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.

[The role of the adreno-cholinergic interaction in the pulmonary hemodynamics changes following myocardial ischemia].

PubMed

Evlakhov, V I; Poiasov, I Z

2014-06-01

In acute experiments in anesthetized rabbits the pulmonary hemodynamics changes were studied following 60 s myocardial ischemia in the region of the descendent left coronary artery in control state and after the blockade of M- or N-cholinoreceptors and acetylcholine infusion. Following myocardial ischemia in control animals the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance was not changed. Following myocardial ischemia after the blockade of M-cholinoreceptors by atropine the changes of pulmonary hemodynamics were the same as in control animals, the cardiac output decreased twice as more as in control animals. Following myocardial ischemia after the blockade of N-cholinoreceptors by hexamethonium the pulmonary hemodynamics changes were the same as in the control rabbits. Following myocardial ischemia after the acetylcholine infusion the pulmonary artery flow decreased more than the cardiac output, the pulmonary vascular resistance was diminished. The disbalance of the cardiac output and pulmonary artery flow changes has revealed the significance of the adreno-cholinergic interaction in the changes of the pulmonary vessels capacitance and resistive functions following myocardial ischemia.

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

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

Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial.

PubMed

McEvoy, Cindy T; Schilling, Diane; Clay, Nakia; Jackson, Keith; Go, Mitzi D; Spitale, Patricia; Bunten, Carol; Leiva, Maria; Gonzales, David; Hollister-Smith, Julie; Durand, Manuel; Frei, Balz; Buist, A Sonia; Peters, Dawn; Morris, Cynthia D; Spindel, Eliot R

2014-05-01

Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. clinicaltrials.gov Identifier: NCT00632476.

Implication of Sarcopenia and Sarcopenic Obesity on Lung Function in Healthy Elderly: Using Korean National Health and Nutrition Examination Survey.

PubMed

Moon, Ji Hyun; Kong, Mi Hee; Kim, Hyeon Ju

2015-11-01

Previous studies have demonstrated a positive association between obesity and decreased lung function. However, the effect of muscle and fat has not been fully assessed, especially in a healthy elderly population. In this study, we evaluated the impact of low muscle mass (LMM) and LMM with obesity on pulmonary impairment in healthy elderly subjects. Our study used data from the Korea National Health and Nutrition Examination Survey from 2008 to 2011. Men and women aged 65 yr or older were included. Muscle mass was measured by dual-energy X-ray absorptiometry. LMM was defined as two standard deviations below the sex-specific mean for young healthy adults. Obesity was defined as body mass index ≥ 25 kg/m(2). The prevalence of LMM in individuals aged over 65 was 11.9%. LMM and pulmonary function (forced vital capacity and forced expiratory volume in 1 second) were independently associated after adjusting for age, sex, body mass index, smoking status, alcohol consumption, and frequency of exercise. LMM with obesity was also related to a decrease in pulmonary function. This study revealed that LMM is an independent risk factor of decreased pulmonary function in healthy Korean men and women over 65 yr of age.

The effects of balneotherapy on acute, process-related, and cumulative peripheral cardiac responses and pulmonary functions in patients with musculoskeletal disorders.

PubMed

Şaş, Senem; Toprak Çelenay, Şeyda; Özer Kaya, Derya

2016-12-20

This study aimed to evaluate the effects of balneotherapy on acute, process-related, and cumulative peripheral cardiac responses and pulmonary functions in patients with musculoskeletal disorders. Ninety-eight patients with musculoskeletal disorders referred to physiotherapy with balneotherapy were recruited. The patients received balneotherapy for 20 min 5 times per week for 2 weeks. Blood pressure and pulse were measured at the 0th, 5th, 10th, 20th, and 30th minutes during the 1st and 10th sessions. All patients were subjected to pulmonary function testing before balneotherapy and after the 10th session. It was found that systolic blood pressure decreased between the 10th and 20th minutes of the 1st session and between the 10th and 20th minutes and the 20th and 30th minutes of the 10th session (P < 0.05). Diastolic blood pressure (DBP) decreased and pulse increased during balneotherapy (P < 0.05). DBP increase and pulse decrease were observed during recovery time (P < 0.05). The blood pressure decreased and the pulse increased after the 1st session and after the 10th session (P < 0.05). Pulmonary function improved after balneotherapy (P < 0.05). Conclusions: Balneotherapy may be effective for improving peripheral cardiopulmonary responses in patients with musculoskeletal disorders.

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 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.

Effects of Aerobic Exercise Applied Early After Coronary Artery Bypass Grafting on Pulmonary Function, Respiratory Muscle Strength, and Functional Capacity: A Randomized Controlled Trial.

PubMed

Borges, Daniel L; Silva, Mayara Gabrielle; Silva, Luan Nascimento; Fortes, João Vyctor; Costa, Erika Thalita; Assunção, Rebeca Pessoa; Lima, Carlos Magno; da Silva Nina, Vinícius José; Bernardo-Filho, Mário; Caputo, Danúbia Sá

2016-09-01

Physical activity is beneficial in several clinical situations and recommended for patients with ischemic heart disease, as well as for those undergoing cardiac surgery. In a randomized controlled trial, 34 patients underwent coronary artery bypass grafting. A randomized control group (n = 15) submitted to conventional physiotherapy. The intervention group (n = 19) received the same protocol plus additional aerobic exercise with cycle ergometer. Pulmonary function by spirometry, respiratory muscle strength by manovacuometry, and functional capacity through 6-minute walking test was assessed before surgery and at hospital discharge. There was significant reduction in pulmonary function in both groups. In both groups, inspiratory muscle strength was maintained while expiratory muscle strength significantly decreased. Functional capacity was maintained in the intervention group (364.5 [324.5 to 428] vs. 348 [300.7 to 413.7] meters, P = .06), but it decreased significantly in control group patients (320 [288.5 to 393.0] vs. 292 [237.0 to 336.0] meters, P = .01). A significant difference in functional capacity was also found in intergroup analyses at hospital discharge (P = .03). Aerobic exercise applied early on coronary artery bypass grafting patients may promote maintenance of functional capacity, with no impact on pulmonary function and respiratory muscle strength when compared with conventional physiotherapy.

Pulmonary function and bronchial hyperreactivity in asthmatic children with house dust mite allergy during prolonged stay in the Italian Alps (Misurina, 1756 m).

PubMed

Boner, A L; Niero, E; Antolini, I; Valletta, E A; Gaburro, D

1985-01-01

The effects of high altitude were evaluated in 14 children with allergic bronchial asthma over an 8-month period. Clinical improvement, as assessed by decreased bronchial lability, was demonstrated by pulmonary function studies. There was a decreased requirement for drugs and steroids were discontinued in our children. The results of this study suggest the use of this approach as a possible adjunct to the management of refractory cases of bronchial asthma.

[Pulmonary function in patients with focal pulmonary tuberculosis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2008-01-01

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), Raw, Rin, Rcx, DLCO-SB, DLCO-SS/VA, PaO2, and PaCO2 were determined in 40 patients with focal pulmonary tuberculosis. Changes were found in lung volumes and capacities in 75%, impaired bronchial patency and pulmonary gas exchange dysfunction were in 57.5 and 25%, respectively. The lung volume and capacity changes appeared mainly as increased TGV and PRV; impaired bronchial patency presented as decreased MEF50, MEF75, and FEV1/VC%; pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SB, PaO2, and PaCO2. The magnitude of the observed functional changes was generally slight. TGV and PRL increased up to 148-187 and 142-223% of the normal values, respectively; MEF50, MEF75, FEV1/VC%, and DLCO decreased to 59-24, 58-26, 78-57, and 78-67% of the normal values and PaO2 and PaCO2 did to 79-69 and 34-30 cm Hg.

Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia.

PubMed

Hirako, Shima; Tsuda, Hiroyuki; Kotani, Tomomi; Sumigama, Seiji; Mano, Yukio; Nakano, Tomoko; Imai, Kenji; Li, Hua; Toyokuni, Shinya; Kikkawa, Fumitaka

2016-09-01

Congenital diaphragmatic hernia (CDH) can induce lung hypoplasia and pulmonary hypertension and is associated with high mortality. The purpose of this study is to examine the efficacy and safety of antenatal Saireito (TJ-114), a traditional Japanese herbal medicine, in a rat CDH model. Sprague-Dawley rats were exposed to an herbicide (nitrofen, 100 mg) on embryonic day 9 (E9) to induce CDH, and antenatal Saireito (2000 mg/kg/day) was orally administered from E10 to E20. On E21, fetuses were delivered. Antenatal Saireito significantly decreased the incidence of CDH (p < 0.01), increased lung volume (p < 0.01), improved alveolarization and pulmonary artery remodeling using histological analysis, and improved respiratory function using gasometric analysis (pH; p < 0.05, and PCO2 ; p < 0.01). In addition, antenatal Saireito significantly decreased endothelin-1 and endothelin receptor A expression in the pulmonary arteries. Taken together, our results demonstrated that antenatal Saireito can improve fetal pulmonary hypoplasia and pulmonary vascular remodeling and, as a result, can improve respiratory function in a rat CDH model. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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.

[Effect of slow-release aminophylline on pulmonary function in obstructive respiratory disease(author's transl)].

PubMed

Wiessmann, K J

1975-09-05

The effects on pulmonary function of a slow-release preparation of an oral broncholytic drug (containing 350 mg aminophylline, released over eight hours) was tested on 26 patients in a double-blind trial. There was a marked reduction of airway resistance and stimulation of breathing with decreased dynamic work of breathing. Distinctly improved alveolar function was demonstrated especially in a fall of arterial CO2 tension, but in some cases there was probably an increase in distribution abnormality. Central haemodynamic changes with a decreased in pulmonary artery pressure and changes in the other values lasted for more than ten hours on the first day of treatment, and were demonstrable on the fourth day even before the drug was taken that day. The criteria of an effective broncholytic slow-release drug with sustained effect were thus fulfilled.

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.

Pulmonary function in obese vs non-obese cats.

PubMed

García-Guasch, Laín; Caro-Vadillo, Alicia; Manubens-Grau, Jordi; Carretón, Elena; Camacho, Aparecido A; Montoya-Alonso, José Alberto

2015-06-01

Obesity is a risk factor in the development of several respiratory diseases. Lung volumes tend to be decreased, especially expiratory reserve volume, increasing expiratory flow limitation during tidal breathing. Barometric whole-body plethysmography is a non-invasive pulmonary function test that allows a dynamic study of breathing patterns. The objective of this study was to compare pulmonary function variables between obese and non-obese cats through the use of barometric whole-body plethysmography. Nine normal-weight and six obese cats were placed in the plethysmograph chamber, and different respiratory variables were measured. There was a significant decrease in tidal volume per kilogram (P = 0.003), minute volume per kilogram (P = 0.001) and peak inspiratory and expiratory flows per kilogram (P = 0.001) in obese cats compared with non-obese cats. Obesity failed to demonstrate a significant increase in bronchoconstriction index variable enhanced pause (Penh), as previously reported in humans and dogs. The results show that feline obesity impairs pulmonary function in cats, although a significant increase in bronchoconstriction indexes was not observed. Non-invasive barometric whole-body plethysmography can help characterise mechanical dysfunction of the airways in obese cats. © ISFM and AAFP 2014.

[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.

[Function in patients with chronic fibrocavernous tuberculosis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2008-01-01

Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, residual volume (RV), R(aw), R(in), R(ex), DLCO-SB, DLCO-SS, PaO2, and PaCO2 were determined in 62 patients with chronic fibrocavernous tuberculosis. Lung dysfunctions were detected in 96.8% of the patients. Changes in lung volumes and capacities were found in 90.3%, impaired bronchial patency was in 90.3%, and pulmonary gas exchange dysfunction was in 79.0%. The lung volume and capacity changes appeared as decreased VC and FVC, decreased and increased TLC, TGV, RV; impaired bronchial patency presented as decreased PEF, MEF25, MEF50, MEF75, and FEV1/VC%; and increased R(aw), R(in), R(ex); pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SB, DLCO-SS, PaO2, and decreased and increased PaCO2. The magnitude of the observed functional changes ranges from slight to significant and drastic with a predominance of considerable and drastic changes in lung volumes and capacities and mild impairments of bronchial patency and pulmonary gas exchange function.

Relationship between pulmonary function and indoor air pollution from coal combustion among adult residents in an inner-city area of southwest China

PubMed Central

Jie, Y.; Houjin, H.; Xun, M.; Kebin, L.; Xuesong, Y.; Jie, X.

2014-01-01

Few studies evaluate the amount of particulate matter less than 2.5 mm in diameter (PM2.5) in relation to a change in lung function among adults in a population. The aim of this study was to assess the association of coal as a domestic energy source to pulmonary function in an adult population in inner-city areas of Zunyi city in China where coal use is common. In a cross-sectional study of 104 households, pulmonary function measurements were assessed and compared in 110 coal users and 121 non-coal users (≥18 years old) who were all nonsmokers. Several sociodemographic factors were assessed by questionnaire, and ventilatory function measurements including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio, and peak expiratory flow rate (PEFR) were compared between the 2 groups. The amount of PM2.5 was also measured in all residences. There was a significant increase in the relative concentration of PM2.5 in the indoor kitchens and living rooms of the coal-exposed group compared to the non-coal-exposed group. In multivariate analysis, current exposure to coal smoke was associated with a 31.7% decrease in FVC, a 42.0% decrease in FEV1, a 7.46% decrease in the FEV1/FVC ratio, and a 23.1% decrease in PEFR in adult residents. The slope of lung function decrease for Chinese adults is approximately a 2-L decrease in FVC, a 3-L decrease in FEV1, and an 8 L/s decrease in PEFR per count per minute of PM2.5 exposure. These results demonstrate the harmful effects of indoor air pollution from coal smoke on the lung function of adult residents and emphasize the need for public health efforts to decrease exposure to coal smoke. PMID:25296361

Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation.

PubMed

Porteous, Mary K; Rivera-Lebron, Belinda N; Kreider, Maryl; Lee, James; Kawut, Steven M

2016-03-01

Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4-93.3) in 6-minute walk distance ([Formula: see text]). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0-21.1; [Formula: see text]). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1-29.5; [Formula: see text]). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis.

Idiopathic Pulmonary Fibrosis: Gender-Age-Physiology Index Stage for Predicting Future Lung Function Decline.

PubMed

Salisbury, Margaret L; Xia, Meng; Zhou, Yueren; Murray, Susan; Tayob, Nabihah; Brown, Kevin K; Wells, Athol U; Schmidt, Shelley L; Martinez, Fernando J; Flaherty, Kevin R

2016-02-01

Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage. Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function ≥ 10% in 6 months predict mortality after accounting for GAP stage. Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or Dlco over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P ≤ .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1). Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of ≥ 10% over 6 months independently predicted death or lung transplantation. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Pulmonary hypertension in hemodialysis patients without arteriovenous fistula: the effect of dialyzer composition.

PubMed

Kiykim, Ahmet Alper; Horoz, Mehmet; Ozcan, Turkay; Yildiz, Ibrahim; Sari, Sibel; Genctoy, Gultekin

2010-01-01

Pulmonary hypertension (PHT) increases mortality rate in hemodialysis (HD) patients. Numerous clinical, hemodynamic, and metabolic abnormalities have been suggested to be associated with the development of PHT in HD patients. We aimed to investigate the acute effects of two different dialyzer membranes on pulmonary arterial pressure (PAP) throughout a HD session in maintenance HD patients. Seventy-four HD patients dialyzed through permanent tunneled jugular central venous catheter were enrolled. A first-use cellulose acetate and high-flux polysulfone dialysis membrane were tested using a crossover design. For each membrane, pre- and post-dialysis pulmonary artery pressures were measured echocardiographically. Elevated pulmonary artery pressure was observed in 68.8% of patients (n = 51), whereas mild PHT was observed in 28.3% of patients (n = 21) and moderate PHT in 40.5% (n = 30). Decrease in pulmonary artery pressure following HD procedure performed using high-flux polysulfone membrane was significantly higher than the decrease observed following HD procedure performed using cellulose acetate membrane (p < 0.05). Significant decrease in pulmonary artery pressures was observed only after HD procedures performed using high-flux polysulfone membrane (p < 0.05). Ultrafiltered volume was only significantly correlated with the decrease in pulmonary artery pressure observed after HD procedure performed through high-flux polysulfone membrane (β = 0.411, p < 0.05). PHT seems to be prevalent among HD patients even in the absence of AV fistula and abnormal cardiac functions. Membrane composition seems to be important, which may overwhelm the improving effects of ultrafiltration.

Differences in the effects of Asian dust on pulmonary function between adult patients with asthma and those with asthma–chronic obstructive pulmonary disease overlap syndrome

PubMed Central

Watanabe, Masanari; Noma, Hisashi; Kurai, Jun; Sano, Hiroyuki; Ueda, Yasuto; Mikami, Masaaki; Yamamoto, Hiroyuki; Tokuyasu, Hirokazu; Kato, Kazuhiro; Konishi, Tatsuya; Tatsukawa, Toshiyuki; Shimizu, Eiji; Kitano, Hiroya

2016-01-01

Background Asian dust (AD) exposure exacerbates pulmonary dysfunction in patients with asthma. Asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS), characterized by coexisting symptoms of asthma and chronic obstructive pulmonary disease, is considered a separate disease entity. Previously, we investigated the effects of AD on pulmonary function in adult patients with asthma. Here, we present the findings of our further research on the differences in the effects of AD exposure on pulmonary function between patients with asthma alone and those with ACOS. Methods Between March and May 2012, we conducted a panel study wherein we monitored daily peak expiratory flow (PEF) values in 231 adult patients with asthma. These patients were divided into 190 patients with asthma alone and 41 patients with ACOS in this study. Daily AD particle levels were measured using light detection and ranging systems. Two heavy AD days (April 23 and 24) were determined according to the Japan Meteorological Agency definition. A linear mixed model was used to estimate the association between PEF and AD exposure. Results Increments in the interquartile range of AD particles (0.018 km−1) led to PEF changes of −0.50 L/min (95% confidence interval, −0.98 to −0.02) in patients with asthma alone and −0.11 L/min (−0.11 to 0.85) in patients with ACOS. The PEF changes after exposure to heavy AD were −2.21 L/min (−4.28 to −0.15) in patients with asthma alone and −2.76 L/min (−6.86 to 1.35) in patients with ACOS. In patients with asthma alone, the highest decrease in PEF values was observed on the heavy AD day, with a subsequent gradual increase over time. Conclusion Our results suggest that the effects of AD exposure on pulmonary function differ between patients with asthma alone and ACOS, with the former exhibiting a greater likelihood of decreased pulmonary function after AD exposure. PMID:26869784

Pre-operative optimisation of lung function

PubMed Central

Azhar, Naheed

2015-01-01

The anaesthetic management of patients with pre-existing pulmonary disease is a challenging task. It is associated with increased morbidity in the form of post-operative pulmonary complications. Pre-operative optimisation of lung function helps in reducing these complications. Patients are advised to stop smoking for a period of 4–6 weeks. This reduces airway reactivity, improves mucociliary function and decreases carboxy-haemoglobin. The widely used incentive spirometry may be useful only when combined with other respiratory muscle exercises. Volume-based inspiratory devices have the best results. Pharmacotherapy of asthma and chronic obstructive pulmonary disease must be optimised before considering the patient for elective surgery. Beta 2 agonists, inhaled corticosteroids and systemic corticosteroids, are the main drugs used for this and several drugs play an adjunctive role in medical therapy. A graded approach has been suggested to manage these patients for elective surgery with an aim to achieve optimal pulmonary function. PMID:26556913

Pulmonary function evaluation during and following Skylab space flights

NASA Technical Reports Server (NTRS)

Sawin, C. F.; Nicogossian, A. E.; Schachter, A. P.; Rummel, J. A.; Michel, E. L.

1974-01-01

Previous experience during the Apollo postflight exercise testing indicated no major changes in pulmonary function. Although pulmonary function has been studied in detail following exposure to hypoxic and hyperoxic environments, few studies have dealt with normoxic environments at reduced total pressure as encountered during the Skylab missions. Forced vital capacity was measured during the preflight and postflight periods of the Skylab 2 mission. Initial in-flight measurements of vital capacity were obtained during the last two weeks of the second manned mission (Skylab 3). Comprehensive pulmonary function screening was accomplished during the Skylab 4 mission. The primary measurements made during Skylab 4 testing included residual volume determination, closing volume, vital capacity, and forced vital capacity and its derivatives. In addition, comprehensive in-flight vital capacity measurements were made during the Skylab 4 mission. Vital capacity was decreased slightly during flight in all Skylab 4 crewmen. No major preflight to postflight changes were observed in the other parameters.

N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats

PubMed Central

2014-01-01

Background The outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function. Methods Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14–28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis. Results The treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71 ± 0.05 for MCT group to 0.50 ± 0.06 for MCT + NAC group, p < 0.05). Right ventricular function was also improved with NAC treatment associated with a significant decrease in cardiomyocyte hypertrophy (625 ± 69 vs. 439 ± 21 μm2 for MCT and MCT + NAC group respectively, p < 0.001) and heart fibrosis (14.1 ± 0.8 vs. 8.8 ± 0.1% for MCT and MCT + NAC group respectively, p < 0.001). Conclusions Through its immuno-modulatory and cardioprotective properties, NAC has beneficial effect on pulmonary vascular and right heart function in experimental PH. PMID:24929652

The Influence of Type 1 Diabetes Mellitus on Pulmonary Function and Exercise Capacity - Results from the Study of Health in Pomerania (SHIP).

PubMed

Stubbe, Beate; Schipf, Sabine; Schäper, Christoph; Felix, Stephan B; Steveling, Antje; Nauck, Matthias; Völzke, Henry; Wallaschofski, Henri; Friedrich, Nele; Ewert, Ralf; Ittermann, Till; Gläser, Sven

2017-01-01

Background: Diabetes mellitus Type 1 (T1DM) is associated with metabolic and microvascular diseases as part of a multi-organ and multi-systemic disorder. The dense network of capillary vessels in the lungs may change during the course of the development of microangiopathy. The connective tissue as well as alveoli may be subjected to non-enzymatic glycosylation of proteins which may in turn affect pulmonary function. Previous studies investigating lung function in patients with type 1 diabetes have only been performed on small numbers of patients. Our study is based on population data of the Study of Health in Pomerania (SHIP). Objective: To investigate the influence of metabolic control on pulmonary system function and to establish a decreased pulmonary system function as a late complication of T1DM in a population based setting. Methods: The study is a case matched study with multiple controls based on participants with T1DM (SHIP-DM-1, n=73) and non-diabetics (SHIP-1, n=292) from the population based study of Pomerania. Data on lung function and exercise performance stratified by age, sex, body mass index and smoking habits in participants with T1DM and without diabetes were matched. Results: Participants with T1DM showed a significantly lower total lung capacity, residual volume and forced vital capacity. The transfer factor for carbon monoxide, the maximum power output and oxygen uptake during exercise were significantly decreased in comparison to the general population without diabetes. Conclusion: The pattern of abnormal pulmonary function as observed in the present study with a reduction in lung volume parameters and reduced oxygen uptake in participants with T1DM suggests a restrictive type of lung disease caused by an intrinsic lung tissue derangement as well as pulmonary microangiopathy. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Pulmonary tolerance in man to continuous oxygen exposure at 3.0, 2.5, 2.0, and 1.5 ATA in Predictive Studies V

NASA Technical Reports Server (NTRS)

Clark, J. M.; Gelfand, R.; Flores, N. D.; Lambertsen, C. J.; Pisarello, J. B.

1987-01-01

Oxygen effects on pulmonary function were measured in normal, resting men who breathed oxygen continuously at 3.0, 2.5, 2.0, and 1.5 ATA to predefined limits of CNS, cardiac, or pulmonary tolerance. Rates of pulmonary symptom intensification and decrease in vital capacity (VC) increased progressively with elevation of inspired oxygen pressure. Although VC decrements occurred concurrently with symptoms, the lung volume changes became prominent when symptoms were still mild. The observed effects were consistent with the interpretation that small airway function is impaired more selectively by oxygen exposure at 3.0 and 2.5 ATA than by exposure at 2.0 and 1.5 ATA. Despite similar VC changes after oxygen exposure at 2.0 ATA for nearly 10 hr and exposure at 1.5 ATA for almost 18 hr, the 2.0 ATA exposure caused greater impairment of pulmonary function and required a longer recovery period.

Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the status of treatment.

PubMed

Khalil, Nasreen; O'Connor, Robert

2004-07-20

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary fibrotic lung disease. The diagnostic histological changes are called usual interstitial pneumonia and are characterized by histological temporal heterogeneity, whereby normal lung tissue is interspersed with interstitial fibrosis, honeycomb cysts and fibroblast foci. Pulmonary functions show restricted volumes and capacities, preserved flows and evidence of decreased gas exchange. High-resolution computed axial tomography demonstrates evidence of fibrosis and lung remodelling such as honeycomb cysts and traction bronchiectasis. There is no known effective treatment for IPF, but lung transplantation improves survival.

[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 function in adolescents with ataxia telangiectasia.

PubMed

McGrath-Morrow, Sharon; Lefton-Greif, Maureen; Rosquist, Karen; Crawford, Thomas; Kelly, Amber; Zeitlin, Pamela; Carson, Kathryn A; Lederman, Howard M

2008-01-01

Pulmonary complications are common in adolescents with ataxia telangiectasia (A-T), however objective measurements of lung function may be difficult to obtain because of underlying bulbar weakness, tremors, and difficulty coordinating voluntary respiratory maneuvers. To increase the reliability of pulmonary testing, minor adjustments were made to stabilize the head and to minimize leaks in the system. Fifteen A-T adolescents completed lung volume measurements by helium dilution. To assess for reproducibility of spirometry testing, 10 A-T adolescents performed spirometry on three separate occasions. Total lung capacity (TLC) was normal or just mildly decreased in 12/15 adolescents tested. TLC correlated positively with functional residual capacity (FRC), a measurement independent of patient effort (R2=0.71). The majority of individuals had residual volumes (RV) greater than 120% predicted (10/15) and slow vital capacities (VC) less than 70% predicted (9/15). By spirometry, force vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) values were reproducible in the 10 individuals who underwent testing on three separate occasions (R=0.97 and 0.96 respectively). Seven of the 10 adolescents had FEV1/FVC ratios>90%. Lung volume measurements from A-T adolescents revealed near normal TLC values with increased RV and decreased VC values. These findings indicate a decreased ability to expire to residual volume rather then a restrictive defect. Spirometry was also found to be reproducible in A-T adolescents suggesting that spirometry testing may be useful for tracking changes in pulmonary function over time in this population. Copyright (c) 2007 Wiley-Liss, Inc.

A systematic review of the role of vitamin insufficiencies and supplementation in COPD.

PubMed

Tsiligianni, Ioanna G; van der Molen, Thys

2010-12-06

Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD. The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms. Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy. A systematic literature review was performed on the association of vitamins and COPD. The role of vitamin supplements in COPD was then evaluated. The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function. High vitamin intake would probably reduce the annual decline of FEV1. There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function.

A neutrophil elastase inhibitor improves lung function during ex vivo lung perfusion.

PubMed

Harada, Masaaki; Oto, Takahiro; Otani, Shinji; Miyoshi, Kentaroh; Okada, Masanori; Iga, Norichika; Nishikawa, Hitoshi; Sugimoto, Seiichiro; Yamane, Masaomi; Miyoshi, Shinichiro

2015-12-01

Ex vivo lung perfusion (EVLP) has been used not only for graft evaluation but also for graft reconditioning prior to lung transplantation. Inflammatory cells such as neutrophils may cause additional graft injury during EVLP. Neutrophil elastase inhibitors protect lungs against neutrophil-induced lung injury, such as acute respiratory distress syndrome. This study aimed to investigate the effect of a neutrophil elastase inhibitor during EVLP. EVLP was performed for 4 h in bilateral pig lungs that had previously experienced warm ischemia for 2 h with or without a neutrophil elastase inhibitor (treated and control groups, respectively; n = 6). Following EVLP, the left lung was transplanted into a recipient pig, and this was followed by observation for 4 h. Pulmonary functions were observed both during EVLP and during the early post-transplant stage. During EVLP, decreases in neutrophil elastase levels (P < 0.001), the wet-dry weight ratio (P < 0.05), and pulmonary vascular resistance (P < 0.01) and increases in the PaO2/FiO2 ratio (P < 0.01) and pulmonary compliance (P < 0.05) were observed in the treated group. After transplantation, decreased pulmonary vascular resistance (P < 0.05) was observed in the treated group. A neutrophil elastase inhibitor attenuated the inflammatory response during EVLP and may decrease the incidence of lung reperfusion injury after transplantation.

Stereotactic body radiotherapy for second primary lung cancer and intra-parenchymal lung metastasis in patients previously treated with surgery: evaluation of indications and predictors of decreased respiratory function.

PubMed

Ishihara, Takeaki; Yamada, Kazunari; Harada, Aya; Yukiue, Haruhiro; Tanahashi, Masayuki; Niwa, Hiroshi; Matsui, Takashi; Yokomura, Koshi; Ejima, Yasuo; Sasaki, Ryohei

2018-05-03

The adaptation criteria for administration of stereotactic body radiotherapy (SBRT) to patients with lung cancer who previously underwent surgery and subsequently developed a second primary lung cancer (SPLC) or intra-parenchymal lung metastasis (IPLM) are controversial, unlike the criteria for repeat surgery. We aimed to evaluate the feasibility of SBRT for these patients. Factors associated with decreased respiratory function were also evaluated. Sixty-nine patients with 89 lesions who underwent SBRT between 2008 and 2017 were analyzed. Of these, 29 were diagnosed with SPLC while the remaining 40 had IPLM. The distribution of histological types was as follows: squamous cell carcinoma (n = 13 lesions); adenocarcinoma (n = 25); non-small cell carcinoma (n = 1); unknown histological type (n = 49). The prescribed doses to the planning target volume (PTV) were 50 Gy in five fractions for 85 lesions and 60 Gy in 10 fractions for four lesions at PTV mean. Over a median follow-up period of 55 months, the 4-year overall survival and local control rates were 50.3% and 87.6%, respectively. Six patients experienced grade 2 radiation pneumonitis and one experienced grade 3. Two patients experienced grade 5 pulmonary fibrosis. Decreased respiratory function was observed in 10 patients (15.1%). On multivariate analysis, the presence of pulmonary disease before SBRT was the only statistically significant factor associated with decreased respiratory function. SBRT is safe and feasible in patients with SPLC or IPLM previously treated surgically. Pre-existing pulmonary disease was a predictive factor for decreased respiratory function.

Variation of heat shock protein gene expression in the brain of cold-induced pulmonary hypertensive chickens.

PubMed

Hassanpour, H; Khosravi Alekoohi, Z; Madreseh, S; Bahadoran, S; Nasiri, L

2016-10-01

Quantitative real-time PCR was carried out to evaluate gene expression of heat shock proteins (HSP) (HSP27, HSP56, HSP60, HSP70, HSP90 and ubiquitin) in the brain (hindbrain, midbrain, forebrain) of chickens with cold-induced pulmonary hypertension. The ratio of the right ventricle to the total ventricle (index of pulmonary hypertension in chickens) was increased in the cold-induced pulmonary hypertensive chickens at 42 d of age compared with control. The HSP genes were expressed in the three parts of the brain in the two experimental groups. In the hindbrain of cold-induced pulmonary hypertensive chickens, the relative gene expression of HSP27, HSP60, HSP70 and HSP90 was decreased while gene expression of HSP56 and ubiquitin was increased compared with controls. In the midbrain of cold induced-pulmonary hypertensive chickens, the expression of HSP56, HSP60, HSP70 and ubiquitin genes was increased compared with controls while HSP27 and HSP90 were decreased. In the forebrain of cold induced-pulmonary hypertensive chickens, the expression of HSP56, HSP60, HSP70 and ubiquitin genes was increased while the expression of the HSP27 gene was decreased compared with controls. It is concluded that overexpression of HSPs in the forebrain and midbrain probably delays the pathological process of cold stress whereas diminished expression of HSP genes in the hindbrain may affect the normal function of brain centres in this area to exacerbate pulmonary hypertension.

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

Grain elevator workers show work-related pulmonary function changes and dose-effect relationships with dust exposure.

PubMed Central

Corey, P; Hutcheon, M; Broder, I; Mintz, S

1982-01-01

The purpose of this study was to determine whether grain handlers underwent work-related changes in their pulmonary function and, if so, to examine the dose-effect relationships with dust exposure. The pulmonary function of grain handlers was measured at the beginning and end of work shifts over a period of one week, during which their exposure to dust was measured daily. The results showed changes indicative of a within-day obstructive change, in addition to a small restrictive defect occurring over the course of a week. Civic outside labourers who were examined as a control group showed a similar within-week obstructive change without any associated restriction of lung volume. The data on the grain handlers were also used to examine the dose-effect relationships of dust exposure, both on baseline pulmonary function and on within-day changes in these measurements. The baseline flow rates of workers who did not wear a mask were found to vary inversely with their average exposure to respirable dust. In addition, the flow rates underwent a within-day decrease that varied directly with their corresponding exposure to respirable dust and was unrelated to mask wearing. The median of the slopes for this relationship indicated that 50% of the subjects had a decrease of at least 923 ml/s in the value of their Vmax50%VC for each 1 mg/m3 increase in the concentration of respirable dust. Non-respirable dust did not have a measurable effect either on the baseline or the within-day changes in pulmonary function. The acute changes were unaffected by age, duration of employment, or extent of smoking. PMID:7138793

The role of the indoor environment: Residential determinants of allergy, asthma and pulmonary function in children from a US-Mexico border community.

PubMed

Svendsen, Erik R; Gonzales, Melissa; Commodore, Adwoa

2018-03-01

The El Paso Children's Health Study examined environmental risk factors for allergy and asthma among fourth and fifth grade schoolchildren living in a major United States-Mexico border city. Complete questionnaire information was available for 5210 children, while adequate pulmonary function data were available for a subset of 1874. Herein we studied indoor environmental health risk factors for allergy and asthma. Several indoor environmental risk factors were associated with allergy and asthma. In particular, we found that ant and spider pest problems, pet dogs, fireplace heat, central air conditioning, humidifier use, and cooking with gas stoves were positively associated with both allergy and asthma prevalence. With regards to asthma severity, our analysis indicated that exposure to pet dogs increased monotonically with increasing asthma severity while the lack of any heat source and gas stove use for cooking decreased monotonically with increasing asthma severity. Lung function also decreased among children who lived in homes with reported cockroach pest problem in the past year without concurrent use of pesticides. These effects on pulmonary function were present even after excluding children with a current physician's diagnosis of asthma. Clinicians and public health professionals may need to look closely at the contribution of these indoor risk factors on pulmonary health and quality of life among susceptible populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of supplementary zinc on body mass index, pulmonary function and hospitalization in children with cystic fibrosis.

PubMed

Ataee, Pedram; Najafi, Mehri; Gharagozlou, Mohammad; Aflatounian, Majid; Mahmoudi, Maryam; Khodadad, Ahmad; Farahmand, Fatemeh; Motamed, Farzaneh; Fallahi, Glolam Hossein; Kalantari, Najmoddin; Soheili, Habib; Modarresi, Vajiheh; Modarresi, Mozhgan Sabbaghian; Rezaei, Nima

2014-01-01

Zinc deficiency, which is common in patients with cystic fibrosis (CF), can lead to several complications that may increase the number of hospital admissions in this group of patients. As supplementary zinc can prevent such complications, this study was performed to evaluate the effect of supplementary zinc on body mass index (BMI), forced expiratory volume in one second (FEV1) and number of hospitalizations in CF patients. In this study, 30 children with CF, who were referred to the Digestive Diseases Clinic of the Children's Medical Center in Tehran, were enrolled. Supplementary zinc of 2 mg/kg per day was administered to all patients. Serum level of zinc, alkaline phosphatase, and albumin as well as BMI, FEV1, and number of hospitalizations were compared before and after zinc administration. Height (p<0.001), weight (p<0.001) and BMI (p=0.001) were significantly increased after zinc, while the number of hospitalizations was significantly decreased (p=0.023). In contrast to patients with normal pulmonary function tests who received supplement therapy, BMI was not increased in those with abnormal pulmonary function after supplementary zinc. Supplementary zinc can increase BMI in CF patients, mostly in those with normal pulmonary function. While supplementary zinc may decrease the number of hospitalizations, other factors can also influence the hospitalization number.

The effects of levosimendan exposure on oxidant/antioxidant status and trace element levels in the pulmonary artery of rats.

PubMed

Ay, Yasin; Aydın, Cemalettin; Basel, Halil; Bektaş, Hava; Bülüt, Gülay; Inan, Bekir; Ay, Nuray Kahraman; Demir, Ismail

2013-06-01

We investigated both the effect of levosimendan and the role of oxidant/antioxidant status and trace element levels in the pulmonary artery of rats. Fourteen male Wistar albino rats were randomly divided into two groups of seven animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12 μg/kg) diluted in 10 ml 0.9 % NaCl was administered intraperitoneally to group 2. Animals of both groups were killed after 3 days, and their pulmonary arteries were harvested to determine changes in tissue oxidant/antioxidant status and trace element levels. The animals in both groups were killed 72 h after the levosimendan exposure treatment, and pulmonary arteries were harvested to determine levels of the lipid peroxidation product MDA and the antioxidant GSH as well as the decreased activity of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA levels increased in pulmonary artery tissues of rats after levosimendan administration. The GSH level decreased in the pulmonary artery of rats after levosimendan treatment. Co, Mn, Fe, Cd and Pb levels were significantly higher (P < 0.001) and Mg, Zn and Cu levels significantly lower (P < 0.001) in the levosimendan group compared to the control group. These results suggest that levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in the pulmonary artery of levosimendan-treated rats. It also caused a decrease or increase in the levels of many minerals in the pulmonary artery, which is an undesirable condition for normal pharmacological function.

PULMONARY CIRCULATION AT EXERCISE

PubMed Central

NAEIJE, R; CHESLER, N

2012-01-01

The pulmonary circulation is a high flow and low pressure circuit, with an average resistance of 1 mmHg.min.L−1 in young adults, increasing to 2.5 mmHg.min.L−1 over 4–6 decades of life. Pulmonary vascular mechanics at exercise are best described by distensible models. Exercise does not appear to affect the time constant of the pulmonary circulation or the longitudinal distribution of resistances. Very high flows are associated with high capillary pressures, up to a 20–25 mmHg threshold associated with interstitial lung edema and altered ventilation/perfusion relationships. Pulmonary artery pressures of 40–50 mmHg, which can be achieved at maximal exercise, may correspond to the extreme of tolerable right ventricular afterload. Distension of capillaries that decrease resistance may be of adaptative value during exercise, but this is limited by hypoxemia from altered diffusion/perfusion relationships. Exercise in hypoxia is associated with higher pulmonary vascular pressures and lower maximal cardiac output, with increased likelihood of right ventricular function limitation and altered gas exchange by interstitial lung edema. Pharmacological interventions aimed at the reduction of pulmonary vascular tone have little effect on pulmonary vascular pressure-flow relationships in normoxia, but may decrease resistance in hypoxia, unloading the right ventricle and thereby improving exercise capacity. Exercise in patients with pulmonary hypertension is associated with sharp increases in pulmonary artery pressure and a right ventricular limitation of aerobic capacity. Exercise stress testing to determine multipoint pulmonary vascular pressures-flow relationships may uncover early stage pulmonary vascular disease. PMID:23105961

One year efficacy and safety of oral sildenafil treatment in severe pulmonary hypertension.

PubMed

Samarzija, Miroslav; Zuljević, Ervin; Jakopović, Marko; Sever, Branko; Knezević, Aleksandar; Dumija, Zeljko; Vidjak, Vinko; Samija, Mirko

2009-09-01

Severe pulmonary hypertension is a progressive disease which leads to limitations of functional status and poor survival. We evaluated efficacy and safety of a short (3 months) and a long term (12 months) sildenafil treatment in patients with severe pulmonary hypertension. We treated 12 patients with pulmonary hypertension with oral sildenafil. Patients were followed at three time points, at baseline, and after 3 and 12 months of treatment. Primary end point was improvement in functional exercise capacity assesed by 6-minute walk test, and secondary end points were changes in right ventricle hemodynamics. We found significant improvement in 6-minute walk test distance from 357 +/- 193 m at baseline to 431 +/- 179 m after three months and further improvement to 501 +/- 159 m after 12 months (p < 0.01); decrease in right ventricule pressure from 107 +/- 42 mmHg at baseline to 87 +/- 32 mmHg after 12 months (p < 0.01); and, decrease in right ventricule diameter from 3.2 +/- 1.1 cm to 2.76 +/- 0.86 cm after twelve months (p < 0.01). Drug-related adverse events were mild and transient in our group of patients. Long-term (12 months) sildenafil treatment is effective and safe in our patients with idiopathic and chronic thrombo-embolic pulmonary hypertension.

Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension

PubMed Central

Christou, Helen; Reslan, Ossama M.; Mam, Virak; Tanbe, Alain F.; Vitali, Sally H.; Touma, Marlin; Arons, Elena; Mitsialis, S. Alex; Kourembanas, Stella

2012-01-01

Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening, and enhances pulmonary vascular responsiveness to vasoconstrictor and vasodilator stimuli. Together with our finding that acidosis decreases VSMC proliferation, the results are consistent with the possibility that nonhypercapnic acidosis promotes differentiation of pulmonary VSMCs to a more contractile phenotype, which may enhance the effectiveness of vasodilator therapies in PH. PMID:22287610

Circulating miRNAs in Pediatric Pulmonary Hypertension Show Promise as Biomarkers of Vascular Function

PubMed Central

Sucharov, Carmen C.; Truong, Uyen; Dunning, Jamie; Ivy, Dunbar; Miyamoto, Shelley; Shandas, Robin

2017-01-01

Background/Objectives The objective of this study was to evaluate the utility of circulating miRNAs as biomarkers of vascular function in pediatric pulmonary hypertension. Method Fourteen pediatric pulmonary arterial hypertension patients underwent simultaneous right heart catheterization (RHC) and blood biochemical analysis. Univariate and stepwise multivariate linear regression was used to identify and correlate measures of reactive and resistive afterload with circulating miRNA levels. Furthermore, circulating miRNA candidates that classified patients according to a 20% decrease in resistive afterload in response to oxygen (O2) or inhaled nitric oxide (iNO) were identified using receiver-operating curves. Results Thirty-two circulating miRNAs correlated with the pulmonary vascular resistance index (PVRi), pulmonary arterial distensibility, and PVRi decrease in response to O2 and/or iNO. Multivariate models, combining the predictive capability of multiple promising miRNA candidates, revealed a good correlation with resistive (r = 0.97, P2−tailed < 0.0001) and reactive (r = 0.86, P2−tailed < 0.005) afterloads. Bland-Altman plots showed that 95% of the differences between multivariate models and RHC would fall within 0.13 (mmHg−min/L)m2 and 0.0085/mmHg for resistive and reactive afterloads, respectively. Circulating miR-663 proved to be a good classifier for vascular responsiveness to acute O2 and iNO challenges. Conclusion This study suggests that circulating miRNAs may be biomarkers to phenotype vascular function in pediatric PAH. PMID:28819545

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

Recovery from welding-fume-exposure-induced lung fibrosis and pulmonary function changes in sprague dawley rats.

PubMed

Sung, Jae Hyuck; Choi, Byung-Gil; Maeng, Seung-Hee; Kim, Soo-Jin; Chung, Yong Hyun; Han, Jeong Hee; Song, Kyung Seuk; Lee, Yong Hwan; Cho, Yong Bong; Cho, Myung-Haing; Kim, Kwang Jong; Hyun, Jin Suk; Yu, Il Je

2004-12-01

Welder's pneumoconiosis has generally been determined as benign based on the absence of pulmonary function abnormalities in welders with marked radiographic abnormalities. Yet, there have also been several reports on welders with respiratory symptoms, indicating lung function impairment, X-ray abnormalities, and extensive fibrosis. Accordingly, this study attempted to investigate the inflammatory responses and pulmonary function changes in rats during a 60-day welding-fume-inhalation exposure period to elucidate the process of fibrosis. The rats were exposed to manual metal-arc stainless-steel welding fumes (MMA-SS) with total suspended particulate concentrations of 64.8 +/- 0.9 (low dose) and 107.8 +/- 2.6 mg/m3 (high dose) for 2 h per day in an inhalation chamber for 60 days. Animals were sacrificed after the initial 2-h exposure and after 15, 30, and 60 days, and the pulmonary function was also measured every week after the daily exposure. Elevated cellular differential counts were also measured in the acellular bronchoalveolar lavage fluid of the rats exposed to the MMA-SS fumes for 60 days. Among the pulmonary function test parameters, only the tidal volume showed a statistically significant and dose-dependent decrease after 35 to 60 days of MMA-SS welding-fume exposure. When the rats exposed to the welding fumes were left for 60 days to recover their lung function and cellular differentiation, recovery was observed in both the high and low-dose rats exposed up to 30 days, resulting in the disappearance of inflammatory cells and restoration of the tidal volume. The rats exposed for 60 days at the low dose also recovered from the inflammation and tidal volume loss, yet the rats exposed for 60 days at the high dose did not fully recover even after a 60-day recovery period. Therefore, when taken together, the results of the current study suggest that a decrease in the tidal volume could be used as an early indicator of pulmonary fibrosis induced by welding-fume exposure in Sprague Dawley rats, and fibrosis would seem to be preventable if the exposure is short-term and moderate.

Lung function, transfusion, pulmonary capillary blood volume and sickle cell disease.

PubMed

Lunt, Alan; McGhee, Emily; Robinson, Polly; Rees, David; Height, Susan; Greenough, Anne

2016-02-01

Lung function abnormalities occur in children with sickle cell disease (SCD) and may be associated with elevated pulmonary blood volume. To investigate that association, we determined whether blood transfusion in SCD children acutely increased pulmonary capillary blood volume (PCBV) and increased respiratory system resistance (Rrs5). Measurements of Rrs5 and spirometry were made before and after blood transfusion in 18 children, median age 14.2 (6.6-18.5) years. Diffusing capacity for carbon monoxide and nitric oxide were assessed to calculate the PCBV. Post transfusion, the median Rrs5 had increased from 127.4 to 141.3% predicted (p<0.0001) and pulmonary capillary blood volume from 39.7 to 64.1 ml/m2 (p<0.0001); forced expiratory volume in one second (p=0.0056) and vital capacity (p=0.0008) decreased. The increase in Rrs5 correlated with the increase in PCBV (r=0.50, p=0.0493). Increased pulmonary capillary blood volume may at least partially explain the lung function abnormalities in SCD children. Copyright © 2015 Elsevier B.V. All rights reserved.

[System analytical approach of lung function and hemodynamics].

PubMed

Naszlady, Attila; Kiss, Lajos

2009-02-15

The authors critically analyse the traditional views in physiology and complete them with new statements based on computer model simulations of lung function and of hemodynamics. Conclusions are derived for the clinical practice as follows: the four-dimensional function curves are similar in both systems; there is a "waterfall" zone in the pulmonary blood perfusion; the various time constants of pulmonary regions can modify the blood gas values; pulmonary capillary pressure is equal to pulmonary arterial diastole pressure; heart is not a pressure pump, but a flow source; ventricles are loaded by the input impedance of the arterial systems and not by the total vascular (ohmlike) resistance; optimum heart rate in rest depends on the length of the aorta; this law of heart rate, based on the principle of resonance is valid along the mammalian allometric line; tachycardia decreases the input impedance; using positive end expiratory pressure respirators the blood gas of pulmonary artery should be followed; coronary circulation should be assessed in beat per milliliter, the milliliter per minute may be false. These statements are compared to related references.

Heparin induced alterations in clearance and distribution of blood-borne microparticles following operative trauma.

