members of the Pediatric Task Force of the Pulmonary Vascular Research Institute (PVRI) were aware of the need to develop a functional classification of pulmonary hypertension in children. The proposed classification follows the same pattern and uses the same criteria as the Dana Point pulmonary hypertension specific classification for adults. Modifications were necessary for children, since age, physical growth and maturation influences the way in which the functional effects of a disease are expressed. It is essential to encapsulate a child's clinical status, to make it possible to review progress with time as he/she grows up, as consistently and as objectively as possible. Particularly in younger children we sought to include objective indicators such as thriving, need for supplemental feeds and the record of school or nursery attendance. This helps monitor the clinical course of events and response to treatment over the years. It also facilitates the development of treatment algorithms for children. We present a consensus paper on a functional classification system for children with pulmonary hypertension, discussed at the Annual Meeting of the PVRI in Panama City, February 2011.

Ambulatory vital signs in the workup of pulmonary embolism using a standardized 3-minute walk test.

PubMed

Amin, Qamar; Perry, Jeffrey J; Stiell, Ian G; Mohapatra, Subhra; Alsadoon, Abdulaziz; Rodger, Marc

2015-05-01

Diagnosing pulmonary embolism can be difficult given its highly variable clinical presentation. Our objective was to determine whether a decrease in oxygen saturation or an increase in heart rate while ambulating could be used as an objective tool in the diagnosis of pulmonary embolism. This was a two-site tertiary-care-centre prospective cohort study that enrolled adult emergency department or thrombosis clinic patients with suspected or newly confirmed pulmonary embolism. Patients were asked to participate in a standardized 3-minute walk test, which assessed ambulatory heart rate and ambulatory oxygen saturation. The primary outcome was pulmonary embolism. We enrolled 114 patients, including 30 with pulmonary embolism (26.3%). A ≥2% absolute decrease in ambulatory oxygen saturation and an ambulatory change in heart rate >10 beats per minute (BPM) were significantly associated with pulmonary embolism. An ambulatory heart rate change of >10 BPM had a sensitivity of 96.6% (95% confidence interval [CI] 83.3 to 99.4) and a specificity of 31.0% (95% CI 22.1 to 45.0) for pulmonary embolism. A ≥2% absolute decrease ambulatory oxygen saturation had a sensitivity of 80.2% (95% CI 62.7 to 90.5) and a specificity of 39.3% (95% CI 29.5 to 50.0) for pulmonary embolism. The combination of both variables yielded a sensitivity of 100.0% (95% CI 87.0 to 100.0) and a specificity of 11.0% (95% CI 6.6 to 21.0). In summary, our study found that an ambulatory heart rate change of >10 BPM or a ≥2% absolute decrease in ambulatory oxygen saturation from baseline during a standardized 3-minute walk test are highly correlated with pulmonary embolism. Although the findings appear promising, neither of these variables can currently be recommended as a screening tool for pulmonary embolism until larger prospective studies examine their performance either alone or with pre-existing rules.

Secondary Pulmonary Hypertension and Right-Sided Heart Failure at Presentation in Grave's Disease.

PubMed

Ganeshpure, Swapnil Panjabrao; Vaidya, Gaurang Nandkishor; Gattani, Vipul

2012-01-01

A young female presented with evidence of right-sided heart failure and was subsequently found to have significant pulmonary artery hypertension (PAH). Because of her normal left ventricular function and pulmonary capillary wedge pressure, the most probable site of etiology seemed to be the pulmonary vasculature. All the common possible secondary causes of PAH were ruled out, but during the investigations, she was found to have elevated thyroid function tests compatible with the diagnosis of Grave's disease. The treatment of Grave's disease, initially by medications and subsequently by radioiodine therapy, was associated with a significant reduction in the pulmonary artery systolic pressure. The purpose of this case report is to highlight one of the unusual and underdiagnosed presentations of Grave's disease.

Right ventricle performances with echocardiography and 99mTc myocardial perfusion imaging in pulmonary arterial hypertension patients.

PubMed

Liu, Jie; Fei, Lei; Huang, Guang-Qing; Shang, Xiao-Ke; Liu, Mei; Pei, Zhi-Jun; Zhang, Yong-Xue