PubMed

Saba, T M; Antikatzides, T G

1979-04-01

The influence of systemic heparin administration on the vascular clearance and tissue distribution of blood-borne microparticles was evaluated in normal rats and rats after operation (laparotomy plus intestinal manipulation) utilizing an (131)I- colloid which is phagocytized by the reticuloendothelial system (RES). Intravenous heparin administration (100 USP/100g body weight) into normal animals three minutes prior to colloid injection (50 mg/lOOg) induced a significant increase in pulmonary localization of the microparticles as compared to nonheparinized control rats, while hepatic and splenic uptake were decreased. Surgical trauma decreased hepatic RE uptake and increased pulmonary localization of the microparticles when injected systemically at 60 minutes postsurgery. Heparin administration 60 minutes after surgery and three minutes prior to colloid injection, magnified the increased pulmonary localization response with an associated further depression of the RES. The ability of heparin to alter both RE clearance function and lung localization of microparticles was dose dependent and a function of the interval between heparin administration and systemic particulate infusion. Thus, low dose heparin administration was capable of stimulating RE activity while heparin in doses of excess of 50 USP units/lOOg body weight decreased RE function. These findings suggest that the functional state of the hepatic RE system can be greatly affected in a dose-dependent manner by systemic heparin administration which may influence distribution of blood-borne microparticles.

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.

Pulmonary function in men after short-term exposure to ozone

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

Hazucha, M.; Silverman, F.; Parent, C.

1973-01-01

Volunteers were exposed to 0.37 or 0.75 ppm ozone for 2 hr in environmental chamber while doing light exercise and resting intermittently. Slight discomfort resulted: dry throat, cough, chest tightness. Reduction in flow rates, FVC, and FEV at 1 and 2 hr was noted. Thus, ozone reached terminal bronchioles and impaired their function. Reduction in pulmonary measurements of maximum flow results were probably due to decreased lung elastic recoil, increased airway resistence, and small airway obstruction.

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.

[The adrenergic mechanisms are involved in the pulmonary hemodynamics changes following experimental myocardial ischemia in rabbits].

PubMed

Evlakhov, V I; Poiasov, I Z

2012-05-01

In acute experiments in anesthetized rabbits the changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied in control animals and after the blockade of alpha-adrenoreceptors by phentolamine or N-cholinoreceptors of autonomic ganglia by hexamethonium. Following myocardial ischemia in control animals the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance was elevated not significantly, the cardiac output decreased more than pulmonary artery flow. Following myocardial ischemia after the blockade of alpha-adrenoreceptors the pulmonary artery flow and cardiac output decreased in the same level and the pulmonary vascular resistance was decreased. In these conditions the pulmonary artery pressure decreased more than in control animals, meanwhile the pulmonary artery flow was decreased in the same level as in the last case. Following myocardial ischemia after the blockade of N-cholinoreceptors the pulmonary hemodynamics changes were the same as they were following myocardial ischemia in the control rabbits, the cardiac output decreased more than pulmonary artery flow. The disbalance of the cardiac output and pulmonary artery flow changes in the case of myocardial ischemia was caused by the pulmonary vessel reactions following activations of the humoral adrenergic mechanisms.

Cigarette smoking and pulmonary diffusion defects in rheumatoid arthritis.

PubMed

Westedt, M L; Hazes, J M; Breedveld, F C; Sterk, P J; Dijkman, J H

1998-01-01

The pathogenesis of lung disease in rheumatoid arthritis (RA) has still to be defined. Risk factors associated with lung involvement in RA were investigated by means of pulmonary function studies in 40 RA patients without apparent lung disease. A decreased carbon monoxide (CO) diffusion capacity indicative of interstitial lung disease (ILD) was the main pulmonary function defect found in the first 20 patients. The occurrence was associated with current cigarette smoking. This association was confirmed in a case control study performed subsequently. These data suggest that ILD in RA is stimulated by smoking and provide an additional argument that modification of smoking behaviour in RA patients might lead to less severe complications.

Decreased apelin and apelin-receptor expression in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.

PubMed

Hofmann, Alejandro D; Friedmacher, Florian; Takahashi, Hiromizu; Hunziker, Manuela; Gosemann, Jan-Hendrik; Puri, Prem

2014-02-01

The high morbidity and mortality in congenital diaphragmatic hernia (CDH) are attributed to severe pulmonary hypoplasia and persistent pulmonary hypertension (PH). PH is characterized by structural changes in pulmonary arteries, resulting in adventitial and medial thickness. These effects are triggered by abnormal apoptosis and proliferation of pulmonary vascular endothelial and smooth muscle cells (SMCs). Apelin (APLN), a target gene of bone morphogenic protein receptor 2 (BMPR2), is known to play an important and manifold role in regulating pulmonary homeostasis promoting endothelial cell (EC) survival, proliferation and migration. In addition to these autocrine effects of apelin, it displays a paracrine function attenuating the response of pulmonary SMCs to growth factors and promoting apoptosis. Apelin exerts its effect via its G-protein-coupled receptor (APLNR) and is solely expressed by pulmonary vascular EC, whereas APLNR is co-localized in pulmonary ECs and SMCs. Dysfunction of BMPR2 and downstream signalling have been shown to disturb the crucial balance of proliferation of SMCs contributing to the pathogenesis of human and experimentally induced PH. We designed this study to investigate the hypothesis that apelin and APLNR signalling are disrupted in the pulmonary vasculature of rats in nitrofen-induced CDH. Pregnant rats were exposed to nitrofen or vehicle on D9 of gestation. Foetuses were sacrificed on D21 and divided into nitrofen and control group (n = 32). Pulmonary RNA was extracted and mRNA levels of APLN and APLNR were determined by quantitative real-time PCR. Protein expression of apelin and APLNR was investigated by western blotting. Confocal immunofluorescence double staining for apelin, APLNR and SMCs were performed. Relative mRNA level of APLN and APLNR were significantly decreased in the CDH group compared to control lungs. Western blotting and confocal microscopy confirmed the qRT-PCR results showing decreased pulmonary protein expression of apelin and APLNR in lungs of nitrofen-exposed foetuses compared to controls. This study provides striking evidence of markedly decreased gene and protein expression of apelin and its receptor APLNR in the pulmonary vasculature of nitrofen-induced CDH. The disruption of the apelin-APLNR signalling axis in the pulmonary vasculature may lead to extensive vascular remodelling and contribute to PPH in the nitrofen-induced CDH model.

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.

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.

Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke.

PubMed

Wolf, Lisa; Herr, Christian; Niederstraßer, Julia; Beisswenger, Christoph; Bals, Robert

2017-01-01

The receptor for advanced glycation endproducts (RAGE) is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/-) mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased respiratory system elastance and increased concentrations of serum protein albumin in bronchoalveolar lavage fluids. Pulmonary expression of RAGE was mainly localized on alveolar epithelial cells and alveolar macrophages. Primary murine alveolar epithelial cells isolated from RAGE-/- mice revealed an altered differentiation and defective barrier formation under in vitro conditions. Stimulation of interferone-y (IFNy)-activated alveolar macrophages deficient for RAGE with Toll-like receptor (TLR) ligands resulted in significantly decreased release of proinflammatory cytokines and chemokines. Exposure to chronic cigarette smoke did not affect emphysema-like changes in lung parenchyma in RAGE-/- mice. Acute cigarette smoke exposure revealed a modified inflammatory response in RAGE-/- mice that was characterized by an influx of macrophages and a decreased keratinocyte-derived chemokine (KC) release. Our data suggest that RAGE regulates the differentiation of alveolar epithelial cells and impacts on the development and maintenance of pulmonary structure. In cigarette smoke-induced lung pathology, RAGE mediates inflammation that contributes to lung damage.

Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease.

PubMed

Klar, Joakim; Blomstrand, Peter; Brunmark, Charlott; Badhai, Jitendra; Håkansson, Hanna Falk; Brange, Charlotte Sollie; Bergendal, Birgitta; Dahl, Niklas

2011-10-01

Genetic factors influencing lung function may predispose to chronic obstructive pulmonary disease (COPD). The fibroblast growth factor 10 (FGF10) signalling pathway is critical for lung development and lung epithelial renewal. The hypothesis behind this study was that constitutive FGF10 insufficiency may lead to pulmonary disorder. Therefore investigation of the pulmonary functions of patients heterozygous for loss of function mutations in the FGF10 gene was performed. The spirometric measures of lung function from patients and non-carrier siblings were compared and both groups were related to matched reference data for normal human lung function. The patients show a significant decrease in lung function parameters when compared to control values. The average FEV1/IVC quota (FEV1%) for the patients is 0.65 (80% of predicted) and reversibility test using Terbutalin resulted in a 3.7% increase in FEV1. Patients with FGF10 haploinsufficiency have lung function parameters indicating COPD. A modest response to Terbutalin confirms an irreversible obstructive lung disease. These findings support the idea that genetic variants affecting the FGF10 signalling pathway are important determinants of lung function that may ultimately contribute to COPD. Specifically, the results show that FGF10 haploinsufficiency affects lung function measures providing a model for a dosage sensitive effect of FGF10 in the development of COPD.

Pulmonary Function and Survival in Idiopathic vs Secondary Usual Interstitial Pneumonia

PubMed Central

Strand, Matthew J.; Sprunger, David; Cosgrove, Gregory P.; Fernandez-Perez, Evans R.; Frankel, Stephen K.; Huie, Tristan J.; Olson, Amy L.; Solomon, Joshua; Brown, Kevin K.

2014-01-01

BACKGROUND: The usual interstitial pneumonia (UIP) pattern of lung injury may occur in the setting of connective tissue disease (CTD), but it is most commonly found in the absence of a known cause, in the clinical context of idiopathic pulmonary fibrosis (IPF). Our objective was to observe and compare longitudinal changes in pulmonary function and survival between patients with biopsy-proven UIP found in the clinical context of either CTD or IPF. METHODS: We used longitudinal data analytic models to compare groups (IPF [n = 321] and CTD-UIP [n = 56]) on % predicted FVC (FVC %) or % predicted diffusing capacity of the lung for carbon monoxide (Dlco %), and we used both unadjusted and multivariable techniques to compare survival between these groups. RESULTS: There were no significant differences between groups in longitudinal changes in FVC % or Dlco % up to diagnosis, or from diagnosis to 10 years beyond (over which time, the mean decrease in FVC % per year [95% CI] was 4.1 [3.4, 4.9] for IPF and 3.5 [1.8, 5.1] for CTD-UIP, P = .49 for difference; and the mean decrease in Dlco % per year was 4.7 [4.0, 5.3] for IPF and 4.3 [3.0, 5.6] for CTD-UIP, P = .60 for difference). Despite the lack of differences in pulmonary function, subjects with IPF had worse survival in unadjusted (log-rank P = .003) and certain multivariable analyses. CONCLUSIONS: Despite no significant differences in changes in pulmonary function over time, patients with CTD-UIP (at least those with certain classifiable CTDs) live longer than patients with IPF—an observation that we suspect is due to an increased rate of mortal acute exacerbations in patients with IPF. PMID:24700149

A systematic review of the role of vitamin insufficiencies and supplementation in COPD

PubMed Central

2010-01-01

Background Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD. The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms. Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy. Methods A systematic literature review was performed on the association of vitamins and COPD. The role of vitamin supplements in COPD was then evaluated. Conclusions The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function. High vitamin intake would probably reduce the annual decline of FEV1. There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function. PMID:21134250

[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.

The natural history of cardiac and pulmonary function decline in patients with duchenne muscular dystrophy.

PubMed

Roberto, Rolando; Fritz, Anto; Hagar, Yolanda; Boice, Braden; Skalsky, Andrew; Hwang, Hosun; Beckett, Laurel; McDonald, Craig; Gupta, Munish

2011-07-01

Retrospective review of scoliosis progression, pulmonary and cardiac function in a series of patients with Duchenne Muscular Dystrophy (DMD). To determine whether operative treatment of scoliosis decreases the rate of pulmonary function loss in patients with DMD. It is generally accepted that surgical intervention should be undertaken in DMD scoliosis once curve sizes reach 35° to allow intervention before critical respiratory decline has occurred. There are conflicting reports, however, regarding the effect of scoliosis stabilization on the rate of pulmonary function decline when compared to nonoperative cohorts. We reviewed spinal radiographs, echocardiograms, and spirometry, hospital, and operative records of all patients seen at our tertiary referral center from July 1, 1992 to June 1, 2007. Data were recorded to Microsoft Excel (Microsoft, Redmond, WA) and analyzed with SAS (SAS Institute, Cary, NC) and R statistical processing software (www.r-project.org). The percent predicted forced vital capacity (PPFVC) decreased 5% per year before operation. The mean PPFVC was 54% (SD = 21%) before operation with a mean postoperative PPFVC of 43% (SD = 14%). Surgical treatment was associated with a 12% decline in PPFVC independent of other treatment variables. PPFVC after operation declined at a rate of 1% per year and while this rate was lower, it was not significantly different than the rate of decline present before operation (P = 0.18). Cardiac function as measured by left ventricular fractional shortening declined at a rate of 1% per year with most individuals exhibiting a left ventricular fractional shortening rate of more than 30 before operation. Operative treatment of scoliosis in DMD using the Luque Galveston method was associated with a reduction of forced vital capacity related to operation. The rate of pulmonary function decline after operation was not significantly reduced when compared with the rate of preoperative forced vital capacity decline.

Influenza Vaccination Coverage Rate according to the Pulmonary Function of Korean Adults Aged 40 Years and Over: Analysis of the Fifth Korean National Health and Nutrition Examination Survey

PubMed Central

2016-01-01

Influenza vaccination is an effective strategy to reduce morbidity and mortality, particularly for those who have decreased lung functions. This study was to identify the factors that affect vaccination coverage according to the results of pulmonary function tests depending on the age. In this cross-sectional study, data were obtained from 3,224 adults over the age of 40 who participated in the fifth National Health and Nutrition Examination Survey and underwent pulmonary function testing in 2012. To identify the factors that affect vaccination rate, logistic regression analysis was conducted after dividing the subjects into two groups based on the age of 65. Influenza vaccination coverage of the entire subjects was 45.2%, and 76.8% for those aged 65 and over. The group with abnormal pulmonary function had a higher vaccination rate than the normal group, but any pulmonary dysfunction or history of COPD did not affect the vaccination coverage in the multivariate analysis. The subjects who were 40-64 years-old had higher vaccination coverage when they were less educated or with restricted activity level, received health screenings, and had chronic diseases. Those aged 65 and over had significantly higher vaccination coverage only when they received regular health screenings. Any pulmonary dysfunction or having COPD showed no significant correlation with the vaccination coverage in the Korean adult population. PMID:27134491

Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies.

PubMed

Yadava, Koshika; Pattaroni, Céline; Sichelstiel, Anke K; Trompette, Aurélien; Gollwitzer, Eva S; Salami, Olawale; von Garnier, Christophe; Nicod, Laurent P; Marsland, Benjamin J

2016-05-01

Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease (COPD). Whether there is a causal relationship between these changes and disease progression remains unknown. To investigate the link between an altered microbiota and disease, we used a murine model of chronic lung inflammation that is characterized by key pathological features found in COPD and compared responses in specific pathogen-free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic). Mice were challenged with LPS/elastase intranasally over 4 weeks, resulting in a chronically inflamed and damaged lung. The ensuing cellular infiltration, histological damage, and decline in lung function were quantified. Similar to human disease, the composition of the pulmonary microbiota was altered in diseased animals. We found that the microbiota richness and diversity were decreased in LPS/elastase-treated mice, with an increased representation of the genera Pseudomonas and Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted, or devoid, of microbiota exhibited an improvement in lung function, reduced inflammation, and lymphoid neogenesis. The absence of microbial cues markedly decreased the production of IL-17A, whereas intranasal transfer of fluid enriched with the pulmonary microbiota isolated from diseased mice enhanced IL-17A production in the lungs of antibiotic-treated or axenic recipients. Finally, in mice harboring a microbiota, neutralizing IL-17A dampened inflammation and restored lung function. Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.

Ambient polycyclic aromatic hydrocarbons and pulmonary function in children

PubMed Central

Padula, Amy M.; Balmes, John R.; Eisen, Ellen A.; Mann, Jennifer; Noth, Elizabeth M.; Lurmann, Frederick W.; Pratt, Boriana; Tager, Ira B.; Nadeau, Kari; Hammond, S. Katharine

2014-01-01

Few studies have examined the relationship between ambient polycyclic aromatic hydrocarbons (PAHs) and pulmonary function in children. Major sources include vehicular emissions, home heating, wildland fires, agricultural burning, and power plants. PAHs are an important component of fine particulate matter that has been linked to respiratory health. This cross-sectional study examines the relationship between estimated individual exposures to the sum of PAHs with 4, 5, or 6 rings (PAH456) and pulmonary function tests (forced expiratory volume in one second (FEV1) and forced expiratory flow between 25% and 75% of vital capacity) in asthmatic and non-asthmatic children. We applied land-use regression to estimate individual exposures to ambient PAHs for averaging periods ranging from 1 week to 1 year. We used linear regression to estimate the relationship between exposure to PAH456 with pre- and postbronchodilator pulmonary function tests in children in Fresno, California (N =297). Among non-asthmatics, there was a statistically significant association between PAH456 during the previous 3 months, 6 months, and 1 year and postbronchodilator FEV1. The magnitude of the association increased with the length of the averaging period ranging from 60 to 110 ml decrease in FEV1 for each 1 ng/m3 increase in PAH456. There were no associations with PAH456 observed among asthmatic children. We identified an association between annual PAHs and chronic pulmonary function in children without asthma. Additional studies are needed to further explore the association between exposure to PAHs and pulmonary function, especially with regard to differential effects between asthmatic and non-asthmatic children. PMID:24938508

Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four species with different lung structures and pulmonary blood pressures.

PubMed

Skovgaard, Nini; Abe, Augusto S; Andrade, Denis V; Wang, Tobias

2005-11-01

Low O2 levels in the lungs of birds and mammals cause constriction of the pulmonary vasculature that elevates resistance to pulmonary blood flow and increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction (HPV) diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts and is considered important for the local matching of ventilation to blood perfusion. In the present study, the effects of acute hypoxia on pulmonary and systemic blood flows and pressures were measured in four species of anesthetized reptiles with diverse lung structures and heart morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman latirostris), rattlesnakes (Crotalus durissus), and tegu lizards (Tupinambis merianae). As previously shown in turtles, hypoxia causes a reversible constriction of the pulmonary vasculature in varanids and caimans, decreasing pulmonary vascular conductance by 37 and 31%, respectively. These three species possess complex multicameral lungs, and it is likely that HPV would aid to secure ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have structurally simple lungs where local ventilation-perfusion inhomogeneities are less likely to occur. However, tegu lizards, which also have simple unicameral lungs, did exhibit HPV, decreasing pulmonary vascular conductance by 32%, albeit at a lower threshold than varanids and caimans (6.2 kPa oxygen in inspired air vs. 8.2 and 13.9 kPa, respectively). Although these observations suggest that HPV is more pronounced in species with complex lungs and functionally divided hearts, it is also clear that other components are involved.

Diffusing capacity and forced vital capacity in 5,003 asbestos-exposed workers: relationships to interstitial fibrosis (ILO profusion score) and pleural thickening.

PubMed

Miller, Albert; Warshaw, Raphael; Nezamis, James

2013-12-01

Asbestosis is an interstitial lung disease whose radiographic severity has long been graded by the International Labour Office (ILO) profusion score. Its effect on pulmonary function is further impacted by asbestos related pleural thickening. This report aims to describe the relationships between radiographic grading of interstitial and pleural fibrosis and a key test of pulmonary function, the diffusing capacity, which measures gas exchange and has rarely been assessed in large groups, and to confirm the relationship to an independent test of pulmonary function, the vital capacity, which measures a mechanical property of the lungs. The data were derived from a survey during the period 1997-2004 of 5,003 workers (all white males) exposed to asbestos in various trades. Tests included chest radiographs read by a certified expert ("B") reader, forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLco). Cigarette smoking was adjusted for in the predictive equation for DLCO . Workers were evaluated at a mobile facility at work sites in four southern states. Both diffusing capacity and vital capacity were negatively correlated with profusion score over the full spectrum of radiographic severity. ILO profusion scores 0/1 (conventionally classified as normal) and 1/0 (conventionally classified as abnormal) were associated with similar diffusing capacity and vital capacity values. The highest profusion scores were associated with a greater proportionate decrease in diffusing capacity than in FVC. Both tests showed an effect of pleural fibrosis. Both radiographic severity graded by the profusion score and pleural thickening are correlated with two independent measures of pulmonary function. FVC (which had been reported in smaller work forces) and DLCO (which has not been reported). Both measures show a decrease from normal to intermediate (0/1, 1/0) scores and a further decrease with greater scores, demonstrating the consistency of radiographic and functional assessments. © 2013 Wiley Periodicals, Inc.

Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

NASA Astrophysics Data System (ADS)

Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

2004-04-01

To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

Decreased pulmonary c-Cbl expression and tyrosine phosphorylation in the nitrofen-induced rat model of congenital diaphragmatic hernia.

PubMed

Friedmacher, Florian; Gosemann, Jan-Hendrik; Takahashi, Hiromizu; Corcionivoschi, Nicolae; Puri, Prem

2013-01-01

The high morbidity of newborn infants with congenital diaphragmatic hernia (CDH) is attributed to pulmonary hypoplasia (PH), which is characterized by a failure of alveolar development. The nitrofen-induced CDH model has been widely used to investigate the pathogenesis of PH in CDH. It has previously been shown that the fibroblast growth factor receptor (FGFR) pathway, which is essential for a proper lung development, is disrupted during late gestation of nitrofen-induced CDH. Casitas B-lineage lymphoma (c-Cbl) proteins are known regulators of signal transduction through FGFRs, indicating their important role during alveolarization in developing lungs. Furthermore, it has been demonstrated that tyrosine phosphorylation of c-Cbl proteins has a pivotal role for their physiological function and activity during fetal lung development. We designed this study to test the hypothesis that pulmonary c-Cbl expression and tyrosine phosphorylation status are decreased in the nitrofen-induced CDH model. Timed-pregnant rats received either 100 mg nitrofen or vehicle on gestation day 9 (D9). Fetuses were harvested on D18 and D21, and lungs were divided into two groups: control and hypoplastic lungs with CDH (CDH(+)) (n = 10 at each time-point, respectively). Pulmonary gene expression levels of c-Cbl were analyzed by quantitative real-time polymerase chain reaction. Western blotting combined with densitometry analysis was used for semi-quantification of protein levels of pulmonary c-Cbl and tyrosine phosphorylation status. Confocal-immunofluorescence staining was performed to evaluate c-Cbl protein expression and distribution. Relative mRNA expression levels of pulmonary c-Cbl were significantly decreased in CDH(+) on D18 and D21 compared to controls. Western blotting showed markedly decreased protein levels of pulmonary c-Cbl and tyrosine phosphorylation status in CDH(+) on D18 and D21. Confocal-immunofluorescence analysis confirmed decreased c-Cbl expression in CDH(+) on D18 and D21 mainly in the distal alveolar epithelium compared to controls. Decreased pulmonary c-Cbl gene and protein expression accompanied by a decreased tyrosine phosphorylation status during the late stages of fetal lung development may result in reduced c-Cbl activity, and thus interfere with the FGFR-mediated alveolarization in the nitrofen-induced CDH model.

Echocardiographic assessment with right ventricular function improvement following ultrasound-accelerated catheter-directed thrombolytic therapy in submassive pulmonary embolism.

PubMed

Doheny, Charles; Gonzalez, Lorena; Duchman, Stanley M; Varon, Joseph; Bechara, Carlos F; Cheung, Mathew; Lin, Peter H

2018-06-01

Introduction The objective of this study was to evaluate the efficacy of ultrasound-accelerated catheter-directed thrombolytic therapy in patients with submassive pulmonary embolism. Methods Clinical records of 46 patients with submassive pulmonary embolism who underwent ultrasound-accelerated catheter-directed pulmonary thrombolysis using tissue plasminogen activator, from 2007 to 2017, were analyzed. All patients experienced clinical symptoms with computed tomography evidence of pulmonary thrombus burden. Right ventricular dysfunction was present in all patients by echocardiographic finding of right ventricle-to-left ventricle ratio > 0.9. Treatment outcome, procedural complications, right ventricular pressures, and thrombus clearance were evaluated. Follow-up evaluation included echocardiographic assessment of right ventricle-to-left ventricle ratio at one month, six months, and one year. Results Technical success was achieved in all patients ( n = 46, 100%). Our patients received an average of 18.4 ± 4.7 mg of tissue plasminogen activator using ultrasound-accelerated thrombolytic catheter with an average infusion time of 16.5± 5.4 h. Clinical success was achieved in all patients (100%). Significant reduction of mean pulmonary artery pressure occurred following the treatment, which decreased from 36 ± 8 to 21 ± 5 mmHg ( p < 0.001). There were no major bleeding complications. All-cause mortality at 30 days was 0%. No patient developed recurrent pulmonary embolism during follow-up. During the follow-up period, 43 patients (93%) showed improvement of right ventricular dysfunction based on echocardiographic assessment. The right ventricle-to-left ventricle ratio decreased from 1.32 ± 0.18 to 0.91 ± 0.13 at the time of hospital discharge ( p < 0.01). The right ventricular function remained improved at 6 months and 12 months of follow-up, as right ventricle-to-left ventricle ratio were 0.92 ± 0.14 ( p < 0.01) and 0.91 ± 0.15 ( p < 0.01), respectively. Conclusion Ultrasound-accelerated catheter-directed thrombolysis is a safe and efficacious treatment for submassive pulmonary embolism. It reduces pulmonary hypertension and improves right ventricular function in patients with submassive pulmonary embolism.

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.

Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension.

PubMed

Bellofiore, Alessandro; Dinges, Eric; Naeije, Robert; Mkrdichian, Hamorabi; Beussink-Nelson, Lauren; Bailey, Melissa; Cuttica, Michael J; Sweis, Ranya; Runo, James R; Keevil, Jon G; Francois, Christopher J; Shah, Sanjiv J; Chesler, Naomi C

2017-03-01

Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH. Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z 0 ), characteristic impedance (Z C , a measure of proximal PA stiffness) and proximal and distal PA compliance (C PA ). In patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (Z C =2.31±0.38 vs 1.33±0.15 WU×m 2 at rest; p=0.003) and PA compliance was decreased (C PA =0.88±0.10 vs 1.32±0.17 mL/mm Hg/m 2 at rest; p=0.0002). Z 0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10 -6 ). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited C PA reduction at maximum exercise. In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z 0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated. 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/.

Modulation of Lung Function by Increased Nitric Oxide Production

PubMed Central

Yadav, Ram Lochan; Yadav, Prakash Kumar

2017-01-01

Introduction Cigarette smoking reduces endogenous Nitric Oxide (NO) production by reducing Nitric Oxide Synthase (NOS) activity, which is one of the probable reason for increased rate of pulmonary diseases in smokers. Nitric oxide/oxygen blends are used in critical care to promote capillary and pulmonary dilation to treat several pulmonary vascular diseases. Among several supplements, the highest NOS activation has been proved for garlic with its unique mechanism of action. Aim To investigate the effect of dietary supplementation of NO producing garlic on pulmonary function of smokers. Materials and Methods The study was conducted on 40 healthy non-smoker (Group A) and 40 chronic smoker (Group B) males with matched age, height and weight. The pulmonary function tests- Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), FEV1/FVC ratio and Peak Expiratory Flow Rate (PEFR) were performed in non-smokers (Group A), smokers (Group B) and smokers after supplementation of approximately 4 gm of raw garlic (2 garlic cloves) per day for three months (Group C). Endogenous NO production was studied in smokers before and after garlic supplementation and in non-smokers without supplementation. The data obtained were compared between the groups using unpaired student’s t-test. The p-value considered significant at <0.05. Results Our results showed that FVC, FEV1, FEV1/FVC ratio and PEFR were reduced significantly along with a significant decreased NOS activity among smokers (Group B) when compared with non-smokers (Group A). Garlic supplementation significantly improved the pulmonary function tests in Group C in comparison to Group B by increasing NOS activity. Conclusion Dietary supplementation of garlic, which might be by increasing NOS activity, has significantly improved pulmonary functions in smokers. PMID:28764150

Isolated Human Pulmonary Artery Structure and Function Pre- and Post-Cardiopulmonary Bypass Surgery.

PubMed

Dora, Kim A; Stanley, Christopher P; Al Jaaly, Emad; Fiorentino, Francesca; Ascione, Raimondo; Reeves, Barnaby C; Angelini, Gianni D

2016-02-23

Pulmonary dysfunction is a known complication after cardiac surgery using cardiopulmonary bypass, ranging from subclinical functional changes to prolonged postoperative ventilation, acute lung injury, and acute respiratory distress syndrome. Whether human pulmonary arterial function is compromised is unknown. The aim of the present study was to compare the structure and function of isolated and cannulated human pulmonary arteries obtained from lung biopsies after the chest was opened (pre-cardiopulmonary bypass) to those obtained at the end of cardiopulmonary bypass (post-cardiopulmonary bypass) from patients undergoing coronary artery bypass graft surgery. Pre- and post-cardiopulmonary bypass lung biopsies were received from 12 patients undergoing elective surgery. Intralobular small arteries were dissected, cannulated, pressurized, and imaged using confocal microscopy. Functionally, the thromboxane mimetic U46619 produced concentration-dependent vasoconstriction in 100% and 75% of pre- and post-cardiopulmonary bypass arteries, respectively. The endothelium-dependent agonist bradykinin stimulated vasodilation in 45% and 33% of arteries pre- and post-cardiopulmonary bypass, respectively. Structurally, in most arteries smooth muscle cells aligned circumferentially; live cell viability revealed that although 100% of smooth muscle and 90% of endothelial cells from pre-cardiopulmonary bypass biopsies had intact membranes and were considered viable, only 60% and 58%, respectively, were viable from post-cardiopulmonary bypass biopsies. We successfully investigated isolated pulmonary artery structure and function in fresh lung biopsies from patients undergoing heart surgery. Pulmonary artery contractile tone and endothelium-dependent dilation were significantly reduced in post-cardiopulmonary bypass biopsies. The decreased functional responses were associated with reduced cell viability. URL: http://www.isrctn.com/ISRCTN34428459. Unique identifier: ISRCTN 34428459. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Acute effects of air pollutants on pulmonary function among students: a panel study in an isolated island.

PubMed

Yoda, Yoshiko; Takagi, Hiroshi; Wakamatsu, Junko; Ito, Takeshi; Nakatsubo, Ryouhei; Horie, Yosuke; Hiraki, Takatoshi; Shima, Masayuki

2017-04-04

Many epidemiological studies on the health effects of air pollutants have been carried out in regions with major sources such as factories and automobiles. However, the health effects of air pollutants in regions without major sources remain unclear. This study investigated the acute effects of ambient air pollution on pulmonary function among healthy students in an isolated island without major artificial sources of air pollutants. A panel study was conducted of 43 healthy subjects who attended a school in an isolated island in the Seto Inland Sea, Japan. We measured the forced expiratory volume in 1 s (FEV 1 ) and peak expiratory flow (PEF) every morning for about 1 month in May 2014. Ambient concentrations of particulate matter ≤ 2.5 μm in diameter (PM 2.5 ), particulate matter between 2.5 and 10 μm in diameter (PM 10-2.5 ), black carbon (BC), ozone (O 3 ), and nitrogen dioxide (NO 2 ) were measured. The associations between the concentrations of air pollutants and pulmonary function were analyzed using mixed-effects models. A decrease in FEV 1 was significantly associated with BC concentrations (-27.28 mL [95%confidence interval (CI):-54.10,-0.46] for an interquartile range (IQR) increase of 0.23 μg/m 3 ). The decrease in PEF was significantly associated with indoor O 3 concentrations (-8.03 L/min [95% CI:-13.02,-3.03] for an IQR increase of 11 ppb). Among subjects with a history of allergy, an increase in PM 2.5 concentrations was significantly associated with low FEV 1 . In subjects with a history of asthma, an inverse association between the indoor O 3 concentration and pulmonary function was observed. Our results demonstrate that increases in BC and O 3 concentrations have acute effects on the pulmonary function among students in an isolated island without major artificial sources of air pollutants.

Respiratory effects among rubberwood furniture factory workers in Thailand.

PubMed

Sriproed, Salakjit; Osiri, Pramuk; Sujirarat, Dusit; Chantanakul, Suttinun; Harncharoen, Kitiphong; Ong-artborirak, Parichat; Woskie, Susan R

2013-01-01

Respiratory symptoms and pulmonary function were examined among 89 rubberwood furniture factory workers. Acute and chronic irritant symptoms were assessed, lung function was measured both pre- and post-shift and personal inhalable dust exposure determined. The only symptoms with a significant increase among high dust level-exposed workers (>1 mg/m(3)) were those related to nasal irritation. High dust level-exposed workers had a significant cross-shift decrease in forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) compared with low dust level-exposed workers and increases in inhalable dust concentration levels (mg/m(3)) were significantly associated with decreases in the peak expiratory flow (PEF) across the work shift. For percent predicted pulmonary function levels, a significant decrement in PEF was found for high versus low rubberwood dust level-exposed workers, after controlling for confounders. These findings suggest the need for an occupational standard for rubberwood dust in Thailand.

Evidence for decreased lipofibroblast expression in hypoplastic rat lungs with congenital diaphragmatic hernia.

PubMed

Friedmacher, Florian; Fujiwara, Naho; Hofmann, Alejandro Daniel; Takahashi, Hiromizu; Gosemann, Jan-Hendrik; Puri, Prem

2014-10-01

Pulmonary hypoplasia (PH) is a serious condition in newborns with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial fibroblasts (LIFs) play an essential role in fetal lung maturation by stimulating alveolarization and lipid homeostasis. In rodents, LIFs are first evident during the canalicular phase of lung development with a significant increase over the last 4 days of gestation. Adipocyte differentiation-related protein (ADRP), a functional lipogenic molecular marker characterizing LIFs, is highly expressed in fetal lungs during this critical time period. We hypothesized that LIF expression in hypoplastic rat lungs is decreased in the nitrofen-induced CDH model, which is accompanied by reduced alveolar ADRP expression and lipid content. On embryonic day 9.5 (E9.5), time-mated rats received either nitrofen or vehicle. Fetuses were sacrificed on selected time points E18.5 and E21.5, and dissected lungs were divided into controls and CDH-associated PH. Pulmonary gene expression levels of ADRP were determined by quantitative real-time polymerase chain reaction. ADRP immunohistochemistry and oil red O staining were used to assess pulmonary protein expression and lipid content. Immunofluorescence double staining for alpha smooth muscle actin, which is known to be absent in LIFs, and lipid droplets was performed to evaluate the pulmonary expression of this specific subset of fibroblasts. Relative mRNA expression of ADRP was significantly reduced in lungs of CDH-associated PH on E18.5 and E21.5 compared to controls. ADRP immunoreactivity and lipid staining were markedly diminished in alveolar mesenchymal cells of CDH-associated PH on E18.5 and E21.5 compared to controls. Confocal laser scanning microscopy demonstrated markedly decreased LIF expression in alveolar interstitium of CDH-associated PH on E18.5 and E21.5 compared to controls. Decreased pulmonary LIF expression during late gestation suggests impaired LIF functioning in the nitrofen-induced CDH model, which may cause disruption in fetal alveolarization and lipid homeostasis, and thus contribute to the development of PH.

Effect of exercise test on pulmonary function of obese adolescents.

PubMed

Faria, Alethéa Guimarães; Ribeiro, Maria Angela G O; Marson, Fernando Augusto Lima; Schivinski, Camila Isabel S; Severino, Silvana Dalge; Ribeiro, José Dirceu; Barros Filho, Antônio A

2014-01-01

to investigate the pulmonary response to exercise of non-morbidly obese adolescents, considering the gender. a prospective cross-sectional study was conducted with 92 adolescents (47 obese and 45 eutrophic), divided in four groups according to obesity and gender. Anthropometric parameters, pulmonary function (spirometry and oxygen saturation [SatO2]), heart rate (HR), blood pressure (BP), respiratory rate (RR), and respiratory muscle strength were measured. Pulmonary function parameters were measured before, during, and after the exercise test. BP and HR were higher in obese individuals during the exercise test (p = 0.0001). SatO2 values decreased during exercise in obese adolescents (p = 0.0001). Obese males had higher levels of maximum inspiratory and expiratory pressures (p = 0.0002) when compared to obese and eutrophic females. Obese males showed lower values of maximum voluntary ventilation, forced vital capacity, and forced expiratory volume in the first second when compared to eutrophic males, before and after exercise (p = 0.0005). Obese females had greater inspiratory capacity compared to eutrophic females (p = 0.0001). Expiratory reserve volume was lower in obese subjects when compared to controls (p ≤ 0,05). obese adolescents presented changes in pulmonary function at rest and these changes remained present during exercise. The spirometric and cardiorespiratory values were different in the four study groups. The present data demonstrated that, in spite of differences in lung growth, the model of fat distribution alters pulmonary function differently in obese female and male adolescents. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload.

PubMed

Apitz, Christian; Honjo, Osami; Humpl, Tilman; Li, Jing; Assad, Renato S; Cho, Mi Y; Hong, James; Friedberg, Mark K; Redington, Andrew N

2012-12-01

Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB + AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. Contractile performance was significantly improved in the PAB + AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB + AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor β genes. Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Pulmonary function in patients with Huntington’s Disease

PubMed Central

2014-01-01

Background Huntington’s disease (HD) is a neurodegenerative disorder characterized by progressive motor, cognitive and psychiatric disturbances. Chest muscle rigidity, respiratory muscle weakness, difficulty in clearing airway secretions and swallowing abnormalities have been described in patients with neurodegenerative disorders including HD. However limited information is available regarding respiratory function in HD patients. The purpose of this study was to investigate pulmonary function of patients with HD in comparison to healthy volunteers, and its association with motor severity. Methods Pulmonary function measures were taken from 18 (11 male, 7 female) manifest HD patients (53 ± 10 years), and 18 (10 male, 8 female) healthy volunteers (52 ± 11 years) with similar anthropometric and life-style characteristics to the recruited HD patients. Motor severity was quantified by the Unified Huntington’s Disease Rating Scale-Total Motor Score (UHDRS-TMS). Maximum respiratory pressure was measured on 3 separate days with a week interval to assess test-retest reliability. Results The test-retest reliability of maximum inspiratory and expiratory pressure measurements was acceptable for both HD patient and control groups (ICC ≥0.92), but the values over 3 days were more variable in the HD group (CV < 11.1%) than in the control group (CV < 7.6%). The HD group showed lower respiratory pressure, forced vital capacity, peak expiratory flow and maximum voluntary ventilation than the control group (p < 0.05). Forced vital capacity, maximum voluntary ventilation and maximum respiratory pressures were negatively (r = -0.57; -0.71) correlated with the UHDRS-TMS (p < 0.05). Conclusion Pulmonary function is decreased in manifest HD patients, and the magnitude of the decrease is associated with motor severity. PMID:24886346

Small changes in lung function in runners with marathon‐induced interstitial lung edema

PubMed Central

Zavorsky, Gerald S.; Milne, Eric N.C.; Lavorini, Federico; Rienzi, Joseph P.; Cutrufello, Paul T.; Kumar, Sridhar S.; Pistolesi, Massimo

2014-01-01

Abstract The purpose of this study was to assess lung function in runners with marathon‐induced lung edema. Thirty‐six (24 males) healthy subjects, 34 (SD 9) years old, body mass index 23.7 (2.6) kg/m2 had posterior/anterior (PA) radiographs taken 1 day before and 21 (6) minutes post marathon finish. Pulmonary function was performed 1–3 weeks before and 73 (27) minutes post finish. The PA radiographs were viewed together, as a set, and evaluated by two experienced readers separately who were blinded as to time the images were obtained. Radiographs were scored for edema based on four different radiological characteristics such that the summed scores for any runner could range from 0 (no edema) to a maximum of 8 (severe interstitial edema). Overall, the mean edema score increased significantly from 0.2 to 1.0 units (P <0.01), and from 0.0 to 2.9 units post exercise in the six subjects that were edema positive (P = 0.03). Despite a 2% decrease in forced vital capacity (FVC, P =0.024) and a 12% decrease in alveolar‐membrane diffusing capacity for carbon monoxide (DmCO, P =0.01), there was no relation between the change in the edema score and the change in DmCO or FVC. In conclusion, (1) mild pulmonary edema occurs in at least 17% of subjects and that changes in pulmonary function cannot predict the occurrence or severity of edema, (2) lung edema is of minimal physiological significance as marathon performance is unaffected, exercise‐induced arterial hypoxemia is unlikely, and postexercise pulmonary function changes are mild. PMID:24973330

Effect of sedation with detomidine and butorphanol on pulmonary gas exchange in the horse.

PubMed

Nyman, Görel; Marntell, Stina; Edner, Anna; Funkquist, Pia; Morgan, Karin; Hedenstierna, Göran

2009-05-07

Sedation with alpha2-agonists in the horse is reported to be accompanied by impairment of arterial oxygenation. The present study was undertaken to investigate pulmonary gas exchange using the Multiple Inert Gas Elimination Technique (MIGET), during sedation with the alpha2-agonist detomidine alone and in combination with the opioid butorphanol. Seven Standardbred trotter horses aged 3-7 years and weighing 380-520 kg, were studied. The protocol consisted of three consecutive measurements; in the unsedated horse, after intravenous administration of detomidine (0.02 mg/kg) and after subsequent butorphanol administration (0.025 mg/kg). Pulmonary function and haemodynamic effects were investigated. The distribution of ventilation-perfusion ratios (VA/Q) was estimated with MIGET. During detomidine sedation, arterial oxygen tension (PaO2) decreased (12.8 +/- 0.7 to 10.8 +/- 1.2 kPa) and arterial carbon dioxide tension (PaCO2) increased (5.9 +/- 0.3 to 6.1 +/- 0.2 kPa) compared to measurements in the unsedated horse. Mismatch between ventilation and perfusion in the lungs was evident, but no increase in intrapulmonary shunt could be detected. Respiratory rate and minute ventilation did not change. Heart rate and cardiac output decreased, while pulmonary and systemic blood pressure and vascular resistance increased. Addition of butorphanol resulted in a significant decrease in ventilation and increase in PaCO2. Alveolar-arterial oxygen content difference P(A-a)O2 remained impaired after butorphanol administration, the VA/Q distribution improved as the decreased ventilation and persistent low blood flow was well matched. Also after subsequent butorphanol no increase in intrapulmonary shunt was evident. The results of the present study suggest that both pulmonary and cardiovascular factors contribute to the impaired pulmonary gas exchange during detomidine and butorphanol sedation in the horse.

Effects of puberty on cystic fibrosis related pulmonary exacerbations in women versus men.

PubMed

Sutton, Shelby; Rosenbluth, Daniel; Raghavan, Deepa; Zheng, Jie; Jain, Raksha

2014-01-01

Epidemiologic data from studies of airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis indicate a gender disparity where women have worse outcomes. The explanation for this is largely unknown. We hypothesize that female sex hormones play a role in this gender disparity, predisposing women to more exacerbations and decreased lung function post-puberty. In Cystic Fibrosis, to determine if puberty marks a point of increasing exacerbations and decreasing lung function in women relative to men. Using the United States Cystic Fibrosis Foundation Patient Registry, we used linear regression to compare lung function and rate of pulmonary exacerbations in men versus women before and after puberty. Of 5,137 subjects who met inclusion criteria, 2,689 were male and 2,448 were female. Average age of puberty was found to be 13.2 ± 2.2 years in men and 11.2 ± 2.0 years of age in women. Percent predicted FEV1 pre- and post-puberty were no different between males versus females (P = 0.44 pre-puberty and P = 0.16 post-puberty). In contrast, women had a significantly higher rate of pulmonary exacerbations post-puberty than men (1.17 ± 1.35 exacerbations per year in women versus 0.95 ± 1.27 in men; P < 0.001) despite controlling for morphometrics, co-morbidities, and microbiologic variables. After puberty, the rate of pulmonary exacerbations increased in adolescent women relative to men with cystic fibrosis, supporting a role for sex hormones in the disease process. Further understanding of the mechanisms that modulate sex hormone receptors in airway disease may serve as future targets for therapy. © 2013 Wiley Periodicals, Inc.

Effects of Puberty on Cystic Fibrosis Related Pulmonary Exacerbations in Women Versus Men

PubMed Central

Sutton, Shelby; Rosenbluth, Daniel; Raghavan, Deepa; Zheng, Jie; Jain, Raksha

2014-01-01

Summary Background Epidemiologic data from studies of airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis indicate a gender disparity where women have worse outcomes. The explanation for this is largely unknown. We hypothesize that female sex hormones play a role in this gender disparity, predisposing women to more exacerbations and decreased lung function post-puberty. Objective In Cystic Fibrosis, to determine if puberty marks a point of increasing exacerbations and decreasing lung function in women relative to men. Methods Using the United States Cystic Fibrosis Foundation Patient Registry, we used linear regression to compare lung function and rate of pulmonary exacerbations in men versus women before and after puberty. Results Of 5,137 subjects who met inclusion criteria, 2,689 were male and 2,448 were female. Average age of puberty was found to be 13.2 ± 2.2 years in men and 11.2 ± 2.0 years of age in women. Percent predicted FEV1 pre-and post-puberty were no different between males versus females (P = 0.44 pre-puberty and P = 0.16 post-puberty). In contrast, women had a significantly higher rate of pulmonary exacerbations post-puberty than men (1.17 ± 1.35 exacerbations per year in women versus 0.95 ± 1.27 in men; P < 0.001) despite controlling for morphometrics, co-morbidities, and microbiologic variables. Conclusion After puberty, the rate of pulmonary exacerbations increased in adolescent women relative to men with cystic fibrosis, supporting a role for sex hormones in the disease process. Further understanding of the mechanisms that modulate sex hormone receptors in airway disease may serve as future targets for therapy. PMID:23460461

Pulmonary effects of ozone and nitrogen dioxide alone and combined in healthy and asthmatic adolescent subjects

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

Koenig, J.Q.; Covert, D.S.; Smith, M.S.

Separate exposures to 0.12 ppm ozone (O3) or 0.18 ppm nitrogen dioxide (NO2) have not demonstrated consistent changes in pulmonary function in adolescent subjects. However, in polluted urban air, O3 and NO2 occur in combination. Therefore, this project was designed to investigate the pulmonary effects of combined O3 and NO2 exposures during intermittent exercise in adolescent subjects. Twelve healthy and twelve well-characterized asthmatic adolescent subjects were exposed randomly to clean air or 0.12 ppm O3 and 0.30 ppm NO2 alone or in combination during 60 minutes of intermittent moderate exercise (32.5 1/min). The inhalation exposures were carried out while themore » subjects breathed on a rubber mouthpiece with nose clips in place. The following pulmonary functional values were measured before and after exposure: peak flow, total respiratory resistance, maximal flow at 50 and 75 percent of expired vital capacity, forced expiratory volume in one second and forced vital capacity (FVC). Statistical significance of pulmonary function changes was tested by analysis of covariance for repeated measures. After exposure to 0.12 ppm O3 a significant decrease was seen in maximal flow at 50% of FVC in asthmatic subjects. After exposure to 0.30 ppm NO2 a significant decrease was seen in FVC also in the asthmatic subjects. One possible explanation for these changes is the multiple comparison effect. No significant changes in any parameters were seen in the asthmatic subjects after the combined O3-NO2 exposure or in the healthy subjects after any of the exposures.« less

Pulmonary function evaluation during the Skylab and Apollo-Soyuz missions.

PubMed

Sawin, C F; Nicogossian, A E; Rummel, J A; Michel, E L

1976-02-01

Previous experience during Apollo postflight exercise testing indicated no major changes in pulmonary function. Pulmonary function has been studied in detail following exposure to hypoxic and hyperoxic normal gravity environments, but no previous study has reported on men exposed to an environment that was both normoxic at 258 torr total pressure and at null gravity as encountered in Skylab. Forced vital capacity (FVC) was measured during the preflight and postflight periods of the Skylab 2 mission. Inflight measurements of vital capacity (VC) were obtained during the last 2 weeks of the second manned mission (Skylab 3). More detailed pulmonary function screening was accomplished during the Skylab 4 mission. The primary measurements made during Skylab 4 testing included residual volume determination (RV), closing volume (CV), VC, FVC and its derivatives. In addition, VC was measured in flight at regular intervals during the Skylab 4 mission. Vital capacity was decreased slightly (-10%) in flight in all Skylab 4 crewmen. No major preflight-to-postflight changes were observed. The Apollo-Soyuz Test Project (ASTP) crewmen were studied using equipment and procedures similar to those employed during Skylab 4. Postflight evaluation of the ASTP crewmen was complicated by their inadvertent exposure to nitrogen tetroxide gas fumes upon reentry.

Pulmonary function evaluation during the Skylab and Apollo-Soyuz missions

NASA Technical Reports Server (NTRS)

Sawin, C. F.; Nicogossian, A. E.; Rummel, J. A.; Michel, E. L.

1976-01-01

Previous experience during Apollo postflight exercise testing indicated no major changes in pulmonary function. Pulmonary function has been studied in detail following exposure to hypoxic and hyperoxic normal gravity environments, but no previous study has reported on men exposed to an environment that was both normoxic at 258 torr total pressure and at null gravity as encountered in Skylab. Forced vital capacity (FVC) was measured during the preflight and postflight periods of the Skylab 2 mission. Inflight measurements of vital capacity (VC) were obtained during the last 2 weeks of the second manned mission (Skylab 3). More detailed pulmonary function screening was accomplished during the Skylab 4 mission. The primary measurements made during Skylab 4 testing included residual volume determination (RV), closing volume (CV), VC, FVC and its derivatives. In addition, VC was measured in flight at regular intervals during the Skylab 4 mission. Vital capacity was decreased slightly (-10%) in flight in all Skylab 4 crewmen. No major preflight-to-postflight changes were observed. The Apollo-Soyuz Test Project (ASTP) crewmen were studied using equipment and procedures similar to those employed during Skylab 4. Postflight evaluation of the ASTP crewmen was complicated by their inadvertent exposure to nitrogen tetroxide gas fumes upon reentry.

Spatiotemporal alterations in Sprouty-2 expression and tyrosine phosphorylation in nitrofen-induced pulmonary hypoplasia.

PubMed

Friedmacher, Florian; Gosemann, Jan-Hendrik; Fujiwara, Naho; Alvarez, Luis A J; Corcionivoschi, Nicolae; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) is a life-threatening condition of newborns presenting with congenital diaphragmatic hernia (CDH). Sprouty-2 functions as a key regulator of fibroblast growth factor receptor (FGFR) signalling in developing foetal lungs. It has been reported that FGFR-mediated alveolarization is disrupted in nitrofen-induced PH. Sprouty-2 knockouts show severe defects in lung morphogenesis similar to nitrofen-induced PH. Upon FGFR stimulation, Sprouty-2 is tyrosine-phosphorylated, which is essential for its physiological function during foetal lung development. We hypothesized that Sprouty-2 expression and tyrosine phosphorylation are altered in nitrofen-induced PH. Time-pregnant rats received either nitrofen or vehicle on gestation day 9 (D9). Foetal lungs were dissected on D18 and D21. Pulmonary Sprouty-2 gene and protein expression levels were analyzed by qRT-PCR, Western blotting and immunohistochemical staining. Relative mRNA expression of Sprouty-2 was significantly decreased in hypoplastic lungs without CDH (0.1050±0.01 vs. 0.3125±0.01; P<.0001) and with CDH (0.1671±0.01 vs. 0.3125±0.01; P<.0001) compared to controls on D18. Protein levels of Sprouty-2 were markedly decreased in hypoplastic lungs on D18 with decreased tyrosine phosphorylation levels on D18 and D21 detected at the molecular weight of Sprouty-2 consistent with Sprouty-2 tyrosine phosphorylation. Sprouty-2 immunoreactivity was markedly decreased in hypoplastic lungs on D18 and D21. Spatiotemporal alterations in pulmonary Sprouty-2 expression and tyrosine phosphorylation during the late stages of foetal lung development may interfere with FGFR-mediated alveolarization in nitrofen-induced PH. © 2013.

Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice.

PubMed

Yamada, Yosuke; Tomaru, Utano; Ishizu, Akihiro; Ito, Tomoki; Kiuchi, Takayuki; Ono, Ayako; Miyajima, Syota; Nagai, Katsura; Higashi, Tsunehito; Matsuno, Yoshihiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu; Miwa, Soichi; Kasahara, Masanori

2015-06-01

Chronic obstructive pulmonary disease (COPD) is a disease common in elderly people, characterized by progressive destruction of lung parenchyma and chronic inflammation of the airways. The pathogenesis of COPD remains unclear, but recent studies suggest that oxidative stress-induced apoptosis in alveolar cells contributes to emphysematous lung destruction. The proteasome is a multicatalytic enzyme complex that plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by oxidative and other stresses. Proteasome activity decreases with aging in many organs including lungs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. However, the role of the proteasome system in the pathogenesis of COPD has not been investigated. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Importantly, apoptotic cells were found in the alveolar walls of the affected lungs. Impaired proteasomal activity also enhanced apoptosis in cigarette smoke extract (CSE)-exposed fibroblastic cells derived from mice and humans in vitro. Notably, aggresome formation and prominent nuclear translocation of apoptosis-inducing factor were observed in CSE-exposed fibroblastic cells isolated from Tg mice. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

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.

Power loss and right ventricular efficiency in patients after tetralogy of Fallot repair with pulmonary insufficiency: clinical implications.

PubMed

Fogel, Mark A; Sundareswaran, Kartik S; de Zelicourt, Diane; Dasi, Lakshmi P; Pawlowski, Tom; Rome, Jack; Yoganathan, Ajit P

2012-06-01

To quantify right ventricular output power and efficiency and correlate these to ventricular function in patients with repaired tetralogy of Fallot. This might aid in determining the optimal timing for pulmonary valve replacement. We reviewed the cardiac catheterization and magnetic resonance imaging data of 13 patients with tetralogy of Fallot (age, 22 ± 17 years). Using pressure and flow measurements in the main pulmonary artery, cardiac output and regurgitation fraction, right ventricular (RV) power output, loss, and efficiency were calculated. The RV function was evaluated using cardiac magnetic resonance imaging. The RV systolic power was 1.08 ± 0.62 W, with 20.3% ± 8.6% power loss owing to 41% ± 14% pulmonary regurgitation (efficiency, 79.7% ± 8.6%; 0.84 ± 0.73 W), resulting in a net cardiac output of 4.24 ± 1.82 L/min. Power loss correlated significantly with the indexed RV end-diastolic and end-systolic volume (R = 0.78, P = .002 and R = 0.69, P = .009, respectively). The normalized RV power output had a significant negative correlation with RV end-diastolic and end-systolic volumes (both R = -0.87, P = .002 and R = -0.68, P = .023, respectively). A rapid decrease occurred in the RV power capacity with an increasing RV volume, with the curve flattening out at an indexed RV end-diastolic and end-systolic volume threshold of 139 mL/m(2) and 75 mL/m(2), respectively. Significant power loss is present in patients with repaired tetralogy of Fallot and pulmonary regurgitation. A rapid decrease in efficiency occurs with increasing RV volume, suggesting that pulmonary valve replacement should be done before the critical value of 139 mL/m(2) and 75 mL/m(2) for the RV end-diastolic and end-systolic volume, respectively, to preserve RV function. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Chest Wall Trauma.

PubMed

Majercik, Sarah; Pieracci, Fredric M

2017-05-01

Chest wall trauma is common, and contributes significantly to morbidity and mortality of trauma patients. Early identification of major chest wall and concomitant intrathoracic injuries is critical. Generalized management of multiple rib fractures and flail chest consists of adequate pain control (including locoregional modalities); management of pulmonary dysfunction by invasive and noninvasive means; and, in some cases, surgical fixation. Multiple studies have shown that patients with flail chest have substantial benefit (decreased ventilator and intensive care unit days, improved pulmonary function, and improved long-term functional outcome) when they undergo surgery compared with nonoperative management. Copyright © 2017 Elsevier Inc. All rights reserved.

[Cardio-Pulmonary-Renal interactions].

PubMed

Samoni, Sara; Husain-Syed, Faeq; De Rosa, Silvia; Ronco, Claudio

2017-03-01

Over the past decade, understanding about feedback mechanisms involving the heart, lung and kidney is significantly improved. Each organ injury may trigger hemodynamic, neuro-hormonal and cellular pathway that may damage diverse organs. Recurrent acute on chronic injury may lead to the advanced stage of disease. On the other hand, chronic pathological conditions may decrease functional reserve leading to a high susceptibility to acute injury. Assessment of functional reserve and dosage of novel biomarkers may allow an early diagnosis and treatment. This review summarizes the current state-of-the-art understanding of cardio-pulmonary-renal interactions. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Hemofiltration in ex vivo lung perfusion-a study in experimentally induced pulmonary edema.

PubMed

Nilsson, Tobias; Hansson, Christoffer; Wallinder, Andreas; Malm, Carl-Johan; Silverborn, Martin; Ricksten, Sven-Erik; Dellgren, Göran

2016-02-01

Ex vivo lung perfusion (EVLP) can potentially reduce pulmonary edema. In a pig model with induced pulmonary edema, we evaluated the effect of hemofiltration (HF) during EVLP on lung function, perfusate oncotic pressure, and lung weight. In anesthetized pigs (n = 14), pulmonary edema was induced by a balloon in the left atrium, combined with crystalloid infusion (20 mL/kg), for 2 hours. The lungs were harvested, stored cold for 2 hours, and randomized to EVLP, with or without a hemofilter (HF and noHF groups, respectively, n = 7 for each). EVLP was performed with cellular perfusate at a hematocrit of 10% to 15%. Oncotic pressure, lung performance, and weight were measured before and after 180 minutes of EVLP reconditioning with or without HF. After in vivo induction of edema, arterial oxygen tension (Pao2)/inspired oxygen fraction (Fio2), and compliance decreased by 63% and 16%, respectively. Pao2/Fio2 was considerably improved at first evaluation ex vivo in both groups. HF increased oncotic pressure by 43% and decreased lung weight by 15%. The effects were negligible in the noHF group. Compliance decreased in both groups during reconditioning, although less so in the HF group (P < .05). Pao2/Fio2, shunt fraction, and oxygen saturation remained unchanged in both groups. Pulmonary flow index decreased in both groups, and was partially reversed by nitroglycerin. Dorsal atelectatic consolidations were seen in both groups. In this lung-edema model, EVLP reconditioning with hyperoncotic solution did not affect the degree of lung edema. HF during EVLP increased perfusate oncotic pressure, decreased lung weight with beneficial effects on compliance, but did not improve lung oxygenation capacity. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities.

PubMed

Ho, Jennifer E; Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O; Hatabu, Hiroto; Latourelle, Jeanne C; Nishino, Mizuki; Dupuis, Josée; Washko, George R; O'Connor, George T; Hunninghake, Gary M

2016-07-01

Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8-2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6-1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3-2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49-4.76; P < 0.001). Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis.

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities

PubMed Central

Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O.; Hatabu, Hiroto; Latourelle, Jeanne C.; Nishino, Mizuki; Dupuis, Josée; Washko, George R.; O’Connor, George T.; Hunninghake, Gary M.

2016-01-01

Rationale: Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. Objectives: We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. Methods: We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Measurements and Main Results: Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8–2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6–1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3–2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49–4.76; P < 0.001). Conclusions: Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis. PMID:26771117

Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses

NASA Technical Reports Server (NTRS)

Erickson, H. H.; Bernard, S. L.; Glenny, R. W.; Fedde, M. R.; Polissar, N. L.; Basaraba, R. J.; Walther, S. M.; Gaughan, E. M.; McMurphy, R.; Hlastala, M. P.

1999-01-01

We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.

Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

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

Zhang, Liang, E-mail: countryspring@sina.com; Ji, Yunxia, E-mail: 413499057@qq.com; Kang, Zechun, E-mail: davidjiangwl@163.com

An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonarymore » fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.« less

A Feline HFpEF Model with Pulmonary Hypertension and Compromised Pulmonary Function.

PubMed

Wallner, Markus; Eaton, Deborah M; Berretta, Remus M; Borghetti, Giulia; Wu, Jichuan; Baker, Sandy T; Feldsott, Eric A; Sharp, Thomas E; Mohsin, Sadia; Oyama, Mark A; von Lewinski, Dirk; Post, Heiner; Wolfson, Marla R; Houser, Steven R

2017-11-29

Heart Failure with preserved Ejection Fraction (HFpEF) represents a major public health problem. The causative mechanisms are multifactorial and there are no effective treatments for HFpEF, partially attributable to the lack of well-established HFpEF animal models. We established a feline HFpEF model induced by slow-progressive pressure overload. Male domestic short hair cats (n = 20), underwent either sham procedures (n = 8) or aortic constriction (n = 12) with a customized pre-shaped band. Pulmonary function, gas exchange, and invasive hemodynamics were measured at 4-months post-banding. In banded cats, echocardiography at 4-months revealed concentric left ventricular (LV) hypertrophy, left atrial (LA) enlargement and dysfunction, and LV diastolic dysfunction with preserved systolic function, which subsequently led to elevated LV end-diastolic pressures and pulmonary hypertension. Furthermore, LV diastolic dysfunction was associated with increased LV fibrosis, cardiomyocyte hypertrophy, elevated NT-proBNP plasma levels, fluid and protein loss in pulmonary interstitium, impaired lung expansion, and alveolar-capillary membrane thickening. We report for the first time in HFpEF perivascular fluid cuff formation around extra-alveolar vessels with decreased respiratory compliance. Ultimately, these cardiopulmonary abnormalities resulted in impaired oxygenation. Our findings support the idea that this model can be used for testing novel therapeutic strategies to treat the ever growing HFpEF population.

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.

Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model

PubMed Central

2011-01-01

Background Human exposure to nanoparticles (NPs) and environmental bacteria can occur simultaneously. NPs induce inflammatory responses and oxidative stress but may also have immune-suppressive effects, impairing macrophage function and altering epithelial barrier functions. The purpose of this study was to assess the potential pulmonary effects of inhalation and instillation exposure to copper (Cu) NPs using a model of lung inflammation and host defense. Methods We used Klebsiella pneumoniae (K.p.) in a murine lung infection model to determine if pulmonary bacterial clearance is enhanced or impaired by Cu NP exposure. Two different exposure modes were tested: sub-acute inhalation (4 hr/day, 5 d/week for 2 weeks, 3.5 mg/m3) and intratracheal instillation (24 hr post-exposure, 3, 35, and 100 μg/mouse). Pulmonary responses were evaluated by lung histopathology plus measurement of differential cell counts, total protein, lactate dehydrogenase (LDH) activity, and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid. Results Cu NP exposure induced inflammatory responses with increased recruitment of total cells and neutrophils to the lungs as well as increased total protein and LDH activity in BAL fluid. Both inhalation and instillation exposure to Cu NPs significantly decreased the pulmonary clearance of K.p.-exposed mice measured 24 hr after bacterial infection following Cu NP exposure versus sham-exposed mice also challenged with K.p (1.4 × 105 bacteria/mouse). Conclusions Cu NP exposure impaired host defense against bacterial lung infections and induced a dose-dependent decrease in bacterial clearance in which even our lowest dose demonstrated significantly lower clearance than observed in sham-exposed mice. Thus, exposure to Cu NPs may increase the risk of pulmonary infection. PMID:21943386

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.

[Pulmonary hypertensive crisis in children with idiopathic pulmonary arterial hypertension undergoing cardiac catheterization: the risk factors and clinical aspects].

PubMed

Zhang, C; Zhu, Y; Li, Q Q; Gu, H

2018-06-02

Objective: To investigate the risk factors, clinical features, treatments, and prevention of pulmonary hypertensive crisis (PHC) in children with idiopathic pulmonary arterial hypertension (IPAH) undergoing cardiac catheterization. Methods: This retrospective study included 67 children who were diagnosed with IPAH and underwent cardiac catheterization between April 2009 and June 2017 in Beijing Anzhen Hospital. The medical histories, clinical manifestations, treatments, and outcomes were characterized. Statistical analyses were performed using t test, χ(2) test and a multiple Logistic regression analysis. Results: During cardiac catheterization, five children developed PHC who presented with markedly elevated pulmonary artery pressure and central venous pressure, decline in systemic arterial pressure and oxygen saturation. Heart rate decreased in 4 cases and increased in the remaining one. After the treatments including cardiopulmonary resuscitation, pulmonary vasodilator therapy, improving cardiac output and blood pressure, and correction of acidosis, 4 of the 5 cases recovered, while 1 died of severe right heart failure with irreversible PHC 3 days after operation. Potential PHC was considered in 7 other patients, whose pulmonary artery pressure increased and exceeded systemic arterial pressure, oxygen saturation decreased, and central venous pressure and vital signs were relatively stable. Univariate analysis showed that the risk factors of PHC in children with IPAH undergoing cardiac catheterization were younger age ( t= 3.160, P= 0.004), low weight ( t= 4.004, P< 0.001), general anesthesia (χ(2)=4.970, P= 0.026), history of syncope (χ(2)=4.948, P= 0.026), and WHO cardiac functional class Ⅲ or Ⅳ (χ(2)=19.013, P< 0.001). Multivariate Logistic regression analysis revealed that worse WHO cardiac functional class ( Wald =13.128, P< 0.001, OR= 15.076, 95% CI : 3.475-65.418) was the independent risk factor of PHC. Conclusions: PHC is a severe and extremely dangerous complication in children with IPAH during cardiac catheterization. WHO cardiac functional class may be associated with PHC. Integrated treatment is required for these patients. Reducing risk factors, early identification, and active treatment may help to prevent the occurrence and progression of PHC.

Outcome following phrenic nerve transfer to musculocutaneous nerve in patients with traumatic brachial palsy: a qualitative systematic review.

PubMed

de Mendonça Cardoso, Marcio; Gepp, Ricardo; Correa, José Fernando Guedes

2016-09-01

The phrenic nerve can be transferred to the musculocutaneous nerve in patients with traumatic brachial plexus palsy in order to recover biceps strength, but the results are controversial. There is also a concern about pulmonary function after phrenic nerve transection. In this paper, we performed a qualitative systematic review, evaluating outcomes after this procedure. A systematic review of published studies was undertaken in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Data were extracted from the selected papers and related to: publication, study design, outcome (biceps strength in accordance with BMRC and pulmonary function) and population. Study quality was assessed using the "strengthening the reporting of observational studies in epidemiology" (STROBE) standard or the CONSORT checklist, depending on the study design. Seven studies were selected for this systematic review after applying inclusion and exclusion criteria. One hundred twenty-four patients completed follow-up, and most of them were graded M3 or M4 (70.1 %) for biceps strength at the final evaluation. Pulmonary function was analyzed in five studies. It was not possible to perform a statistical comparison between studies because the authors used different parameters for evaluation. Most of the patients exhibited a decrease in pulmonary function tests immediately after surgery, with recovery in the following months. Study quality was determined using STROBE in six articles, and the global score varied from 8 to 21. Phrenic nerve transfer to the musculocutaneous nerve can recover biceps strength ≥M3 (BMRC) in most patients with traumatic brachial plexus injury. Early postoperative findings revealed that the development of pulmonary symptoms is rare, but it cannot be concluded that the procedure is safe because there is no study evaluating pulmonary function in old age.

DIETARY OMEGA-3 FATTY ACIDS MODIFIED THE ASSOCIATION OF PULMONARY FUNCTION WITH AIR POLLUTION IN ADOLESCENTS

EPA Science Inventory

Previous children's studies in North America and Germany have shown that ambient sulfate particles are associated with an increased prevalence of bronchitis and decreased lung function. We have now investigated the ability of dietary intake of anti-inflammatory omega-3 fatty aci...

Beneficial effects of a novel agonist of the adenosine A2A receptor on monocrotaline-induced pulmonary hypertension in rats

PubMed Central

Alencar, Allan K N; Pereira, Sharlene L; Montagnoli, Tadeu L; Maia, Rodolfo C; Kümmerle, Arthur E; Landgraf, Sharon S; Caruso-Neves, Celso; Ferraz, Emanuelle B; Tesch, Roberta; Nascimento, José H M; de Sant'Anna, Carlos M R; Fraga, Carlos A M; Barreiro, Eliezer J; Sudo, Roberto T; Zapata-Sudo, Gisele

2013-01-01

Background and Purpose Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, right ventricular hypertrophy and increased right ventricular systolic pressure. Here, we investigated the effects of a N-acylhydrazone derivative, 3,4-dimethoxyphenyl-N-methyl-benzoylhydrazide (LASSBio-1359), on monocrotaline (MCT)-induced pulmonary hypertension in rats. Experimental Approach PAH was induced in male Wistar rats by a single i.p. injection of MCT (60 mg·kg−1) and 2 weeks later, oral LASSBio-1359 (50 mg·kg−1) or vehicle was given once daily for 14 days. Echocardiography was used to measure cardiac function and pulmonary artery dimensions, with histological assay of vascular collagen. Studies of binding to human recombinant adenosine receptors (A1, A2A, A3) and of docking with A2A receptors were also performed. Key Results MCT administration induced changes in vascular and ventricular structure and function, characteristic of PAH. These changes were reversed by treatment with LASSBio-1359. MCT also induced endothelial dysfunction in pulmonary artery, as measured by diminished relaxation of pre-contracted arterial rings, and this dysfunction was reversed by LASSBio-1359. In pulmonary artery rings from normal Wistar rats, LASSBio-1359 induced relaxation, which was decreased by the adenosine A2A receptor antagonist, ZM 241385. In adenosine receptor binding studies, LASSBio-1359 showed most affinity for the A2A receptor and in the docking analyses, binding modes of LASSBio-1359 and the A2A receptor agonist, CGS21680, were very similar. Conclusion and Implications In rats with MCT-induced PAH, structural and functional changes in heart and pulmonary artery were reversed by treatment with oral LASSBio-1359, most probably through the activation of adenosine A2A receptors. PMID:23530610

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

Evaluation of pulmonary dysfunctions and acid–base imbalances induced by Chlamydia psittaci in a bovine model of respiratory infection

PubMed Central

2014-01-01

Background Chlamydia psittaci (Cp) is a respiratory pathogen capable of inducing acute pulmonary zoonotic disease (psittacosis) or persistent infection. To elucidate the pathogenesis of this infection, a translational large animal model was recently introduced by our group. This study aims at quantifying and differentiating pulmonary dysfunction and acid–base imbalances induced by Cp. Methods Forty-two calves were grouped in (i) animals inoculated with Cp (n = 21) and (ii) controls sham-inoculated with uninfected cell culture (n = 21). For pulmonary function testing, impulse oscillometry, capnography, and FRC (functional residual capacity) measurement were applied to spontaneously breathing animals. Variables of acid–base status were assessed in venous blood using both (i) traditional Henderson-Hasselbalch and (ii) strong ion approach. Results Both obstructive and restrictive pulmonary disorders were induced in calves experimentally inoculated with Cp. Although disorders in respiratory mechanics lasted for 8–11 days, the pattern of spontaneous breathing was mainly altered in the period of acute illness (until 4 days post inoculation, dpi). Expiration was more impaired than inspiration, resulting in elevated FRC. Ventilation was characterised by a reduction in tidal volume (−25%) combined with an increased percentage of dead space volume and a significant reduction of alveolar volume by 10%. Minute ventilation increased significantly (+50%) due to a compensatory doubling of respiratory rate. Hyperventilatory hypocapnia at 2–3 dpi resulted in slightly increased blood pH at 2 dpi. However, the acid–base equilibrium was additionally influenced by metabolic components, i.e. the systemic inflammatory response, all of which were detected with help of the strong ion theory. Decreased concentrations of albumin (2–10 dpi), a negative acute-phase marker, resulted in a decrease in the sum of non-volatile weak acids (Atot), revealing an alkalotic effect. This was counterbalanced by acidic effects of decreased strong ion difference (SID), mediated by the interplay between hypochloraemia (alkalotic effect) and hyponatraemia (acidic effect). Conclusions This bovine model was found to be suitable for studying pathophysiology of respiratory Cp infection and may help elucidating functional host-pathogen interactions in the mammalian lung. PMID:24517577

Imbalance of caveolin-1 and eNOS expression in the pulmonary vasculature of experimental diaphragmatic hernia.

PubMed

Hofmann, Alejandro; Gosemann, Jan-Hendrik; Takahashi, Toshiaki; Friedmacher, Florian; Duess, Johannes W; Puri, Prem

2014-08-01

Caveolin-1 (Cav-1) exerts major regulatory functions on intracellular signaling pathways originating at the plasma membrane. Cav-1 is a key regulator in adverse lung remodeling and the development of pulmonary hypertension (PH) regulating vasomotor tone through its ability to reduce nitric oxide (NO) production. This low-output endothelial NO synthase (eNOS) derived NO maintains normal pulmonary vascular homeostasis. Cav-1 deficiency leads to increased bioavailability of NO, which has been linked to increased nitrosative stress. Inhibition of eNOS reduced oxidant production and reversed PH, supporting the concept that Cav-1 regulation of eNOS activity is crucial to endothelial homeostasis in lungs. We designed this study to investigate the hypothesis that expression of Cav-1 is downregulated while eNOS expression is upregulated by the pulmonary endothelium in the nitrofen-induced congenital diaphragmatic hernia (CDH). Pregnant rats were exposed to nitrofen or vehicle on day 9.5 (D9.5). Fetuses were sacrificed on D21 and divided into nitrofen and control groups. Quantitative real-time polymerase chain reaction, Western blotting, and confocal immunofluorescence were performed to determine pulmonary gene expression levels and protein expression of Cav-1 and eNOS. Pulmonary Cav-1 gene expression levels were significantly decreased, while eNOS gene expression was significantly increased in nitrofen-induced CDH(+). Western blotting and confocal microscopy revealed decreased pulmonary Cav-1 protein expression, while eNOS protein expression was increased in CDH(+) compared to controls. The striking evidence of markedly decreased gene and protein expression of Cav-1 with concurrently increased eNOS gene and protein expression in the pulmonary vasculature suggests that activation of eNOS secondary to Cav-1 deficiency may play an important role in the pathogenesis of PH in the nitrofen-induced CDH. © 2014 Wiley Periodicals, Inc.

Heterozygous Null Bone Morphogenetic Protein Receptor Type 2 Mutations Promote SRC Kinase-dependent Caveolar Trafficking Defects and Endothelial Dysfunction in Pulmonary Arterial Hypertension*

PubMed Central

Prewitt, Allison R.; Ghose, Sampa; Frump, Andrea L.; Datta, Arumima; Austin, Eric D.; Kenworthy, Anne K.; de Caestecker, Mark P.

2015-01-01

Hereditary pulmonary arterial hypertension (HPAH) is a rare, fatal disease of the pulmonary vasculature. The majority of HPAH patients inherit mutations in the bone morphogenetic protein type 2 receptor gene (BMPR2), but how these promote pulmonary vascular disease is unclear. HPAH patients have features of pulmonary endothelial cell (PEC) dysfunction including increased vascular permeability and perivascular inflammation associated with decreased PEC barrier function. Recently, frameshift mutations in the caveolar structural protein gene Caveolin-1 (CAV-1) were identified in two patients with non-BMPR2-associated HPAH. Because caveolae regulate endothelial function and vascular permeability, we hypothesized that defects in caveolar function might be a common mechanism by which BMPR2 mutations promote pulmonary vascular disease. To explore this, we isolated PECs from mice carrying heterozygous null Bmpr2 mutations (Bmpr2+/−) similar to those found in the majority of HPAH patients. We show that Bmpr2+/− PECs have increased numbers and intracellular localization of caveolae and caveolar structural proteins CAV-1 and Cavin-1 and that these defects are reversed after blocking endocytosis with dynasore. SRC kinase is also constitutively activated in Bmpr2+/− PECs, and localization of CAV-1 to the plasma membrane is restored after treating Bmpr2+/− PECs with the SRC kinase inhibitor 3-(4-chlorophenyl)-1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP2). Late outgrowth endothelial progenitor cells isolated from HPAH patients show similar increased activation of SRC kinase. Moreover, Bmpr2+/− PECs have impaired endothelial barrier function, and barrier function is restored after treatment with PP2. These data suggest that heterozygous null BMPR2 mutations promote SRC-dependent caveolar trafficking defects in PECs and that this may contribute to pulmonary endothelial barrier dysfunction in HPAH patients. PMID:25411245

Abnormal pulmonary function and respiratory muscle strength findings in Chinese patients with Parkinson's disease and multiple system atrophy--comparison with normal elderly.

PubMed

Wang, Yao; Shao, Wei-bo; Gao, Li; Lu, Jie; Gu, Hao; Sun, Li-hua; Tan, Yan; Zhang, Ying-dong

2014-01-01

There have been limited comparative data regarding the investigations on pulmonary and respiratory muscle function in the patients with different parkinsonism disorders such as Parkinson's disease (PD) and multiple system atrophy (MSA) versus normal elderly. The present study is aiming to characterize the performance of pulmonary function and respiratory muscle strength in PD and MSA, and to investigate the association with severity of motor symptoms and disease duration. Pulmonary function and respiratory muscle strength tests were performed in 30 patients with PD, 27 with MSA as well as in 20 age-, sex-, height-, weight-matched normal elderly controls. All the patients underwent United Parkinson's disease rating scale (UPDRS) or united multiple system atrophy rating scale (UMSARS) separately as diagnosed. Vital capacity, forced expiratory volume in 1 second and forced vital capacity decreased, residual volume and ratio of residual volume to total lung capacity increased in both PD and MSA groups compared to controls (p<0.05). Diffusing capacity was decreased in the MSA group, compared with PD and normal elderly control groups (p<0.05). Respiratory muscle strength was lower in both PD and MSA groups than in controls (p<0.05). The values representing spirometry function and respiratory muscle strength were found to have a negative linear correlation with mean score of UPDRS-III in PD and mean score of UMSARS-I in MSA. Respiratory muscle strength showed a negative linear correlation with the mean score of UMSARS-II and disease duration in MSA patients. These findings suggest that respiratory dysfunction is involved in PD and MSA. Respiratory muscle strength is remarkably reduced, and some of the parameters correlate with disease duration and illness severity. The compromised respiratory function in neurodegenerative disorders should be the focus of further researches.

Computed Tomographic Airway Morphology in Chronic Obstructive Pulmonary Disease. Remodeling or Innate Anatomy?

PubMed

Diaz, Alejandro A; Estépar, Raul San José; Washko, George R

2016-01-01

Computed tomographic measures of central airway morphology have been used in clinical, epidemiologic, and genetic investigation as an inference of the presence and severity of small-airway disease in smokers. Although several association studies have brought us to believe that these computed tomographic measures reflect airway remodeling, a careful review of such data and more recent evidence may reveal underappreciated complexity to these measures and limitations that prompt us to question that belief. This Perspective offers a review of seminal papers and alternative explanations of their data in the light of more recent evidence. The relationships between airway morphology and lung function are observed in subjects who never smoked, implying that native airway structure indeed contributes to lung function; computed tomographic measures of central airways such as wall area, lumen area, and total bronchial area are smaller in smokers with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease; and the airways are smaller as disease severity increases. The observations suggest that (1) native airway morphology likely contributes to the relationships between computed tomographic measures of airways and lung function; and (2) the presence of smaller airways in those with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease as well as their decrease with disease severity suggests that smokers with chronic obstructive pulmonary disease may simply have smaller airways to begin with, which put them at greater risk for the development of smoking-related disease.

Non-invasive pulmonary function test on Morquio Patients

PubMed Central

Kubaski, Francyne; Tomatsu, Shunji; Patel, Pravin; Shimada, Tsutomu; Xie, Li; Yasuda, Eriko; Mason, Robert; Mackenzie, William G.; Theroux, Mary; Bober, Michael B.; Oldham, Helen M.; Orii, Tadao; Shaffer, Thomas H.

2015-01-01

In clinical practice, respiratory function tests are difficult to perform in Morquio syndrome patients due to their characteristic skeletal dysplasia, small body size and lack of cooperation of young patients, where in some cases, conventional spirometry for pulmonary function is too challenging. To establish feasible clinical pulmonary endpoints and determine whether age impacts lung function in Morquio patients non-invasive pulmonary tests and conventional spirometry were evaluated. The non-invasive pulmonary tests: impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography in conjunction with conventional spirometry were evaluated in twenty-two Morquio patients (18 Morquio A and 4 Morquio B) (7 males), ranging from 3 and 40 years of age. Twenty-two patients were compliant with non-invasive tests (100%) with exception of IOS (81.8%–18 patients). Seventeen patients (77.3%) were compliant with spirometry testing. All subjects had normal vital signs at rest including > 95% oxygen saturation, end tidal CO2 (38–44 mmHg), and age-appropriate heart rate (mean=98.3, standard deviation=19) (two patients were deviated). All patients preserved normal values in impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography, although predicted forced expiratory volume total (72.8 ± 6.9 SE%) decreased with age and was below normal; phase angle (35.5 ± 16.5 Degrees), %Rib Cage (41.6 ± 12.7%), resonant frequency, and forced expiratory volume in one second/forced expiratory volume total (110.0 ± 3.2 SE%) were normal and not significantly impacted by age. The proposed non-invasive pulmonary function tests are able to cover a greater number of patients (young patients and/or wheel-chair bound), thus providing a new diagnostic approach for the assessment of lung function in Morquio syndrome which in many cases may be difficult to evaluate. Morquio patients studied herein demonstrated no clinical or functional signs of restrictive and/or obstructive lung disease. PMID:26116954

Ethanol intoxication prolongs post-burn pulmonary inflammation: role of alveolar macrophages

PubMed Central

Shults, Jill A.; Curtis, Brenda J.; Boe, Devin M.; Ramirez, Luis; Kovacs, Elizabeth J.

2016-01-01

In this study, the role and fate of AMs were examined in pulmonary inflammation after intoxication and injury. Clinical evidence has revealed that half of all burn patients brought to the emergency department are intoxicated at the time of injury. This combined insult results in amplified neutrophil accumulation and pulmonary edema, with an increased risk of lung failure and mortality, relative to either insult alone. We believe that this excessive pulmonary inflammation, which also parallels decreased lung function, is mediated in part by AMs. Restoration of lung tissue homeostasis is dependent on the eradication of neutrophils and removal of apoptotic cells, both major functions of AMs. Thirty minutes after binge ethanol intoxication, mice were anesthetized and given a 15% total body surface area dorsal scald injury. At 24 h, we found a 50% decrease in the total number of AMs (P < 0.05) and observed a proinflammatory phenotype on the remaining lung AMs. Loss of AMs paralleled a 6-fold increase in the number of TUNEL+ lung apoptotic cells (P < 0.05) and a 3.5-fold increase in the percentage of annexin V+ apoptotic cells in BAL (P < 0.05), after intoxication and injury, relative to controls. In contrast to the reduction in the number of cells, AMs from intoxicated and injured mice had a 4-fold increase in efferocytosis (P < 0.05). In summary, these data suggest that loss of AMs may delay resolution of inflammation, resulting in the pulmonary complications and elevated mortality rates observed in intoxicated and burn-injured patients. PMID:27531926

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile.

PubMed

Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Balmes, John R; Liaw, Jane; Troncoso, Patricia; Dauphiné, David C; Nardone, Anthony; Smith, Allan H

2016-12-15

Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60μg/L; and Arica, with long-term water concentrations ≤10μg/L. Compared to adults never exposed >10μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath=5.56, 90% confidence interval (CI): 2.68-11.5), and decreases in pulmonary function (e.g., 224mL decrease in forced vital capacity in nonsmokers, 90% CI: 97-351mL). Subjects with long-term exposure to arsenic water concentrations near 60μg/L also had increases in some pulmonary symptoms and reduced lung function. Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative assessment of lung ventilation and microstructure in an animal model of idiopathic pulmonary fibrosis using hyperpolarized gas MRI.

PubMed

Stephen, Michael J; Emami, Kiarash; Woodburn, John M; Chia, Elaine; Kadlecek, Stephen; Zhu, Jianliang; Pickup, Stephen; Ishii, Masaru; Rizi, Rahim R; Rossman, Milton

2010-11-01

The use of hyperpolarized (3)He magnetic resonance imaging as a quantitative lung imaging tool has progressed rapidly in the past decade, mostly in the assessment of the airway diseases chronic obstructive pulmonary disease and asthma. This technique has shown potential to assess both structural and functional information in healthy and diseased lungs. In this study, the regional measurements of structure and function were applied to a bleomycin rat model of interstitial lung disease. Male Sprague-Dawley rats (weight, 300-350 g) were administered intratracheal bleomycin. After 3 weeks, apparent diffusion coefficient and fractional ventilation were measured by (3)He magnetic resonance imaging and pulmonary function testing using a rodent-specific plethysmography chamber. Sensitized and healthy animals were then compared using threshold analysis to assess the potential sensitivity of these techniques to pulmonary abnormalities. No significant changes were observed in total lung volume and compliance between the two groups. Airway resistance elevated and forced expiratory volume significantly declined in the 3-week bleomycin rats, and fractional ventilation was significantly decreased compared to control animals (P < .0004). The apparent diffusion coefficient of (3)He showed a smaller change but still a significant decrease in 3-week bleomycin animals (P < .05). Preliminary results suggest that quantitative (3)He magnetic resonance imaging can be a sensitive and noninvasive tool to assess changes in an animal interstitial lung disease model. This technique may be useful for longitudinal animal studies and also in the investigation of human interstitial lung diseases. Copyright © 2010 AUR. Published by Elsevier Inc. All rights reserved.

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

PubMed Central

Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Balmes, John R; Liaw, Jane; Troncoso, Patricia; Dauphiné, David C; Nardone, Anthony; Smith, Allan H

2016-01-01

Background Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958–1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤10 μg/L. Results Compared to adults never exposed >10 μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 ml decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 ml). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. PMID:27725189

Omeprazole Attenuates Pulmonary Aryl Hydrocarbon Receptor Activation and Potentiates Hyperoxia-Induced Developmental Lung Injury in Newborn Mice.

PubMed

Shivanna, Binoy; Zhang, Shaojie; Patel, Ananddeep; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E; Moorthy, Bhagavatula

2015-11-01

Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in human preterm infants and a similar lung phenotype characterized by alveolar simplification in newborn mice. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury (HLI) in adult mice. Whether OM activates pulmonary AhR and protects C57BL/6J newborn mice against hyperoxia-induced developmental lung (alveolar and pulmonary vascular simplification, inflammation, and oxidative stress) injury (HDLI) is unknown. Therefore, we tested the hypothesis that OM will activate pulmonary AhR and mitigate HDLI in newborn mice. Newborn mice were treated daily with i.p. injections of OM at doses of 10 (OM10) or 25 (OM25) mg/kg while being exposed to air or hyperoxia (FiO2 of 85%) for 14 days, following which their lungs were harvested to determine alveolarization, pulmonary vascularization, inflammation, oxidative stress, vascular injury, and AhR activation. To our surprise, hyperoxia-induced alveolar and pulmonary vascular simplification, inflammation, oxidative stress, and vascular injury were augmented in OM25-treated animals. These findings were associated with attenuated pulmonary vascular endothelial growth factor receptor 2 expression and decreased pulmonary AhR activation in the OM25 group. We conclude that contrary to our hypothesis, OM decreases functional activation of pulmonary AhR and potentiates HDLI in newborn mice. These observations are consistent with our previous findings, which suggest that AhR activation plays a protective role in HDLI in newborn mice. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

ACE and sIL-2R correlate with lung function improvement in sarcoidosis during methotrexate therapy.

PubMed

Vorselaars, Adriane D M; van Moorsel, Coline H M; Zanen, Pieter; Ruven, Henk J T; Claessen, Anke M E; van Velzen-Blad, Heleen; Grutters, Jan C

2015-02-01

In sarcoidosis, the search for disease activity markers that correlate with treatment response is ongoing. The aim of this study was to investigate the pattern of two proposed markers, serum angiotensin-converting enzyme (ACE) and soluble IL-2 receptor (sIL-2R) during methotrexate (MTX) therapy in sarcoidosis patients. We analysed 114 sarcoidosis patients who used MTX for six months, consisting of a subgroup of 76 patients with a pulmonary indication for treatment and a subgroup of 38 patients with an extra-pulmonary indication. ACE and sIL-2R serum levels were measured at baseline and after six months of treatment. Correlation coefficients (R) and odds ratios (ORs) were calculated to study the correlation and predictive effect of serum ACE and sIL-2R levels for pulmonary improvement. High baseline levels of ACE correlated significantly with lung function improvement after treatment (R = 0.45, p < 0.0001; stronger in the pulmonary subgroup R 0.57, p < 0.0001). ACE baseline levels >90 U/l predicted a 10% improvement in overall lung function (OR 3.55; CI 1.34-9.38), with the highest prediction level for 10% improvement in DLCO (OR 4.63; CI 1.23-17.4). After six months of MTX, mean ACE decreased with 17.2 U/l (p < 0.0001) and sIL-2R with 1850 pg/ml (p < 0.0001). Decreases in both ACE and sIL-2R correlated with an increase in lung function. The strongest correlation was found with change in DLCO in the pulmonary subgroup (ACE R = 0.63, P < 0.0001; sIL-2R R = 0.56, P < 0.0001). Baseline and serial serum ACE and sIL-2R levels correlate well with lung function improvement during MTX treatment. Serial measurements of these biomarkers are helpful in monitoring treatment effects in sarcoidosis patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

The efficacy of incentive spirometry in patients with COPD.

PubMed

Basoglu, Ozen Kacmaz; Atasever, Alev; Bacakoglu, Feza

2005-06-01

Although incentive spirometry (IS) is frequently used to prevent postoperative pulmonary complications, its efficacy in patients with COPD has not been documented. The aim of this study was to evaluate the effects of IS on pulmonary function tests, arterial blood gases, dyspnoea and health-related quality of life in patients hospitalized for COPD. A total of 27 consecutive patients (mean age, 68.4 +/- 7.9 years; 26 males) admitted for COPD exacerbations were recruited for the study. In total, 15 (IS treatment group) used IS for 2 months, together with medical treatment. The remaining 12 (medical treatment group) were given only medical treatment. Pulmonary function and blood gases were measured. Assessment of dyspnoea by visual analogue scale (VAS) and quality of life using the St. George's Respiratory Questionnaire (SGRQ) were performed at admission and after 2 months of treatment. The activity, impact and total scores for the SGRQ improved (all P < or = 0.0001), PaCO2 values decreased (P = 0.02), PaO2 and PAO2 values increased (P = 0.02 and P = 0.01, respectively) in the IS treatment group. However, there were no significant differences between the measurements made pretreatment and after 2 months of medical therapy in the medical treatment group, with regards to pulmonary function, blood gases, SGRQ scores and VAS. The use of IS appears to improve arterial blood gases and health-related quality of life in patients with COPD exacerbations, although it does not alter pulmonary function parameters.

Experimental human exposure to inhaled grain dust and ammonia: towards a model of concentrated animal feeding operations.

PubMed

Sigurdarson, Sigurdur T; O'Shaughnessy, Patrick T; Watt, Janet A; Kline, Joel N

2004-10-01

Ammonia and endotoxin-rich dust are present in high concentrations in swine confinement facilities; exposure to this environment is linked to workers' respiratory problems. We hypothesized that experimental exposure to ammonia and dust would impair pulmonary function, and that these exposures would be synergistic. We exposed six normal subjects and eight subjects with mild asthma to ammonia (16-25 ppm) and/or endotoxin-rich grain dust (4 mg/m3). Pulmonary function and exhaled NOx were measured before and after exposure. There was no significant change in pulmonary function in the normal subjects following any of the exposure conditions. Among asthmatics, a significant transient decrease in FEV1 was induced by grain dust, but was not altered by ammonia; increased bronchial hyperreactivity was also noted in this group. In a vulnerable population, exposure to grain dust results in transient airflow obstruction. Short-term exposure to ammonia does not increase this response.

Comparing the Efficacy of Tadalafil Versus Placebo on Pulmonary Artery Systolic Pressure and Right Ventricular Function in Patients with Beta-Thalassaemia Intermedia.

PubMed

Jalalian, Rozita; Moghadamnia, Ali Akbar; Tamaddoni, Ahmad; Khafri, Soraya; Iranian, Mohammadreza

2017-07-01

Conventional oral therapies in the management of pulmonary hypertension in people without haemoglobinopathies are of limited value in thalassaemia patients because of toxicity and poor effectiveness. This study was conducted to assess the effect of tadalafil on pulmonary artery pressure and right ventricular systolic function in patients with beta-thalassaemia intermedia. Forty-four patients with beta-thalassaemia intermedia with pulmonary hypertension based on transthoracic echocardiography (TTE) were entered in the study. Patients with hepatic or renal insufficiency and also patients who were treated with organic nitrates or alpha-blockers were excluded. The patients were randomly divided into two groups (n=22) and they were treated for six weeks with tadalafil (40mg daily) or placebo. The pulmonary artery systolic pressure (PASP), tricuspid regurgitation velocity (TRV) and parameters related to systolic function of the right ventricle were measured by the TTE before and after treatment. Significant improvement in TRV (3.02±0.02 m/s-2.52±0.06 m/s), PASP (45.31±0.66 mmHg-34.26±1.15mmHg) and parameters related to systolic function of the right ventricle were observed in the group who received tadalafil compared to placebo (p< 0.05). Tadalafil significantly decreased PASP and TRV in patients with beta-thalassaemia intermedia. Likewise, tadalafil improved right ventricular systolic function in the patients. Copyright © 2016 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.

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.

Nonlinear model for offline correction of pulmonary waveform generators.

PubMed

Reynolds, Jeffrey S; Stemple, Kimberly J; Petsko, Raymond A; Ebeling, Thomas R; Frazer, David G

2002-12-01

Pulmonary waveform generators consisting of motor-driven piston pumps are frequently used to test respiratory-function equipment such as spirometers and peak expiratory flow (PEF) meters. Gas compression within these generators can produce significant distortion of the output flow-time profile. A nonlinear model of the generator was developed along with a method to compensate for gas compression when testing pulmonary function equipment. The model and correction procedure were tested on an Assess Full Range PEF meter and a Micro DiaryCard PEF meter. The tests were performed using the 26 American Thoracic Society standard flow-time waveforms as the target flow profiles. Without correction, the pump loaded with the higher resistance Assess meter resulted in ten waveforms having a mean square error (MSE) higher than 0.001 L2/s2. Correction of the pump for these ten waveforms resulted in a mean decrease in MSE of 87.0%. When loaded with the Micro DiaryCard meter, the uncorrected pump outputs included six waveforms with MSE higher than 0.001 L2/s2. Pump corrections for these six waveforms resulted in a mean decrease in MSE of 58.4%.

The effect of exposure to SO2 on the respiratory system of power-station workers.