2018-05-01

Right heart catheterization is commonly used to measure right ventricle hemodynamic parameters and is the gold standard for pulmonary arterial hypertension diagnosis; however, it is not suitable for patients' long-term follow-up. Non-invasive echocardiography and nuclear medicine have been applied to measure right ventricle anatomy and function, but the guidelines for the usefulness of clinical parameters remain to be established. The goal of this study is to identify reliable clinical parameters of right ventricle function in pulmonary arterial hypertension patients and analyze the relationship of these clinical parameters with the disease severity of pulmonary arterial hypertension. In this study, 23 normal subjects and 23 pulmonary arterial hypertension patients were recruited from January 2015 to March 2016. Pulmonary arterial hypertension patients were classified into moderate and severe pulmonary arterial hypertension groups according to their mean pulmonary arterial pressure levels. All the subjects were subjected to physical examination, chest X-ray, 12-lead electrocardiogram, right heart catheterization, two-dimensional echocardiography, and technetium 99m ( 99m Tc) myocardial perfusion imaging. Compared to normal subjects, the right heart catheterization indexes including right ventricle systolic pressure, right ventricle end diastolic pressure, pulmonary artery systolic pressure, pulmonary artery diastolic pressure, pulmonary vascular resistance, and right ventricle end systolic pressure increased in pulmonary arterial hypertension patients and were correlated with mean pulmonary arterial pressure levels. Echocardiography parameters, including tricuspid regurgitation peak velocity, tricuspid regurgitation pressure gradient, tricuspid annular plane systolic excursion and fractional area, right ventricle-myocardial performance index, were significantly associated with the mean pulmonary arterial pressure levels in pulmonary arterial hypertension patients. Furthermore, myocardial perfusion imaging was not observed in the normal subjects but in pulmonary arterial hypertension patients, especially severe pulmonary arterial hypertension subgroup, and showed potential diagnostic properties for pulmonary arterial hypertension. In conclusion, mean pulmonary arterial pressure levels are correlated with several right heart catheterization and echocardiography markers in pulmonary arterial hypertension patients; echocardiography and 99m Tc myocardial perfusion can be used to evaluate right ventricle performance in pulmonary arterial hypertension patients. Impact statement In this study, we analyzed the clinical parameters for evaluating RV function, including right ventricle catheterization (RHC), echocardiography, and technetium 99m ( 99m Tc) myocardial perfusion imaging (MPI) in normal Asian subjects and PAH patients ( n = 23 for each group). Our results demonstrated that six RHC indexes, four echocardiography indexes and MPI index were significantly altered in PAH patients and correlated with the levels of mean pulmonary arterial pressure. Importantly, we evaluated the diagnostic performance of MPI and found that MPI has a strong diagnostic accuracy in PAH patients. The findings from this study will be of interest to clinical investigators who make diagnosis and therapeutic strategies for PAH patients.

Occupational PAH Exposures during Prescribed Pile Burns

PubMed Central

Robinson, M. S.; Anthony, T. R.; Littau, S. R.; Herckes, P.; Nelson, X.; Poplin, G. S.; Burgess, J. L.

2008-01-01

Wildland firefighters are exposed to particulate matter and gases containing polycyclic aromatic hydrocarbons (PAHs), many of which are known carcinogens. Our objective was to evaluate the extent of firefighter exposure to particulate and PAHs during prescribed pile burns of mainly ponderosa pine slash and determine whether these exposures were correlated with changes in urinary 1-hydroxypyrene (1-HP), a PAH metabolite. Personal and area sampling for particulate and PAH exposures were conducted on the White Mountain Apache Tribe reservation, working with 21 Bureau of Indian Affairs/Fort Apache Agency wildland firefighters during the fall of 2006. Urine samples were collected pre- and post-exposure and pulmonary function was measured. Personal PAH exposures were detectable for only 3 of 16 PAHs analyzed: naphthalene, phenanthrene, and fluorene, all of which were identified only in vapor-phase samples. Condensed-phase PAHs were detected in PM2.5 area samples (20 of 21 PAHs analyzed were detected, all but naphthalene) at concentrations below 1 μg m−3. The total PAH/PM2.5 mass fractions were roughly a factor of two higher during smoldering (1.06 ± 0.15) than ignition (0.55 ± 0.04 μg mg−1). There were no significant changes in urinary 1-HP or pulmonary function following exposure to pile burning. In summary, PAH exposures were low in pile burns, and urinary testing for a PAH metabolite failed to show a significant difference between baseline and post-exposure measurements. PMID:18515848

Effect of pirfenidone on wound healing in lung transplant patients.

PubMed

Mortensen, Amber; Cherrier, Lauren; Walia, Rajat

2018-01-01

The drug pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor beta, a known contributor to wound healing. We evaluated whether patients taking pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether pirfenidone should be discontinued prior to listing to allow for a wash-out period. We retrospectively reviewed patients who underwent lung transplantation for pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January 2014 to December 2015. We describe 18 patients who took pirfenidone up to a month before transplant. Aside from one patient who experienced sternal dehiscence due to a surgical issue, all remaining patients did well with no evidence of airway dehiscence. Each of these 17 patients had been on pirfenidone for at least 30 days; nine patients had been on pirfenidone for over 90 days. Baseline characteristics including age, sex, body mass index, renal function, liver function, glucose level, pre-transplant corticosteroid use, and post-transplant immunosuppressant therapy were similar. In our experience, pirfenidone may be safely continued until lung transplantation. Only one patient in our series experienced impaired wound healing related to a surgical issue, even when pirfenidone was continued until lung transplantation. We found no evidence of impaired wound healing or airway complications after lung transplantation in patients who were treated with pirfenidone before lung transplantation.