PubMed

Froom, P; Sackstein, G; Cohen, C; Lerman, Y; Kristal-Boneh, E; Ribak, J

1998-01-01

Sulfur dioxide (SO2) is generally recognized as a respiratory irritant, but its effects if any at low levels of exposure are uncertain. We studied 38 power station technicians exposed to 0.8 ppm (parts per million) 8-h weighted levels of sulfur dioxide, and compared them to workers performing similar tasks without such exposure. Those exposed complained 5.8 times more frequently of cough (95% CI =1.8-20.6, P < 0.001), and also had significantly more sputum production. There was also a trend for increasing prevalence of dyspnea. On the other hand there was no decrease in pulmonary function test values. In the eight exposed subjects who complained of dyspnea, there was a significant decrease in pulmonary flow values. We conclude that power station workers exposed to low levels of SO2 have increased respiratory symptoms, and deserve compensation if their symptoms become chronic. The pulmonary function tests were not different from the control subjects, but there may be a small group who are prone to long-term morbidity. Additional studies are warranted to confirm our findings, and to define immediate and long-term morbidity due to low exposure to SO2.

Pulmonary function recovery demonstrated by ventilation-perfusion scan after posterior vertebral column resection for severe adolescent idiopathic scoliosis: a case report.

PubMed

Fujii, Takeshi; Watanabe, Kota; Toyama, Yoshiaki; Matsumoto, Morio

2014-09-01

Case report. To describe a case in which a patient regained pulmonary function, assessed by ventilation-perfusion scans, after undergoing posterior vertebral column resection (VCR) to correct severe adolescent idiopathic scoliosis (AIS) with associated pulmonary dysfunction. Pulmonary improvement after corrective surgery for AIS has been reported. Ventilation-perfusion scans are useful for assessing pulmonary function. However, these scans have not been used to examine the recovery of pulmonary function after VCR for severe AIS with pulmonary dysfunction. A patient was described in whom ventilation-perfusion scans were used to examine improvements in impaired air ventilation and blood perfusion after VCR surgery for severe AIS. The relevant literature was reviewed. An 18-year-old male came to Keio University Hospital with exertional dyspnea associated with severe AIS. Radiographs showed severe scoliosis of 91° at T6-T12, and hypokyphosis of 6° at T5-T12. Computed tomographic scans showed narrowing of the thoracic cage on the convex side of the main thoracic curve, with the vertebral bodies at the apex of the curve obstructing the right main bronchus. Pulmonary function tests revealed a percent vital capacity of 44% and percent forced expiratory volume in 1 second of 76%. A ventilation-perfusion scan showed decreased air ventilation and blood perfusion in the right lung. The patient underwent posterior correction surgery, which used segmental pedicle screws with a VCR at T9. The scoliosis was corrected to 28°, and the kyphosis to 14°. Postoperative computed tomographic scans showed expansion of the right main bronchus. A ventilation-perfusion scan conducted 1 year after surgery showed clear improvement in both ventilation and blood perfusion in the right lung. The patient's forced expiratory volume in 1 second had increased to 91%. This is the first report in which ventilation-perfusion scans were used to examine improvements in impaired air ventilation and blood perfusion after VCR surgery in a patient with severe AIS. N/A.

Effects of nitrogen dioxide on pulmonary function in human subjects: an environmental chamber study

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

Kerr, H.D.; Kulle, T.J.; McIlhany, M.L.

Twenty human subjects with asthma and chronic bronchitis and 10 normal, healthy adults were exposed to 0.5 ppM of nitrogen dioxide for 2 h in an environmental chamber. Seven of the 13 subjects with asthma experienced symptoms with exposure, while only one each of the subjects with chronic bronchitis and the healthy, normal group experienced symptoms. Significant pulmonary function changes from control values with exposure to NO/sub 2/ were observed in decreased quasistatic compliance for the 10 normal subjects and the 20 subjects with asthma and chronic bronchitis. In addition, functional residual capacity increased significantly for the 20 subjects withmore » asthma and chronic bronchitis. The subjects with asthma and the subjects with chronic bronchitis as separate groups, however, did not show any significant changes with exposure. With this study we are reasonably confident that exposure of subjects with asthma and chronic bronchitis to 0.5 ppM NO/sub 2/ for 2 h does not produce a significant decrement in their pulmonary function.« less

Pulmonary rehabilitation coupled with negative pressure ventilation decreases decline in lung function, hospitalizations, and medical cost in COPD

PubMed Central

Huang, Hung-Yu; Chou, Pai-Chien; Joa, Wen-Ching; Chen, Li-Fei; Sheng, Te-Fang; Lin, Horng-Chyuan; Yang, Lan-Yan; Pan, Yu-Bin; Chung, Fu-Tsai; Wang, Chun-Hua; Kuo, Han-Pin

2016-01-01

Abstract Pulmonary rehabilitation (PR) brings benefits to patients with chronic obstructive pulmonary disease (COPD). Negative pressure ventilation (NPV) increases ventilation and decreases hyperinflation as well as breathing work in COPD. We evaluated the long-term effects of a hospital-based PR program coupled with NPV support in patients with COPD on clinical outcomes. One hundred twenty-nine patients with COPD were followed up for more than 5 years, with the NPV group (n = 63) receiving the support of NPV (20–30 cm H2O delivery pressure for 60 min) and unsupervised home exercise program of 20 to 30 min daily walk, while the control group (n = 6) only received unsupervised home exercise program. Pulmonary function tests and 6 min walk tests (6MWT) were performed every 3 to 6 months. Emergency room (ER) visits and hospitalization with medical costs were recorded. A significant time-by-group interaction in the yearly decline of forced expiratory volume in 1 s in the control group analyzed by mixed-model repeated-measure analysis was found (P = 0.048). The 6MWT distance of the NPV group was significantly increased during the first 4 years, with the interaction of time and group (P = 0.003), the time alone (P = 0.014), and the quadratic time (P < 0.001) being significant between the 2 groups. ER exacerbations and hospitalizations decreased by 66% (P < 0.0001) and 54% (P < 0.0001) in the NPV group, respectively. Patients on PR program coupled with NPV had a significant reduction of annual medical costs (P = 0.022). Our hospital-based multidisciplinary PR coupled with NPV reduced yearly decline of lung function, exacerbations, and hospitalization rates, and improved walking distance and medical costs in patients with COPD during a 5-year observation PMID:27741132

Pulmonary rehabilitation coupled with negative pressure ventilation decreases decline in lung function, hospitalizations, and medical cost in COPD: A 5-year study.

PubMed

Huang, Hung-Yu; Chou, Pai-Chien; Joa, Wen-Ching; Chen, Li-Fei; Sheng, Te-Fang; Lin, Horng-Chyuan; Yang, Lan-Yan; Pan, Yu-Bin; Chung, Fu-Tsai; Wang, Chun-Hua; Kuo, Han-Pin

2016-10-01

Pulmonary rehabilitation (PR) brings benefits to patients with chronic obstructive pulmonary disease (COPD). Negative pressure ventilation (NPV) increases ventilation and decreases hyperinflation as well as breathing work in COPD. We evaluated the long-term effects of a hospital-based PR program coupled with NPV support in patients with COPD on clinical outcomes.One hundred twenty-nine patients with COPD were followed up for more than 5 years, with the NPV group (n = 63) receiving the support of NPV (20-30 cm H2O delivery pressure for 60 min) and unsupervised home exercise program of 20 to 30 min daily walk, while the control group (n = 6) only received unsupervised home exercise program. Pulmonary function tests and 6 min walk tests (6MWT) were performed every 3 to 6 months. Emergency room (ER) visits and hospitalization with medical costs were recorded.A significant time-by-group interaction in the yearly decline of forced expiratory volume in 1 s in the control group analyzed by mixed-model repeated-measure analysis was found (P = 0.048). The 6MWT distance of the NPV group was significantly increased during the first 4 years, with the interaction of time and group (P = 0.003), the time alone (P = 0.014), and the quadratic time (P < 0.001) being significant between the 2 groups. ER exacerbations and hospitalizations decreased by 66% (P < 0.0001) and 54% (P < 0.0001) in the NPV group, respectively. Patients on PR program coupled with NPV had a significant reduction of annual medical costs (P = 0.022).Our hospital-based multidisciplinary PR coupled with NPV reduced yearly decline of lung function, exacerbations, and hospitalization rates, and improved walking distance and medical costs in patients with COPD during a 5-year observation.

Biventricular Heart Remodeling After Percutaneous or Surgical Pulmonary Valve Implantation: Evaluation by Cardiac Magnetic Resonance.

PubMed

Secchi, Francesco; Resta, Elda C; Cannaò, Paola M; Pluchinotta, Francesca; Piazza, Luciane; Butera, Gianfranco; Carminati, Mario; Sardanelli, Francesco

2017-11-01

The aim of this study was to evaluate the impact of percutaneous pulmonary valve implantation (PPVI) and surgical pulmonary valve replacement (SPVR) on biventricular and pulmonary valve function using cardiac magnetic resonance. Thirty-five patients aged 20±8 years (mean±SD) underwent PPVI, whereas 16 patients aged 30±11 years underwent SPVR. Cardiac magnetic resonance examinations were performed before and after the procedures with an average follow-up interval of 10 months. Cine steady-state free precession sequences for cardiac function and phase-contrast sequences for pulmonary flow were performed. The right ventricle (RV) and left ventricle (LV) functions were evaluated using a dedicated software. The RV end-diastolic volume index (mL/m) decreased significantly after PPVI and SPVR, from 74 to 64 (P=0.030) and from 137 to 83 (P=0.001), respectively. The RV ejection fraction increased significantly after SPVR, from 47% to 53% (P=0.038). The LV end-diastolic volume index increased significantly after PPVI, from 66 to 76 mL/m (P<0.001). The LV stroke volume index increased significantly after PPVI, from 34 to 43 mL/m (P=0.004). The analysis of bivariate correlations showed that in patients undergoing SPVR the RV changes after the procedure were positively correlated to LV changes in terms of end-systolic volume index (r=0587; P=0.017) and ejection fraction (r=0.681; P=0.004). A RV volumetric reduction and a positive effect on ventricular-ventricular interaction were observed after both PPVI and SPVR. After PPVI, a positive volumetric LV remodeling was found. No LV remodeling was found after SPVR. After both procedures, the replaced pulmonary valve functioned well.

Pulmonary function disparities exist and persist in Hispanic patients with cystic fibrosis: A longitudinal analysis.

PubMed

McGarry, Meghan E; Neuhaus, John M; Nielson, Dennis W; Burchard, Esteban; Ly, Ngoc P

2017-12-01

Hispanic patients with cystic fibrosis (CF) have decreased life expectancy compared to non-Hispanic white patients. Pulmonary function is a main predictor of life expectancy in CF. Ethnic differences in pulmonary function in CF have been understudied. The objective was to compare longitudinal pulmonary function between Hispanic and non-Hispanic white patients with CF. This cohort study of 15 018 6-25 years old patients in the CF Foundation Patient Registry from 2008 to 2013 compared FEV 1 percent predicted and longitudinal change in FEV 1 percent predicted in Hispanic to non-Hispanic white patients. We used linear mixed effects models with patient-specific slopes and intercepts, adjusting for 14 demographic and clinical variables. We did sub-analyses by CFTR class, F508del copies, and PERT use. Hispanic patients had lower FEV 1 percent predicted (79.9%) compared with non-Hispanic white patients (85.6%); (-5.8%, 95%CI -6.7% to -4.8%, P < 0.001), however, there was no difference in FEV 1 decline over time. Patients on PERT had a larger difference between Hispanic and non-Hispanic white patients in FEV 1 percent predicted than patients not on PERT (-6.0% vs -4.1%, P = 0.02). The ethnic difference in FEV 1 percent predicted was not statistically significant between CFTR classes (Class I-III: -6.1%, Class IV-V: -5.9%, Unclassified: -5.7%, P > 0.05) or between F508del copies (None: -7.6%, Heterozygotes: -5.6%, Homozygotes: -5.3%, P > 0.05). Disparities in pulmonary function exist in Hispanic patients with CF early in life and then persist without improving or worsening over time. It is valuable to investigate the factors contributing to pulmonary function in Hispanic patients with CF. © 2017 Wiley Periodicals, Inc.

Effect of sedation with detomidine and butorphanol on pulmonary gas exchange in the horse

PubMed Central

Nyman, Görel; Marntell, Stina; Edner, Anna; Funkquist, Pia; Morgan, Karin; Hedenstierna, Göran

2009-01-01

Background Sedation with α2-agonists in the horse is reported to be accompanied by impairment of arterial oxygenation. The present study was undertaken to investigate pulmonary gas exchange using the Multiple Inert Gas Elimination Technique (MIGET), during sedation with the α2-agonist detomidine alone and in combination with the opioid butorphanol. Methods Seven Standardbred trotter horses aged 3–7 years and weighing 380–520 kg, were studied. The protocol consisted of three consecutive measurements; in the unsedated horse, after intravenous administration of detomidine (0.02 mg/kg) and after subsequent butorphanol administration (0.025 mg/kg). Pulmonary function and haemodynamic effects were investigated. The distribution of ventilation-perfusion ratios (VA/Q) was estimated with MIGET. Results During detomidine sedation, arterial oxygen tension (PaO2) decreased (12.8 ± 0.7 to 10.8 ± 1.2 kPa) and arterial carbon dioxide tension (PaCO2) increased (5.9 ± 0.3 to 6.1 ± 0.2 kPa) compared to measurements in the unsedated horse. Mismatch between ventilation and perfusion in the lungs was evident, but no increase in intrapulmonary shunt could be detected. Respiratory rate and minute ventilation did not change. Heart rate and cardiac output decreased, while pulmonary and systemic blood pressure and vascular resistance increased. Addition of butorphanol resulted in a significant decrease in ventilation and increase in PaCO2. Alveolar-arterial oxygen content difference P(A-a)O2 remained impaired after butorphanol administration, the VA/Q distribution improved as the decreased ventilation and persistent low blood flow was well matched. Also after subsequent butorphanol no increase in intrapulmonary shunt was evident. Conclusion The results of the present study suggest that both pulmonary and cardiovascular factors contribute to the impaired pulmonary gas exchange during detomidine and butorphanol sedation in the horse. PMID:19422714

Alterations in NO- and PGI2- dependent function in aorta in the orthotopic murine model of metastatic 4T1 breast cancer: relationship with pulmonary endothelial dysfunction and systemic inflammation.

PubMed

Buczek, E; Denslow, A; Mateuszuk, L; Proniewski, B; Wojcik, T; Sitek, B; Fedorowicz, A; Jasztal, A; Kus, E; Chmura-Skirlinska, A; Gurbiel, R; Wietrzyk, J; Chlopicki, S

2018-05-22

Patients with cancer develop endothelial dysfunction and subsequently display a higher risk of cardiovascular events. The aim of the present work was to examine changes in nitric oxide (NO)- and prostacyclin (PGI 2 )-dependent endothelial function in the systemic conduit artery (aorta), in relation to the formation of lung metastases and to local and systemic inflammation in a murine orthotopic model of metastatic breast cancer. BALB/c female mice were orthotopically inoculated with 4T1 breast cancer cells. Development of lung metastases, lung inflammation, changes in blood count, systemic inflammatory response (e.g. SAA, SAP and IL-6), as well as changes in NO- and PGI 2 -dependent endothelial function in the aorta, were examined 2, 4, 5 and 6 weeks following cancer cell transplantation. As early as 2 weeks following transplantation of breast cancer cells, in the early metastatic stage, lungs displayed histopathological signs of inflammation, NO production was impaired and nitrosylhemoglobin concentration in plasma was decreased. After 4 to 6 weeks, along with metastatic development, progressive leukocytosis and systemic inflammation (as seen through increased SAA, SAP, haptoglobin and IL-6 plasma concentrations) were observed. Six weeks following cancer cell inoculation, but not earlier, endothelial dysfunction in aorta was detected; this involved a decrease in basal NO production and a decrease in NO-dependent vasodilatation, that was associated with a compensatory increase in cyclooxygenase-2 (COX-2)- derived PGI 2 production. In 4 T1 metastatic breast cancer in mice early pulmonary metastasis was correlated with lung inflammation, with an early decrease in pulmonary as well as systemic NO availability. Late metastasis was associated with robust, cancer-related, systemic inflammation and impairment of NO-dependent endothelial function in the aorta that was associated with compensatory upregulation of the COX-2-derived PGI 2 pathway.

A Randomized, Placebo-controlled Trial of Roflumilast. Effect on Proline-Glycine-Proline and Neutrophilic Inflammation in Chronic Obstructive Pulmonary Disease.

PubMed

Wells, J Michael; Jackson, Patricia L; Viera, Liliana; Bhatt, Surya P; Gautney, Joshua; Handley, Guy; King, R Wilson; Xu, Xin; Gaggar, Amit; Bailey, William C; Dransfield, Mark T; Blalock, J Edwin

2015-10-15

Roflumilast is a therapeutic agent in the treatment of chronic obstructive pulmonary disease (COPD). It has antiinflammatory effects; however, it is not known whether it can affect a biologic pathway implicated in COPD pathogenesis and progression. The self-propagating acetyl-proline-glycine-proline (AcPGP) pathway is a novel means of neutrophilic inflammation that is pathologic in the development of COPD. AcPGP is produced by extracellular matrix collagen breakdown with prolyl endopeptidase and leukotriene A4 hydrolase serving as the enzymes responsible for its production and degradation, respectively. We hypothesized that roflumilast would decrease AcPGP, halting the feed-forward cycle of inflammation. We conducted a single-center, placebo-controlled, randomized study investigating 12 weeks of roflumilast treatment added to current therapy in moderate-to-severe COPD with chronic bronchitis. Subjects underwent sputum and blood analyses, pulmonary function testing, exercise tolerance, and quality-of-life assessment at 0, 4, and 12 weeks. Twenty-seven patients were enrolled in the intention-to-treat analysis. Roflumilast treatment decreased sputum AcPGP by more than 50% (P < 0.01) and prolyl endopeptidase by 46% (P = 0.02), without significant improvement in leukotriene A4 hydrolase activity compared with placebo. Roflumilast also reduces other inflammatory markers. There were no significant changes in lung function, quality of life, or exercise tolerance between roflumilast- and placebo-treated groups. Roflumilast reduces pulmonary inflammation through decreasing prolyl endopeptidase activity and AcPGP. As expected for lower AcPGP levels, markers of neutrophilic inflammation are blunted. Inhibiting this self-propagating pathway lessens the overall inflammatory burden, which may alter the natural history of COPD, including the risk of exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT 01572948).

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.

Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

PubMed Central

Lakshminrusimha, Satyan; Wedgwood, Stephen; Czech, Lyubov; Gugino, Sylvia F.; Russell, James A.; Farrow, Kathryn N.; Steinhorn, Robin H.

2012-01-01

In the pulmonary vasculature, cGMP levels are regulated by soluble guanylate cyclase (sGC) and phosphodiesterase 5 (PDE5). We previously reported that lambs with persistent pulmonary hypertension of the newborn (PPHN) demonstrate increased reactive oxygen species (ROS) and altered sGC and PDE5 activity, with resultant decreased cGMP. The objective of this study was to evaluate the effects of hydrocortisone on pulmonary vascular function, ROS, and cGMP in the ovine ductal ligation model of PPHN. PPHN lambs were ventilated with 100% O2 for 24 h. Six lambs received 5 mg/kg hydrocortisone every 8 h times three doses (PPHN-hiHC), five lambs received 3 mg/kg hydrocortisone followed by 1 mg·kg−1·dose−1 times two doses (PPHN-loHC), and six lambs were ventilated with O2 alone (PPHN). All groups were compared with healthy 1-day spontaneously breathing lambs (1DSB). O2 ventilation of PPHN lambs decreased sGC activity, increased PDE5 activity, and increased ROS vs. 1DSB lambs. Both hydrocortisone doses significantly improved arterial-to-alveolar ratios relative to PPHN lambs, decreased PDE5 activity, and increased cGMP relative to PPHN lambs. High-dose hydrocortisone also increased sGC activity, decreased PDE5 expression, decreased ROS, and increased total vascular SOD activity vs. PPHN lambs. These data suggest that hydrocortisone treatment in clinically relevant doses improves oxygenation and decreases hyperoxia-induced changes in sGC and PDE5 activity, increasing cGMP levels. Hydrocortisone reduces ROS levels in part by increasing SOD activity in PPHN lambs ventilated with 100% O2. We speculate that hydrocortisone increases cGMP by direct effects on sGC and PDE5 expression and by attenuating abnormalities induced by oxidant stress. PMID:22198909

Determination of fluid extraction and osmotic conductance sigma K in the lung with hypertonic NaCl infusion. I. Theory.

PubMed

Hunter, M; Lee, J

1992-11-01

A dispersion and extraction model of the lung is developed to assess how the infusion of hypertonic saline into the pulmonary artery changes the gravimetric density of pulmonary venous blood. The dispersion analysis is built on the indicator dilution curve measured for the pulmonary circulation. The extraction model consists of microvascular and interstitial compartments separated by a permeable pulmonary endothelium. Because the density of fluid extracted by the hypertonic disturbance is lower than the blood density, the extraction leads to a decrease in blood density. Two cases of fluid extraction are analyzed, a hypertonic infusion to elevate the osmotic pressure in the pulmonary arterial blood in the form of a step function and an infusion performed over a period of 1 sec. Both cases show that the dispersion significantly attenuates the changes in osmotic pressure and density as they are transported by the blood along the pulmonary vasculature. Because the model has taken into account the effect of dispersion and pulmonary blood flow, the equations developed here provide the basis to calculate from the density change in pulmonary venous blood the characteristics of osmotic extraction intrinsic to the lung.

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.

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.

Sarcoidosis in children: HRCT findings and correlation with pulmonary function tests.

PubMed

Sileo, C; Epaud, R; Mahloul, M; Beydon, N; Elia, D; Clement, A; Le Pointe, H Ducou

2014-12-01

High-resolution computed tomography (HRCT) plays an important role in the diagnosis and staging of pulmonary sarcoidosis, but implies radiation exposure. In this light, we aimed to describe HRCT findings as well as their relationship with pulmonary function tests (PFT) in children with pulmonary sarcoidosis. In a retrospective study, 18 pediatric patients with sarcoidosis, including 12 with pulmonary abnormalities (PA group) and 6 without pulmonary abnormalities (APA group) were followed over a 16-year period. Relationships between HRCT scores and PFT were studied by non-parametric Spearman's test at diagnosis and by restricted maximum likelihood (REML) analysis during follow-up. Forty-three HRCT were scored. Twelve patients showed abnormal HRCT findings at diagnosis with multiple nodules or micronodules, while ground-glass opacities were seen in 11 patients. Ten patients exhibited pleural thickening or thickening of the fissure and 6 had interlobular septal thickening at diagnosis. No correlation between HRCT and forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), forced expiratory flow during the mid-half of the FVC (FEF(25-75)) and specific dynamical compliance (SpecC(Ldyn)) was found at diagnosis. However, linear mixed models showed that changes in total HRCT scores over time were significantly associated with SpecC(Ldyn), FVC, and FEV1 modifications. Radiologic findings in children with pulmonary sarcoidosis were similar to those in adults. HRCT and PFT are both essential investigations at diagnosis; however, the correlation between HRCT pulmonary parenchymal findings and PFT over time suggests the possibility of reducing the number of HRCT during follow-up to decrease unnecessary radiation exposure. © 2013 Wiley Periodicals, Inc.

Home-based pulmonary rehabilitation improves clinical features and systemic inflammation in chronic obstructive pulmonary disease patients.

PubMed

do Nascimento, Eloisa Sanches Pereira; Sampaio, Luciana Maria Malosá; Peixoto-Souza, Fabiana Sobral; Dias, Fernanda Dultra; Gomes, Evelim Leal Freitas Dantas; Greiffo, Flavia Regina; Ligeiro de Oliveira, Ana Paula; Stirbulov, Roberto; Vieira, Rodolfo Paula; Costa, Dirceu

2015-01-01

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic airflow limitation that leads beyond the pulmonary changes to important systemic effects. COPD is characterized by pulmonary and systemic inflammation. However, increases in the levels of inflammatory cytokines in plasma are found even when the disease is stable. Pulmonary rehabilitation improves physical exercise capacity and quality of life and decreases dyspnea. The aim of this study was to evaluate whether a home-based pulmonary rehabilitation (HBPR) program improves exercise tolerance in COPD patients, as well as health-related quality of life and systemic inflammation. This prospective study was conducted at the Laboratory of Functional Respiratory Evaluation, Nove de Julho University, São Paulo, Brazil. After anamnesis, patients were subjected to evaluations of health-related quality of life and dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test, incremental shuttle walk test, and blood test for quantification of systemic inflammatory markers (interleukin [IL]-6 and IL-8). At the end of the evaluations, patients received a booklet containing the physical exercises to be performed at home, three times per week for 8 consecutive weeks. Around 25 patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There was a significant increase in the walked distance and the maximal inspiratory pressure, improvements on two components from the health-related quality-of-life questionnaire, and a decrease in plasma IL-8 levels after the intervention. The HBPR is an important and viable alternative to pulmonary rehabilitation for the treatment of patients with COPD; it improves exercise tolerance, inspiratory muscle strength, quality of life, and systemic inflammation in COPD patients.

Inhalation exposure to JP-8 jet fuel alters pulmonary function and substance P levels in Fischer 344 rats.

PubMed

Pfaff, J; Parton, K; Lantz, R C; Chen, H; Hays, A M; Witten, M L

1995-01-01

In a simulated military flightline exposure protocol, Fischer 344 rats (F344) were used to investigate the pulmonary effects of JP-8 jet fuel inhalation. Exposures were nose only and for 1 h daily. Groups were exposed for 7 days (7D) or 28 days (28D). Each exposure group had a matched longitudinal control group (LC7 and LC28). Exposure concentrations of 520 mg m-3 caused an increase in dynamic compliance after 7 days of exposure, but compliance changes were not seen with continued exposure (28D, 495 mg m-3). Pulmonary resistance was increased in both 7- and 28-day JP-8-exposed groups. Changes in pulmonary function were accompanied by a decrease in substance P concentrations from the bronchoalveolar lavage fluid (BALF). No significant change was observed in BALF levels of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, which is a marker of endothelial cell function. The JP-8-exposed rats gained significantly less weight during the study period than the LC7 and LC28 groups, and the lungs of the 7D group were heavier by wet lung/body weight ratio (WtL/WtB). Alveolar clearance of technetium-labelled diethylenetriamine pentaacetate ([99mTc]DTPA) was increased in jet fuel-exposed groups. Light microscopy showed no pathological evidence of lung injury. Recovery from the early pulmonary effects of JP-8 inhalation occurred with continued exposure, as seen by recovery of pulmonary compliance and WtL/WtB.

Effect of nutritional status in individuals with chronic obstructive pulmonary disease undergoing pulmonary rehabilitation.

PubMed

Günay, Ersin; Kaymaz, Dicle; Selçuk, Nursel Türkoglu; Ergün, Pinar; Sengül, Fatma; Demir, Nese

2013-11-01

Chronic obstructive pulmonary disease (COPD) is considered a worldwide major public health problem. Weight loss, muscle and fat mass depletion are common nutritional problems in COPD patients and are determinant factors in pulmonary function, health status, disability and mortality. We aimed to assess the relationships between nutritional status and perception of dyspnoea, pulmonary function tests (PFT), exercise capacity and health-related quality of life (HRQoL) using the subjective global assessment (SGA) in COPD patients who were referred for pulmonary rehabilitation programme. A total of 163 patients with stable COPD who are candidates for outpatient pulmonary rehabilitation programme were included in this study. Nutritional status for all patients was assessed by SGA. Association of SGA scores (A, B and C) and anthropometric measurements, PFT, dyspnoea scales (Medical Research Council and resting BORG scale), HRQoL (St. George Respiratory Questionnaire and Chronic Respiratory Diseases Questionnaire) and exercise testing (shuttle walking test) were studied for statistical significance. Based on SGA, 9.2% of patients were severely malnourished (SGA-C). There were significant decreases in forced expiratory volume in the first second (FEV1 ) (P = 0.009), Medical Research Council scales (P < 0.001) and exercise capacity (incremental shuttle walking test (P = 0.001) and endurance shuttle walking test (P = 0.009)) in SGA-C. Deterioration in anthropometric measurements and HRQoL measures were observed in malnourished patients. Identifying the nutritional status and determining any requirement for nutritional supplement is an important component of comprehensive pulmonary rehabilitation programme. SGA is an easy and practical method to assess nutritional status in pulmonary rehabilitation candidate patients with stable COPD. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

MicroRNA-124 Controls the Proliferative, Migratory, and Inflammatory Phenotype of Pulmonary Vascular Fibroblasts

PubMed Central

Wang, Daren; Zhang, Zhang; Li, Min; Frid, Maria G.; Flockton, Amanda R.; McKeon, B. Alexandre; Yeager, Michael E.; Fini, Mehdi A.; Morrell, Nicholas W.; Pullamsetti, Soni S.; Velegala, Sivareddy; Seeger, Werner; McKinsey, Timothy A.; Sucharov, Carmen C.; Stenmark, Kurt R.

2014-01-01

Rationale Pulmonary hypertensive remodeling is characterized by excessive proliferation, migration, and proinflammatory activation of adventitial fibroblasts. In culture, fibroblasts maintain a similar activated phenotype. The mechanisms responsible for generation/maintenance of this phenotype remain unknown. Objective We hypothesized that aberrant expression of microRNA-124 (miR-124) regulates this activated fibroblast phenotype and sought to determine the signaling pathways through which miR-124 exerts effects. Methods and Results We detected significant decreases in miR-124 expression in fibroblasts isolated from calves and humans with severe pulmonary hypertension. Overexpression of miR-124 by mimic transfection significantly attenuated proliferation, migration, and monocyte chemotactic protein-1 expression of hypertensive fibroblasts, whereas anti–miR-124 treatment of control fibroblasts resulted in their increased proliferation, migration, and monocyte chemotactic protein-1 expression. Furthermore, the alternative splicing factor, polypyrimidine tract–binding protein 1, was shown to be a direct target of miR-124 and to be upregulated both in vivo and in vitro in bovine and human pulmonary hypertensive fibroblasts. The effects of miR-124 on fibroblast proliferation were mediated via direct binding to the 3′ untranslated region of polypyrimidine tract–binding protein 1 and subsequent regulation of Notch1/phosphatase and tensin homolog/FOXO3/p21Cip1 and p27Kip1 signaling. We showed that miR-124 directly regulates monocyte chemotactic protein-1 expression in pulmonary hypertension/idiopathic pulmonary arterial hypertension fibroblasts. Furthermore, we demonstrated that miR-124 expression is suppressed by histone deacetylases and that treatment of hypertensive fibroblasts with histone deacetylase inhibitors increased miR-124 expression and decreased proliferation and monocyte chemotactic protein-1 production. Conclusions Stable decreases in miR-124 expression contribute to an epigenetically reprogrammed, highly proliferative, migratory, and inflammatory phenotype of hypertensive pulmonary adventitial fibroblasts. Thus, therapies directed at restoring miR-124 function, including histone deacetylase inhibitors, should be investigated. PMID:24122720

Stenotrophomonas maltophilia Virulence and Specific Variations in Trace Elements during Acute Lung Infection: Implications in Cystic Fibrosis

PubMed Central

Crocetta, Valentina; Consalvo, Ada; Zappacosta, Roberta; Di Ilio, Carmine; Di Bonaventura, Giovanni

2014-01-01

Metal ions are necessary for the proper functioning of the immune system, and, therefore, they might have a significant influence on the interaction between bacteria and host. Ionic dyshomeostasis has been recently observed also in cystic fibrosis (CF) patients, whose respiratory tract is frequently colonized by Stenotrophomonas maltophilia. For the first time, here we used an inductively mass spectrometry method to perform a spatial and temporal analysis of the pattern of changes in a broad range of major trace elements in response to pulmonary infection by S. maltophilia. To this, DBA/2 mouse lungs were comparatively infected by a CF strain and by an environmental one. Our results showed that pulmonary ionomic profile was significantly affected during infection. Infected mice showed increased lung levels of Mg, P, S, K, Zn, Se, and Rb. To the contrary, Mn, Fe, Co, and Cu levels resulted significantly decreased. Changes of element concentrations were correlated with pulmonary bacterial load and markers of inflammation, and occurred mostly on day 3 post-exposure, when severity of infection culminated. Interestingly, CF strain – significantly more virulent than the environmental one in our murine model - provoked a more significant impact in perturbing pulmonary metal homeostasis. Particularly, exposure to CF strain exclusively increased P and K levels, while decreased Fe and Mn ones. Overall, our data clearly indicate that S. maltophilia modulates pulmonary metal balance in a concerted and virulence-dependent manner highlighting the potential role of the element dyshomeostasis during the progression of S. maltophilia infection, probably exacerbating the harmful effects of the loss of CF transmembrane conductance regulator function. Further investigations are required to understand the biological significance of these alterations and to confirm they are specifically caused by S. maltophilia. PMID:24586389

In situ cardiac perfusion reveals interspecific variation of intraventricular flow separation in reptiles.

PubMed

Joyce, William; Axelsson, Michael; Altimiras, Jordi; Wang, Tobias

2016-07-15

The ventricles of non-crocodilian reptiles are incompletely divided and provide an opportunity for mixing of oxygen-poor blood and oxygen-rich blood (intracardiac shunting). However, both cardiac morphology and in vivo shunting patterns exhibit considerable interspecific variation within reptiles. In the present study, we develop an in situ double-perfused heart approach to characterise the propensity and capacity for shunting in five reptile species: the turtle Trachemys scripta, the rock python Python sebae, the yellow anaconda Eunectes notaeus, the varanid lizard Varanus exanthematicus and the bearded dragon Pogona vitticeps To simulate changes in vascular bed resistance, pulmonary and systemic afterloads were independently manipulated and changes in blood flow distribution amongst the central outflow tracts were monitored. As previously demonstrated in Burmese pythons, rock pythons and varanid lizards exhibited pronounced intraventricular flow separation. As pulmonary or systemic afterload was raised, flow in the respective circulation decreased. However, flow in the other circulation, where afterload was constant, remained stable. This correlates with the convergent evolution of intraventricular pressure separation and the large intraventricular muscular ridge, which compartmentalises the ventricle, in these species. Conversely, in the three other species, the pulmonary and systemic flows were strongly mutually dependent, such that the decrease in pulmonary flow in response to elevated pulmonary afterload resulted in redistribution of perfusate to the systemic circuit (and vice versa). Thus, in these species, the muscular ridge appeared labile and blood could readily transverse the intraventricular cava. We conclude that relatively minor structural differences between non-crocodilian reptiles result in the fundamental changes in cardiac function. Further, our study emphasises that functionally similar intracardiac flow separation evolved independently in lizards (varanids) and snakes (pythons) from an ancestor endowed with the capacity for large intracardiac shunts. © 2016. Published by The Company of Biologists Ltd.

Lung function profiles and aerobic capacity of adult cigarette and hookah smokers after 12 weeks intermittent training.

PubMed

Koubaa, Abdessalem; Triki, Moez; Trabelsi, Hajer; Masmoudi, Liwa; Zeghal, Khaled N; Sahnoun, Zouhair; Hakim, Ahmed

2015-01-01

Introduction Pulmonary function is compromised in most smokers. Yet it is unknown whether exercise training improves pulmonary function and aerobic capacity in cigarette and hookah smokers and whether these smokers respond in a similar way as do non-smokers. Aim To evaluate the effects of an interval exercise training program on pulmonary function and aerobic capacity in cigarette and hookah smokers. Methods Twelve cigarette smokers, 10 hookah smokers, and 11 non-smokers participated in our exercise program. All subjects performed 30 min of interval exercise (2 min of work followed by 1 min of rest) three times a week for 12 weeks at an intensity estimated at 70% of the subject's maximum aerobic capacity ([Formula: see text]). Pulmonary function was measured using spirometry, and maximum aerobic capacity was assessed by maximal exercise testing on a treadmill before the beginning and at the end of the exercise training program. Results As expected, prior to the exercise intervention, the cigarette and hookah smokers had significantly lower pulmonary function than the non-smokers. The 12-week exercise training program did not significantly affect lung function as assessed by spirometry in the non-smoker group. However, it significantly increased both forced expiratory volume in 1 second and peak expiratory flow (PEF) in the cigarette smoker group, and PEF in the hookah smoker group. Our training program had its most notable impact on the cardiopulmonary system of smokers. In the non-smoker and cigarette smoker groups, the training program significantly improved [Formula: see text] (4.4 and 4.7%, respectively), v [Formula: see text] (6.7 and 5.6%, respectively), and the recovery index (7.9 and 10.5%, respectively). Conclusions After 12 weeks of interval training program, the increase of [Formula: see text] and the decrease of recovery index and resting heart rate in the smoking subjects indicated better exercise tolerance. Although the intermittent training program altered pulmonary function only partially, both aerobic capacity and life quality were improved. Intermittent training should be advised in the clinical setting for subjects with adverse health behaviors.

Lung function profiles and aerobic capacity of adult cigarette and hookah smokers after 12 weeks intermittent training.

PubMed

Koubaa, Abdessalem; Triki, Moez; Trabelsi, Hajer; Masmoudi, Liwa; Zeghal, Khaled N; Sahnoun, Zouhair; Hakim, Ahmed

2015-01-01

Pulmonary function is compromised in most smokers. Yet it is unknown whether exercise training improves pulmonary function and aerobic capacity in cigarette and hookah smokers and whether these smokers respond in a similar way as do non-smokers. To evaluate the effects of an interval exercise training program on pulmonary function and aerobic capacity in cigarette and hookah smokers. Twelve cigarette smokers, 10 hookah smokers, and 11 non-smokers participated in our exercise program. All subjects performed 30 min of interval exercise (2 min of work followed by 1 min of rest) three times a week for 12 weeks at an intensity estimated at 70% of the subject's maximum aerobic capacity (VO2max). Pulmonary function was measured using spirometry, and maximum aerobic capacity was assessed by maximal exercise testing on a treadmill before the beginning and at the end of the exercise training program. As expected, prior to the exercise intervention, the cigarette and hookah smokers had significantly lower pulmonary function than the non-smokers. The 12-week exercise training program did not significantly affect lung function as assessed by spirometry in the non-smoker group. However, it significantly increased both forced expiratory volume in 1 second and peak expiratory flow (PEF) in the cigarette smoker group, and PEF in the hookah smoker group. Our training program had its most notable impact on the cardiopulmonary system of smokers. In the non-smoker and cigarette smoker groups, the training program significantly improved VO2max (4.4 and 4.7%, respectively), v VO2max (6.7 and 5.6%, respectively), and the recovery index (7.9 and 10.5%, respectively). After 12 weeks of interval training program, the increase of VO2max and the decrease of recovery index and resting heart rate in the smoking subjects indicated better exercise tolerance. Although the intermittent training program altered pulmonary function only partially, both aerobic capacity and life quality were improved. Intermittent training should be advised in the clinical setting for subjects with adverse health behaviors.

Acute control of pulmonary regurgitation with a balloon "valve". An experimental investigation.

PubMed

Siwek, L G; Applebaum, R E; Jones, M; Clark, R E

1985-09-01

Operations for certain congenital cardiac lesions can produce pulmonary regurgitation. Pulmonary regurgitation contributes to right ventricular dysfunction, which may cause early postoperative morbidity and mortality. To ameliorate the problems of pulmonary regurgitation during the early postoperative period, we evaluated a method for its acute control. Complete pulmonary valvectomy was performed utilizing inflow occlusion in eight sheep. A catheter with a 15 ml spherical balloon was positioned in the pulmonary arterial trunk; its inflation and deflation were regulated by an intra-aortic balloon pump unit. Blood flow from the pulmonary arterial trunk and forward and regurgitant fraction were determined from electromagnetic flow transducer recordings. The regurgitant fraction with uncontrolled pulmonary regurgitation was 38% +/- 3% (forward flow = 42 +/- 5 ml/beat and regurgitant flow = 16 +/- 2 ml/beat). Inflation of the balloon during diastole was timed to completely eliminate pulmonary regurgitation. This balloon control of pulmonary regurgitation increased pulmonary arterial diastolic pressure from 12 +/- 1 to 17 +/- 1 mm Hg (p less than 0.0001) and decreased pulmonary arterial systolic pressure from 31 +/- 3 to 27 +/- 1 mm Hg (p = 0.06). Pulmonary arterial pulse pressure decreased from 19 +/- 3 to 9 +/- 1 mm Hg (p less than 0.003). Elimination of pulmonary regurgitation decreased right ventricular stroke volume (25 +/- 3 versus 42 +/- 5 ml/beat, p less than 0.0002) and resulted in a 46% reduction in right ventricular stroke work (5.0 +/- 0.6 versus 9.4 +/- 1.0 gm-m/beat, p less than 0.001) with no change in net forward pulmonary artery flow. Thus, acute pulmonary regurgitation can be controlled and this control improves overall hemodynamic status and decreases right ventricular work.

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

Right ventricular function during acute exacerbation of severe equine asthma.

PubMed

Decloedt, A; Borowicz, H; Slowikowska, M; Chiers, K; van Loon, G; Niedzwiedz, A

2017-09-01

Pulmonary hypertension has been described in horses with severe equine asthma, but its effect on the right ventricle has not been fully elucidated. To evaluate right ventricular structure and function after a 1-week period of pulmonary hypertension secondary to acute exacerbation of severe equine asthma. Prospective study. A clinical episode of severe equine asthma was induced experimentally in six susceptible horses. Examinations in remission and on day 7 of the clinical episode included a physical examination with clinical scoring, echocardiography, arterial blood gas measurements, venous blood sampling for cardiac biomarkers, intracardiac pressure measurements, right ventricular and right atrial myocardial biopsies, airway endoscopy and bronchoalveolar lavage. After 1 month of recovery, physical examination, echocardiography and cardiac biomarker analysis were repeated. Echocardiographic and pressure measurements were compared with those in 10 healthy control horses. All horses developed clinical signs of acute pulmonary obstruction. Right heart pressures increased significantly. Altered right ventricular function could be detected by tissue Doppler and speckle tracking echocardiography. Cardiac troponin concentrations did not increase significantly, but were highly elevated in one horse which exercised in the paddock prior to sampling. Focal neutrophil infiltration was present in two myocardial samples. Even in remission, asthmatic horses showed a thicker right ventricular wall, an increased left ventricular end-systolic eccentricity index at chordal level and decreased right ventricular longitudinal strain compared with controls. The induced clinical episode was rather mild and the number of horses was limited because of the invasive nature of the study. Pulmonary obstruction in asthmatic horses induces pulmonary hypertension with right ventricular structural and functional changes. © 2017 EVJ Ltd.

Effects of air pollution on children’s pulmonary health

NASA Astrophysics Data System (ADS)

Tabaku, Afrim; Bejtja, Gazmend; Bala, Silvana; Toci, Ervin; Resuli, Jerina

2011-12-01

IntroductionMany reports regarding the effects of air pollution on children's respiratory health have appeared in the scientific literature. Some investigators found increases in persistent cough and phlegm, bronchitis, and early respiratory infections in communities with poor air quality. The purpose of this survey was to compare the pulmonary function of children living in urban area of Tirana city with children living in suburban area of the city. Material and methodsThis survey is carried out during 2004-2005 period on 238 children living in urban area and in 72 children living in suburban area, measuring dynamic pulmonary function. A questionnaire was used to collect data on sex, current respiratory symptoms, allergy diagnosed by the physician, parent education and smoking habit of parents, presence of animals, synthetic carpets and moulds in their houses. The selection of schools, and children included in this survey was done by randomized method. Also, we have measured and classic air pollutants. ResultsComparing the results of values of pulmonary function of two groups of children, we have shown that differences were significant ( p 0.001), whereas comparing symptoms were for cough ( p 0.011) and for phlegm ( p 0.032). The level of particulate matter (PM10) and total suspended matter (TSP) were over the recommended limit values, whereas the levels of other pollutants have resulted within recommended levels of World Health Organization (WHO) ConclusionsThe results of this survey suggest that air pollution is associated with respiratory health of children causing a slight decrease in values of pulmonary function in children of urban area compared with those of suburban area.

[Combined pulmonary fibrosis and emphysema (CPFE)--limitation of usual lung function test and challenge at practice].

PubMed

Takai, Daiya

2014-12-01

Spirometry and the flow-volume curve test are commonly performed lung function tests. However, a unique clinical entity occasionally shows almost normal data in these tests, and is therefore missed on screening tests. The clinical entity of combined pulmonary emphysema and pulmdoary fibrosis was recognized and documented in the 90's in Japan, the USA, and Europe. Typical emphysema shows obstructive disorders, and pulmonary fibrosis shows restrictive disorders. Thus, the combination of both should lead to a combined disorder pattern in lung function tests, but this is not the case. In 2005, Cottin reported and redefined this combination of emphysema and fibrosis of the lung as "Combined Pulmonary Fibrosis and Emphysema" (CPFE). The patients are typically heavily smoking males who show an almost normal lung function. The upper lobe of these patients usually shows severe emphysema, which contributes to a static volume and a late phase in the forced volume test. On the other hand their lower lobe shows fibrotic change. The fibrotic portion contributes to early phase flow in the flow-volume curve. These mechanisms are a reason for the normal pattern appearance in lung function tests in CPFE patients. As a matter of course, these patients have damaged upper and lower lobes: their diffusing capacity of the lung shows a low performance, their saturation of blood hemoglobin decreases soon after light exercise, and their KL-6 (a blood marker of pulmonary fibrosis) usually shows a high value. They are considered a high risk group regarding complications of post-surgical treatment. Thus, when medical technologists identify suspicious cases, they should advise doctors to add diffusing capacity and KL-6 tests. (Review).

Investigation of Acute Pulmonary Deficits Associated with Biomass Fuel Cookstove Emissions in Rural Bangladesh

PubMed Central

Medgyesi, Danielle N.; Holmes, Heather A.; Angermann, Jeff E.

2017-01-01

The use of solid biomass fuels in cookstoves has been associated with chronic health impacts that disproportionately affect women worldwide. Solid fuel stoves that use wood, plant matter, and cow dung are commonly used for household cooking in rural Bangladesh. This study investigates the immediate effects of acute elevated cookstove emission exposures on pulmonary function. Pulmonary function was measured with spirometry before and during cooking to assess changes in respiratory function during exposure to cookstove emissions for 15 females ages 18–65. Cookstove emissions were characterized using continuous measurements of particulate matter (PM2.5—aerodynamic diameter <2.5 μm) concentrations at a 1 s time resolution for each household. Several case studies were observed where women ≥40 years who had been cooking for ≥25 years suffered from severe pulmonary impairment. Forced expiratory volume in one second over forced vital capacity (FEV1/FVC) was found to moderately decline (p = 0.06) during cooking versus non-cooking in the study cohort. The study found a significant (α < 0.05) negative association between 3- and 10-min maximum PM2.5 emissions during cooking and lung function measurements of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC obtained during cooking intervals. This study found that exposure to biomass burning emissions from solid fuel stoves- associated with acute elevated PM2.5 concentrations- leads to a decrease in pulmonary function, although further research is needed to ascertain the prolonged (e.g., daily, for multiple years) impacts of acute PM2.5 exposure on immediate and sustained respiratory impairment. PMID:28617349

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia.

PubMed

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-10-24

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia

PubMed Central

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-01-01

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic. PMID:27783043

Effects of age, socioeconomic status, and menstrual cycle on pulmonary response to ozone

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

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

The purpose of this study was to investigate the effects of age, socioeconomic status, and menstrual cycle phase on the pulmonary response to ozone exposure. Three hundred seventy-two healthy white and black young adults, between the ages of 18 and 35 y, were exposed only once to 0.0, 0.12, 0.18, 0.24, 0.30, or 0.40 ppm ozone for 2.3 h. Prior to and after exposure, pulmonary function tests were obtained. Prior to exposure, each subject completed a personal and family-history questionnaire. The response to this questionnaire were used to investigate age, socioeconomic status, and menstrual cycle phase effects on pulmonary responsivenessmore » to ozone. We concluded that the ages of subjects, within the age range studied, had an effect on responsiveness (i.e., decrements in forced expiratory volume in 1 s decreased as the subjects` ages decreased). Socioeconomic status, as reflected by education of fathers, also appeared to affect forced expiratory volume in 1-s responsiveness to ozone, with the middle socioeconomic group being the most responsive. The phase of menstrual cycle did not have an impact on individual responsiveness to ozone. 14 refs., 4 figs.« less

No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

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

Stanic, Sinisa, E-mail: sinisa.stanic@carle.com; Paulus, Rebecca; Timmerman, Robert D.

2014-04-01

Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signedmore » rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.« less

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.

Effect of Balloon Pulmonary Angioplasty on Respiratory Function in Patients With Chronic Thromboembolic Pulmonary Hypertension.

PubMed

Akizuki, Mina; Serizawa, Naoki; Ueno, Atsuko; Adachi, Taku; Hagiwara, Nobuhisa

2017-03-01

Balloon pulmonary angioplasty (BPA) in chronic thromboembolic pulmonary hypertension (CTEPH) improves hemodynamics and exercise capacity. However, its effect on respiratory function is unclear. Our objective was to investigate the effect of BPA on respiratory function. We enrolled patients with inoperable CTEPH who underwent BPA primarily in lower lobe arteries (first series) and upper and middle lobe arteries (second series). We compared changes in hemodynamics and respiratory function between different BPA fields. Sixty-two BPA sessions were performed in 13 consecutive patients. Mean pulmonary arterial pressure and pulmonary vascular resistance significantly improved from 44 ± 8 to 23 ± 5 mm Hg and 818 ± 383 to 311 ± 117 dyne/s/cm -5 . The percent predicted diffusion capacity of lung for carbon monoxide (Dlco) decreased after BPA in the lower lung field (from 60% ± 8% to 54% ± 8%) with no recovery. Percent Dlco increased after BPA in the upper middle lung field (from 53% ± 6% to 58% ± 6%) and continued to improve during the follow-up (from 58% ± 6% to 64% ± 11%). The ventilation/Co 2 production (V˙e/V˙co 2 ) slope significantly improved after BPA in the lower lung field (from 51 ± 13 to 41 ± 8) and continued to improve during the follow-up (from 41 ± 8 to 35 ± 7); however, the V˙e/V˙co 2 slope remained unchanged after BPA in the upper/middle lung field. Changes in % Dlco and the V˙e/V˙co 2 slope differed significantly between lower and upper/middle lung fields. The effect of BPA on respiratory function in patients with CTEPH differed depending on the lung field. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Oxidant and enzymatic antioxidant status (gene expression and activity) in the brain of chickens with cold-induced pulmonary hypertension

NASA Astrophysics Data System (ADS)

Hassanpour, Hossein; Khalaji-Pirbalouty, Valiallah; Nasiri, Leila; Mohebbi, Abdonnaser; Bahadoran, Shahab

2015-11-01

To evaluate oxidant and antioxidant status of the brain (hindbrain, midbrain, and forebrain) in chickens with cold-induced pulmonary hypertension, the measurements of lipid peroxidation, protein oxidation, antioxidant capacity, enzymatic activity, and gene expression (for catalase, glutathione peroxidase, and superoxide dismutases) were done. There were high lipid peroxidation/protein oxidation and low antioxidant capacity in the hindbrain of cold-induced pulmonary hypertensive chickens compared to control ( P < 0.05). In the hypertensive chickens, superoxide dismutase activity was decreased (forebrain, midbrain, and hindbrain), while catalase activity was increased (forebrain and midbrain) ( P < 0.05). Glutathione peroxidase activity did not change. Relative gene expression of catalase and superoxide dismutases (1 and 2) was downregulated, while glutathione peroxidase was upregulated in the brain of the cold-induced pulmonary hypertensive chickens. Probably, these situations in the oxidant and antioxidant status of the brain especially hindbrain may change its function at cardiovascular center and sympathetic nervous system to exacerbate pulmonary hypertension.

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

Indoor environmental factors associated with pulmonary function among adults in an acid rain-plagued city in Southwest China.

PubMed

Yu, Jie; Zhang, Longju; Luo, Ya; Tang, Yin; Tuo, Fangxu; Yang, Jiaqi; Xu, Jie

2017-04-01

To assess the association of indoor environmental risk factors with respiratory function among adults in an acid rain-plagued city in China where coal use is frequent. The subjects were randomly selected in the winter season. Information on selected home environmental factors was collected through administered questionnaires. Additionally, pulmonary function tests, including Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 s (FEV 1 ), FEV 1 /FVC and Peak Expiratory Flow Rate (PEFR) were also performed in participants. This study showed that, among a variety of risk factors, coal fuel use, cooking oil fumes and active and passive smoking exposure together with asthma in childhood were important factors for deterioration of pulmonary function among adults in the winter season (p < 0.05). Additionally, subjects whose kitchen was located in the living room or bedroom, who opened their windows only occasionally or never, who noted the presence of cooking oil fumes and pests, whose bedroom was shared by 3 or more residents and who kept pets tended to exhibit lower values of FVC, FEV 1 and PEFR values compared with non-exposed counterparts (p < 0.05). This study demonstrated impaired pulmonary function among adults who were exposed to indoor risk factors, such as coal fires and cigarette smoking compared to non-users in the winter season and emphasizes the need for public health efforts to decrease exposure to indoor air pollution.

Cardioprotective effect of cerium oxide nanoparticles in monocrotaline rat model of pulmonary hypertension: A possible implication of endothelin-1.

PubMed

Nassar, Seham Zakaria; Hassaan, Passainte S; Abdelmonsif, Doaa A; ElAchy, Samar Nabil

2018-05-15

Cerium oxide nanoparticles (CeO 2 NPs) have been recently introduced into the medical field for their antioxidant properties. The ability of CeO 2 NPs alone or in combination with spironolactone (SP) to attenuate monocrotaline (MCT)-induced pulmonary hypertension and associated right ventricular hypertrophy was studied in rats. A special emphasis was given to endothelin-1 pathway. Pulmonary hypertension was induced in albino rats by a single subcutaneous injection of MCT (60 mg/kg). Rats received either single CeO 2 NPs therapy or combined therapy with SP for 2 weeks. CeO 2 NPs improved pulmonary function tests with concomitant decrease in serum endothelin-1 and pulmonary expression of endothelin-1 and its receptor ETAR. Besides, CeO 2 NPs diminished MCT-induced right ventricular hypertrophy and reduced cardiac oxidative stress and apoptosis. CeO 2 NPs could improve pulmonary hypertension and associated right ventricular hypertrophy with no additive value for SP. Besides being an antioxidant, CeO 2 NPs work through endothelin-1 pathway to improve pulmonary hypertension. Copyright © 2018 Elsevier Inc. All rights reserved.

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)

TU-CD-BRA-11: Application of Bone Suppression Technique to Inspiratory/expiratory Chest Radiography

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

Tanaka, R; Sanada, S; Sakuta, K

Purpose: The bone suppression technique based on advanced image processing can suppress the conspicuity of bones on chest radiographs, creating soft tissue images normally obtained by the dual-energy subtraction technique. This study was performed to investigate the usefulness of bone suppression technique in quantitative analysis of pulmonary function in inspiratory/expiratory chest radiography. Methods: Commercial bone suppression image processing software (ClearRead; Riverain Technologies) was applied to paired inspiratory/expiratory chest radiographs of 107 patients (normal, 33; abnormal, 74) to create corresponding bone suppression images. The abnormal subjects had been diagnosed with pulmonary diseases, such as pneumothorax, pneumonia, emphysema, asthma, and lung cancer.more » After recognition of the lung area, the vectors of respiratory displacement were measured in all local lung areas using a cross-correlation technique. The measured displacement in each area was visualized as displacement color maps. The distribution pattern of respiratory displacement was assessed by comparison with the findings of lung scintigraphy. Results: Respiratory displacement of pulmonary markings (soft tissues) was able to be quantified separately from the rib movements on bone suppression images. The resulting displacement map showed a left-right symmetric distribution increasing from the lung apex to the bottom region of the lung in many cases. However, patients with ventilatory impairments showed a nonuniform distribution caused by decreased displacement of pulmonary markings, which were confirmed to correspond to area with ventilatory impairments found on the lung scintigrams. Conclusion: The bone suppression technique was useful for quantitative analysis of respiratory displacement of pulmonary markings without any interruption of the rib shadows. Abnormal areas could be detected as decreased displacement of pulmonary markings. Inspiratory/expiratory chest radiography combined with the bone suppression technique has potential for predicting local lung function on the basis of dynamic analysis of pulmonary markings. This work was partially supported by Nakatani Foundation, Grant-in-aid for Scientific Research (C) of Ministry of Education, Culture, Sports, Science and Technology, JAPAN (Grant number : 24601007), and Nakatani Foundation, Mitsubishi Foundation, and the he Mitani Foundation for Research and Development. Yasushi Kishitani is a staff of TOYO corporation.« less

[Increased risk of chronic obstructive pulmonary disease among tunnel construction workers].

PubMed

Ulvestad, Bente; Lund, May Brit

2003-08-28

As tunnel workers are exposed to particles from drilling, blasting and diesel exhaust, we aimed to assess the occurrence of respiratory symptoms and lung function decline in underground construction workers and relate these findings to exposure. 212 tunnel workers and a reference group of 205 outdoor construction workers participated in a cross-sectional study. Respiratory symptoms and lung function were studied in relation to exposure. A subgroup of 29 non-smoking concrete workers who had been exposed to tunnel environment for one year, were examined by acoustic rhinometry, exhaled NO, spirometry and a questionnaire. Finally 122 tunnel workers were included in a prospective study in 1991 and re-examined in 1999. Among the tunnel workers the prevalence of chronic obstructive pulmonary disease (COPD) was 14% vs. 8% in the reference subjects. Compared to the reference subjects, the tunnel workers had a significant decrease in FEV1, related to years of exposure. Concrete workers from the tunnel site had significantly increased exhaled NO levels and nasal mucosal swelling compared to subjects who had performed similar tasks outdoors. The decrease in FEV1 was associated with cumulative exposure to respirable dust and quartz. Inhalation of construction-generated dust and gases enhances the risk of chronic obstructive pulmonary disease in tunnel workers.

Illness perceptions and coping with disease in chronic obstructive pulmonary disease: Effects on health-related quality of life.

PubMed

Vaske, Isabelle; Kenn, Klaus; Keil, Daniel C; Rief, Winfried; Stenzel, Nikola M

2017-10-01

This study investigated the effects of illness perceptions and coping with disease on health-related quality of life in chronic obstructive pulmonary disease. Therefore, participants ( N = 444) completed online questionnaires assessing illness severity (chronic obstructive pulmonary disease stage), Illness Perceptions Questionnaire, coping with disease (Essener Coping Questionnaire), and health-related quality of life (short form-12). Hierarchical regression and moderation analyses were conducted. The results showed that health-related quality of life was predicted by illness perceptions and several aspects of coping with disease. The association between illness perceptions and health-related quality of life was mediated by the corresponding coping with disease subscales. It is concluded that in order to prevent decreasing health-related quality of life in chronic obstructive pulmonary disease, treatment may be adjusted by promoting coping with disease and functional illness perceptions.

Respiratory muscle strength and pulmonary function in children with rhinitis and asthma after a six-minute walk test.

PubMed

Soares, Ana Alice de Almeida; Barros, Camila Moraes; Santos, Cássia Giulliane Costa; Dos Santos, Maria Renata Aragão; Silva, José Rodrigo Santos; Silva Junior, Walderi Monteiro da; Simões, Silvia de Magalhães

2018-03-01

Rhinitis and asthma decrease quality of life. Few studies have assessed the performance of children with asthma or rhinitis under submaximal exercise. We evaluated maximal respiratory pressures, spirometric parameters, and ability to sustain submaximal exercise in these children before and after the 6-minute walk test (6MWT), compared to healthy children. This cross-sectional, analytical study included 89 children aged 6-12 years in outpatient follow-up: 27 healthy (H), 31 with rhinitis (R), and 31 with mild asthma under control (A). Pulmonary function parameters and maximal respiratory pressures were measured before and 5, 10, and 30 minutes after the 6MWT. Wilcoxon test was used to compare numerical numerical variables between two groups and analysis of variance or Kruskal-Wallis test for comparison among three groups. Total distance traveled in the 6MWT was similar among the three groups. Compared to pre-test values, VEF1 (Forced Expiratory Volume in 1 second), VEF0.75 (Forced Expiratory Volume in 0.75 second), and FEF25-75 (Forced Expiratory Flow 25-75% of the Forced Vital Capacity - CVF - curve) decreased significantly after the 6MWT in group A, and VEF0.75, FEF25-75, and VEF1/CVF decreased significantly in group R. Groups A and R had lower Maximum Inspiratory Pressure values than group H before and after the 6MWT at all time points assessed. The findings suggest that children with rhinitis and mild asthma present with alterations in respiratory muscle strength and pulmonary function not associated with clinical complaints, reinforcing the concept of the united airways.

Effects of inhalation of acidic compounds on pulmonary function in allergic adolescent subjects

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

Koenig, J.Q.; Covert, D.S.; Pierson, W.E.

There is concern about the human health effects of inhalation of acid compounds found in urban air pollution. It was the purpose of this study to investigate three of these acid compounds, sulfur dioxide (SO/sub 2/), sulfuric acid (H/sub 2/SO/sub 4/), and nitric acid (HNO/sub 3/) in a group of allergic adolescent subjects. Subjects were exposed during rest and moderate exercise to 0.7 mumole/m/sup 3/ (68 micrograms/m/sup 3/) H/sub 2/SO/sub 4/, 4.0 mumole/m/sup 3/ (0.1 ppm) SO/sub 2/, or 2.0 mumole/m/sup 3/ (0.05 ppm) HNO/sub 3/. Pulmonary functions (FEV1, total respiratory resistance, and maximal flow) were measured before and aftermore » exposure. Preliminary analysis based on nine subjects indicates that exposure to 0.7 mumole/m/sup 3/ H/sub 2/SO/sub 4/ alone and in combination with SO/sub 2/ caused significant changes in pulmonary function, whereas exposure to air or SO/sub 2/ alone did not. FEV1 decreased an average of 6% after exposure to H/sub 2/SO/sub 4/ alone and 4% when the aerosol was combined with SO/sub 2/. The FEV1 decrease was 2% after both air and SO/sub 2/ exposures. Total respiratory resistance (RT) increased 15% after the combined H/sub 2/SO/sub 4/ exposures, 12% after H/sub 2/SO/sub 4/ alone, and 7% after exposure to air. After exposures to HNO3 alone, FEV1 decreased by 4%, and RT increased by 23%. These results are preliminary; final conclusions must wait for completion of the study.« less

Assessment of multislice CT to quantify pulmonary emphysema function and physiology in a rat model

NASA Astrophysics Data System (ADS)

Cao, Minsong; Stantz, Keith M.; Liang, Yun; Krishnamurthi, Ganapathy; Presson, Robert G., Jr.

2005-04-01

Purpose: The purpose of this study is to evaluate multi-slice computed tomography technology to quantify functional and physiologic changes in rats with pulmonary emphysema. Method: Seven rats were scanned using a 16-slice CT (Philips MX8000 IDT) before and after artificial inducement of emphysema. Functional parameters i.e. lung volumes were measured by non-contrast spiral scan during forced breath-hold at inspiration and expiration followed by image segmentation based on attenuation threshold. Dynamic CT imaging was performed immediately following the contrast injection to estimate physiology changes. Pulmonary perfusion, fractional blood volume, and mean transit times (MTTs) were estimated by fitting the time-density curves of contrast material using a compartmental model. Results: The preliminary results indicated that the lung volumes of emphysema rats increased by 3.52+/-1.70mL (p<0.002) at expiration and 4.77+/-3.34mL (p<0.03) at inspiration. The mean lung densities of emphysema rats decreased by 91.76+/-68.11HU (p<0.01) at expiration and low attenuation areas increased by 5.21+/-3.88% (p<0.04) at inspiration compared with normal rats. The perfusion for normal and emphysema rats were 0.25+/-0.04ml/s/ml and 0.32+/-0.09ml/s/ml respectively. The fractional blood volumes for normal and emphysema rats were 0.21+/-0.04 and 0.15+/-0.02. There was a trend toward faster MTTs for emphysema rats (0.42+/-0.08s) than normal rats (0.89+/-0.19s) with p<0.006, suggesting that blood flow crossing the capillaries increases as the capillary volume decreases and which may cause the red blood cells to leave the capillaries incompletely saturated with oxygen if the MTTs become too short. Conclusion: Quantitative measurement using CT of structural and functional changes in pulmonary emphysema appears promising for small animals.

Effect of occupational silica exposure on pulmonary function.

PubMed

Hertzberg, Vicki Stover; Rosenman, Kenneth D; Reilly, Mary Jo; Rice, Carol H

2002-08-01

To assess the effect of occupational silica exposure on pulmonary function. Epidemiologic evaluation based on employee interview, plant walk-through, and information abstracted from company medical records, employment records, and industrial hygiene measurements. Drawn from 1,072 current and former hourly wage workers employed before January 1, 1986. Thirty-six individuals with radiographic evidence of parenchymal changes consistent with asbestosis or silicosis were excluded. In addition, eight individuals whose race was listed as other than white or black were excluded. Analysis of spirometry data (FVC, FEV1, FEV1/FVC) only using the test results that met American Thoracic Society criteria for reproducibility and acceptability shows decreasing percent-predicted FVC and FEV1 and decreasing FEV1/FVC in relationship to increasing silica exposure among smokers. Logistic regression analyses of abnormal FVC and abnormal FEV1 values (where abnormal is defined as < 95% confidence limit for predicted using the Knudson prediction equations) show odds ratios of 1.49 and 1.68, respectively, for occurrence of abnormal result with 40 years of exposure at the Occupational Safety and Health Administration (OSHA)-allowable level of 0.1 mg/m3. Longitudinal analyses of FVC and FEV1 measurements show a 1.6 mL/yr and 1.1 mL/yr, respectively, decline per milligram/cubic meter mean silica exposure (p = 0.011 and p = 0.001, respectively). All analyses were adjusted for weight, height, age, ethnicity, smoking status, and other silica exposures. Systematic problems leading to measurement error were possible, but would have been nondifferential in effect and not related to silica measurements. There is a consistent association between increased pulmonary function abnormalities and estimated measures of cumulative silica exposure within the current allowable OSHA regulatory level. Despite concerns about the quality control of the pulmonary function measurements use in these analyses, our results support the need to lower allowable air levels of silica and increase efforts to encourage cessation of cigarette smoking among silica-exposed workers.

[Lung dysfunction in patients with severe chronic obstructive bronchitis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2005-01-01

VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Raw, Rin, Rex, DLCO-SS, PaO2, and PaCO2 were determined in 36 patients with severe chronic obstructive lung disease (FEV1 < 50% of the normal value). All the patients were found to have impaired bronchial patency and changes in lung volumes and capacities; 83.3% of the patients had pulmonary gas exchange dysfunction. Impaired bronchial patency mainly appeared as decreased FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, Raw, Rin, Rex; altered lung volumes and capacities manifested by increased RV, TGV, and TLC, and by decreased VC and FVC; pulmonary gas exchange dysfunction showed up as lowered PaO2 and DLCO-SS, as decreased or increased PaCO2. The observed bronchial patency disorders varied from significant to severe; functional changes in lung volumes and capacities were mild to severe.

Controlled lung reperfusion to reduce pulmonary ischaemia/reperfusion injury after cardiopulmonary bypass in a porcine model.

PubMed

Slottosch, Ingo; Liakopoulos, Oliver; Kuhn, Elmar; Deppe, Antje; Lopez-Pastorini, Alberto; Schwarz, David; Neef, Klaus; Choi, Yeong-Hoon; Sterner-Kock, Anja; Jung, Kristina; Mühlfeld, Christian; Wahlers, Thorsten

2014-12-01

Ischaemia/reperfusion (I/R) injury of the lungs contributes to pulmonary dysfunction after cardiac surgery with cardiopulmonary bypass (CPB), leading to increased morbidity and mortality of patients. This study investigated the value of controlled lung reperfusion strategies on lung ischaemia-reperfusion injury in a porcine CPB model. Pigs were subjected to routine CPB for 120 min with 60 min of blood cardioplegic cardiac arrest (CCA). Following CCA, the uncontrolled reperfusion (UR, n = 6) group was conventionally weaned from CPB. Two groups underwent controlled lung reperfusion strategies (CR group: controlled reperfusion conditions, n = 6; MR group: controlled reperfusion conditions and modified reperfusate, n = 6) via the pulmonary artery before CPB weaning. Sham-operated pigs (n = 7) served as controls. Animals were followed up until 4 h after CPB. Pulmonary function, haemodynamics, markers of inflammation, endothelial injury and oxidative stress as well as morphological lung alterations were analysed. CPB (UR group) induced deterioration of pulmonary function (lung mechanics, oxygenation index and lung oedema). Also, controlled lung reperfusion groups (CR and MR) presented with pulmonary dysfunction after CPB. However, compared with UR, controlled lung reperfusion strategies (CR and MR) improved lung mechanics and reduced markers of oxidative stress, but without alteration of haemodynamics, oxygenation, inflammation, endothelial injury and lung morphology. Both controlled reperfusion groups were similar without relevant differences. Controlled lung reperfusion strategies attenuated a decrease in lung mechanics and an increase in oxidative stress, indicating an influence on CPB-related pulmonary injury. However, they failed to avoid completely CPB-related lung injury, implying the need for additional strategies given the multifactorial pathophysiology of postoperative pulmonary dysfunction. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Time course of lung function changes in atypical pneumonia.

PubMed Central

Benusiglio, L N; Stalder, H; Junod, A F

1980-01-01

We measured pulmonary function in each of 21 patients suffering from "atypical", non-bacterial pneumonia during the acute illness and during convalescence (two to 18 months) to study the course and the nature of functional impairment at different stages of the disease. In six patients, no aetiological agent was found. An aetiological agent was identified in 15 of the patients: Mycoplasma pneumoniae (seven patients), influenza A (three patients), parainfluenza 3 (one patient), varicella (two patients), Q fever (one patient), coxsackie B3 (one patient). At the time of admission we observed a restrictive pattern in 52%, an obstructive pattern (decreased FEV1/FVC ratio) in 52% abnormalities in distribution of ventilation (abnormal slope of phase 3) in 63%, and abnormalities in gas exchange (increased AaDO2) in 75% of the patients. The frequency of abnormalities in these pulmonary function tests decreased dramatically after two to four weeks and nearly disappeared in most patients during convalescence. The only major residual abnormality was a decreased FEV1/FVC ratio in five subjects, four of whom were smokers. However, when MMEF and V75 were measured at this stage, their average value for all the groups of patients with the exclusion of the Mycoplasma pneumoniae group, was markedly reduced. These data suggest that small airways involvement can be demonstrated during the convalescence of patients recovering from various types of atypical pneumonia other than those caused by Mycoplasma pneumoniae. PMID:7444825

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.

Hypoxemia, hypercapnia, and breathing pattern in patients with chronic obstructive pulmonary disease.

PubMed

Parot, S; Miara, B; Milic-Emili, J; Gautier, H

1982-11-01

The results of lung function tests (total and functional residual capacities, residual volume/total lung capacity ratio, forced expiratory volume in one second) breathing patterns and arterial PO2 and PCO2 were studied in 651 ambulatory male patients with chronic obstructive pulmonary disease, functionally and clinically stable. Function tests were only loosely correlated with gas tensions: abnormalities in mechanics and in gas exchange are not necessarily related. In patients matched for the degree of obstruction, the breathing pattern depended upon both PaO2 and PaCO2. Isolated hypoxemia was accompanied by increased respiratory frequency without any variation in tidal volume: this suggests that the chemoreceptive systems still responded to changes in PaO2. Isolated hypercapnia was accompanied by a decrease in tidal volume and an increase in respiratory frequency. Consequently, the dead space/tidal volume ratio increased, leading to a drop in alveolar ventilation and to CO2 retention.

A 2-year follow-up of spirometric parameters in workers of a tile and ceramic industry, Yazd, southeastern Iran.

PubMed

Mehrparvar, A H; Mirmohammadi, S J; Mostaghaci, M; Davari, M H; Hashemi, S H

2013-04-01

Respiratory diseases cause a considerable amount of morbidity and mortality in the world. Pulmonary function tests are important measures for the diagnosis and management of respiratory disorders. Workers in tile and ceramic industry are exposed to high amounts of respiratory pollutants. To identify the changes in spirometric parameters in a 2-year period among tile and ceramic workers in Yazd and compare it with a control group. The study was conducted in 5 tile and ceramic factories selected by cluster sampling between 2009 and 2011 in Yazd, southeastern Iran. Demographic data and spirometric parameters of participants were recorded. Spirometric parameters were significantly reduced during the 2 years. The largest decrease was observed in FVC (≈500 mL) in ball-mill and grinding after 2 years. Decrease in all spirometric parameters was significantly higher in industrial workers than office workers. Respiratory exposure in tile and ceramic industry can significantly affect pulmonary function tests.

Chronic obstructive pulmonary disease and glucose metabolism: a bitter sweet symphony

PubMed Central

2012-01-01

Chronic obstructive pulmonary disease, metabolic syndrome and diabetes mellitus are common and underdiagnosed medical conditions. It was predicted that chronic obstructive pulmonary disease will be the third leading cause of death worldwide by 2020. The healthcare burden of this disease is even greater if we consider the significant impact of chronic obstructive pulmonary disease on the cardiovascular morbidity and mortality. Chronic obstructive pulmonary disease may be considered as a novel risk factor for new onset type 2 diabetes mellitus via multiple pathophysiological alterations such as: inflammation and oxidative stress, insulin resistance, weight gain and alterations in metabolism of adipokines. On the other hand, diabetes may act as an independent factor, negatively affecting pulmonary structure and function. Diabetes is associated with an increased risk of pulmonary infections, disease exacerbations and worsened COPD outcomes. On the top of that, coexistent OSA may increase the risk for type 2 DM in some individuals. The current scientific data necessitate a greater outlook on chronic obstructive pulmonary disease and chronic obstructive pulmonary disease may be viewed as a risk factor for the new onset type 2 diabetes mellitus. Conversely, both types of diabetes mellitus should be viewed as strong contributing factors for the development of obstructive lung disease. Such approach can potentially improve the outcomes and medical control for both conditions, and, thus, decrease the healthcare burden of these major medical problems. PMID:23101436

Exercise facilitates early recognition of cardiac and vascular remodeling in chronic thromboembolic pulmonary hypertension in swine.

PubMed

Stam, Kelly; van Duin, Richard W B; Uitterdijk, André; Cai, Zongye; Duncker, Dirk J; Merkus, Daphne

2018-03-01

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 4% of patients after pulmonary embolism and is accompanied by an impaired exercise tolerance, which is ascribed to the increased right ventricular (RV) afterload in combination with a ventilation/perfusion (V/Q) mismatch in the lungs. The present study aimed to investigate changes in arterial Po 2 and hemodynamics in response to graded treadmill exercise during development and progression of CTEPH in a novel swine model. Swine were chronically instrumented and received multiple pulmonary embolisms by 1) microsphere infusion (Spheres) over 5 wk, 2) endothelial dysfunction by administration of the endothelial nitric oxide synthase inhibitor N ω -nitro-l-arginine methyl ester (L-NAME) for 7 wk, 3) combined pulmonary embolisms and endothelial dysfunction (L-NAME + Spheres), or 4) served as sham-operated controls (sham). After a 9 wk followup, embolization combined with endothelial dysfunction resulted in CTEPH, as evidenced by mean pulmonary artery pressures of 39.5 ± 5.1 vs. 19.1 ± 1.5 mmHg (Spheres, P < 0.001), 22.7 ± 2.0 mmHg (L-NAME, P < 0.001), and 20.1 ± 1.5 mmHg (sham, P < 0.001), and a decrease in arterial Po 2 that was exacerbated during exercise, indicating V/Q mismatch. RV dysfunction was present after 5 wk of embolization, both at rest (trend toward increased RV end-systolic lumen area, P = 0.085, and decreased stroke volume index, P = 0.042) and during exercise (decreased stroke volume index vs. control, P = 0.040). With sustained pulmonary hypertension, RV hypertrophy (Fulton index P = 0.022) improved RV function at rest and during exercise, but this improvement was insufficient in CTEPH swine to result in an exercise-induced increase in cardiac index. In conclusion, embolization in combination with endothelial dysfunction results in CTEPH in swine. Exercise increased RV afterload, exacerbated the V/Q mismatch, and unmasked RV dysfunction. NEW & NOTEWORTHY Here, we present the first double-hit chronic thromboembolic pulmonary hypertension swine model. We show that embolization as well as endothelial dysfunction is required to induce sustained pulmonary hypertension, which is accompanied by altered exercise hemodynamics and an exacerbated ventilation/perfusion mismatch during exercise.

Effects of side lying on lung function in older individuals.

PubMed

Manning, F; Dean, E; Ross, J; Abboud, R T

1999-05-01

Body positioning exerts a strong effect on pulmonary function, but its effect on other components of the oxygen transport pathway are less well understood, especially the effects of side-lying positions. This study investigated the interrelationships between side-lying positions and indexes of lung function such as spirometry, alveolar diffusing capacity, and inhomogeneity of ventilation in older individuals. Nineteen nonsmoking subjects (mean age=62.8 years, SD=6.8, range=50-74) with no history of cardiac or pulmonary disease were tested over 2 sessions. The test positions were sitting and left side lying in one session and sitting and right side lying in the other session. In each of the positions, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single-breath pulmonary diffusing capacity (DLCO/VA), and the slope of phase III (DN2%/L) of the single-breath nitrogen washout test to determine inhomogeneity of ventilation were measured. Compared with measurements obtained in the sitting position, FVC and FEV1 were decreased equally in the side-lying positions, but no change was observed in DLCO/VA or DN2%/L. Side-lying positions resulted in decreases in FVC and FEV1, which is consistent with the well-documented effects of the supine position. These findings further support the need for prescriptive rather than routine body positioning of patients with risks of cardiopulmonary compromise and the need to use upright positions in which lung volumes and capacities are maximized.

CCL21 and IP-10 as blood biomarkers for pulmonary involvement in systemic lupus erythematosus patients.

PubMed

Odler, B; Bikov, A; Streizig, J; Balogh, C; Kiss, E; Vincze, K; Barta, I; Horváth, I; Müller, V

2017-05-01

Biomarkers for pulmonary manifestations in systemic lupus erythematosus (SLE) are missing. Plasma samples of nine SLE patients with known pulmonary involvement (SLE pulm ) and nine SLE patients without pulmonary involvement (SLE) were tested by multiplex microarray analysis for various cyto- and chemokines. Significantly decreased lung function paramters for forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity for carbon monoxide (DL CO ) and diffusion of CO corrected on lung volume (KL CO ) were observed in SLE pulm as compared to SLE patients. CC chemokine ligand 21 (CCL21) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in SLE pulm , than in patients without pulmonary manifestations. CCL21 correlated negatively with DL CO ( r = -0.73; p < 0.01) and KL CO ( r = -0.62; p < 0.01), while IP-10 with FVC and forced expiratory volume one second. Receiver Operating Characteristics (ROC) analysis confirmed high sensitivity and specificity for the separation of SLE patients with and without pulmonary involvement for the chemokines CCL21 (Area Under Curve (AUC): 0.85; sensitivity%: 88.90; specificity%: 75.00; p < 0.01) and IP-10 (AUC: 0.82; sensitivity%: 66.67, specificity%: 100; p < 0.01). Pleuropulmonary manifestations in SLE patients associated with lung functional and DL CO /KL CO changes and were associated with significant increase in CCL21 and IP-10. These chemokines might serve as potential biomarkers of lung involvement in SLE patients.

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.

Genetic deletion of apolipoprotein A-I increases airway hyperresponsiveness, inflammation, and collagen deposition in the lung

PubMed Central

Wang, Weiling; Xu, Hao; Shi, Yang; Nandedkar, Sandhya; Zhang, Hao; Gao, Haiqing; Feroah, Thom; Weihrauch, Dorothee; Schulte, Marie L.; Jones, Deron W.; Jarzembowski, Jason; Sorci-Thomas, Mary; Pritchard, Kirkwood A.

2010-01-01

The relationship between high-density lipoprotein and pulmonary function is unclear. To determine mechanistic relationships we investigated the effects of genetic deletion of apolipoprotein A-I (apoA-I) on plasma lipids, paraoxonase (PON1), pro-inflammatory HDL (p-HDL), vasodilatation, airway hyperresponsiveness and pulmonary oxidative stress, and inflammation. ApoA-I null (apoA-I−/−) mice had reduced total and HDL cholesterol but increased pro-inflammatory HDL compared with C57BL/6J mice. Although PON1 protein was increased in apoA-I−/− mice, PON1 activity was decreased. ApoA-I deficiency did not alter vasodilatation of facialis arteries, but it did alter relaxation responses of pulmonary arteries. Central airway resistance was unaltered. However, airway resistance mediated by tissue dampening and elastance were increased in apoA-I−/− mice, a finding also confirmed by positive end-expiratory pressure (PEEP) studies. Inflammatory cells, collagen deposition, 3-nitrotyrosine, and 4-hydroxy-2-nonenal were increased in apoA-I−/− lungs but not oxidized phospholipids. Colocalization of 4-hydroxy-2-nonenal with transforming growth factor β-1 (TGFβ-1 was increased in apoA-I−/− lungs. Xanthine oxidase, myeloperoxidase and endothelial nitric oxide synthase were increased in apoA-I−/− lungs. Dichlorodihydrofluorescein-detectable oxidants were increased in bronchoalveolar lavage fluid (BALF) in apoA-I−/− mice. In contrast, BALF nitrite+nitrate levels were decreased in apoA-I−/− mice. These data demonstrate that apoA-I plays important roles in limiting pulmonary inflammation and oxidative stress, which if not prevented, will decrease pulmonary artery vasodilatation and increase airway hyperresponsiveness. PMID:20498409

The ratio of (18)F-FDG activity uptake between the right and left ventricle in patients with pulmonary hypertension correlates with the right ventricular function.

PubMed

Yang, Tao; Wang, Lei; Xiong, Chang-Ming; He, Jian-Guo; Zhang, Yan; Gu, Qing; Zhao, Zhi-Hui; Ni, Xin-Hai; Fang, Wei; Liu, Zhi-Hong

2014-05-01

It is known that patients with pulmonary hypertension (PH) can have elevated F-FDG uptake in the right ventricle (RV) on PET imaging. This study was designed to assess possible relationship between FDG uptake of ventricles and the function/hemodynamics of the RV in patients with PH. Thirty-eight patients with PH underwent FDG PET imaging in both fasting and glucose-loading conditions. The standard uptake value (SUVs) corrected for partial volume effect in both RV and left ventricle (LV) were measured. The ratio of FDG uptake between RV to LV (SUVR/L) was calculated. Right heart catheterization and cardiac magnetic resonance (CMR) were performed in all patients within 1 week. The FDG uptake levels by the ventricles were compared with the result form the right heart catheterization and CMR. The SUV of RV (SUVR) and SUV of LV were significantly higher in glucose-loading condition than in fasting condition. In both fasting and glucose-loading conditions, SUVR and SUVR/L showed reverse correlation with right ventricular ejection fraction derived from CMR. In addition, in both fasting and glucose-loading conditions, SUVR and SUVR/L showed positive correlations with pulmonary vascular resistance. However, only SUVR/L in glucose-loading condition could independently predict right ventricular ejection fraction after adjusted for age, body mass index, sex, mean right atrial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance (P = 0.048). The FDG uptake of RV increases with decreased right ventricular function in patients with PH. Increased FDG uptake ratio between RV and LV might be useful to assess the right ventricular function.

Three-dimensional Echocardiography of Right Ventricular Function Correlates with Severity of Pediatric Pulmonary Hypertension.

PubMed

Jone, Pei-Ni; Patel, Sonali S; Cassidy, Courtney; Ivy, David Dunbar

2016-12-01

Right ventricular function and biomarkers of B-type natriuretic peptide (BNP) and N-Terminal pro-BNP (NT pro-BNP) are used to determine the severity of right ventricular failure and outcomes from pulmonary hypertension. Real-time three-dimensional echocardiography (3DE) is a novel quantitative measure of the right ventricle and decreases the geometric assumptions from conventional two-dimensional echocardiography (2DE). We correlated right ventricular functional measures using 2DE and single-beat 3DE with biomarkers and hemodynamics to determine the severity of pediatric pulmonary hypertension. We retrospectively evaluated 35 patients (mean age 12.67 ± 5.78 years) with established pulmonary hypertension who had echocardiograms and biomarkers on the same day. Ten out of 35 patients had hemodynamic evaluation within 3 days. 2DE evaluation included tricuspid annular plane systolic excursion (TAPSE), right ventricular myocardial performance index from tissue Doppler imaging (RV TDI MPI), and right ventricular fractional area change (FAC). Three-dimensional echocardiography evaluation included right ventricular ejection fraction (EF), end-systolic volume, and end-diastolic volume. The quality of the 3DE was graded as good, fair, or poor. Pearson correlation coefficients were utilized to evaluate between biomarkers and echocardiographic parameters and between hemodynamics and echocardiography. Three-dimensional echocardiography and FAC correlated significantly with BNP and NT pro-BNP. TAPSE and RV TDI MPI did not correlate significantly with biomarkers. 3D right ventricular EF correlated significantly with hemodynamics. Two-dimensional echocardiography did not correlate with hemodynamics. Single-beat 3DE is a noninvasive, feasible tool in the quantification of right ventricular function and maybe more accurate than conventional 2DE in evaluating severity of pulmonary hypertension. © 2016 Wiley Periodicals, Inc.

Epidural anaesthesia and analgesia - effects on surgical stress responses and implications for postoperative nutrition.

PubMed

Holte, K; Kehlet, H

2002-06-01

Surgical injury leads to an endocrine-metabolic and inflammatory response with protein catabolism, increased cardiovascular demands, impaired pulmonary function and paralytic ileus, the most important release mechanisms being afferent neural stimuli and inflammatory mediators. Epidural local anaesthetic blockade of afferent stimuli reduces endocrine metabolic responses, and improve postoperative catabolism. Furthermore, dynamic pain relief is achieved with improved pulmonary function and a pronounced reduction of postoperative ileus, thereby providing optimal conditions for improved mobilization and oral nutrition, and preservation of body composition and muscle function. Studies integrating continuous epidural local anaesthetics with enforced early nutrition and mobilization uniformly suggest an improved recovery, decreased hospital stay and convalescence. Epidural local anaesthetics should be included in a multi-modal rehabilitation programme after major surgical procedures in order to facilitate oral nutrition, improve recovery and reduce morbidity.

[Interpretation and use of routine pulmonary function tests: Spirometry, static lung volumes, lung diffusion, arterial blood gas, methacholine challenge test and 6-minute walk test].

PubMed

Bokov, P; Delclaux, C

2016-02-01

Resting pulmonary function tests (PFT) include the assessment of ventilatory capacity: spirometry (forced expiratory flows and mobilisable volumes) and static volume assessment, notably using body plethysmography. Spirometry allows the potential definition of obstructive defect, while static volume assessment allows the potential definition of restrictive defect (decrease in total lung capacity) and thoracic hyperinflation (increase in static volumes). It must be kept in mind that this evaluation is incomplete and that an assessment of ventilatory demand is often warranted, especially when facing dyspnoea: evaluation of arterial blood gas (searching for respiratory insufficiency) and measurement of the transfer coefficient of the lung, allowing with the measurement of alveolar volume to calculate the diffusing capacity of the lung for CO (DLCO: assessment of alveolar-capillary wall and capillary blood volume). All these pulmonary function tests have been the subject of an Americano-European Task force (standardisation of lung function testing) published in 2005, and translated in French in 2007. Interpretative strategies for lung function tests have been recommended, which define abnormal lung function tests using the 5th and 95th percentiles of predicted values (lower and upper limits of normal values). Thus, these recommendations need to be implemented in all pulmonary function test units. A methacholine challenge test will only be performed in the presence of an intermediate pre-test probability for asthma (diagnostic uncertainty), which is an infrequent setting. The most convenient exertional test is the 6-minute walk test that allows the assessment of walking performance, the search for arterial desaturation and the quantification of dyspnoea complaint. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Effect of left ventricular diastolic dysfunction on left atrial appendage function and thrombotic potential in nonvalvular atrial fibrillation.

PubMed

Demirçelik, Muhammed Bora; Çetin, Mustafa; Çiçekcioğlu, Hülya; Uçar, Özgül; Duran, Mustafa

2014-05-01

We aimed to investigate effects of left ventricular diastolic dysfunction on left atrial appendage functions, spontaneous echo contrast and thrombus formation in patients with nonvalvular atrial fibrillation. In 58 patients with chronic nonvalvular atrial fibrilation and preserved left ventricular systolic function, left atrial appendage functions, left atrial spontaneous echo contrast grading and left ventricular diastolic functions were evaluated using transthoracic and transoesophageal echocardiogram. Patients divided in two groups: Group D (n=30): Patients with diastolic dysfunction, Group N (n=28): Patients without diastolic dysfunction. Categorical variables in two groups were evaluated with Pearson's chi-square or Fisher's exact test. The significance of the lineer correlation between the degree of spontaneous echo contrast (SEC) and clinical measurements was evaluated with Spearman's correlation analysis. Peak pulmonary vein D velocity of the Group D was significantly higher than the Group N (p=0.006). However, left atrial appendage emptying velocity, left atrial appendage lateral wall velocity, peak pulmonary vein S, pulmonary vein S/D ratio were found to be significantly lower in Group D (p=0.028, p<0.001, p<0.001; p<0.001). Statistically significant negative correlation was found between SEC in left atrium and left atrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities respectively (r=-0.438, r=-0.328, r=-0.233, r=-0.447). Left atrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities were significantly lower in SEC 2-3-4 than SEC 1 (p=0.003, p=0.029, p<0.001, p=0.002). In patients with nonvalvular atrial fibrillation and preserved left ventricular ejection fraction, left atrial appendage functions are decreased in patients with left ventricular diastolic dysfunction. Left ventricular diastolic dysfunction may constitute a potential risk for formation of thrombus and stroke.

Time-series analysis of lung texture on bone-suppressed dynamic chest radiograph for the evaluation of pulmonary function: a preliminary study

NASA Astrophysics Data System (ADS)

Tanaka, Rie; Matsuda, Hiroaki; Sanada, Shigeru

2017-03-01

The density of lung tissue changes as demonstrated on imagery is dependent on the relative increases and decreases in the volume of air and lung vessels per unit volume of lung. Therefore, a time-series analysis of lung texture can be used to evaluate relative pulmonary function. This study was performed to assess a time-series analysis of lung texture on dynamic chest radiographs during respiration, and to demonstrate its usefulness in the diagnosis of pulmonary impairments. Sequential chest radiographs of 30 patients were obtained using a dynamic flat-panel detector (FPD; 100 kV, 0.2 mAs/pulse, 15 frames/s, SID = 2.0 m; Prototype, Konica Minolta). Imaging was performed during respiration, and 210 images were obtained over 14 seconds. Commercial bone suppression image-processing software (Clear Read Bone Suppression; Riverain Technologies, Miamisburg, Ohio, USA) was applied to the sequential chest radiographs to create corresponding bone suppression images. Average pixel values, standard deviation (SD), kurtosis, and skewness were calculated based on a density histogram analysis in lung regions. Regions of interest (ROIs) were manually located in the lungs, and the same ROIs were traced by the template matching technique during respiration. Average pixel value effectively differentiated regions with ventilatory defects and normal lung tissue. The average pixel values in normal areas changed dynamically in synchronization with the respiratory phase, whereas those in regions of ventilatory defects indicated reduced variations in pixel value. There were no significant differences between ventilatory defects and normal lung tissue in the other parameters. We confirmed that time-series analysis of lung texture was useful for the evaluation of pulmonary function in dynamic chest radiography during respiration. Pulmonary impairments were detected as reduced changes in pixel value. This technique is a simple, cost-effective diagnostic tool for the evaluation of regional pulmonary function.

Beneficial Effects of Renal Denervation on Pulmonary Vascular Remodeling in Experimental Pulmonary Artery Hypertension.

PubMed

Qingyan, Zhao; Xuejun, Jiang; Yanhong, Tang; Zixuan, Dai; Xiaozhan, Wang; Xule, Wang; Zongwen, Guo; Wei, Hu; Shengbo, Yu; Congxin, Huang

2015-07-01

Activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system is closely associated with pulmonary arterial hypertension. We hypothesized that renal denervation decreases renin-angiotensin-aldosterone activity and inhibits the progression of pulmonary arterial hypertension. Twenty-two beagles were randomized into 3 groups. The dogs' pulmonary dynamics were measured before and 8 weeks after injection of 0.1mL/kg dimethylformamide (control dogs) or 2mg/kg dehydromonocrotaline (pulmonary arterial hypertension and pulmonary arterial hypertension + renal denervation dogs). Eight weeks after injection, neurohormone levels and pulmonary tissue morphology were measured. Levels of plasma angiotensin II and endothelin-1 were significantly increased after 8 weeks in the pulmonary arterial hypertension dogs and were higher in the lung tissues of these dogs than in those of the control and renal denervation dogs (mean [standard deviation] angiotensin II: 65 [9.8] vs 38 [6.7], 46 [8.1]; endothelin-1: 96 [10.3] vs 54 [6.2], 67 [9.4]; P < .01). Dehydromonocrotaline increased the mean pulmonary arterial pressure (16 [3.4] mmHg vs 33 [7.3] mmHg; P < .01), and renal denervation prevented this increase. Pulmonary smooth muscle cell proliferation was higher in the pulmonary arterial hypertension dogs than in the control and pulmonary arterial hypertension + renal denervation dogs. Renal denervation attenuates pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental pulmonary arterial hypertension. The effect of renal denervation may contribute to decreased neurohormone levels. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Decreased Pulmonary Function Measured in Children Exposed to High Environmental Relative Moldiness Index Homes

EPA Science Inventory

Background: Mold exposures have been associated with respiratory diseases including asthma but the quantification of this relationship has been limited because of the metrics used. Objectives: Our objective was to evaluate the respiratory health of a cohort of children with as...

Silicosis Appears Inevitable Among Former Denim Sandblasters: A 4-Year Follow-up Study.

PubMed

Akgun, Metin; Araz, Omer; Ucar, Elif Yilmazel; Karaman, Adem; Alper, Fatih; Gorguner, Metin; Kreiss, Kathleen

2015-09-01

The course of denim sandblasting silicosis is unknown. We aimed to reevaluate former sandblasters studied in 2007 for incident silicosis, radiographic progression, pulmonary function loss, and mortality and to examine any associations between these outcomes and previously demonstrated risk factors for silicosis. We defined silicosis on chest radiograph as category 1/0 small opacity profusion using the International Labor Organization classification. We defined radiographic progression as a profusion increase of two or more subcategories, development of a new large opacity, or an increase in large opacity category. We defined pulmonary function loss as a ≥ 12% decrease in FVC. Among the 145 former sandblasters studied in 2007, 83 were reassessed in 2011. In the 4-year follow-up period, nine (6.2%) had died at a mean age of 24 years. Of the 74 living sandblasters available for reexamination, the prevalence of silicosis increased from 55.4% to 95.9%. Radiographic progression, observed in 82%, was associated with younger age, never smoking, foreman work, and sleeping at the workplace. Pulmonary function loss, seen in 66%, was positively associated with never smoking and higher initial FVC % predicted. Death was associated with never smoking, foreman work, number of different denim-sandblasting places of work, sleeping at the workplace, and lower pulmonary function, of which only the number of different places worked remained in multivariate analyses. This 4-year follow-up suggests that almost all former denim sandblasters may develop silicosis, despite short exposures and latency.

Mortality trends due to chronic obstructive pulmonary disease in Brazil.