Pulmonary function in children with development coordination disorder.

PubMed

Wu, Sheng K; Cairney, John; Lin, Hsiao-Hui; Li, Yao-Chuen; Song, Tai-Fen

2011-01-01

The purpose of this study was to compare pulmonary function in children with developmental coordination disorder (DCD) with children who are typically developing (TD), and also analyze possible gender differences in pulmonary function between these groups. The Movement ABC test was used to identify the movement coordination ability of children. Two hundred and fifty participants (90 children with DCD and 160 TD children) aged 9-10 years old completed this study. Using the KoKo spirometry, forced vital capacity (FVC) and forced expiratory volume in 1s (FEV(1.0)) were used to measure pulmonary function. The 800-m run was also conducted to assess cardiopulmonary fitness of children in the field. There was a significant difference in pulmonary function between TD children and those with DCD. The values of FVC and FEV(1.0) in TD children were significantly higher than in children with DCD. A significant, but low correlation (r = -0.220, p < .001) was found between total score on the MABC and FVC; similarly, a positive but low correlation (r = 0.252, p < .001) was found between total score on the MABC and the completion time of 800-m run. However, no significant correlation between FVC and the time of 800-m run was found (p > .05). Significant correlations between total score on the MABC and the completion time of the 800-m run (r = 0.352, p < .05) and between FVC and the time of 800-m run (r = -0.285, p < .05) were observed in girls with DCD but not boys with this condition. Based on the results of this study, pulmonary function in children with DCD was significantly lower than that of TD children. The field test, 800-m run, may not be a good indicator to distinguish aerobic ability between children with DCD and those who are TD. It is possible that poor pulmonary function in children with DCD is due to reduced physical activity in this population. Copyright © 2010 Elsevier Ltd. All rights reserved.

Monitoring pulmonary function with superimposed pulmonary gas exchange curves from standard analyzers.

PubMed

Zar, Harvey A; Noe, Frances E; Szalados, James E; Goodrich, Michael D; Busby, Michael G

2002-01-01

A repetitive graphic display of the single breath pulmonary function can indicate changes in cardiac and pulmonary physiology brought on by clinical events. Parallel advances in computer technology and monitoring make real-time, single breath pulmonary function clinically practicable. We describe a system built from a commercially available airway gas monitor and off the shelf computer and data-acquisition hardware. Analog data for gas flow rate, O2, and CO2 concentrations are introduced into a computer through an analog-to-digital conversion board. Oxygen uptake (VO2) and carbon dioxide output (VCO2) are calculated for each breath. Inspired minus expired concentrations for O2 and CO2 are displayed simultaneously with the expired gas flow rate curve for each breath. Dead-space and alveolar ventilation are calculated for each breath and readily appreciated from the display. Graphs illustrating the function of the system are presented for the following clinical scenarios; upper airway obstruction, bronchospasm, bronchopleural fistula, pulmonary perfusion changes and inadequate oxygen delivery. This paper describes a real-time, single breath pulmonary monitoring system that displays three parameters graphed against time: expired flow rate, oxygen uptake and carbon dioxide production. This system allows for early and rapid recognition of treatable conditions that may lead to adverse events without any additional patient measurements or invasive procedures. Monitoring systems similar to the one described in this paper may lead to a higher level of patient safety without any additional patient risk.

Lung Function in Pregnancy in Langerhans Cell Histiocytosis.

PubMed

Radzikowska, Elżbieta; Wiatr, Elżbieta; Franczuk, Monika; Bestry, Iwona; Roszkowski-Śliż, Kazimierz

2018-01-01

Pulmonary Langerhans cell histiocytosis (LCH) is a rare disease, affecting usually young people. The course of the disease is variable. In some pulmonary LCH patients a severe lung destruction and progression in spite of chemotherapy is observed, but in others just a cessation of smoking induces a regression of the disease. In the present study we seek to determine the influence of pregnancy on pulmonary function in LCH patients, an unchartered area of research. We addressed the issue by investigating eight pregnant women out of the 45 women hospitalized with the diagnosis of pulmonary LCH in the period from 2000 to 2015. For five of the eight pregnant women it was the second gestation. The median follow-up period was 120 months (range 72-175 months). Ten healthy children were born by a C-section. Two spontaneous miscarriages in the seventh week of gestation, and one tubal ectopic pregnancy were recorded. We found that pregnancy did not significantly influence pulmonary function assessed by the following indices: forced expiratory volume in 1 s (FEV1), lung vital capacity (VC), total lung capacity (TLC), residual volume (RV), diffusing capacity of the lungs for carbon monoxide (DLCO), and the distance and arterial oxygen saturation in 6-min walk test. Only one patient in the third trimester of pregnancy experienced bilateral pneumothorax, with persistent air leak. In all patients, delivery and postpartum period were uneventful. We conclude that pregnancy in pulmonary LCH patients is safe and not associated with deterioration of pulmonary function or blood oxygenation.