PubMed

Graudenz, Gustavo Silveira; Gazotto, Gabriel Pereira

2014-01-01

The purpose of this study was to update and analyze data on mortality trend due to chronic obstructive pulmonary disease (COPD) in Brazil. Initially, the specific COPD mortality rates were calculated from 1989 to 2009 using data collected from DATASUS (Departamento de Informática do SUS - Brazilian Health System Database). Then, the polynomial regression models from the observed functional relation were estimated based on mortality coefficients and study years. We verified that the general mortality rates due to COPD in Brazil showed an increasing trend from 1989 to 2004, and then decreased. Both genders showed the same increasing tendencies until 2004 and decreased thereafter. The age group under 35 years old showed a linear decreasing trend. All other age groups showed quadratic tendencies, with increases until the years of 1998-1999 and then decreasing. The South and Southeast regions showed the highest COPD mortality rates with increasing trends until the years 2001-2002 and then decreased. The North, Northeast and Central-West regions showed lower mortality rates but increasing trend. This is the first report of COPD mortality stabilization in Brazil since 1980.

The overloaded right heart and ventricular interdependence.

PubMed

Naeije, Robert; Badagliacca, Roberto

2017-10-01

The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Efficacy of an mHealth intervention to stimulate physical activity in COPD patients after pulmonary rehabilitation.

PubMed

Vorrink, Sigrid N W; Kort, Helianthe S M; Troosters, Thierry; Zanen, Pieter; Lammers, Jan-Willem J

2016-10-01

Physical inactivity in patients with chronic obstructive pulmonary disease (COPD) is associated with poor health status and increased disease burden. The present study aims to test the efficacy of a previously developed mobile (m)Health intervention to improve or maintain physical activity in patients with COPD after pulmonary rehabilitation.A randomised controlled trial was performed in 32 physiotherapy practices in the Netherlands. COPD patients were randomised into intervention or usual care groups. The intervention consisted of a smartphone application for the patients and a monitoring website for the physiotherapists. Measurements were performed at 0, 3, 6 and 12 months. Physical activity, functional exercise capacity, lung function, health-related quality of life and body mass index were assessed.157 patients started the study and 121 completed it. There were no significant positive effects of the intervention on physical activity (at 0 months: intervention 5824±3418 steps per weekday, usual care 5717±2870 steps per weekday; at 12 months: intervention 4819±2526 steps per weekday, usual care 4950±2634 steps per weekday; p=0.811) or on the secondary end-points. There was a significant decrease over time in physical activity (p<0.001), lung function (p<0.001) and mastery (p=0.017), but not in functional exercise capacity (p=0.585).Although functional exercise capacity did not deteriorate, our mHealth intervention did not improve or maintain physical activity in patients with COPD after a period of pulmonary rehabilitation. Copyright ©ERS 2016.

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.

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.

Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact.

PubMed

Yang, Tian; Wang, Jinyuan; Pang, Yamei; Dang, Xiaomin; Ren, Hui; Liu, Ya; Chen, Mingwei; Shang, Dong

2016-11-01

Pulmonary silicosis is characterized by lung fibrosis, which leads to impairment of pulmonary function; the specific mechanism remains to be fully elucidated Emodin shows antifibrotic effects in several organs with fibrosis, however, it has not been investigated in pulmonary silicosis. In the present study, the possible mechanism of lung fibrosis and the antifibrotic effect of emodin in silica inhalation‑induced lung fibrosis were investigated. Pulmonary silica particle inhalation was used to induce lung fibrosis in mice. Emodin and or the sirtuin 1 (Sirt1) inhibitor, nicotinamide, were used to treat the modeled animals. Pulmonary function was assessed using an occlusion method. The deposition of collagen I and α‑smooth muscle actin (SMA) in the lung tissue were detected using fluorescence staining; transforming growth factor‑β1 (TGF‑β1) in the bronchoalveolar lavage fluid (BALF) was examined using an enzyme‑linked immunosorbent assay; TGF-β1/Sirt1/small mothers against decapentaplegic (Smad) signaling activation in lung tissue was also examined. The molecular contacts between emodin were evaluated using liquid chromatography‑mass spectrometry analysis. The deposition of collagen I and α‑SMA in lung tissues were found to be elevated following silica exposure, however, this was relieved by emodin treatment. The pulmonary function of the animals was impaired by silica inhalation, and this was improved by emodin administration. However, the therapeutic effects of emodin on lung fibrosis were impaired by nicotinamide administration. The levels of TGF‑β1 in the BALF and lung tissue were elevated by silica inhalation, however, they were not affected by either emodin or nicotinamide treatment. Additionally, emodin was found to increase the expression level of Sirt1, which decreased the level of deacetylated Smad3 to attenuate collagen deposition. Furthermore, the data suggested that there was direct binding between emodin and Sirt1. Sirt1‑regulated TGF‑β1/Smad signaling was involved in silica inhalation‑induced lung fibrosis. Emodin attenuated this lung fibrosis to improve pulmonary function by targeting Sirt1, which regulated TGF-β1/Smad fibrotic signaling.

Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact

PubMed Central

Yang, Tian; Wang, Jinyuan; Pang, Yamei; Dang, Xiaomin; Ren, Hui; Liu, Ya; Chen, Mingwei; Shang, Dong

2016-01-01

Pulmonary silicosis is characterized by lung fibrosis, which leads to impairment of pulmonary function; the specific mechanism remains to be fully elucidated Emodin shows antifibrotic effects in several organs with fibrosis, however, it has not been investigated in pulmonary silicosis. In the present study, the possible mechanism of lung fibrosis and the antifibrotic effect of emodin in silica inhalation-induced lung fibrosis were investigated. Pulmonary silica particle inhalation was used to induce lung fibrosis in mice. Emodin and or the sirtuin 1 (Sirt1) inhibitor, nicotinamide, were used to treat the modeled animals. Pulmonary function was assessed using an occlusion method. The deposition of collagen I and α-smooth muscle actin (SMA) in the lung tissue were detected using fluorescence staining; transforming growth factor-β1 (TGF-β1) in the bronchoalveolar lavage fluid (BALF) was examined using an enzyme-linked immunosorbent assay; TGF-β1/Sirt1/small mothers against decapentaplegic (Smad) signaling activation in lung tissue was also examined. The molecular contacts between emodin were evaluated using liquid chromatography-mass spectrometry analysis. The deposition of collagen I and α-SMA in lung tissues were found to be elevated following silica exposure, however, this was relieved by emodin treatment. The pulmonary function of the animals was impaired by silica inhalation, and this was improved by emodin administration. However, the therapeutic effects of emodin on lung fibrosis were impaired by nicotinamide administration. The levels of TGF-β1 in the BALF and lung tissue were elevated by silica inhalation, however, they were not affected by either emodin or nicotinamide treatment. Additionally, emodin was found to increase the expression level of Sirt1, which decreased the level of deacetylated Smad3 to attenuate collagen deposition. Furthermore, the data suggested that there was direct binding between emodin and Sirt1. Sirt1-regulated TGF-β1/Smad signaling was involved in silica inhalation-induced lung fibrosis. Emodin attenuated this lung fibrosis to improve pulmonary function by targeting Sirt1, which regulated TGF-β1/Smad fibrotic signaling. PMID:27748907

Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol

PubMed Central

Chen, Yucai; Yuan, Tianyi; Zhang, Huifang; Yan, Yu; Wang, Danshu; Fang, Lianhua; Lu, Yang; Du, Guanhua

2017-01-01

The endothelial-to-mesenchymal transition (EndMT) has been demonstrated to be involved in pulmonary vascular remodeling. It is partly attributed to oxidative and inflammatory stresses in endothelial cells. In current study, we conducted a series of experiments to clarify the effect of salvianolic acid A (SAA), a kind of polyphenol compound, in the process of EndMT in human pulmonary arterial endothelial cells and in vivo therapeutic efficacy on vascular remodeling in monocrotaline (MCT)-induced EndMT. EndMT was induced by TGFβ1 in human pulmonary arterial endothelial cells (HPAECs). SAA significantly attenuated EndMT, simultaneously inhibited cell migration and reactive oxygen species (ROS) formation. In MCT-induced pulmonary arterial hypertension (PAH) model, SAA improved vascular function, decreased TGFβ1 level and inhibited inflammation. Mechanistically, SAA stimulated Nrf2 translocation and subsequent heme oxygenase-1 (HO-1) up-regulation. The effect of SAA on EndMT in vitro was abolished by ZnPP, a HO-1 inhibitor. In conclusion, this study indicates a deleterious impact of oxidative stress on EndMT. Polyphenol antioxidant treatment may provide an adjunctive action to alleviate pulmonary vascular remodeling via inhibiting EndMT. PMID:28924387

Idiopathic pulmonary fibrosis may be a disease of recurrent, tractional injury to the periphery of the aging lung: a unifying hypothesis regarding etiology and pathogenesis.

PubMed

Leslie, Kevin O

2012-06-01

Idiopathic pulmonary fibrosis is a progressive, fatal lung disease occurring in older individuals. Despite 50 years of accrued data about the disease, little progress has been made in slowing functional loss or in decreasing patient mortality. To present a novel hypothesis on the etiology and pathogenesis of idiopathic pulmonary fibrosis. Published data are reviewed regarding the epidemiology, clinical presentation, natural history, radiologic findings, and pathologic findings in patients with idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis may be predisposed genetically to tractional injury to the peripheral lung. The result is recurrent damage to the epithelial-mesenchymal interface, preferentially at the outer edges of the basilar lung lobules where tractional stress is high during inspiration, compliance is relatively low, and there is a greater tendency for alveolar collapse at end-expiration. A distinctive "reticular network of injury" (the fibroblast focus) forms, attended by a prolonged phase of wound repair (tear and slow repair). Discrete areas of alveolar collapse are observed in scar at the periphery of the lung lobules. The cycle repeats over many years resulting in progressive fibrous remodeling and replacement of the alveoli in a lobule by bronchiolar cysts surrounded by scar (honeycomb lung). Abnormalities in surfactant function are proposed as a potential mechanism of initial lung damage. Age of onset may be a function of a required threshold of environmental exposures (eg, cigarette smoking) or other comorbid injury to the aging lung. Evidence supporting this hypothesis is presented and potential mechanisms are discussed. A potential role for contributing cofactors is presented.

Outcomes after surgical pulmonary embolectomy for acute submassive and massive pulmonary embolism: A single-center experience.

PubMed

Pasrija, Chetan; Kronfli, Anthony; Rouse, Michael; Raithel, Maxwell; Bittle, Gregory J; Pousatis, Sheelagh; Ghoreishi, Mehrdad; Gammie, James S; Griffith, Bartley P; Sanchez, Pablo G; Kon, Zachary N

2018-03-01

Ideal treatment strategies for submassive and massive pulmonary embolism remain unclear. Recent reports of surgical pulmonary embolectomy have demonstrated improved outcomes, but surgical technique and postoperative outcomes continue to be refined. The aim of this study is to describe in-hospital survival and right ventricular function after surgical pulmonary embolectomy for submassive and massive pulmonary embolism with excessive predicted mortality (≥5%). All patients undergoing surgical pulmonary embolectomy (2011-2015) were retrospectively reviewed. Patients with pulmonary embolism were stratified as submassive, massive without arrest, and massive with arrest. Submassive was defined as normotensive with right ventricular dysfunction. Massive was defined as prolonged hypotension due to the pulmonary embolism. Preoperative demographics, intraoperative variables, and postoperative outcomes were compared. A total of 55 patients were identified: 28 as submassive, 18 as massive without arrest, and 9 as massive with arrest. All patients had a right ventricle/left ventricle ratio greater than 1.0. Right ventricular dysfunction decreased from moderate preoperatively to none before discharge (P < .001). In-hospital and 1-year survival were 93% and 91%, respectively, with 100% survival in the submassive group. No patients developed renal failure requiring hemodialysis at discharge or had a postoperative stroke. In this single institution experience, surgical pulmonary embolectomy is a safe and effective therapy to treat patients with a submassive or massive pulmonary embolism. Although survival in this study is higher than previously reported for patients treated with medical therapy alone, a prospective trial comparing surgical therapy with medical therapy is necessary to further elucidate the role of surgical pulmonary embolectomy in the treatment of pulmonary embolism. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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.

Incentive spirometry for preventing pulmonary complications after coronary artery bypass graft.

PubMed

Freitas, E R F S; Soares, B G O; Cardoso, J R; Atallah, A N

2007-07-18

Following coronary artery bypass graft (CABG), the main causes of postoperative morbidity and mortality are postoperative pulmonary complications, respiratory dysfunction and arterial hypoxemia. Incentive spirometry is a treatment technique that uses a mechanical device (an incentive spirometer) to reduce such pulmonary complications during postoperative care. To assess the effects of incentive spirometry for preventing postoperative pulmonary complications in adults undergoing CABG. We searched CENTRAL on The Cochrane Library (Issue 2, 2004), MEDLINE (1966 to December 2004), EMBASE (1980 to December 2004), LILACS (1982 to December 2004), the Physiotherapy Evidence Database (PEDro) (1980 to December 2004), Allied & Complementary Medicine (AMED) (1985 to December 2004), CINAHL (1982 to December 2004), and the Database of Abstracts of Reviews of Effects (DARE) (1994 to December 2004). References were checked and authors contacted. No language restrictions were applied. Randomized controlled trials comparing incentive spirometry with any type of prophylactic physiotherapy for prevention of postoperative pulmonary complications in adults undergoing CABG. Two reviewers independently evaluated the quality of trials using the guidelines of the Cochrane Reviewers' Handbook and extracted data from included trials. Four trials with 443 participants contributed to this review. There was no significant difference in pulmonary complications (atelectasis and pneumonia) between treatment with incentive spirometry and treatment with positive pressure breathing techniques (continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP) and intermittent positive pressure breathing (IPPB)) or preoperative patient education. Patients treated with incentive spirometry had worse pulmonary function and arterial oxygenation compared with positive pressure breathing (CPAP, BiPAP, IPPB). Individual small trials suggest that there is no evidence of benefit from incentive spirometry in reducing pulmonary complications and in decreasing the negative effects on pulmonary function in patients undergoing CABG. In view of the modest number of patients studied, methodological shortcomings and poor reporting of the included trials, these results should be interpreted cautiously. An appropriately powered trial of high methodological rigour is needed to determine those patients who may derive benefit from incentive spirometry following CABG.

Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP): Rationale, design, and methods of a randomized, controlled trial of vitamin C supplementation in pregnancy for the primary prevention of effects of in utero tobacco smoke exposure on infant lung function and respiratory health.

PubMed

McEvoy, Cindy T; Milner, Kristin F; Scherman, Ashley J; Schilling, Diane G; Tiller, Christina J; Vuylsteke, Brittany; Shorey-Kendrick, Lyndsey E; Spindel, Eliot R; Schuff, Robert; Mitchell, Julie; Peters, Dawn; Metz, Jill; Haas, David; Jackson, Keith; Tepper, Robert S; Morris, Cynthia D

2017-07-01

Despite strong anti-smoking efforts, at least 12% of American women cannot quit smoking when pregnant resulting in >450,000 smoke-exposed infants born yearly. Smoking during pregnancy is the largest preventable cause of childhood respiratory illness including wheezing and asthma. Recent studies have shown a protective effect of vitamin C supplementation on the lung function of offspring exposed to in utero smoke in a non-human primate model and an initial human trial. Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) is a randomized, double-blind, placebo-controlled trial to evaluate pulmonary function at 3months of age in infants delivered to pregnant smokers randomized to 500mg/day of vitamin C versus placebo during pregnancy. Secondary aims evaluate the incidence of wheezing through 12months and pulmonary function testing at 12months of age. Women are randomized between 13 and 23weeks gestation from clinical sites in Portland, Oregon at Oregon Health & Science University and PeaceHealth Southwest Medical Center and in Indianapolis, Indiana at Indiana University and Wishard Hospital. Vitamin C supplementation occurs from randomization to delivery. Monthly contact with participants and monitoring of medical records is performed to document medication adherence, changes in smoking and medical history, and adverse events. Pulmonary function testing of offspring occurs at 3 and 12months of age and incidence of wheezing and respiratory illness through 12months is captured via at least quarterly questionnaires. Ancillary studies are investigating the impact of vitamin C on placental blood flow and DNA methylation. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Aging on the Respiratory System.

ERIC Educational Resources Information Center

Levitzky, Michael G.

1984-01-01

Relates alterations in respiratory system functions occurring with aging to changes in respiratory system structure during the course of life. Main alterations noted include loss of alveolar elastic recoil, alteration in chest wall structure and decreased respiratory muscle strength, and loss of surface area and changes in pulmonary circulation.…

PPAR-γ Regulates Carnitine Homeostasis and Mitochondrial Function in a Lamb Model of Increased Pulmonary Blood Flow

PubMed Central

Rafikov, Ruslan; Kumar, Sanjiv; Hou, Yali; Oishi, Peter E.; Datar, Sanjeev A.; Raff, Gary; Fineman, Jeffrey R.; Black, Stephen M.

2012-01-01

Objective Carnitine homeostasis is disrupted in lambs with endothelial dysfunction secondary to increased pulmonary blood flow (Shunt). Our recent studies have also indicated that the disruption in carnitine homeostasis correlates with a decrease in PPAR-γ expression in Shunt lambs. Thus, this study was carried out to determine if there is a causal link between loss of PPAR-γ signaling and carnitine dysfunction, and whether the PPAR-γ agonist, rosiglitazone preserves carnitine homeostasis in Shunt lambs. Methods and Results siRNA-mediated PPAR-γ knockdown significantly reduced carnitine palmitoyltransferases 1 and 2 (CPT1 and 2) and carnitine acetyltransferase (CrAT) protein levels. This decrease in carnitine regulatory proteins resulted in a disruption in carnitine homeostasis and induced mitochondrial dysfunction, as determined by a reduction in cellular ATP levels. In turn, the decrease in cellular ATP attenuated NO signaling through a reduction in eNOS/Hsp90 interactions and enhanced eNOS uncoupling. In vivo, rosiglitazone treatment preserved carnitine homeostasis and attenuated the development of mitochondrial dysfunction in Shunt lambs maintaining ATP levels. This in turn preserved eNOS/Hsp90 interactions and NO signaling. Conclusion Our study indicates that PPAR-γ signaling plays an important role in maintaining mitochondrial function through the regulation of carnitine homeostasis both in vitro and in vivo. Further, it identifies a new mechanism by which PPAR-γ regulates NO signaling through Hsp90. Thus, PPAR-γ agonists may have therapeutic potential in preventing the endothelial dysfunction in children with increased pulmonary blood flow. PMID:22962578

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...

Pulmonary inflammation-induced loss and subsequent recovery of skeletal muscle mass require functional poly-ubiquitin conjugation.

PubMed

Ceelen, Judith J M; Schols, Annemie M W J; Thielen, Nathalie G M; Haegens, Astrid; Gray, Douglas A; Kelders, Marco C J M; de Theije, Chiel C; Langen, Ramon C J

2018-05-02

Pulmonary inflammation in response to respiratory infections can evoke muscle wasting. Increased activity of the ubiquitin (Ub)-proteasome system (UPS) and the autophagy lysosome pathway (ALP) have been implicated in inflammation-induced muscle atrophy. Since poly-Ub conjugation is required for UPS-mediated proteolysis and has been implicated in the ALP, we assessed the effect of impaired ubiquitin conjugation on muscle atrophy and recovery following pulmonary inflammation, and compared activation and suppression of these proteolytic systems to protein synthesis regulation. Pulmonary inflammation was induced in mice by an intratracheal instillation of LPS. Proteolysis (UPS and ALP) and synthesis signaling were examined in gastrocnemius muscle homogenates. Ub-conjugation-dependency of muscle atrophy and recovery was addressed using Ub-K48R (K48R) mice with attenuated poly-ubiquitin conjugation, and compared to UBWT control mice. Pulmonary inflammation caused a decrease in skeletal muscle mass which was accompanied by a rapid increase in expression of UPS and ALP constituents and reduction in protein synthesis signaling acutely after LPS. Muscle atrophy was attenuated in K48R mice, while ALP and protein synthesis signaling were not affected. Muscle mass recovery starting 72 h post LPS, correlated with reduced expression of UPS and ALP constituents and restoration of protein synthesis signaling. K48R mice however displayed impaired recovery of muscle mass. Pulmonary inflammation-induced muscle atrophy is in part attributable to UPS-mediated proteolysis, as activation of ALP- and suppression of protein synthesis signaling occur independently of poly-Ub conjugation during muscle atrophy. Recovery of muscle mass following pulmonary inflammation involves inverse regulation of proteolysis and protein synthesis signaling, and requires a functional poly-Ub conjugation.

Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis.

PubMed

Espindola, Milena S; Habiel, David M; Narayanan, Rohan; Jones, Isabelle; Coelho, Ana L; Murray, Lynne A; Jiang, Dianhua; Noble, Paul W; Hogaboam, Cory M

2018-06-01

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling, which progressively abolishes lung function in an RTK (receptor tyrosine kinase)-dependent manner. Gas6 (growth arrest-specific 6) ligand, Tyro3 (TYRO3 protein tyrosine kinase 3), and Axl (anexelekto) RTK expression and activity are increased in IPF. To determine if targeting these RTK pathways would inhibit fibroblast activation and the development of pulmonary fibrosis. Quantitative genomic, proteomic, and functional analyses were used to determine Gas6/TAM (Tyro3, Axl, and Mertk [MER proto-oncogene, tyrosine kinase]) RTK expression and activation in tissues and fibroblasts from normal and IPF lungs. The profibrotic impact of these RTK pathways were also examined in bleomycin-induced pulmonary fibrosis and in SCID/Bg mice that developed pulmonary fibrosis after the intravenous administration of primary IPF fibroblasts. Gas6, Axl, and Tyro3 were increased in both rapidly and slowly progressive IPF compared with normal lung samples and fibroblasts. Targeting these pathways with either specific antibodies directed at Gas6 or Axl, or with small-molecule TAM inhibitors indicated that the small molecule-mediated targeting approach was more efficacious in both in vitro and in vivo studies. Specifically, the TAM receptor inhibitor R428 (also known as BGB324) significantly inhibited the synthetic, migratory, and proliferative properties of IPF fibroblasts compared with the other Gas6/TAM receptor targeting agents. Finally, loss of Gas6 expression decreased lung fibrotic responses to bleomycin and treatment with R428 inhibited pulmonary fibrosis in humanized SCID/Bg mice. Gas6/TAM receptor activity contributes to the activation of pulmonary fibroblasts in IPF, suggesting that targeting this RTK pathway might be an effective antifibrotic strategy in this disease.

Grape seed extract ameliorates bleomycin-induced mouse pulmonary fibrosis.

PubMed

Liu, Qi; Jiang, Jun-Xia; Liu, Ya-Nan; Ge, Ling-Tian; Guan, Yan; Zhao, Wei; Jia, Yong-Liang; Dong, Xin-Wei; Sun, Yun; Xie, Qiang-Min

2017-05-05

Pulmonary fibrosis is common in a variety of inflammatory lung diseases, such as interstitial pneumonia, chronic obstructive pulmonary disease, and silicosis. There is currently no effective clinical drug treatment. It has been reported that grape seed extracts (GSE) has extensive pharmacological effects with minimal toxicity. Although it has been found that GSE can improve the lung collagen deposition and fibrosis pathology induced by bleomycin in rat, its effects on pulmonary function, inflammation, growth factors, matrix metalloproteinases and epithelial-mesenchymal transition remain to be researched. In the present study, we studied whether GSE provided protection against bleomycin (BLM)-induced mouse pulmonary fibrosis. ICR strain mice were treated with BLM in order to establish pulmonary fibrosis models. GSE was given daily via intragastric administration for three weeks starting at one day after intratracheal instillation. GSE at 50 or 100mg/kg significantly reduced BLM-induced inflammatory cells infiltration, proinflammatory factor protein expression, and hydroxyproline in lung tissues, and improved pulmonary function in mice. Additionally, treatment with GSE also significantly impaired BLM-induced increases in lung fibrotic marker expression (collagen type I alpha 1 and fibronectin 1) and decreases in an anti-fibrotic marker (E-cadherin). Further investigation indicated that the possible molecular targets of GSE are matrix metalloproteinases-9 (MMP-9) and TGF-β1, given that treatment with GSE significantly prevented BLM-induced increases in MMP-9 and TGF-β1 expression in the lungs. Together, these results suggest that supplementation with GSE may improve the quality of life of lung fibrosis patients by inhibiting MMP-9 and TGF-β1 expression in the lungs. Copyright © 2017 Elsevier B.V. All rights reserved.

Dextromethorphan mediated bitter taste receptor activation in the pulmonary circuit causes vasoconstriction.

PubMed

Upadhyaya, Jasbir D; Singh, Nisha; Sikarwar, Anurag S; Chakraborty, Raja; Pydi, Sai P; Bhullar, Rajinder P; Dakshinamurti, Shyamala; Chelikani, Prashen

2014-01-01

Activation of bitter taste receptors (T2Rs) in human airway smooth muscle cells leads to muscle relaxation and bronchodilation. This finding led to our hypothesis that T2Rs are expressed in human pulmonary artery smooth muscle cells and might be involved in regulating the vascular tone. RT-PCR was performed to reveal the expression of T2Rs in human pulmonary artery smooth muscle cells. Of the 25 T2Rs, 21 were expressed in these cells. Functional characterization was done by calcium imaging after stimulating the cells with different bitter agonists. Increased calcium responses were observed with most of the agonists, the largest increase seen for dextromethorphan. Previously in site-directed mutational studies, we have characterized the response of T2R1 to dextromethorphan, therefore, T2R1 was selected for further analysis in this study. Knockdown with T2R1 specific shRNA decreased mRNA levels, protein levels and dextromethorphan-induced calcium responses in pulmonary artery smooth muscle cells by up to 50%. To analyze if T2Rs are involved in regulating the pulmonary vascular tone, ex vivo studies using pulmonary arterial and airway rings were pursued. Myographic studies using porcine pulmonary arterial and airway rings showed that stimulation with dextromethorphan led to contraction of the pulmonary arterial and relaxation of the airway rings. This study shows that dextromethorphan, acting through T2R1, causes vasoconstrictor responses in the pulmonary circuit and relaxation in the airways.

How do patients conceptualize chronic obstructive pulmonary disease?

PubMed

Goldman, R E; Mennillo, L; Stebbins, P; Parker, D R

2017-08-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States, yet even at risk or diagnosed patients misunderstand COPD and its consequences for their quality of life and mortality. This study explored how patients conceptualize the causes, symptoms, consequences, treatment, and risk for developing COPD. The study consisted of six focus groups: 39 participants who were adults > 40 and current smoker or have COPD symptoms, family history, or exposures. Although many participants had some familiarity with the breathing, lung function, physical, emotional, and social consequences of COPD, confusion and misunderstanding prevailed. Few knew that COPD, chronic bronchitis, and emphysema are synonymous. Some participants claimed that they "only" had bronchitis and/or emphysema and not COPD. Some participants described behavioral adaptations to decrease symptom impact and others expressed strong interest in learning how to increase daily functioning. Insufficient knowledge and persisting misconceptions about COPD can prevent patients from accessing life-enhancing strategies. Patients can benefit from (1) providers clarifying COPD's connection to chronic bronchitis and emphysema to aid them in recognizing the need for mitigating action; (2) encouraging smoking cessation, specifically to stem worsening of disease; and (3) explaining lifestyle adaptations for easing daily life despite decreased lung function.

Impaired Right Ventricular-Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction: An Ancillary Analysis From the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) Trial.

PubMed

Hussain, Imad; Mohammed, Selma F; Forfia, Paul R; Lewis, Gregory D; Borlaug, Barry A; Gallup, Dianne S; Redfield, Margaret M

2016-04-01

Right ventricular (RV) dysfunction (RVD) is a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). The physiological perturbations associated with RVD or RV function indexed to load (RV-pulmonary arterial [PA] coupling) in HFpEF have not been defined. HFpEF patients with marked impairment in RV-PA coupling may be uniquely sensitive to sildenafil. In a subset of HFpEF patients enrolled in the Phosphodiesteas-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial, physiological variables and therapeutic effect of sildenafil were examined relative to the severity of RVD (tricuspid annular plane systolic excursion [TAPSE]) and according to impairment in RV-PA coupling (TAPSE/pulmonary artery systolic pressure) ratio. The prevalence of atrial fibrillation and diuretic use, n-terminal probrain natriuretic peptide levels, renal dysfunction, neurohumoral activation, myocardial necrosis and fibrosis biomarkers, and the severity of diastolic dysfunction all increased with severity of RVD. Peak oxygen consumption decreased and ventilatory inefficiency (VE/VCO2 slope) increased with increasing severity of RVD. Many but not all physiological derangements were more closely associated with the TAPSE/pulmonary artery systolic pressure ratio. Compared with placebo, at 24 weeks, TAPSE decreased, and peak oxygen consumption and VE/CO2 slope were unchanged with sildenafil. There was no interaction between RV-PA coupling and treatment effect, and sildenafil did not improve TAPSE, peak oxygen consumption, or VE/VCO2 in patients with pulmonary hypertension and RVD. HFpEF patients with RVD and impaired RV-PA coupling have more advanced heart failure. In RELAX patients with RVD and impaired RV-PA coupling, sildenafil did not improve RV function, exercise capacity, or ventilatory efficiency. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867. © 2016 American Heart Association, Inc.

Maternal exposure to fine particulate air pollution induces epithelial-to-mesenchymal transition resulting in postnatal pulmonary dysfunction mediated by transforming growth factor-β/Smad3 signaling.

PubMed

Tang, Wenting; Du, Lili; Sun, Wen; Yu, Zhiqiang; He, Fang; Chen, Jingsi; Li, Xiaomei; Li, Xiuying; Yu, Lin; Chen, Dunjin

2017-02-05

Fine particles from air pollution, also called particulate matter, less than 2.5 micrometers in diameter (PM2.5), are a threat to child health. Epidemiological investigations have related maternal exposure to PM2.5 to postnatal respiratory symptoms, such as frequent wheezing, chronic cough, and lung function decrements. However, only few experimental animal studies have been performed to study the effects of PM2.5.The aim of this study was to investigate the effects of maternal exposure to PM2.5 on postnatal pulmonary dysfunction in a rat model and to examine the mechanism of PM2.5-induced morphological pulmonary changes.Timed pregnant Sprague-Dawley rats were treated with PM2.5 (0.1, 0.5, 2.5, or 7.5mg/kg) once every three days from day 0 to 18 of pregnancy. After delivery, pups were sacrificed on postnatal day (PND)1 and 28. The effects of transforming growth factor-beta (TGF-β) on epithelial-mesenchymal transition (EMT) were determined by immunohistochemistry, Western blotting, and quantitative RT-PCR. The offspring underwent pulmonary function measurements on PND28, lung tissues were histopathologically examined, and markers of oxidative stress were measured. Maternally PM2.5-exposed offspring pups displayed significant decreases in lung volume parameters, compliance, and airflow during expiration on PND28. The PM2.5-exposed group showed interstitial proliferation in lung histology, significant oxidative stress in lungs, and up-regulation of TGF-β-induced EMT via increased vimentin and α-smooth muscle actin and decreased E-cadherin levels on PND1 and PND28.These results suggest that EMT up-regulation mediated by the TGF-β/Smad3 pathway plays a role in postnatal pulmonary dysfunction associated with maternal exposure to PM2.5. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

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

Steinmaus, Craig, E-mail: craigs@berkeley.edu

Background: Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods: We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤ 10 μg/L. Results: Compared to adults never exposed > 10 μg/L, adults born in Antofagasta during the high exposuremore » period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 mL decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 mL). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions: Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. - Highlights: • Based on its unique geology, lifetime arsenic exposure can be assessed in north Chile. • Signs and symptoms of lung disease were associated with early-life arsenic exposure. • Evidence of lung disease was also associated with moderate arsenic exposure.« less

Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: possible involvement of angiotensin-converting enzyme-2.

PubMed

Han, Su-Xia; He, Guang-Ming; Wang, Tao; Chen, Lei; Ning, Yun-Ye; Luo, Feng; An, Jin; Yang, Ting; Dong, Jia-Jia; Liao, Zeng-Lin; Xu, Dan; Wen, Fu-Qiang

2010-05-15

Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

Nano-Se attenuates cyclophosphamide-induced pulmonary injury through modulation of oxidative stress and DNA damage in Swiss albino mice.

PubMed

Bhattacharjee, Arin; Basu, Abhishek; Biswas, Jaydip; Bhattacharya, Sudin

2015-07-01

Chemotherapy is an integral part of modern day treatment regimen but anticancer drugs fail to demarcate between cancerous and normal cells thereby causing severe form of systemic toxicity. Among which pulmonary toxicity is a dreadful complication developed in cancer patients upon cyclophosphamide (CP) therapy. Oxidative stress, fibrosis, and apoptosis are the major patho-mechanisms involved in CP-induced pulmonary toxicity. In the present study, we have synthesized Nano-Se, nanotechnology-based new form of elemental selenium which has significantly lower toxicity and acceptable bioavailability. In order to meet the need of effective drugs against CP-induced adverse effects, nano selenium (Nano-Se) was tested for its possible protective efficacy on CP-induced pulmonary toxicity and bone marrow toxicity. CP intoxication resulted in structural and functional lung impairment which was revealed by massive histopathological changes. Lung injury was associated with oxidative stress/lipid peroxidation as evident by increased in reactive oxygen species, nitric oxide level, and malondialdehyde (MDA) formation with decreased in level of antioxidants such as reduced glutathione, glutathione-S-transferase, glutathione peroxidase, superoxide dismutase, and catalase. Furthermore, CP at a dose of 25 mg/kg b.w. increased pulmonary DNA damage ('comet tail') and triggered DNA fragmentation and apoptosis in mouse bone marrow cells. On the other hand, Nano-Se at a dose of 2 mg Se/kg b.w., significantly inhibited CP-induced DNA damage in bronchoalveolar lavage cells, and decreased the apoptosis and percentage of DNA fragmentation in bone marrow cells and also antagonized the reduction of the activities of antioxidant enzymes and the increase level of MDA. Thus, our results suggest that Nano-Se in pre- and co-administration may serve as a promising preventive strategy against CP-induced pulmonary toxicity.

Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

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

Han Suxia; He Guangming; Wang Tao

Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along withmore » increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.« less

Paraseptal Emphysema: Prevalence and Distribution on CT and Association with Interstitial Lung Abnormalities

PubMed Central

Araki, Tetsuro; Nishino, Mizuki; Zazueta, Oscar E.; Gao, Wei; Dupuis, Josée; Okajima, Yuka; Latourelle, Jeanne C.; Rosas, Ivan O.; Murakami, Takamichi; O’Connor, George T.; Washko, George R.; Hunninghake, Gary M.; Hatabu, Hiroto

2015-01-01

Objective To investigate the prevalence and distribution of paraseptal emphysema on chest CT images in the Framingham Heart Study (FHS) population, and assess its impact on pulmonary function. Also pursued was the association with interstitial lung abnormalities. Materials and Methods We assessed 2633 participants in the FHS for paraseptal emphysema on chest CT. Characteristics of participants, including age, sex, smoking status, clinical symptoms, and results of pulmonary function tests, were compared between those with and without paraseptal emphysema. The association between paraseptal emphysema and interstitial lung abnormalities was investigated. Results Of the 2633 participants, 86 (3%) had pure paraseptal emphysema (defined as paraseptal emphysema with no other subtypes of emphysema other than paraseptal emphysema or a very few centrilobular emphysema involved) in at least one lung zone. The upper zone of the lungs was almost always involved. Compared to the participants without paraseptal emphysema, those with pure paraseptal emphysema were significantly older, and were more frequently male and smokers (mean 64 years, 71% male, mean 36 pack-years, p<0.001) and had significantly decreased FEV1/FVC% (p=0.002), and diffusion capacity of carbon monoxide (DLCO) (p=0.002). There was a significant association between pure paraseptal emphysema and interstitial lung abnormalities (p<0.001). Conclusions The prevalence of pure paraseptal emphysema was 3% in the FHS population, predominantly affects the upper lung zone, and contributes to decreased pulmonary function. Cigarette smoking, aging, and male gender were the factors associated with the presence of paraseptal emphysema. Significant association between paraseptal emphysema and interstitial lung abnormalities was observed. PMID:25868675

Pulmonary function test in traffic police personnel in Pondicherry.

PubMed

Pal, Pravati; John, Robert A; Dutta, T K; Pal, G K

2010-01-01

Traffic policemen working in the busy traffic signal areas get exposed to the vehicular emissions for years together. The fumes, chemicals and particles present in the emission are reported to be damaging to the lung functions of these individuals. Since there were no data available on the PFT parameters of traffic police personnel of Pondicherry, this study was taken up to assess the effect of traffic air pollution on their pulmonary functions. PFT parameters were recorded in age- and BMI-matched 30 traffic police personnel (study group) and 30 general police personnel (control group) of male gender. As chronic smoking is known to be a critical factor in altering lung function, PFT parameters were compared between the smokers as well as nonsmokers of both the groups. In nonsmokers, there was significant decrease in VC (P < 0.05), FEV1 (P < 0.01), FEF-25 (P < 0.05) and PIF (P < 0.05) in study group compared to the control group. In smokers, there was significant decrease in VC (P < 0.05), FEV1 (P <00001), PEF (P < 0.0001), MVV (P < 0.0001), FEF-25 (P < 0.0001), and PIF (P < 0.01) in study group compared to the control group. These changes indicate restriction to the lung expansion, obstruction and narrowing of the airways in traffic police personnel compared to the general police personnel. This may be due to exposure to vehicular pollution for several hours in a day for many years causing decreased functional capacity of the lungs and chronic smoking worsens the condition.

Additional mechanism for left ventricular dysfunction: chronic pulmonary regurgitation decreases left ventricular preload in patients with tetralogy of Fallot.

PubMed

Ylitalo, Pekka; Jokinen, Eero; Lauerma, Kirsi; Holmström, Miia; Pitkänen-Argillander, Olli M

2018-02-01

Right ventricular dysfunction in patients with tetralogy of Fallot and significant pulmonary regurgitation may lead to systolic dysfunction of the left ventricle due to altered ventricular interaction. We were interested in determining whether chronic pulmonary regurgitation affects the preload of the left ventricle. In addition, we wanted to study whether severe chronic pulmonary regurgitation would alter the preload of the left ventricle when compared with patients having preserved pulmonary valve annulus. The study group comprised 38 patients with tetralogy of Fallot who underwent surgical repair between 1990 and 2003. Transannular patching was required in 21 patients to reconstruct the right ventricular outflow tract. Altogether, 48 age- and gender-matched healthy volunteers were recruited. Cardiac MRI was performed on all study patients to assess the atrial and ventricular volumes and function. Severe pulmonary regurgitation (>30 ml/m2) was present in 13 patients, of whom 11 had a transannular patch, but only two had a preserved pulmonary valve annulus. The ventricular preload volumes from both atria were significantly reduced in patients with severe pulmonary regurgitation, and left ventricular stroke volumes (44.1±4.7 versus 58.9±10.7 ml/m2; p<0.0001) were smaller compared with that in patients with pulmonary regurgitation <30 ml/m2 or in controls. In patients with tetralogy of Fallot, severe pulmonary regurgitation has a significant effect on volume flow through the left atrium. Reduction in left ventricular preload volume may be an additional factor contributing to left ventricular dysfunction.

Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis

PubMed Central

Inomata, Minoru; Nishioka, Yasuhiko; Azuma, Arata

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. The molecular mechanisms involved in the progression of IPF are not fully understood; however, the platelet-derived growth factor (PDGF)/PDGF receptor pathway is thought to play a critical role in fibrogenesis of the lungs. Other growth factors, including fibroblast growth factor and vascular endothelial growth factor, are also thought to contribute to the pathogenesis of pulmonary fibrosis. Nintedanib is an inhibitor of multiple tyrosine kinases, including receptors for PDGF, fibroblast growth factor, and vascular endothelial growth factor. In the Phase II TOMORROW trial, treatment with 150 mg of nintedanib twice daily showed a trend to slow the decline in lung function and significantly decrease acute exacerbations in patients with IPF, while showing an acceptable safety profile. The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 trial, the time to the first acute exacerbation significantly increased in IPF patients who were treated with 150 mg of nintedanib twice daily. Pirfenidone, another antifibrotic drug, was shown to limit the decline in pulmonary function in patients with IPF in the ASCEND trial. Combination therapy with nintedanib and pirfenidone is anticipated, although further evaluation of its long-term safety is needed. There is limited evidence for the safety of the combination therapy although a Phase II trial conducted in Japan demonstrated that combination therapy with nintedanib and pirfenidone was tolerable for 1 month. Available antifibrotic agents (ie, pirfenidone and N-acetylcysteine) have limited efficacy as single therapies for IPF; therefore, further study of combination therapy with antifibrotic agents is needed. PMID:26346347

Cardiovascular effects in rats after intratracheal instillation of metal welding particles

PubMed Central

Zheng, Wen; Antonini, James M.; Lin, Yen-Chang; Roberts, Jenny R.; Kashon, Michael L.; Castranova, Vincent; Kan, Hong

2015-01-01

Studies have indicated that pulmonary exposure to welding fumes can induce a series of adverse effects in the respiratory system, including infection, bronchitis, siderosis and decreased pulmonary function. Recent clinical and epidemiological studies have found that pulmonary exposure to welding fumes is also associated with a higher incidence of cardiovascular events. However, there is insufficient evidence to confirm a direct effect of welding fumes on the cardiovascular system. The present study investigated the effects of pulmonary exposure to welding fumes on the heart and the vascular system in rats. Two chemically distinct welding fumes generated from manual metal arc-hard surfacing (MMA-HS) and gas metal arc-mild steel (GMA-MS) welding were tested. Three groups of rats were instilled intratracheally with MMA-HS (2 mg/rat), GMA-MS (2 mg/rat) or saline as control once a week for seven weeks. On days 1 and 7 after the last treatment, basal cardiovascular function and the cardiovascular response to increasing doses of adrenoreceptor agonists were assessed. MMA-HS treatment reduced the basal levels of left ventricle end-systolic pressure and dP/dtmax at 1 day post-treatment, and decreased dP/dtmin in response to isoproterenol (ISO) at 7 days post-treatment. Unlike MMA-HS, GMA-MS only affected left ventricular end-diastolic pressure in response to ISO at 7 days post-treatment. Treatment with MMA-HS or GMA-MS did not alter heart rate and blood pressure. Our findings suggest that exposure to different welding fumes can induce different adverse effects on the cardiovascular system, and that cardiac contractility may be a sensitive indicator of cardiovascular dysfunction. PMID:25600139

Cardiovascular effects in rats after intratracheal instillation of metal welding particles.

PubMed

Zheng, Wen; Antonini, James M; Lin, Yen-Chang; Roberts, Jenny R; Kashon, Michael L; Castranova, Vincent; Kan, Hong

2015-01-01

Studies have indicated that pulmonary exposure to welding fumes can induce a series of adverse effects in the respiratory system, including infection, bronchitis, siderosis and decreased pulmonary function. Recent clinical and epidemiological studies have found that pulmonary exposure to welding fumes is also associated with a higher incidence of cardiovascular events. However, there is insufficient evidence to confirm a direct effect of welding fumes on the cardiovascular system. The present study investigated the effects of pulmonary exposure to welding fumes on the heart and the vascular system in rats. Two chemically distinct welding fumes generated from manual metal arc-hard surfacing (MMA-HS) and gas metal arc-mild steel (GMA-MS) welding were tested. Three groups of rats were instilled intratracheally with MMA-HS (2 mg/rat), GMA-MS (2 mg/rat) or saline as control once a week for seven weeks. On days 1 and 7 after the last treatment, basal cardiovascular function and the cardiovascular response to increasing doses of adrenoreceptor agonists were assessed. MMA-HS treatment reduced the basal levels of left ventricle end-systolic pressure and dP/dt(max) at 1 day post-treatment, and decreased dP/dt(min) in response to isoproterenol (ISO) at 7 days post-treatment. Unlike MMA-HS, GMA-MS only affected left ventricular end-diastolic pressure in response to ISO at 7 days post-treatment. Treatment with MMA-HS or GMA-MS did not alter heart rate and blood pressure. Our findings suggest that exposure to different welding fumes can induce different adverse effects on the cardiovascular system, and that cardiac contractility may be a sensitive indicator of cardiovascular dysfunction.

Declining Pulmonary Function in Populations with Long-term Exposure to Polycyclic Aromatic Hydrocarbons-Enriched PM2.5.

PubMed

Shen, Meili; Xing, Jie; Ji, Qianpeng; Li, Zhihui; Wang, Yanhua; Zhao, Hongwei; Wang, Qingrong; Wang, Ting; Yu, Liwei; Zhang, Xiuchuan; Sun, Yaxin; Zhang, Zhihu; Niu, Yong; Wang, Huanqiang; Chen, Wen; Dai, Yufei; Su, Wenge; Duan, Huawei

2018-06-05

This study assesses the effects of long-term exposure to ambient air pollutants on inflammatory response and lung function. We selected 390 male coke oven workers with exposure to polycyclic aromatic hydrocarbons (PAHs) and fine particulate matter (PM 2.5 ) and 115 control workers. The average duration in the exposed group was 9.10 years. The total amount of PAHs was more enriched in PM 2.5 which collected from the coke oven workshops compared with the control areas. Correspondingly, the internal PAHs exposure indicated by urinary 1-hydroxypyrene (1-OHP) in the exposure group increased 25.7-fold compared to that of the control group. Moreover, the increasing level of urinary 1-OHP was associated with the decrease of forced expiratory volume in 1 s to forced vital capacity ratio (FEV 1 /FVC). In non-current smokers of exposure group, inverse correlation of 1-OHP with FEV 1 /FVC was also found. Particularly, an exposure duration-dependent decline in FEV 1 /FVC and mean forced expiratory flow between 25% and 75% of forced vital capacity (FEF 25-75% ) indicated that small airways were functionally obstructed. Furthermore, the increasing serum high-sensitivity C-reactive protein (hs-CRP) was correlated with the decline in pulmonary function in all subjects. These findings provide a clue that long-term exposure to PAHs-enriched PM 2.5 impairs pulmonary function in occupational population.

Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes

PubMed Central

Santhosh, KT; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, AJ; Dakshinamurti, S

2011-01-01

BACKGROUND AND PURPOSE Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor–mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. EXPERIMENTAL APPROACH We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca2+ response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. KEY RESULTS Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. CONCLUSIONS AND IMPLICATIONS TP receptor sensitivity and EC50 for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca2+ mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. PMID:21385177

Reduced serum club cell protein as a pulmonary damage marker for chronic fine particulate matter exposure in Chinese population.

PubMed

Wang, Yanhua; Duan, Huawei; Meng, Tao; Shen, Meili; Ji, Qianpeng; Xing, Jie; Wang, Qingrong; Wang, Ting; Niu, Yong; Yu, Tao; Liu, Zhong; Jia, Hongbing; Zhan, Yuliang; Chen, Wen; Zhang, Zhihu; Su, Wenge; Dai, Yufei; Zhang, Xuchun; Zheng, Yuxin

2018-03-01

Exposure to fine particulate matter (PM 2.5 ) pollution is associated with increased morbidity and mortality from respiratory diseases. However, few population-based studies have been conducted to assess the alterations in circulating pulmonary proteins due to long-term PM 2.5 exposure. We designed a two-stage study. In the first stage (training set), we assessed the associations between PM 2.5 exposure and levels of pulmonary damage markers (CC16, SP-A and SP-D) and lung function in a coke oven emission (COE) cohort with 558 coke plant workers and 210 controls. In the second stage (validation set), significant initial findings were validated by an independent diesel engine exhaust (DEE) cohort with 50 DEE exposed workers and 50 controls. Serum CC16 levels decreased in a dose response manner in association with both external and internal PM 2.5 exposures in the two cohorts. In the training set, serum CC16 levels decreased with increasing duration of occupational PM 2.5 exposure history. An interquartile range (IQR) (122.0μg/m 3 ) increase in PM 2.5 was associated with a 5.76% decrease in serum CC16 levels, whereas an IQR (1.06μmol/mol creatinine) increase in urinary 1-hydroxypyrene (1-OHP) concentration was associated with a 5.36% decrease in serum CC16 levels in the COE cohort. In the validation set, the concentration of serum CC16 in the PM 2.5 exposed group was 22.42% lower than that of the controls and an IQR (1.24μmol/mol creatinine) increase in urinary 1-OHP concentration was associated with a 12.24% decrease in serum CC16 levels in the DEE cohort. Serum CC16 levels may be a sensitive marker for pulmonary damage in populations with high PM 2.5 exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pulmonary responses of healthy young adults exposed to 0.06 and 0.08 ppm ozone

EPA Science Inventory

Background. Previous studies have shown small but significant decreases in spirometric lung function in healthy young adults exposed to 0.08 ppm ozone. It is unclear, however, if such effects may are seen at concentrations below 0.08 ppm. Methods. A group of 30 healthy young adul...

Lung volumes during sustained microgravity on Spacelab SLS-1

NASA Technical Reports Server (NTRS)

Elliott, Ann R.; Prisk, Gordon Kim; Guy, Harold J. B.; West, John B.

1994-01-01

Gravity is known to influence the topographical gradients of pulmonary ventilation, perfusion, and pleural pressures. The effect of sustained microgravity on lung volumes has not previously been investigated. Pulmonary function tests were performed by four subjects before, during, and after 9 days of microgravity exposure. Ground measurements were made in standing and supine postures. Tests were performed using a bag-in-box and flowmeter system and a respiratory mass spectrometer. Measurements of tidal volume (V(sub T)), expiratory reserve volume (ERV), inspiratory and expiratory vital capacities (IVC, EVC), functional residual capacity (FRC), and residual volume (RV) were made. During microgravity, V(sub T) decreased by 15%. IVC and EVC were slightly reduced during the first 24 hrs of microgravity and returned to 1 g standing values within 72 hrs after the onset of microgravity. FRC was reduced by 15% and ERV decreased by 10-20%. RV was significantly reduced by 18%. The reductions in FRC, ERV, and V(sub T) during microgravity are probably due to the cranial shift of the diaphragm and an increase in intrathoracic blood volume.

[EFFICIENCY OF COMBINATION OF ROFLUMILAST AND QUERCETIN FOR CORRECTION OXYGEN- INDEPENDENT MECHANISMS AND PHAGOCYTIC ACTIVITY OF MACROPHAGE CELLS OF PATIENTS WITH ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE WHEN COMBINED WITH CORONARY HEART DISEASE].

PubMed

Gerych, P; Yatsyshyn, R

2015-01-01

Studied oxygen independent reaction and phagocytic activity of macrophage cells of patients with chronic obstructive pulmonary disease (COPD) II-III stage when combined with coronary heart disease (CHD). The increasing oxygen independent reactions monocytes and neutrophils and a decrease of the parameters that characterize the functional state of phagocytic cells, indicating a decrease in the functional capacity of macrophage phagocytic system (MPS) in patients with acute exacerbation of COPD, which runs as its own or in combination with stable coronary heart disease angina I-II. FC. Severity immunodeficiency state in terms of cellular component of nonspecific immunity in patients with acute exacerbation of COPD II-III stage in conjunction with the accompanying CHD increases with the progression of heart failure. Inclusion of basic therapy of COPD exacerbation and standard treatment of coronary artery disease and drug combinations Roflumilastand quercetin causes normalization of phagocytic indices MFS, indicating improved immune status and improves myocardial perfusion in terms of daily ECG monitoring.

Relationships Among Health-Related Quality of Life, Pulmonary Health, and Newborn Screening for Cystic Fibrosis

PubMed Central

Becker, Tara; Laxova, Anita; Grieve, Adam; Racine Gilles, Caroline N.; Rock, Michael J.; Gershan, William M.; Green, Christopher G.; Farrell, Philip M.

2011-01-01

Background: The objective of this study was to examine relationships between pulmonary health and health-related quality of life (HRQOL) in patients with cystic fibrosis (CF) evaluated longitudinally in the Wisconsin Newborn Screening Project. Methods: Patients aged 8 to 18 years (mean ± SD, 13.5 ± 2.8) in early diagnosis (n = 45) and control (n = 50) groups completed Cystic Fibrosis Questionnaires (CFQs) to measure HRQOL at three data points over a 2-year period. Pulmonary health was evaluated concurrently by the Wisconsin chest x-ray scoring system (WCXR) and pulmonary function tests (PFTs). Results: WCXR showed significant group differences (P ≤ .023), with the early diagnosis group showing more-severe lung disease. When adjusted for group differences in mucoid Pseudomonas aeruginosa status and pancreatic status, however, WCXR differences and PFT data were not significant. Most patients (74%) had FEV1 values ≥ 80% predicted (within normal range). For patients aged < 14 years, as WCXR scores worsened CFQ respiratory and physical domain scores decreased (both P ≤ .007). FEV1/FVC showed a positive relationship with the respiratory and physical domains (both P ≤ .006). WCXR scores for patients aged ≥ 14 years were associated with CFQ weight, respiratory, and health domains (all P ≤ .011). FEV1 was associated with CFQ weight, respiratory, health, and physical domains (all P ≤ .003). Changes in pulmonary health were not associated with changes in CFQ over time. Significant group differences on the CFQ-Child social functioning domain favored the control group. Conclusions: To our knowledge, this study is the first to compare pulmonary outcomes with HRQOL indicators assessed by serial, standardized, patient-reported outcome measures for patients with CF identified either through newborn screening or diagnosed by use of traditional methods. This study found no benefits of newborn screening for pulmonary health or HRQOL after controlling for risk factors. Using WCXR and PFT data collectively helped to identify associations between pulmonary health and HRQOL. PMID:21106659

Host lung immunity is severely compromised during tropical pulmonary eosinophilia: role of lung eosinophils and macrophages.

PubMed

Sharma, Pankaj; Sharma, Aditi; Vishwakarma, Achchhe Lal; Agnihotri, Promod Kumar; Sharma, Sharad; Srivastava, Mrigank

2016-04-01

Eosinophils play a central role in the pathogenesis of tropical pulmonary eosinophilia, a rare, but fatal, manifestation of filariasis. However, no exhaustive study has been done to identify the genes and proteins of eosinophils involved in the pathogenesis of tropical pulmonary eosinophilia. In the present study, we established a mouse model of tropical pulmonary eosinophilia that mimicked filarial manifestations of human tropical pulmonary eosinophilia pathogenesis and used flow cytometry-assisted cell sorting and real-time RT-PCR to study the gene expression profile of flow-sorted, lung eosinophils and lung macrophages during tropical pulmonary eosinophilia pathogenesis. Our results show that tropical pulmonary eosinophilia mice exhibited increased levels of IL-4, IL-5, CCL5, and CCL11 in the bronchoalveolar lavage fluid and lung parenchyma along with elevated titers of IgE and IgG subtypes in the serum. Alveolar macrophages from tropical pulmonary eosinophilia mice displayed decreased phagocytosis, attenuated nitric oxide production, and reduced T-cell proliferation capacity, and FACS-sorted lung eosinophils from tropical pulmonary eosinophilia mice upregulated transcript levels of ficolin A and anti-apoptotic gene Bcl2,but proapoptotic genes Bim and Bax were downregulated. Similarly, flow-sorted lung macrophages upregulated transcript levels of TLR-2, TLR-6, arginase-1, Ym-1, and FIZZ-1 but downregulated nitric oxide synthase-2 levels, signifying their alternative activation. Taken together, we show that the pathogenesis of tropical pulmonary eosinophilia is marked by functional impairment of alveolar macrophages, alternative activation of lung macrophages, and upregulation of anti-apoptotic genes by eosinophils. These events combine together to cause severe lung inflammation and compromised lung immunity. Therapeutic interventions that can boost host immune response in the lungs might thus provide relief to patients with tropical pulmonary eosinophilia. © Society for Leukocyte Biology.

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.

RNA interference targeting carbohydrate sulfotransferase 3 diminishes macrophage accumulation, inhibits MMP-9 expression and promotes lung recovery in murine pulmonary emphysema.

PubMed

Kai, Yoshiro; Tomoda, Koichi; Yoneyama, Hiroyuki; Yoshikawa, Masanori; Kimura, Hiroshi

2015-12-09

Chondroitin sulfate proteoglycans are an important mediators in inflammation and leukocyte trafficking. However, their roles in pulmonary emphysema have not been explored. In a murine model of elastase-induced pulmonary emphysema, we found increased carbohydrate sulfotransferase 3 (CHST3), a specific enzyme that synthesizes chondroitin 6-sulfate proteoglycan (C6SPG). To elucidate the role of C6SPG, we investigated the effect of small interfering RNA (siRNA) targeting CHST3 that inhibits C6SPG-synthesis on the pathogenesis of pulmonary emphysema. Mice were intraperitoneally injected with CHST3 siRNA or negative control siRNA on day0 and 7 after intratracheal instillation of elastase. Histology, respiratory function, glycosaminoglycans (GAGs) content, bronchoalveolar lavage (BAL), elastin staining and gene expressions of tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-9 mRNA were evaluated on day7 and/or day21. CHST3 mRNA increased at day 7 and decreased thereafter in lung. CHST3 siRNA successfully inhibited the expression of CHST3 mRNA throughout the study and this was associated with significant reduction of GAGs and C6SPG. Airway destruction and respiratory function were improved by the treatment with CHST3 siRNA. CHST3 siRNA reduced the number of macrophages both in BAL and lung parenchyma and also suppressed the increased expressions of TNF-α and MMP-9 mRNA. Futhermore, CHST3 siRNA improved the reduction of the elastin in the alveolar walls. CHST3 siRNA diminishes accumulation of excessive macrophages and the mediators, leading to accelerate the functional recovery from airway damage by repair of the elastin network associated with pulmonary emphysema.

Lung function in retired coke oven plant workers.

PubMed Central

Chau, N; Bertrand, J P; Guenzi, M; Mayer, L; Téculescu, D; Mur, J M; Patris, A; Moulin, J J; Pham, Q T

1992-01-01

Lung function was studied in 354 coke oven plant workers in the Lorraine collieries (Houillères du Bassin de Lorraine, France) who retired between 1963 and 1982 and were still alive on 1 January 1988. A spirometric examination was performed on 68.4% of them in the occupational health service. Occupational exposure to respiratory hazards throughout their career was retraced for each subject. No adverse effect of occupational exposure on ventilatory function was found. Ventilatory function was, however negatively linked with smoking and with the presence of a respiratory symptom or discrete abnormalities visible on pulmonary x ray films. The functional values were mostly slightly lower than predicted values and the most reduced index was the mean expiratory flow, FEF25-75%. The decrease in forced expiratory volume in one second (FEV1) was often parallel to that in forced vital capacity (FVC), but it was more pronounced for subjects who had worked underground, for smokers of more than 30 pack-years, and for subjects having a respiratory symptom. Pulmonary function indices were probably overestimated because of the exclusion of deceased subjects and the bias of the participants. PMID:1599869

Changes of Pulmonary Pathology and Gene Expressions After Simvastatin Treatment in the Monocrotaline-Induced Pulmonary Hypertension Rat Model

PubMed Central

Lee, Yun Hee; Kim, Kwan Chang; Cho, Min-Sun

2011-01-01

Background and Objectives Simvastatin's properties are suggestive of a potential pathophysiologic role in pulmonary hypertension. The objectives of this study were to investigate changes of pulmonary pathology and gene expressions, including endothelin (ET)-1, endothelin receptor A (ERA), inducible nitric oxide synthase (NOS2), endothelial nitric oxide synthase (NOS3), matrix metalloproteinase (MMP) 2, tissue inhibitor of matrix metalloproteinases (TIMP) and caspase 3, and to evaluate the effect of simvastatin on monocrotaline (M)-induced pulmonary hypertension. Materials and Methods Six week old male Sprague-Dawley rats were treated, as follows: control group, subcutaneous (sc) injection of saline; M group, sc injection of M (60 mg/kg); and simvastatin group, sc injection of M (60 mg/kg) plus 10 mg/kg/day simvastatin orally. Results On day 28, right ventricular hypertrophy (RVH) significantly decreased in the simvastatin group compared to the M group. Similarly, right ventricular pressure significantly decreased in the simvastatin group on day 28. From day 7, the ratio of medial thickening of the pulmonary artery was significantly increased in the M group, but there was no significant change in the simvastatin group. The number of muscular pulmonary arterioles was significantly reduced in the simvastatin group. On day 5, gene expressions of ET-1, ERA, NOS2, NOS3, MMP and TIMP significantly decreased in the simvastatin group. Conclusion Administration of simvastatin exerted weak inhibitory effects on RVH and on the number of muscular pulmonary arterioles, during the development of M-induced pulmonary hypertension in rats. Simvastatin decreased gene expressions on day 5. PMID:22022327

beta(2)-adrenoceptor antagonist ICI 118,551 decreases pulmonary vascular tone in mice via a G(i/o) protein/nitric oxide-coupled pathway.

PubMed

Wenzel, Daniela; Knies, Ralf; Matthey, Michaela; Klein, Alexandra M; Welschoff, Julia; Stolle, Vanessa; Sasse, Philipp; Röll, Wilhelm; Breuer, Johannes; Fleischmann, Bernd K

2009-07-01

beta(2)-adrenoceptors are important modulators of vascular tone, particularly in the pulmonary circulation. Because neurohormonal activation occurs in pulmonary arterial hypertension, we have investigated the effect of different adrenergic vasoactive substances on tone regulation in large and small pulmonary arteries, as well as in systemic vessels of mice. We found that the beta(2)-adrenoceptor antagonist ICI 118,551 (ICI) evoked a decrease of vascular tone in large pulmonary arteries and reduced the sensitivity of pulmonary arteries toward different contracting agents, eg, norepinephrine, serotonin, or endothelin. ICI proved to act specifically on pulmonary vessels, because it shifted the dose-response curve of norepinephrine to the right in pulmonary arteries, whereas there was no effect in the aorta. Pharmacological experiments proved that the right shift of the norepinephrine dose-response curve by ICI was mediated via a beta(2)-adrenoceptor/G(i/o) protein-dependent pathway enhancing NO production in the endothelium; these results were corroborated in beta-adrenoceptor and endothelial NO synthase knockout mice where ICI had no effect. ICI increased vascular lumen diameter in lung sections and reduced pulmonary arterial pressure under normoxia and under hypoxia in the isolated perfused lung model. These effects were found to be physiologically relevant, because ICI specifically decreased pulmonary but not systemic blood pressure in vivo. Thus, the beta(2)-adrenoceptor antagonist ICI is a pulmonary arterial-specific vasorelaxant and, therefore, a potentially interesting novel therapeutic agent for the treatment of pulmonary arterial hypertension.

Acute Lung Injury Edema Fluid Decreases Net Fluid Transport across Human Alveolar Epithelial Type II Cells*

PubMed Central

Lee, Jae W.; Fang, Xiaohui; Dolganov, Gregory; Fremont, Richard D.; Bastarache, Julie A.; Ware, Lorraine B.; Matthay, Michael A.

2009-01-01

Most patients with acute lung injury (ALI) have reduced alveolar fluid clearance that has been associated with higher mortality. Several mechanisms may contribute to the decrease in alveolar fluid clearance. In this study, we tested the hypothesis that pulmonary edema fluid from patients with ALI might reduce the expression of ion transport genes responsible for vectorial fluid transport in primary cultures of human alveolar epithelial type II cells. Following exposure to ALI pulmonary edema fluid, the gene copy number for the major sodium and chloride transport genes decreased. By Western blot analyses, protein levels of αENaC, α1Na,K-ATPase, and cystic fibrosis transmembrane conductance regulator decreased as well. In contrast, the gene copy number for several inflammatory cytokines increased markedly. Functional studies demonstrated that net vectorial fluid transport was reduced for human alveolar type II cells exposed to ALI pulmonary edema fluid compared with plasma (0.02±0.05 versus 1.31±0.56 μl/cm2/h, p<0.02). An inhibitor of p38 MAPK phosphorylation (SB202190) partially reversed the effects of the edema fluid on net fluid transport as well as gene and protein expression of the main ion transporters. In summary, alveolar edema fluid from patients with ALI induced a significant reduction in sodium and chloride transport genes and proteins in human alveolar epithelial type II cells, effects that were associated with a decrease in net vectorial fluid transport across human alveolar type II cell monolayers. PMID:17580309

Increased activation of NADPH oxidase 4 in the pulmonary vasculature in experimental diaphragmatic hernia.

PubMed

Gosemann, Jan-H; Friedmacher, Florian; Hunziker, Manuela; Alvarez, Luis; Corcionivoschi, Nicolae; Puri, Prem

2013-01-01

Persistent pulmonary hypertension remains a major cause of mortality and morbidity in congenital diaphragmatic hernia (CDH). NADPH oxidases (Nox) are the main source of superoxide production in vasculature. Nox4 is highly expressed in the smooth muscle and endothelial cells of the vascular wall and increased activity has been reported in the pulmonary vasculature of both experimental and human pulmonary hypertension. Peroxisome proliferator-activated receptor (PPARγ) is a key regulator of Nox4 expression. Targeted depletion of PPARγ results in pulmonary hypertension phenotype whereas activation of PPARγ attenuates pulmonary hypertension and reduces Nox4 production. The nitrofen-induced CDH model is an established model to study the pathogenesis of pulmonary hypertension in CDH. It has been previously reported that PPARγ-signaling is disrupted during late gestation and H(2)O(2) production is increased in nitrofen-induced CDH. We designed this study to investigate the hypothesis that Nox4 expression and activation is increased and vascular PPARγ is decreased in nitrofen-induced CDH. Pregnant rats were treated with either nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on D21 and divided into control and CDH. RT-PCR, western blotting and confocal-immunofluorescence-double-staining were performed to determine pulmonary expression levels of PPARγ, Nox4 and Nox4-activation (p22(phox)). There was a marked increase in medial and adventitial thickness in pulmonary arteries of all sizes in CDH compared to controls. Pulmonary Nox4 levels were significantly increased whereas PPARγ levels were decreased in nitrofen-induced CDH compared to controls. Western blotting revealed increased pulmonary protein expression of the Nox4-activating subunit p22(phox) and decreased protein expression of PPARγ in CDH compared to controls. Confocal-microscopy confirmed markedly increased pulmonary expression of the Nox4 activating subunit p22(phox) accompanied by decreased perivascular PPARγ expression in lungs of nitrofen-exposed fetuses compared to controls. To our knowledge, the present study is the first to report increased Nox4 production in the pulmonary vasculature of nitrofen-induced CDH. Down-regulation of the PPARγ-signaling pathway may lead to increased superoxide production, resulting in pulmonary vascular dysfunction and contributing to pulmonary hypertension in the nitrofen-induced CDH model. PPARγ-activation inhibiting Nox4 production may therefore represent a potential therapeutic approach for the treatment of pulmonary hypertension in CDH.

Potentiation of pulmonary reflex response to capsaicin 24h following whole-body acrolein exposure is mediated by TRPV1.

PubMed

Hazari, Mehdi S; Rowan, William H; Winsett, Darrell W; Ledbetter, Allen D; Haykal-Coates, Najwa; Watkinson, William P; Costa, Daniel L

2008-02-01

Pulmonary C-fibers are stimulated by irritant air pollutants producing apnea, bronchospasm, and decrease in HR. Chemoreflex responses resulting from C-fiber activation are sometimes mediated by TRPV1 and release of substance P. While acrolein has been shown to stimulate C-fibers, the persistence of acrolein effects and the role of C-fibers in these responses are unknown. These experiments were designed to determine the effects of whole-body acrolein exposure and pulmonary chemoreflex response post-acrolein. Rats were exposed to either air or 3 ppm acrolein for 3 h while ventilatory function and HR were measured; 1-day later response to capsaicin challenge was measured in anesthetized rats. Rats experienced apnea and decrease in HR upon exposure to acrolein, which was not affected by either TRPV1 antagonist or NK(1)R antagonist pretreatment. Twenty-four hours later, capsaicin caused apnea and bronchoconstriction in control rats, which was potentiated in rats exposed to acrolein. Pretreatment with TRPV1 antagonist or NK(1)R antagonist prevented potentiation of apneic response and bronchoconstriction 24h post-exposure. These data suggest that although potentiation of pulmonary chemoreflex response 24h post-acrolein is mediated by TRPV1 and release of substance P, cardiopulmonary inhibition during whole-body acrolein exposure is mediated through other mechanisms.

Long-term results of percutaneous balloon valvuloplasty in pulmonary valve stenosis in the pediatric population.

PubMed

Merino-Ingelmo, Raquel; Santos-de Soto, José; Coserria-Sánchez, Félix; Descalzo-Señoran, Alfonso; Valverde-Pérez, Israel

2014-05-01

Percutaneous pulmonary valvuloplasty is the preferred interventional procedure for pulmonary valve stenosis. The aim of this study was to evaluate the effectiveness of this technique, assess the factors leading to its success, and determine the long-term results in the pediatric population. The study included 53 patients with pulmonary valve stenosis undergoing percutaneous balloon valvuloplasty between December 1985 and December 2000. Right ventricular size and functional echocardiographic parameters, such as pulmonary regurgitation and residual transvalvular gradient, were assessed during long-term follow-up. Peak-to-peak transvalvular gradient decreased from 74 mmHg [interquartile range, 65-100 mmHg] to 20 mmHg [interquartile range, 14-34 mmHg]. The procedure was unsuccessful in 2 patients (3.77%). The immediate success rate was 73.58%. Follow-up ranged from 10 years to 24 years (median, 15 years). During follow-up, all patients developed late pulmonary regurgitation which was assessed as grade II in 58.4% and grade III in 31.2%. There was only 1 case of long-term restenosis (2.1%). Severe right ventricular dilatation was observed in 27.1% of the patients. None of the patients developed significant right ventricular dysfunction. Pulmonary valve replacement was not required in any of the patients. Percutaneous balloon valvuloplasty is an effective technique in the treatment of pulmonary valve stenosis with good long-term results. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

The effects of obesity on lung volumes and oxygenation.

PubMed

Littleton, Stephen W; Tulaimat, Aiman

2017-03-01

Obesity can cause hypoxemia by decreasing lung volumes to where there is closure of lung units during normal breathing. Studies describing this phenomenon are difficult to translate into clinical practice. We wanted to determine the lung volume measurements that are associated with hypoxemia in obese patients, and explore how we could use these measurements to identify them. We collected pulmonary function test results and arterial blood gas data on 118 patients without obstruction on pulmonary function testing. We included only patients with normal chest imaging and cardiac testing within one year of the pulmonary function test, to exclude other causes of hypoxemia. We found that as BMI increases, the mean paO 2 , ERV % predicted, and ERV/TLC decrease (BMI 20-30 kg/m 2 : paO 2 =90±8 mmHg, ERV% predicted 112±50, ERV/TLC (%) 19.7±6.5; BMI 30-40 kg/m 2 : paO 2 =84±10 mmHg, ERV% predicted 84±40 ERV/TLC(%) 13.6±7.6; BMI>40 kg/m 2 : paO 2 78 ±12 mmHg, ERV% predicted 64±27 ERV/TLC(%) 11.4±5.8, ANOVA p<0.001). The A-a gradient increases as BMI increases (r=0.42, p<0.001). This correlation was stronger in men (r=0.54) than in women (r=0.35). The paO 2 is lower in patients with a low ERV than in those with a normal ERV (p<0.001). In a multivariate linear regression, only the ERV/TLC predicted (%), age, and BMI were associated with oxygenation (r 2 for A-a gradient =0.28, p=0.036). In obese patients without cardiopulmonary disease, oxygen levels decrease as BMI increases. This effect is associated with the obesity-related reduction in ERV and is independent of hypoventilation. Published by Elsevier Ltd.

Pathophysiological effect of fat embolism in a canine model of pulmonary contusion.

PubMed

Elmaraghy, A W; Aksenov, S; Byrick, R J; Richards, R R; Schemitsch, E H

1999-08-01

The objective of this study was to determine the individual and combined effects of pulmonary contusion and fat embolism on the hemodynamics and pulmonary pathophysiology in a canine model of acute traumatic pulmonary injury. After a thoracotomy, twenty-one skeletally mature dogs were randomly assigned to one of three groups. Unilateral pulmonary contusion alone was produced in Group 1 (seven dogs); pulmonary contusion and fat embolism, in Group 2 (seven dogs); and fat embolism alone, in Group 3 (seven dogs). Pulmonary contusion was produced by standardized compression of the left lung with a piezoelectric force transducer. Fat embolism was produced by femoral and tibial reaming followed by pressurization of the intramedullary canals. Cardiac output, systolic blood pressure, peak airway pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, partial pressure of arterial oxygen, and partial pressure of carbon dioxide were monitored for all groups. From these data, several outcome parameters were calculated: total thoracic compliance, alveolar-arterial oxygen gradient, and ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration. All of the dogs were killed after eight hours, and tissue samples were obtained from the brain, kidneys, and lungs for histological analysis. Lung samples were assigned scores for pulmonary edema (the presence of fluid in the alveoli) and inflammation (the presence of neutrophils or hyaline membranes, or both). The percentage of the total area occupied by fat was determined. Pulmonary contusion alone caused a significant increase in the alveolar-arterial oxygen gradient but only after seven hours (p = 0.034). Fat embolism alone caused a significant transient decrease in systolic blood pressure (p = 0.001) and a significant transient increase in pulmonary arterial pressure (p = 0.01) and pulmonary capillary wedge pressure (p = 0.015). Fat embolism alone also caused a significant sustained decrease in the ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration (p = 0.0001) and a significant increase in the alveolar-arterial oxygen gradient (p = 0.0001). The combination of pulmonary contusion and fat embolism caused a significant transient increase in pulmonary capillary wedge pressure (p = 0.0013) as well as a significant sustained decrease in partial pressure of arterial oxygen (p = 0.0001) and a significant decrease in systolic blood pressure (p = 0.001) that lasted for an hour. Pulmonary contusion followed by fat embolism caused a significant increase in peak airway pressure (p = 0.015), alveolar-arterial oxygen gradient (p = 0.0001), and pulmonary arterial pressure (p = 0.01), and these effects persisted for five hours. Total thoracic compliance was decreased 6.4 percent by pulmonary contusion alone, 4.6 percent by fat embolism alone, and 23.5 percent by pulmonary contusion followed by fat embolism. The ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration was decreased 23.7 percent by pulmonary contusion alone, 52.3 percent by fat embolism alone, and 65.8 percent by pulmonary contusion followed by fat embolism. The mean pulmonary edema score was significantly higher with the combined injury than with either injury alone (p = 0.0001). None of the samples from the lungs demonstrated inflammation. Fat embolism combined with pulmonary contusion resulted in a significantly greater mean percentage of the area occupied by fat in the noncontused right lung than in the contused left lung (p = 0.001); however, no significant difference between the right and left lungs could be detected with fat embolism alone. The mean percentage of the glomerular and cerebral areas occupied by fat was greater with fat embolism combined with pulmonary contusion than with fat embolism alone (p = 0.0001 and p = 0.01, respectively). (ABSTRACT TRUNCATED)

Pulmonary FGF-18 gene expression is downregulated during the canalicular-saccular stages in nitrofen-induced hypoplastic lungs.

PubMed

Takahashi, Hiromizu; Friedmacher, Florian; Fujiwara, Naho; Hofmann, Alejandro; Kutasy, Balazs; Gosemann, Jan-Hendrik; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH) represents one of the major challenges in neonatal intensive care. However, the molecular pathogenesis of PH is still poorly understood. In developing fetal lungs, fibroblast growth factor 18 (FGF-18) plays a crucial role in distal airway maturation. FGF-18 knockouts show smaller lung sizes with reduced alveolar spaces and thicker interstitial mesenchymal compartments, highlighting its important function for fetal lung growth and differentiation. We hypothesized that pulmonary FGF-18 gene expression is downregulated during late gestation in nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetuses were harvested on D18 and D21, and lungs were divided into three groups: controls, hypoplastic lungs without CDH [CDH(-)], and hypoplastic lungs with CDH [CDH(+)] (n = 24 at each time-point). Pulmonary FGF-18 gene expression levels were analyzed by qRT-PCR. Immunohistochemistry was performed to investigate FGF-18 protein expression/distribution. Relative mRNA levels of pulmonary FGF-18 gene expression were significantly decreased in CDH(-) and CDH(+) on D18 and D21 compared to controls (p < 0.05 and p < 0.01, respectively). Immunoreactivity of FGF-18 was markedly diminished in mesenchymal cells surrounding the airway epithelium on D18 and D21 compared to controls. Downregulation of FGF-18 gene expression in nitrofen-induced hypoplastic lungs suggests that decreased FGF-18 expression during the canalicular-saccular stages may interfere with saccular-alveolar differentiation and distal airway maturation resulting in PH.

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.

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230.

PubMed

Egger, Christine; Gérard, Christelle; Vidotto, Nella; Accart, Nathalie; Cannet, Catherine; Dunbar, Andrew; Tigani, Bruno; Piaia, Alessandro; Jarai, Gabor; Jarman, Elizabeth; Schmid, Herbert A; Beckmann, Nicolau

2014-06-15

Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity and alveolar surface area, secondary to alveolar epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and deposition of extracellular matrix. The effects of oropharyngeal aspiration of bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal administration of ovalbumin to actively sensitized Brown Norway rats on total lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were investigated here. Lung injury and volume were quantified by using nongated or respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo techniques]. Lung function of bleomycin-challenged rats was examined additionally using a flexiVent system. Postmortem analyses included histology of collagen and hydroxyproline assays. Bleomycin induced an increase of MRI-assessed total lung volume, lung dry and wet weights, and hydroxyproline content as well as collagen amount. In bleomycin-treated rats, gated MRI showed an increased volume of the lung in the inspiratory and expiratory phases of the respiratory cycle and a temporary decrease of tidal volume. Decreased dynamic lung compliance was found in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung volume was consistent with tissue deposition during fibrotic processes resulting in decreased lung elasticity, whereas influences by edema or emphysema could be excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI remained unchanged. The somatostatin analog, SOM230, was shown to have therapeutic effects on established bleomycin-induced fibrosis in rats. This work suggests MRI-detected total lung volume as readout for tissue-deposition in small rodent bleomycin models of pulmonary fibrosis. Copyright © 2014 the American Physiological Society.

Reduction of Pulmonary Function After Surgical Lung Resections of Different Volume

PubMed Central

Cukic, Vesna

2014-01-01

Introduction: In recent years 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 with common etiologic factor - smoking cigarettes. Objective: To determine how big the loss of lung function is after surgical resection of lung of different range. Methods: The study was done on 58 patients operated at the Clinic for thoracic surgery KCU Sarajevo, previously treated at the Clinic for pulmonary diseases “Podhrastovi” in the period from 01.06.2012. to 01.06.2014. The following resections were done: pulmectomy (left, right), lobectomy (upper, lower: left and right). The values of postoperative pulmonary function were compared with preoperative ones. As a parameter of lung function we used FEV1 (forced expiratory volume in one second), and changes in FEV1 are expressed in liters and in percentage of the recorded preoperative and normal values of FEV1. Measurements of lung function were performed seven days before and 2 months after surgery. Results: Postoperative FEV1 was decreased compared to preoperative values. After pulmectomy the maximum reduction of FEV1 was 44%, and after lobectomy it was 22% of the preoperative values. Conclusion: Patients with airway obstruction are limited in their daily life before the surgery, and an additional loss of lung tissue after resection contributes to their inability. Potential benefits of lung resection surgery should be balanced in relation to postoperative morbidity and mortality. PMID:25568542

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.

Naja naja atra venom ameliorates pulmonary fibrosis by inhibiting inflammatory response and oxidative stress.

PubMed

Cui, Kui; Kou, Jian-Qun; Gu, Jin-Hua; Han, Rong; Wang, Guanghui; Zhen, Xuechu; Qin, Zheng-Hong

2014-12-02

Naja naja atra venom (NNAV) displays diverse pharmacological actions including analgesia, anti-inflammation and immune regulation.In this study, we investigated the effects of NNAV on pulmonary fibrosis and its mechanisms of action. To determine if Naja naja atra venom (NNAV) can produce beneficial effects on pulmonary fibrosis, two marine models of pulmonary fibrosis were produced with bleomycin (BLM) and lipopolysaccharide (LPS). NNAV (30, 90, 270 μg/kg) was orally administered once a day started five days before BLM and LPS until to the end of experiment. The effects of NNAV treatment on pulmonary injury were evaluated with arterial blood gas analysis, hydroxyproline (HYP) content assessment and HE/Masson staining. The effects of NNAV treatment on inflammatory related cytokines, fibrosis related TGF-β/Smad signaling pathway and oxidative stress were examined. The results showed that NNAV improved the lung gas-exchange function and attenuated the fibrotic lesions in lung. NNAV decreased IL-1β and TNF-α levels in serum in both pulmonary fibrosis models. NNAV inhibited the activation of NF-κB in LPS-induced and TGF-β/Smad pathway in BLM-induced pulmonary fibrosis. Additionally, NNAV also increased the levels of SOD and GSH and reduced the levels of MDA in BLM-induced pulmonary fibrosis model. The present study indicates that NNAV attenuates LPS- and BLM-induced lung fibrosis. Its mechanisms of action are associated with inhibiting inflammatory response and oxidative stress. The study suggests that NNAV might be a potential therapeutic drug for treatment of pulmonary fibrosis.

Manipulating parallel circuits: the perioperative management of patients with complex congenital cardiac disease.

PubMed

Lawrenson, John; Eyskens, Benedicte; Vlasselaers, Dirk; Gewillig, Marc

2003-08-01

In all patients undergoing cardiac surgery, the effective delivery of oxygen to the tissues is of paramount importance. In the patient with relatively normal cardiac structures, the pulmonary and systemic circulations are relatively independent of each other. In the patient with a functional single ventricle, the pulmonary and systemic circulations are dependent on the same pump. As a consequence of this interdependency, the haemodynamic changes following complex palliative procedures, such as the Norwood operation, can be difficult to understand. Comparison of the newly created surgical connections to a simple set of direct current electrical circuits may help the practitioner to successfully care for the patient. In patients undergoing complex palliations, the pulmonary and systemic circulations can be compared to two circuits in parallel. Manipulations of variables, such as resistance or flow, in one circuit, can profoundly affect the performance of the other circuit. A large pulmonary flow might result in a large increase in the saturation of haemoglobin with oxygen returning to the heart via the pulmonary veins at the expense of a decreased systemic flow. Accurate balancing of these parallel circulations requires an appreciation of all interventions that can affect individual components of both circulations.

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.

Chronic Alcohol Induces M2 Polarization Enhancing Pulmonary Disease Caused by Exposure to Particulate Air Pollution

PubMed Central

Thevenot, Paul; Saravia, Jordy; Giaimo, Joseph; Happel, Kyle I.; Dugas, Tammy R.; Cormier, Stephania A.

2013-01-01

Background Chronic alcohol consumption causes persistent oxidative stress in the lung, leading to impaired alveolar macrophage (AM) function and impaired immune responses. AMs play a critical role in protecting the lung from particulate matter (PM) inhalation by removing particulates from the airway and secreting factors which mediate airway repair. We hypothesized AM dysfunction caused by chronic alcohol consumption increases the severity of injury caused by particulate matter inhalation. Methods Age- and sex-matched C57BL6 mice were fed the Lieber-DeCarli liquid diet containing either alcohol or an iso-caloric substitution (control diet) for 8 weeks. Mice from both diet groups were exposed to combustion derived PM (CDPM) for the final 2 weeks. AM number, maturation, and polarization status were assessed by flow cytometry. Noninvasive and invasive strategies were used to assess pulmonary function and correlated with histomorphological assessments of airway structure and matrix deposition. Results Co-exposure to alcohol and CDPM decreased AM number and maturation status (CD11c expression) while increasing markers of M2 activation (IL-4Rα, Ym1, Fizz1 expression and IL-10 and TGF-β production). Changes in AM function were accompanied by decreased airway compliance and increased elastance. Altered lung function was attributable to elevated collagen content localized to the small airways and loss of alveolar integrity. Intranasal administration of neutralizing antibody to TGF-β during the CDPM exposure period improved changes in airway compliance and elastance while reducing collagen content caused by co-exposure. Conclusion CDPM inhalation causes enhanced disease severity in the alcoholic lung by stimulating the release of latent TGF-β stores in AMs. The combinatorial effect of elevated TGF-β, M2 polarization of AMs, and increased oxidative stress impairs pulmonary function by increasing airway collagen content and compromising alveolar integrity. PMID:23763452

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.

REACTIVE OXYGEN AND NITROGEN SPECIES IN PULMONARY HYPERTENSION

PubMed Central

Tabima, Diana M.; Frizzell, Sheila; Gladwin, Mark T.

2013-01-01

Pulmonary vascular disease can be defined as either a disease affecting the pulmonary capillaries and pulmonary arterioles, termed pulmonary arterial hypertension, or as a disease affecting the left ventricle, called pulmonary venous hypertension. Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary circulation characterized by endothelial dysfunction, as well as intimal and smooth muscle proliferation. Progressive increases in pulmonary vascular resistance and pressure impair the performance of the right ventricle, resulting in declining cardiac output, reduced exercise capacity, right heart failure, and ultimately death. While the primary and heritable forms of the disease are thought to affect over 5,000 patients in the U.S., the disease can occur secondary to congenital heart disease, most advanced lung diseases, and many systemic diseases. Multiple studies implicate oxidative stress in the development of PAH. Further, this oxidative stress has been shown to be associated with alterations in reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO) signaling pathways, whereby bioavailable NO is decreased and ROS and RNS production are increased. Many canonical ROS and NO signaling pathways are simultaneously disrupted in PAH, with increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and xanthine oxidoreductase, uncoupling of endothelial NO synthase (eNOS), and reduction in mitochondrial number, as well as impaired mitochondrial function. Upstream dysregulation of ROS/NO redox homeostasis impairs vascular tone and contributes to the pathological activation of anti-apoptotic and mitogenic pathways, leading to cell proliferation and obliteration of the vasculature. This manuscript will review the available data regarding the role of oxidative and nitrosative stress and endothelial dysfunction in the pathophysiology of pulmonary hypertension, and provide a description of targeted therapies for this disease. PMID:22401856

Long-term effects of prenatal hypoxia on endothelium-dependent relaxation responses in pulmonary arteries of adult sheep.

PubMed

Liu, Jie; Gao, Yuansheng; Negash, Sewite; Longo, Lawrence D; Raj, J Usha

2009-03-01

Chronic hypoxia during the course of pregnancy is a common insult to the fetus. However, its long-term effect on the pulmonary vasculature in adulthood has not been described. In this study, the vasorelaxation responses of conduit pulmonary arteries in adult female sheep that were chronically hypoxic as fetuses and raised postnatally at sea level were investigated. Vessel tension studies revealed that endothelium-dependent relaxation responses were attenuated in pulmonary arteries from adult sheep that experienced prenatal hypoxia. Endothelial nitric oxide synthase (eNOS) protein expression was unchanged, but eNOS activity was significantly decreased in pulmonary arteries from prenatally hypoxic sheep. Protein expression of eNOS partners, caveolin-1, calmodulin, and heat shock protein 90 (Hsp90) did not change following prenatal hypoxia. However, the association between eNOS and caveolin-1, its inhibitory binding partner, was significantly increased, whereas association between eNOS and its stimulatory partners calmodulin and Hsp90 was greatly decreased. Furthermore, phosphorylation of Ser(1177) in eNOS decreased, whereas phosphorylation of Thr(495) increased, in the prenatally hypoxic pulmonary arteries, events that are related to eNOS activity. These data demonstrate that prenatal hypoxia results in persistent abnormalities in endothelium-dependent relaxation responses of pulmonary arteries in adult sheep due to decreased eNOS activity resulting from altered posttranslational regulation.

Long-term effects of prenatal hypoxia on endothelium-dependent relaxation responses in pulmonary arteries of adult sheep

PubMed Central

Liu, Jie; Gao, Yuansheng; Negash, Sewite; Longo, Lawrence D.; Raj, J. Usha

2009-01-01

Chronic hypoxia during the course of pregnancy is a common insult to the fetus. However, its long-term effect on the pulmonary vasculature in adulthood has not been described. In this study, the vasorelaxation responses of conduit pulmonary arteries in adult female sheep that were chronically hypoxic as fetuses and raised postnatally at sea level were investigated. Vessel tension studies revealed that endothelium-dependent relaxation responses were attenuated in pulmonary arteries from adult sheep that experienced prenatal hypoxia. Endothelial nitric oxide synthase (eNOS) protein expression was unchanged, but eNOS activity was significantly decreased in pulmonary arteries from prenatally hypoxic sheep. Protein expression of eNOS partners, caveolin-1, calmodulin, and heat shock protein 90 (Hsp90) did not change following prenatal hypoxia. However, the association between eNOS and caveolin-1, its inhibitory binding partner, was significantly increased, whereas association between eNOS and its stimulatory partners calmodulin and Hsp90 was greatly decreased. Furthermore, phosphorylation of Ser1177 in eNOS decreased, whereas phosphorylation of Thr495 increased, in the prenatally hypoxic pulmonary arteries, events that are related to eNOS activity. These data demonstrate that prenatal hypoxia results in persistent abnormalities in endothelium-dependent relaxation responses of pulmonary arteries in adult sheep due to decreased eNOS activity resulting from altered posttranslational regulation. PMID:19136582

Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells.

PubMed

Abraham, Nader G; Quan, Shuo; Mieyal, Paul A; Yang, Liming; Burke-Wolin, Theresa; Mingone, Christopher J; Goodman, Alvin I; Nasjletti, Alberto; Wolin, Michael S

2002-11-01

Carbon monoxide (CO) stimulates guanylate cyclase (GC) and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels. We transfected rat-lung pulmonary endothelial cells with a retrovirus-mediated human heme oxygenase (hHO)-1 gene. Pulmonary cells that expressed hHO-1 exhibited a fourfold increase in HO activity associated with decreases in the steady-state levels of heme and cGMP without changes in soluble GC (sGC) and endothelial nitric oxide synthase (NOS) proteins or basal nitrite production. Heme elicited significant increases in CO production and intracellular cGMP levels in both pulmonary endothelial and pulmonary hHO-1-expressing cells. N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly decreased cGMP levels in heme-treated pulmonary endothelial cells but not heme-treated hHO-1-expressing cells. In the presence of exogenous heme, CO and cGMP levels in hHO-1-expressing cells exceeded the corresponding levels in pulmonary endothelial cells. Acute exposure of endothelial cells to SnCl2, which is an inducer of HO-1, increased cGMP levels, whereas chronic exposure decreased heme and cGMP levels. These results indicate that prolonged overexpression of HO-1 ultimately decreases sGC activity by limiting the availability of cellular heme. Heme activates sGC and enhances cGMP levels via a mechanism that is largely insensitive to NOS inhibition.

CFTR and lung homeostasis

PubMed Central

Matalon, Sadis

2014-01-01

CFTR is a cAMP-activated chloride and bicarbonate channel that is critical for lung homeostasis. Decreases in CFTR expression have dire consequences in cystic fibrosis (CF) and have been suggested to be a component of the lung pathology in chronic obstructive pulmonary disease. Decreases or loss of channel function often lead to mucus stasis, chronic bacterial infections, and the accompanying chronic inflammatory responses that promote progressive lung destruction, and, eventually in CF, lung failure. Here we discuss CFTR's functional role airway surface liquid hydration and pH, in regulation of other channels such as the epithelial sodium channel, and in regulating inflammatory responses in the lung. PMID:25381027

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.

Screening adolescent athletes for exercise-induced asthma.

PubMed

Feinstein, R A; LaRussa, J; Wang-Dohlman, A; Bartolucci, A A

1996-04-01

To pilot test an exercise-induced asthma (EIA) screening program using a submaximal step-test and pulmonary function test (PFT) to identify athletes with EIA and to determine if a physical examination or self-reported history could be used to predict the existence of EIA. Screening and diagnostic testing using a convenience sample. Birmingham, Alabama, during athletic preparticipation examination (PPE). Fifty-two African-American, male football players aged 14-18 years being evaluated for participation in scholastic athletics. No athlete refused participation. Four were excluded because of need for further evaluation unrelated to any pulmonary condition. Each athlete completed a medical history, allergy history, physical examination, preexercise pulmonary function test (PFT), submaximal step-test, and a series of postexercise PFTs. Major outcome measurements were changes in forced expiration volume in 1s (FEV1) or peak expiratory flow rate (PEFR) after completing an exercise challenge. Seventeen of 48 athletes had a > or = 15% decrease in PEFR after exercise. Nine of 48 athletes had a > or = 15% decrease in FEV1 after exercise. The only self-reported item that differentiated subjects with normal and abnormal PFTs was a personal history of asthma (p < 0.05). Many athletes can be identified as having abnormal PFTs by use of a submaximal step-test as an exercise challenge. Self-reporting questionnaires and PPEs do not appear to be sensitive enough to identify athletes with this condition. If validated by future studies, this protocol could be used for the diagnosis of EIA.

Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats.

PubMed

Liu, Zibing; Geng, Wenye; Jiang, Chuanwei; Zhao, Shujun; Liu, Yong; Zhang, Ying; Qin, Shucun; Li, Chenxu; Zhang, Xinfang; Si, Yanhong

2017-09-01

Chronic obstructive pulmonary disease induced by tobacco smoke has been regarded as a great health problem worldwide. The purpose of this study is to evaluate the protective effect of hydrogen-rich saline, a novel antioxidant, on chronic obstructive pulmonary disease and explore the underlying mechanism. Sprague-Dawley rats were made chronic obstructive pulmonary disease models via tobacco smoke exposure for 12 weeks and the rats were treated with 10 ml/kg hydrogen-rich saline intraperitoneally during the last 4 weeks. Lung function testing indicated hydrogen-rich saline decreased lung airway resistance and increased lung compliance and the ratio of forced expiratory volume in 0.1 s/forced vital capacity in chronic obstructive pulmonary disease rats. Histological analysis revealed that hydrogen-rich saline alleviated morphological impairments of lung in tobacco smoke-induced chronic obstructive pulmonary disease rats. ELISA assay showed hydrogen-rich saline lowered the levels of pro-inflammatory cytokines (IL-8 and IL-6) and anti-inflammatory cytokine IL-10 in bronchoalveolar lavage fluid and serum of chronic obstructive pulmonary disease rats. The content of malondialdehyde in lung tissue and serum was also determined and the data indicated hydrogen-rich saline suppressed oxidative stress reaction. The protein expressions of mucin MUC5C and aquaporin 5 involved in mucus hypersecretion were analyzed by Western blot and ELISA and the data revealed that hydrogen-rich saline down-regulated MUC5AC level in bronchoalveolar lavage fluid and lung tissue and up-regulated aquaporin 5 level in lung tissue of chronic obstructive pulmonary disease rats. In conclusion, these results suggest that administration of hydrogen-rich saline exhibits significant protective effect on chronic obstructive pulmonary disease through alleviating inflammation, reducing oxidative stress and lessening mucus hypersecretion in tobacco smoke-induced chronic obstructive pulmonary disease rats. Impact statement This study was designed to evaluate protective effect of hydrogen-rich saline, a novel antioxidant, on tobacco smoke (TS)-induced chronic obstructive pulmonary disease (COPD) in rats and explore the underlying mechanism. Our results suggest that administration of hydrogen-rich saline improves lung function and alleviates morphological impairments of lung through alleviating inflammation, reducing oxidative stress and lessening mucus hypersecretion in TS-induced COPD rats.

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.

Pulmonary Responses in Healthy Young Adults Exposed to Low Concentration of Ozone for 6.6 Hours with Mild Exercise

EPA Science Inventory

Rational: Recent studies have shown small but significant decreases in lung function following a prolonged exposure (6.6 hour) of healthy young adults to levels of ozone (0.08 ppm) near the current 8 hour standard. It is unclear, however, if such effects may be extended to concen...

Endothelial bioreactor system ameliorates multiple organ dysfunction in septic rats.

PubMed

Ma, Shuai; Lin, Yuli; Deng, Bo; Zheng, Yin; Hao, Chuanming; He, Rui; Ding, Feng

2016-12-01

The endothelium is a potentially valuable target for sepsis therapy. We have previously studied an extracorporeal endothelial cell therapy system, called the endothelial bioreactor (EBR), which prolonged the survival time of endotoxemia sepsis in swine. To further study of the therapeutic effects and possible mechanisms, we established a miniature EBR system for septic rats induced by cecal ligation and puncture (CLP). In the miniature EBR system, the extracorporeal circulation first passed through a mini-hemofilter, and the ultrafiltrate (UF) was separated, then the UF passed through an EBR (a 1-mL cartridge containing approximately 2 × 10(6) endothelial cells grown on microcarriers) and interact with endothelial cells. Eighteen hours after CLP, the rats were treated for 4 h with this extracorporeal system containing either endothelial cells (EBR group) or no cells (sham EBR group). Physiologic and biochemical parameters, cytokines, endothelial functions, and 7-day survival time were monitored. In vitro, the pulmonary endothelial cells of the septic rats were treated with the EBR system and the resulting changes in their functions were monitored. The EBR system ameliorated CLP-induced sepsis compared with the sham EBR system. After CLP, the 7-day survival rate of sham-treated rats was only 25.0 %, while in the EBR-treated group, it increased to 57.1 % (p = 0.04). The EBR system protected the liver and renal function and ameliorated the kidney and lung injury. Meanwhile, this therapy reduced pulmonary vascular leakage and alleviated the infiltration of inflammatory cells in the lungs, especially neutrophils. Furthermore, after the EBR treatment both in vivo and in vitro, the expression of intercellular adhesion molecule-1 and the secretion of CXCL1 and CXCL2 of pulmonary endothelium decreased, which helped to alleviate the adhesion and chemotaxis of neutrophils. In addition, the EBR system decreased CD11b expression and intracellular free calcium level of peripheral blood neutrophils, modulated the activation of these neutrophils. The EBR system significantly ameliorated CLP-induced sepsis and improved survival and organ functions. Compared with the sham EBR system, this extracorporeal endothelial therapy may be involved in modulating the function of pulmonary endothelial cells, reducing the adhesion and chemotaxis of neutrophil, and modulating the activation of peripheral blood neutrophils.

Body Weight and Body Mass Index in Patients with End-Stage Cystic Fibrosis Stabilize After the Start of Enteral Tube Feeding.

PubMed

Hollander, Francis M; de Roos, Nicole M; Belle van Meerkerk, Gerdien; Teding van Berkhout, Ferdinand; Heijerman, Harry G M; van de Graaf, Ed A

2017-11-01

Enteral tube feeding (ETF) is widely used in patients with cystic fibrosis (CF) and end-stage lung disease, but previous studies have been limited to investigating whether ETF improves outcomes in patients with moderately or mildly impaired pulmonary function. This study investigated body weight, body mass index (BMI; calculated as kg/m 2 ), pulmonary function, and the presence of CF-related diabetes before and after the start of ETF. This was a retrospective observational study. Data from 26 adult patients in an outpatient setting who had end-stage CF (19 women) and had been using ETF for at least 6 months between 2000 and 2014 were analyzed. Body weight, BMI, pulmonary function (forced expiratory volume in 1 second as percent of predicted) and incidence of CF-related diabetes from 6 months before to 6 months after starting ETF. Time effects were tested with one-way analysis of variance for data that were normally distributed and the Friedman test for non-parametric data. Correlations were tested with Pearson's r or Spearman's ρ, depending on the distribution of the data. Mean body weight increased by 3.5 kg (95% CI 2.2 to 4.8 kg) after patients started ETF. In women, mean BMI decreased by 0.7 in the 6 months before the start of ETF (P<0.05) and increased by 1.4 in the 6 months thereafter (P<0.05). In men, BMI changes were similar (-0.8 and +1.1), but not statistically significant. Forced expiratory volume in 1 second as percent of predicted significantly decreased in time from a median of 28% to 26% at the start of ETF to 25% after 6 months (P=0.0013), with similar trends in women and men. There was no correlation between changes in weight and lung function. CF-related diabetes was already present in 12 patients and developed in 1 more patient after the start of ETF. ETF improved body weight and BMI but not pulmonary function in 26 patients with end-stage CF. Clinical outcomes were similar in women and men, but the sample size of men was too small to determine statistical significance. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

The Effects of Game-Based Breathing Exercise on Pulmonary Function in Stroke Patients: A Preliminary Study.

PubMed

Joo, Sunghee; Shin, Doochul; Song, Changho

2015-06-22

Reduction of respiratory function along with hemiparesis leads to decreased endurance, dyspnea, and increased sedentary behavior, as well as to an increased risk of stroke. The main purpose of this study was to investigate the preliminary effects of game-based breathing exercise (GBE) on pulmonary function in stroke patients. Thirty-eight in-patients with stroke (22 men, 16 women) were recruited for the study. Participants were randomly allocated into 2 groups: patients assigned to the GBE group (n=19), and the control group (n=19). The GBE group participated in a GBE program for 25 minutes a day, 3 days a week, during a 5 week period. For the same period, both groups participated in a conventional stroke rehabilitation program. Forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), FEV1/FVC, and maximum voluntary ventilation (MVV) were measured by a spirometer in pre- and post-testing. The GBE group had significantly improved FVC, FEV1, and MVV values compared with the control group (p<0.05), although there was no significant difference in FEV1/FVC value between groups. Significant short-term effects of the GBE program on pulmonary function in stroke patients were recorded in this study. These findings gave some indications that it may be feasible to include GBE in rehabilitation interventions with this population.

Potential use of TNF-α inhibitors in systemic sclerosis.

PubMed

Murdaca, Giuseppe; Spanò, Francesca; Contatore, Miriam; Guastalla, Andrea; Puppo, Francesco

2014-01-01

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities and variable involvement of organs. TNF-α has a central role in initial host response to infections and in the pathogenesis of various systemic immune-mediated diseases. Serum levels of TNF-α are elevated in patients with SSc and favor the development of pulmonary fibrosis and pulmonary arterial hypertension. Inflammatory arthritis can occur in patients with SSc. Infliximab and etanercept may improve the inflammatory arthritis and disability in SSc. TNF-α inhibitors reduce the systemic inflammation, improve the endothelial function decreasing the risk of pulmonary arterial hypertension progression and of acute cardiovascular and/or cerebrovascular events. Physicians need to be aware of the potential risks of tuberculosis reactivation and opportunistic infections. Randomized controlled trials with TNF-α inhibitors in patients with SSc are needed to confirm the potential role of these agents in the treatment of SSc.

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.

Exposure to neonatal cigarette smoke causes durable lung changes but does not potentiate cigarette smoke–induced chronic obstructive pulmonary disease in adult mice

PubMed Central

McGrath-Morrow, Sharon; Malhotra, Deepti; Lauer, Thomas; Collaco, J. Michael; Mitzner, Wayne; Neptune, Enid; Wise, Robert; Biswal, Shyam

2016-01-01

The impact of early childhood cigarette smoke (CS) exposure on CS-induced chronic obstructive pulmonary disease (COPD) is unknown. This study was performed to evaluate the individual and combined effects of neonatal and adult CS exposure on lung structure, function, and gene expression in adult mice. To model a childhood CS exposure, neonatal C57/B6 mice were exposed to 14 days of CS (Neo CS). At 10 weeks of age, Neo CS and control mice were exposed to 4 months of CS. Pulmonary function tests, bronchoalveolar lavage, and lung morphometry were measured and gene expression profiling was performed on lung tissue. Mean chord lengths and lung volumes were increased in neonatal and/or adult CS-exposed mice. Differences in immune, cornified envelope protein, muscle, and erythrocyte genes were found in CS-exposed lung. Neonatal CS exposure caused durable structural and functional changes in the adult lung but did not potentiate CS-induced COPD changes. Cornified envelope protein gene expression was decreased in all CS-exposed mice, whereas myosin and erythrocyte gene expression was increased in mice exposed to both neonatal and adult CS, suggesting an adaptive response. Additional studies may be warranted to determine the utility of these genes as biomarkers of respiratory outcomes. PMID:21649527

Pulmonary edema associated with upper airway obstruction in dogs.

PubMed

Algren, J T; Price, R D; Buchino, J J; Stremel, R W

1993-12-01

In order to evaluate the effect of acute upper airway obstruction upon pulmonary edema (PE) formation, we studied seven dogs that were subjected to inspiratory obstruction for three hours. Hypoxia was avoided by the administration of supplemental oxygen during the study period. Six dogs developed pulmonary vascular congestion, and four developed histologic findings of PE. Inspiratory intrapleural pressure decreased to -28 +/- 4 mmHg in dogs that developed PE and to -23 +/- 2 mmHg in dogs that did not. Transmural pulmonary artery pressure and pulmonary artery wedge pressure did not increase significantly. Central venous pressure during inspiration (CVPi) increased in all dogs, and CVP at end expiration (CVPe) was significantly higher in dogs with PE. Dogs that developed PE experienced a decrease in cardiac output and an increase in systemic vascular resistance. Furthermore, alveolar ventilation declined in dogs with PE, ultimately resulting in ventilatory failure. Pulmonary edema formation was not preceded by an increase in pulmonary vascular pressures but was associated with higher CVP, pulmonary vascular congestion, and hypercarbia.

Low pulmonary function in individuals with impaired fasting glucose: the 2007-2009 Korea national health and nutrition examination survey.

PubMed

Lee, Yun Jeong; Kim, Na Kyung; Yang, Ju Yean; Noh, Jung Hyun; Lee, Sung-Soon; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Dong-Jun

2013-01-01

To investigate the association between fasting plasma glucose level and pulmonary function. Nutritional information, pulmonary function data, and laboratory test data from 9,223 subjects from the fourth Korea National Health and Nutrition Examination Survey were examined. The participants were divided into five groups according to fasting plasma glucose (FPG) level: normal fasting glucose (NFG)1, FPG <90 mg/dl; NFG2, FPG 90-99 mg/dl; impaired fasting glucose (IFG)1: FPG 100-109 mg/dl; IFG2, FPG 110-125 mg/dl; and diabetes, FPG ≥126 mg/dl and/or current anti-diabetes medications. After adjustment for several variables, the percentage of predicted forced vital capacity(FVC%) decreased with increasing fasting plasma glucose level in both sexes[men: (mean ± SEM) 92.0±0.3 in NFG1; 91.9±0.3 in NFG2; 92.0±0.4 in IFG1; 90.2±0.7 in IFG2; and 89.9±0.5 in diabetes, P = 0.004; women: 93.7±0.3 in NFG1; 93.7±0.3 in NFG2; 93.1±0.5 in IFG1; 91.1±0.9 in IFG2; and 90.7±0.6 in diabetes, P<0.001]. A logistic regression analysis found that IFG2 and diabetes were independently associated with the lowest quintile of predicted FVC% (IFG2: odds ratio [95%CI], 1.50 [1.18-1.89], P = 0.001; diabetes: 1.56 [1.30-1.88], P<0.001) using NFG1 as a control. The current data suggest that forced vital capacity may begin to decrease in the higher range of IFG.

Exposure to Cooking Fumes and Acute Reversible Decrement in Lung Functional Capacity.

PubMed

Neghab, Masoud; Delikhoon, Mahdieh; Norouzian Baghani, Abbas; Hassanzadeh, Jafar

2017-10-01

Being exposed to cooking fumes, kitchen workers are occupationally at risk of multiple respiratory hazards. No conclusive evidence exists as to whether occupational exposure to these fumes is associated with acute and chronic pulmonary effects and symptoms of respiratory diseases. To quantify the exposure levels and evaluate possible chronic and acute pulmonary effects associated with exposure to cooking fumes. In this cross-sectional study, 60 kitchen workers exposed to cooking fumes and 60 unexposed employees were investigated. The prevalence of respiratory symptoms among these groups was determined through completion of a standard questionnaire. Pulmonary function parameters were also measured before and after participants' work shift. Moreover, air samples were collected and analyzed to quantify their aldehyde, particle, and volatile organic contents. The mean airborne concentrations of formaldehyde, acetaldehyde, and acrolein was 0.45 (SD 0.41), 0.13 (0.1), and 1.56 (0.41) mg/m 3 , respectively. The mean atmospheric concentrations of PM 1 , PM 2.5 , PM 7 , PM 10 , and total volatile organic compounds (TVOCs) was 3.31 (2.6), 12.21 (5.9), 44.16 (16.6), 57 (21.55) μg/m 3 , and 1.31 (1.11) mg/m 3 , respectively. All respiratory symptoms were significantly (p<0.05) more prevalent in exposed group. No significant difference was noted between the pre-shift mean of spirometry parameters of exposed and unexposed group. However, exposed workers showed cross-shift decrease in most spirometry parameters, significantly lower than the pre-shift values and those of the comparison group. Exposure to cooking fumes is associated with a significant increase in the prevalence of respiratory symptoms as well as acute reversible decrease in lung functional capacity.

Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data.

PubMed

Yamazaki, Hiroyoshi; Kobayashi, Noriko; Taketsuna, Masanori; Tajima, Koyuki; Murakami, Masahiro

2017-05-01

To evaluate the long-term safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. This prospective, multicenter, noninterventional, post-marketing surveillance included patients with PAH who were observed for up to 2 years after initiation of tadalafil. Safety was assessed by analyzing the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included the assessment of the change in World Health Organization (WHO) functional classification of PAH, 6-minute walk test, cardiac catheterization, and echocardiography. Among 1676 patients analyzed for safety, the overall incidence of ADRs was 31.2%. The common ADRs (≥1.0%) were headache (7.0%), diarrhea (1.9%), platelet count decreased (1.8%), anemia, epistaxis, and nausea (1.6% each), flushing (1.3%), hepatic function abnormal (1.1%), hot flush, and myalgia (1.0% each). The common SADRs (≥0.3%) were cardiac failure (0.7%), interstitial lung disease, worsening of PAH, and platelet count decreased (0.3% each). Among 1556 patients analyzed for effectiveness, the percentages of patients with improvement of WHO functional class at 3 months, 1 year, and 2 years after the initiation of tadalafil, and last observation were 17.1%, 24.8%, 28.9%, and 22.5%, respectively. At all observation points (except pulmonary regurgitation pressure gradient at end diastole at 3 months), the mean 6-minute walk distance, cardiac catheterization, and echocardiogram measurements showed statistically significant improvement. This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.

Long term effects of exposure to automobile exhaust on the pulmonary function of female adults in Tokyo, Japan

PubMed Central

Sekine, K; Shima, M; Nitta, Y; Adachi, M

2004-01-01

Aims: To investigate the chronic effects of air pollution caused mainly by automobiles in healthy adult females. Methods: Respiratory symptoms were investigated in 5682 adult females who had lived in the Tokyo metropolitan area for three years or more in 1987; 733 of them were subjected to pulmonary function tests over eight years from 1987 to 1994. The subjects were divided into three groups by the level of air pollution they were exposed to during the study period. The concentrations of nitrogen dioxide and suspended particulate matter were the highest in group 1, and the lowest in group 3. Results: The prevalence rates of respiratory symptoms in group 1 were higher than those in groups 2 and 3, except for wheezing. Multiple logistic regression analysis showed significant differences in persistent phlegm and breathlessness. The subjects selected for the analysis of pulmonary function were 94, 210, and 102 females in groups 1, 2, and 3, respectively. The annual mean change of FEV1 in group 1 was the largest (-0.020 l/y), followed by that in group 2 (-0.015 l/y), and that in group 3 (-0.009 l/y). Testing for trends showed a significant larger decrease of FEV1 with the increase in the level of air pollution. Conclusions: The subjects living in areas with high levels of air pollution showed higher prevalence rates of respiratory symptoms and a larger decrease of FEV1 compared with those living in areas with low levels of air pollution. Since the traffic density is larger in areas with high air pollution, the differences among the groups may reflect the effect of air pollution attributable to particulate matter found in automobile exhaust. PMID:15031394

Off-pump versus on-pump coronary artery revascularization: effects on pulmonary function.

PubMed

e Silva, Ana M R P; Saad, Roberto; Stirbulov, Roberto; Rivetti, Luiz A

2010-07-01

Many studies have shown important changes in lung function tests after coronary artery surgeries. It is controversial if off-pump surgery can give a better and shorter recovery than the on-pump. A prospective study was conducted on 42 patients submitted to coronary artery surgery and divided into two groups: 21 off-pump using intraluminal shunt (G (I)) and 21 on-pump (G (II)), matched by the anatomical location of the coronary arteries lesions. All patients had spirometric evaluation, blood gas measurements and alveolo-arterial oxygen gradient (A-aDO(2)), at the fourth and 10th postoperative days (PO(4) and PO(10)). Preoperatively, G(I) and G(II) had similar results (P>0.372). Spirometry showed decreases at PO(4) and remained decreased until PO(10) for both groups, with significant differences between the groups. The blood gas measurements showed reduction in arterial oxygen pressure (PaO(2)) and carbon dioxide pressure (PaCO(2)), while there was an increase in A-aDO(2) at PO(4) and PO(10) in both groups. The results suggest that different changes occur in pulmonary function when the surgery is performed with or without cardiopulmonary bypass. The off-pump patients showed significantly greater improvement than the on-pump group.

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

Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD.

PubMed

Wang, Yajie; Jiang, Xue; Zhang, Lihai; Wang, Lihong; Li, Zhu; Sun, Wuzhuang

2014-01-01

This study is conducted to investigate an effect of simvastatin on cigarette smoke-induced COPD. Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of simvastatin. Heart and lung tissues were harvested for histopathologic and morphometric analysis. Body weight of rat, mean liner intercept (MLI), mean alveolar number (MAN), lung function test, mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) and 5-HTT level in serum and BALF were examined in experimental rats, respectively. Application of simvastatin mitigated peribronchiolar inflammation and pulmonary bullae formed in the smoke-exposed lungs with weight gain as compared to the smoking rats (P < 0.05). Simvastatin-treated rats showed slight but significant decreases in MLI and MAN with a partial reversal of lung function decline (all P < 0.05). Treatment with simvastatin resulted in a significant decrease not only in mPAP and RVHI but also in a 5-HTT level in serum and BALF (P < 0.01 or 0.05) with a good correlation between the 5-HTT level and mPAP or RVHI (r = 0.693 and 0.479; 0.675 and 0.508). Simvastatin partly reverses lung function decline and attenuates structural impairments of lung and right ventricle possibly through reducing 5-HTT content in the model of COPD.

Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD

PubMed Central

Wang, Yajie; Jiang, Xue; Zhang, Lihai; Wang, Lihong; Li, Zhu; Sun, Wuzhuang

2014-01-01

Objectives: This study is conducted to investigate an effect of simvastatin on cigarette smoke-induced COPD. Methods: Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of simvastatin. Heart and lung tissues were harvested for histopathologic and morphometric analysis. Body weight of rat, mean liner intercept (MLI), mean alveolar number (MAN), lung function test, mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) and 5-HTT level in serum and BALF were examined in experimental rats, respectively. Results: Application of simvastatin mitigated peribronchiolar inflammation and pulmonary bullae formed in the smoke-exposed lungs with weight gain as compared to the smoking rats (P < 0.05). Simvastatin-treated rats showed slight but significant decreases in MLI and MAN with a partial reversal of lung function decline (all P < 0.05). Treatment with simvastatin resulted in a significant decrease not only in mPAP and RVHI but also in a 5-HTT level in serum and BALF (P < 0.01 or 0.05) with a good correlation between the 5-HTT level and mPAP or RVHI (r = 0.693 and 0.479; 0.675 and 0.508). Conclusion: Simvastatin partly reverses lung function decline and attenuates structural impairments of lung and right ventricle possibly through reducing 5-HTT content in the model of COPD. PMID:25674219

Prevalence of gastro-esophageal reflux disease in patients with difficult to control asthma and effect of proton pump inhibitor therapy on asthma symptoms, reflux symptoms, pulmonary function and requirement for asthma medications.

PubMed

Sandur, V; Murugesh, M; Banait, V; Rathi, P M; Bhatia, S J; Joshi, J M; Kate, A

2014-01-01

The hypothesis that GER can trigger or exacerbate asthma is supported by several clinical trials that have shown amelioration in asthma symptoms and/or an improvement in pulmonary function after antireflux therapy. To investigate the prevalence of GER in patients with difficult to control asthma and to determine the effect of omeprazole on asthma symptoms, reflux symptoms, pulmonary function and on the requirement of asthma medications. Patients with difficult to control asthma were recruited into the study. All patients underwent esophageal manometry and 24 hour esophageal pH monitoring. Pulmonary function tests were done before and after treatment. The severity of asthma and reflux was assessed by a 1 week pulmonary symptom score(PSS) and reflux symptom score(RSS) respectively before and after treatment. Those who had an abnormal pH study (pH <4 in the distal esophagus for >5% of the time) underwent anti-GER treatment with lifestyle changes, and a proton pump inhibitor (omeprazole 40 mg, bid) for 3 months. Asthma medications were added or deleted based on severity of asthma. Out of 250 asthmatic patients screened, forty patients fulfilled the inclusion criteria. Twenty eight of 40 patients(70%) were diagnosed to have GERD. Of the patients 28 with GER, 8 patients(28.5%) had no reflux symptoms. On 24 hr pH metry, the percentage time pH <4.0 was 10.81 ± 4.72 and 1.11 ± 1.21; Deemester score was 37.65 ± 14.54 and 4.89 ± 6.39 (p-value is 0.0001) in GERD and non-GERD patients respectively.In GERD group, post treatment reflux symptom score(RSS) improved from 22.39 ± 14.99 to 1.04 ± 1.07, pulmonary symptom score(PSS) improved from 27.14 ± 7.49 to 13.82 ± 4.21 and night time asthma symptom score(NASS) improved from 6.71 ± 1.80 to 3.04 ± 1.23 (p-value <0.0001). After treatment, FEV1 and PEFR increased from 1.38 ± 0.57 and 4.14 ± 1.97 to 1.47 ± 0.54 and 5.56 ± 1.72, respectively (p-value 0.00114). PPI therapy improves nocturnal asthma symptoms, daytime asthma symptoms, pulmonary function and decreases requirement of asthma medications in these patients.

Incentive spirometry for preventing pulmonary complications after coronary artery bypass graft.

PubMed

Freitas, Eliane R F S; Soares, Bernardo G O; Cardoso, Jefferson R; Atallah, Álvaro N

2012-09-12

Incentive spirometry (IS) is a treatment technique that uses a mechanical device to reduce pulmonary complications during postoperative care. This is an update of a Cochrane review first published in 2007. Update the previously published systematic review to compare the effects of IS for preventing postoperative pulmonary complications in adults undergoing coronary artery bypass graft (CABG). We searched CENTRAL and DARE on The Cochrane Library (Issue 2 of 4 2011), MEDLINE OVID (1948 to May 2011), EMBASE (1980 to Week 20 2011), LILACS (1982 to July 2011) , the Physiotherapy Evidence Database (PEDro) (1980 to July 2011), Allied & Complementary Medicine (AMED) (1985 to May 2011), CINAHL (1982 to May 2011). Randomised controlled trials comparing IS with any type of prophylactic physiotherapy for prevention of postoperative pulmonary complications in adults undergoing CABG. Two reviewers independently evaluated trial quality using the guidelines of the Cochrane Handbook for Systematic Reviews and extracted data from included trials. For continuous outcomes, we used the generic inverse variance method for meta-analysis and for dichotomous data we used the Peto Odds Ratio. This update included 592 participants from seven studies (two new and one that had been excluded in the previous review in 2007. There was no evidence of a difference between groups in the incidence of any pulmonary complications and functional capacity between treatment with IS and treatment with physical therapy, positive pressure breathing techniques (including continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP) and intermittent positive pressure breathing (IPPB), active cycle of breathing techniques (ACBT) or preoperative patient education. Patients treated with IS had worse pulmonary function and arterial oxygenation compared with positive pressure breathing. Based on these studies there was no improvement in the muscle strength between groups who received IS demonstrated by maximal inspiratory pressure and maximal expiratory pressure . Our update review suggests there is no evidence of benefit from IS in reducing pulmonary complications and in decreasing the negative effects on pulmonary function in patients undergoing CABG. In view of the modest number of patients studied, methodological shortcomings and poor reporting of the included trials, these results should still be interpreted cautiously. An appropriately powered trial of high methodological rigour is needed to determine if there are patients who may derive benefit from IS following CABG.

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.

Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes.

PubMed

Santhosh, K T; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, A J; Dakshinamurti, S

2011-07-01

Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor-mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca(2+) response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. TP receptor sensitivity and EC(50) for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca(2+) mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Clinical usefulness of end-tidal CO2 profiles during incremental exercise in patients with chronic thromboembolic pulmonary hypertension.

PubMed

Ramos, R P; Ferreira, E V M; Valois, F M; Cepeda, A; Messina, C M S; Oliveira, R K; Araújo, A T V; Teles, C A; Neder, J A; Nery, L E; Ota-Arakaki, J S

2016-11-01

Great ventilation to carbon dioxide output (ΔV˙E/ΔV˙CO 2 ) and reduced end-tidal partial pressures for CO 2 (PetCO 2 ) during incremental exercise are hallmarks of chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (IPAH). However, CTEPH is more likely to involve proximal arteries, which may lead to poorer right ventricle-pulmonary vascular coupling and worse gas exchange abnormalities. Therefore, abnormal PetCO 2 profiles during exercise may be more prominent in patients with CTEPH and could be helpful to indicate disease severity. Seventy patients with CTEPH and 34 with IPAH underwent right heart catheterization and cardiopulmonary exercise testing. According to PetCO 2 pattern during exercise, patients were classified as having an increase or stabilization in PetCO 2 up to the gas exchange threshold (GET), an abrupt decrease in the rest-exercise transition or a progressive and slow decrease throughout exercise. A subgroup of patients with CTEPH underwent a constant work rate exercise test to obtain arterial blood samples during steady-state exercise. Multivariate logistic regression analyses showed that progressive decreases in PetCO 2 and SpO 2 were better discriminative parameters than ΔV˙E/ΔV˙CO 2 to distinguish CTEPH from IPAH. This pattern of PetCO 2 was associated with worse functional impairment and greater reduction in PaCO 2 during exercise. Compared to patients with IPAH, patients with CTEPH present more impaired gas exchange during exercise, and PetCO 2 abnormalities may be used to identify more clinically and hemodynamically severe cases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis.

PubMed

Benza, Raymond L; Miller, Dave P; Foreman, Aimee J; Frost, Adaani E; Badesch, David B; Benton, Wade W; McGoon, Michael D

2015-03-01

Data from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) were used previously to develop a risk score calculator to predict 1-year survival. We evaluated prognostic implications of changes in the risk score and individual risk-score parameters over 12 months. Patients were grouped by decreased, unchanged, or increased risk score from enrollment to 12 months. Kaplan-Meier estimates of subsequent 1-year survival were made based on change in the risk score during the initial 12 months of follow-up. Cox regression was used for multivariable analysis. Of 2,529 patients in the analysis cohort, the risk score was decreased in 800, unchanged in 959, and increased in 770 at 12 months post-enrollment. Six parameters (functional class, systolic blood pressure, heart rate, 6-minute walk distance, brain natriuretic peptide levels, and pericardial effusion) each changed sufficiently over time to improve or worsen risk scores in ≥5% of patients. One-year survival estimates in the subsequent year were 93.7%, 90.3%, and 84.6% in patients with a decreased, unchanged, and increased risk score at 12 months, respectively. Change in risk score significantly predicted future survival, adjusting for risk at enrollment. Considering follow-up risk concurrently with risk at enrollment, follow-up risk was a much stronger predictor, although risk at enrollment maintained a significant effect on future survival. Changes in REVEAL risk scores occur in most patients with pulmonary arterial hypertension over a 12-month period and are predictive of survival. Thus, serial risk score assessments can identify changes in disease trajectory that may warrant treatment modifications. Copyright © 2015 International Society for Heart and Lung Transplantation. All rights reserved.

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...

Pulmonary Cerium Dioxide Nanoparticles Exposure Differentially Impairs Coronary and Mesenteric Arteriolar Reactivity

PubMed Central

Minarchick, Valerie C; Stapleton, Phoebe A; Porter, Dale W; Wolfarth, Michael G; Çiftyürek, Engin; Barger, Mark; Sabolsky, Edward M.; Nurkiewicz, Timothy R

2013-01-01

Cerium dioxide nanoparticles (CeO2 NPs) are an engineered nanomaterial that possesses unique catalytic, oxidative and reductive properties. Currently, CeO2 NPs are being used as a fuel catalyst but these properties are also utilized in the development of potential drug treatments for radiation and stroke protection. These uses of CeO2 NPs present a risk for human exposure; however, to date no studies have investigated the effects of CeO2 NPs on the microcirculation following pulmonary exposure. Previous studies in our laboratory with other nanomaterials have shown impairments in normal microvascular function after pulmonary exposures. Therefore, we predicted that CeO2 NP exposure would cause microvascular dysfunction that is dependent on the tissue bed and dose. Twenty-four hour post exposure to CeO2 NPs (0–400 μg), mesenteric and coronary arterioles were isolated and microvascular function was assessed. Our results provided evidence that pulmonary CeO2 NP exposure impairs endothelium-dependent and -independent arteriolar dilation in a dose-dependent manner. The CeO2 NP exposure dose which causes a 50% impairment in arteriolar function (EC50) was calculated and ranged from 15 – 100 μg depending on the chemical agonist and microvascular bed. Microvascular assessments with acetylcholine revealed a 33–75% reduction in function following exposure. Additionally, there was a greater sensitivity to CeO2 NP exposure in the mesenteric microvasculature due to the 40% decrease in the calculated EC50 compared to the coronary microvasculature EC50. CeO2 NP exposure increased mean arterial pressure in some groups. Taken together these observed microvascular changes may likely have detrimental effects on local blood flow regulation and contribute to cardiovascular dysfunction associated with particle exposure. PMID:23645470

Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase.

PubMed

Guerrero-Orriach, José Luis; Ariza-Villanueva, Daniel; Florez-Vela, Ana; Garrido-Sánchez, Lourdes; Moreno-Cortés, María Isabel; Galán-Ortega, Manuel; Ramírez-Fernández, Alicia; Alcaide Torres, Juan; Fernandez, Concepción Santiago; Navarro Arce, Isabel; Melero-Tejedor, José María; Rubio-Navarro, Manuel; Cruz-Mañas, José

2016-01-01

To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery.

World Trade Center dyspnea: bronchiolitis obliterans with functional improvement: a case report.

PubMed

Mann, Jack M; Sha, Kenneth K; Kline, Gary; Breuer, Frank-Uwe; Miller, Albert

2005-09-01

Bronchiolitis obliterans is a severe, often progressive, lung disease characterized by cough, exertional dyspnea, and airflow obstruction. It has been ascribed to specific causes such as lung or bone marrow transplant, medications for rheumatoid disease, and most recently in association with exposure to environmental agents. A 42-year-old, previously healthy New York City Highway Patrol officer who arrived at the World Trade Center (WTC), "ground zero," early on September 11, 2001 was evaluated. He has been followed for over 2 years with serial chest radiographs, CT scans, and pulmonary function studies. He eventually underwent an open lung biopsy. His dyspnea started on September 12, 2001 and progressed despite aggressive therapy with inhaled bronchodilator as well as oral and inhaled corticosteroids. At no time did he have any radiographic evidence of pulmonary disease. His forced vital capacity (FVC) decreased from 5.32 L in October 2001 to 2.86 L in January 2003. He underwent an open lung biopsy because of the persistent exertional dyspnea coupled with the loss of over 2 L of lung volume. The pathological findings were chronic bronchiolitis with focal obliterative bronchiolitis and rare non-necrotizing granuloma. Symptoms and pulmonary function improved after therapy with Azithromycin was added to his treatment. This process is believed to be secondary to his massive exposure to the cloud of dust that followed the collapse of the WTC. It is our conviction that many of those present at the WTC on September 11 who have persistent dyspnea and deterioration of pulmonary function may have a similar pathologic process despite absence of abnormalities on CT of the chest. In view of the many signs and symptoms seen in first responders we feel that these findings provide important information about the pathophysiology and treatment of progressive disease resulting from this exposure.

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.

Cross-sectional study on the endotoxin exposure and lung function impairment in the workers of textile industry near Lahore, Pakistan.

PubMed

Ghani, Nadia; Khalid, Anum; Tahir, Arifa

2016-07-01

To examine the effects of airborne endotoxin on lung function impairment in exposure-response relationships among the workers of textile industry. The cross-sectional study was conducted at Lahore College for Women University, Lahore, Pakistan, from January to August 2014, and comprised textile mill workers. The participants were divided into exposed and control groups. A questionnaire was used to ask workers about the potential adverse health effects of their occupation. The pulmonary function test was carried out by spirometer. Endotoxin levels in the samples were determined using the key quality characteristics limulus amebocyte lysate. The data was analysed to determine the correlation between the endotoxin exposure duration and pulmonary function test parameters. There were 200 subjects subdivided into 100 each inexposed and control groups. Overall, 160(80%) were not aware of safety measures and the remaining 40(20%) were partially practising. Changes in pulmonary function due to endotoxin exposure showed decreased force vital capacity, flow rate and peak expiratory flow parameters significantly different (p<0.05, p<0.001). The endotoxin concentration was between 12EU/m3 and 300EU/m3. Airborne endotoxin concentrations in textile plants exceeded the Dutch health-based guidance limit of 90EU/m3 and was associated with respiratory health effects. Prolonged exposure to airborne endotoxin caused constant lung impairment. Proper safety measures should be adopted to avoid the inhalation of cotton dust.

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.

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.

Impaired lung function in individuals chronically exposed to biomass combustion.

PubMed

da Silva, Luiz Fernando Ferraz; Saldiva, Silvia Regina Dias Médici; Saldiva, Paulo Hilário Nascimento; Dolhnikoff, Marisa

2012-01-01

The use of biomass for cooking and heating is considered an important factor associated with respiratory diseases. However, few studies evaluate the amount of particulate matter less than 2.5 μm in diameter (PM2.5), symptoms and lung function in the same population. To evaluate the respiratory effects of biomass combustion and compare the results with those of individuals from the same community in Brazil using liquefied petroleum gas (Gas). 1402 individuals in 260 residences were divided into three groups according to exposure (Gas, Indoor-Biomass, Outside-Biomass). Respiratory symptoms were assessed using questionnaires. Reflectance of paper filters was used to assess particulate matter exposure. In 48 residences the amount of PM2.5 was also quantified. Pulmonary function tests were performed in 120 individuals. Reflectance index correlated directly with PM2.5 (r=0.92) and was used to estimate exposure (ePM2.5). There was a significant increase in ePM2.5 in Indoor-Biomass and Outside-Biomass, compared to Gas. There was a significantly increased odds ratio (OR) for cough, wheezing and dyspnea in adults exposed to Indoor-Biomass (OR=2.93, 2.33, 2.59, respectively) and Outside-Biomass (OR=1.78, 1.78, 1.80, respectively) compared to Gas. Pulmonary function tests revealed both Non-Smoker-Biomass and Smoker-Gas individuals to have decreased %predicted-forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC) as compared to Non-Smoker-Gas. Pulmonary function tests data was inversely correlated with duration and ePM2.5. The prevalence of airway obstruction was 20% in both Non-Smoker-Biomass and Smoker-Gas subjects. Chronic exposure to biomass combustion is associated with increased prevalence of respiratory symptoms, reduced lung function and development of chronic obstructive pulmonary disease. These effects are associated with the duration and magnitude of exposure and are exacerbated by tobacco smoke. Copyright © 2011 Elsevier Inc. All rights reserved.

Activation of GPER ameliorates experimental pulmonary hypertension in male rats.

PubMed

Alencar, Allan K; Montes, Guilherme C; Montagnoli, Tadeu; Silva, Ananssa M; Martinez, Sabrina T; Fraga, Aline G; Wang, Hao; Groban, Leanne; Sudo, Roberto T; Zapata-Sudo, Gisele

2017-01-15

Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling that leads to pulmonary congestion, uncompensated right-ventricle (RV) failure, and premature death. Preclinical studies have demonstrated that the G protein-coupled estrogen receptor (GPER) is cardioprotective in male rats and that its activation elicits vascular relaxation in rats of either sex. To study the effects of GPER on the cardiopulmonary system by the administration of its selective agonist G1 in male rats with monocrotaline (MCT)-induced PH. Rats received a single intraperitoneal injection of MCT (60mg/kg) for PH induction. Experimental groups were as follows: control, MCT+vehicle, and MCT+G1 (400μg/kg/daysubcutaneous). Animals (n=5pergroup) were treated with vehicle or G1 for 14days after disease onset. Activation of GPER attenuated exercise intolerance and reduced RV overload in PH rats. Rats with PH exhibited echocardiographic alterations, such as reduced pulmonary flow, RV hypertrophy, and left-ventricle dysfunction, by the end of protocol. G1 treatment reversed these PH-related abnormalities of cardiopulmonary function and structure, in part by promoting pulmonary endothelial nitric oxide synthesis, Ca 2+ handling regulation and reduction of inflammation in cardiomyocytes, and a decrease of collagen deposition by acting in pulmonary and cardiac fibroblasts. G1 was effective to reverse PH-induced RV dysfunction and exercise intolerance in male rats, a finding that have important implications for ongoing clinical evaluation of new cardioprotective and vasodilator drugs for the treatment of the disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Arm Activity During Daily Life in Individuals With Chronic Obstructive Pulmonary Disease.

PubMed

Janaudis-Ferreira, Tania; Mathur, Sunita; Romano, Julia Marie; Goldstein, Roger Samuel; Brooks, Dina

2016-01-01

To determine whether individuals with chronic obstructive pulmonary disease (COPD) have decreased arm activity during daily life compared with healthy controls and explore the relationships between arm activity during daily life and arm functional measures in individuals with COPD. This was a prospective cross-sectional study that included 30 people with COPD and 14 healthy controls. Subjects attended a single assessment session in which measurements of arm exercise capacity, arm functional performance, self-perception of performance during activities of daily living (ADL), shoulder and elbow flexion force and biceps and triceps thickness were performed. On completion of this session, participants were issued a wrist actigraph and asked to wear the device on the dominant arm for 24 hours for 7 consecutive days. Compared with healthy controls, patients with COPD presented decreased total activity level in daily life (P = .001). When corrected for walking, the level of arm activity did not differ between individuals with COPD and healthy controls (P = .62). No correlations were found between arm activity and arm exercise capacity, arm functional performance, upper limb muscle strength, and self-perception of performance during ADL (r =-0.20 to 0.14; all P ≥ .10). Arm activity intensity in individuals with COPD did not differ from that of healthy controls when measured by a wrist actigraph. Moreover, arm activity was not associated with other clinical outcomes of arm function. Disability during ADL is multifactorial, and only limited inferences of function can be made from accelerometer data.

Differentially Expressed Plasma MicroRNAs and the Potential Regulatory Function of Let-7b in Chronic Thromboembolic Pulmonary Hypertension

PubMed Central

Guo, Lijuan; Yang, Yuanhua; Liu, Jie; Wang, Lei; Li, Jifeng; Wang, Ying; Liu, Yan; Gu, Song; Gan, Huili; Cai, Jun; Yuan, Jason X.-J.; Wang, Jun; Wang, Chen

2014-01-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease characterized by misguided thrombolysis and remodeling of pulmonary arteries. MicroRNAs are small non-coding RNAs involved in multiple cell processes and functions. During CTEPH, circulating microRNA profile endued with characteristics of diseased cells could be identified as a biomarker, and might help in recognition of pathogenesis. Thus, in this study, we compared the differentially expressed microRNAs in plasma of CTEPH patients and healthy controls and investigated their potential functions. Microarray was used to identify microRNA expression profile and qRT-PCR for validation. The targets of differentially expressed microRNAs were identified in silico, and the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes pathway database were used for functional investigation of target gene profile. Targets of let-7b were validated by fluorescence reporter assay. Protein expression of target genes was determined by ELISA or western blotting. Cell migration was evaluated by wound healing assay. The results showed that 1) thirty five microRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs, which was shown to be related to the disease pathogenesis by in silico analysis, gave diagnostic efficacy of both sensitivity and specificity >0.9. 2) Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease to about 0.25 fold in CTEPH patients. 3) ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs) as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs). These results suggested that CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of CTEPH by affecting ET-1 expression and the function of PAECs and PASMCs. PMID:24978044

Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies

PubMed Central

Tan, Jiangning; Tedrow, John R.; Dutta, Justin A.; Juan-Guardela, Brenda; Nouraie, Mehdi; Chu, Yanxia; Trejo Bittar, Humberto; Ramani, Kritika; Biswas, Partha S.; Veraldi, Kristen L.; Kaminski, Naftali; Zhang, Yingze

2016-01-01

Rationale: Relaxin is a hormone that has been considered as a potential therapy for patients with fibrotic diseases. Objectives: To gauge the potential efficacy of relaxin-based therapies in idiopathic pulmonary fibrosis (IPF), we studied gene expression for relaxin/insulin-like family peptide receptor 1 (RXFP1) in IPF lungs and controls. Methods: We analyzed gene expression data obtained from the Lung Tissue Research Consortium and correlated RXFP1 gene expression data with cross-sectional clinical and demographic data. We also employed ex vivo donor and IPF lung fibroblasts to test RXFP1 expression in vitro. We tested CGEN25009, a relaxin-like peptide, in lung fibroblasts and in bleomycin injury. Measurements and Main Results: We found that RXFP1 is significantly decreased in IPF. In patients with IPF, the magnitude of RXFP1 gene expression correlated directly with diffusing capacity of the lung for carbon monoxide (P < 0.0001). Significantly less RXFP1 was detected in vitro in IPF fibroblasts than in donor controls. Transforming growth factor-β decreased RXFP1 in both donor and IPF lung fibroblasts. CGEN25009 was effective at decreasing bleomycin-induced, acid-soluble collagen deposition in vivo. The relaxin-like actions of CGEN25009 were abrogated by RXFP1 silencing in vitro, and, in comparison with donor lung fibroblasts, IPF lung fibroblasts exhibited decreased sensitivity to the relaxin-like effects of CGEN25009. Conclusions: IPF is characterized by the loss of RXFP1 expression. RXFP1 expression is directly associated with pulmonary function in patients with IPF. The relaxin-like effects of CGEN25009 in vitro are dependent on expression of RXFP1. Our data suggest that patients with IPF with the highest RXFP1 expression would be predicted to be most sensitive to relaxin-based therapies. PMID:27310652

Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies.

PubMed

Tan, Jiangning; Tedrow, John R; Dutta, Justin A; Juan-Guardela, Brenda; Nouraie, Mehdi; Chu, Yanxia; Trejo Bittar, Humberto; Ramani, Kritika; Biswas, Partha S; Veraldi, Kristen L; Kaminski, Naftali; Zhang, Yingze; Kass, Daniel J

2016-12-01

Relaxin is a hormone that has been considered as a potential therapy for patients with fibrotic diseases. To gauge the potential efficacy of relaxin-based therapies in idiopathic pulmonary fibrosis (IPF), we studied gene expression for relaxin/insulin-like family peptide receptor 1 (RXFP1) in IPF lungs and controls. We analyzed gene expression data obtained from the Lung Tissue Research Consortium and correlated RXFP1 gene expression data with cross-sectional clinical and demographic data. We also employed ex vivo donor and IPF lung fibroblasts to test RXFP1 expression in vitro. We tested CGEN25009, a relaxin-like peptide, in lung fibroblasts and in bleomycin injury. We found that RXFP1 is significantly decreased in IPF. In patients with IPF, the magnitude of RXFP1 gene expression correlated directly with diffusing capacity of the lung for carbon monoxide (P < 0.0001). Significantly less RXFP1 was detected in vitro in IPF fibroblasts than in donor controls. Transforming growth factor-β decreased RXFP1 in both donor and IPF lung fibroblasts. CGEN25009 was effective at decreasing bleomycin-induced, acid-soluble collagen deposition in vivo. The relaxin-like actions of CGEN25009 were abrogated by RXFP1 silencing in vitro, and, in comparison with donor lung fibroblasts, IPF lung fibroblasts exhibited decreased sensitivity to the relaxin-like effects of CGEN25009. IPF is characterized by the loss of RXFP1 expression. RXFP1 expression is directly associated with pulmonary function in patients with IPF. The relaxin-like effects of CGEN25009 in vitro are dependent on expression of RXFP1. Our data suggest that patients with IPF with the highest RXFP1 expression would be predicted to be most sensitive to relaxin-based therapies.

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.

Immediate clinical and haemodynamic benefits of restoration of pulmonary valvar competence in patients with pulmonary hypertension.

PubMed

Lurz, P; Nordmeyer, J; Coats, L; Taylor, A M; Bonhoeffer, P; Schulze-Neick, I

2009-04-01

To analyse the potential benefit of restoration of pulmonary valvar competence in patients with severe pulmonary regurgitation (PR) and pulmonary hypertension (PH) associated with congenital heart disease. Retrospective study. Tertiary paediatric and adult congenital heart cardiac centre. Percutaneous pulmonary valve implantation (PPVI). All patients who underwent PPVI for treatment of PR in the presence of PH (mean PAP >25 mm Hg). Seven patients with severe PH as a result of congenital heart disease and severe PR underwent PPVI. The valve implantation procedure was feasible and uncomplicated in all seven cases, successfully abolishing PR. There was a significant increase in diastolic (15.4 (7.3) to 34.0 (8.5) mm Hg; p = 0.007) and mean (29.7 (8.1) to 41.3 (12.9) mm Hg; p = 0.034) pulmonary artery pressures, and an improvement in NYHA functional class (from median IV to median III; p<0.008). Peripheral oxygen saturations rose from 85.9% (11.0%) to 91.7% (8.3%) (p = 0.036). Right ventricular (RV) volumes decreased (from 157.0 (44.7) to 140.3 (53.3) ml/m(2)), while effective RV stroke volume increased (from 23.4 (9.3) to 41.0 (11.6) ml/m(2)). During a median follow-up of 20.3 months (range 1.3-47.5), valvar competence was well maintained despite near systemic pulmonary pressures. None of the valved stents were explanted during follow-up. Trans-catheter treatment of PR in patients with PH is well tolerated and leads to clinical and haemodynamic improvement, most probably caused by a combination of increased pulmonary perfusion pressures and RV efficiency.

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.

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.

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.

The immediate effect of individual manipulation techniques on pulmonary function measures in persons with chronic obstructive pulmonary disease

PubMed Central

Noll, Donald R; Johnson, Jane C; Baer, Robert W; Snider, Eric J

2009-01-01

Background The use of manipulation has long been advocated in the treatment of chronic obstructive pulmonary disease (COPD), but few randomized controlled clinical trials have measured the effect of manipulation on pulmonary function. In addition, the effects of individual manipulative techniques on the pulmonary system are poorly understood. Therefore, the purpose of this study was to determine the immediate effects of four osteopathic techniques on pulmonary function measures in persons with COPD relative to a minimal-touch control protocol. Methods Persons with COPD aged 50 and over were recruited for the study. Subjects received five, single-technique treatment sessions: minimal-touch control, thoracic lymphatic pump (TLP) with activation, TLP without activation, rib raising, and myofascial release. There was a 4-week washout period between sessions. Protocols were given in random order until all five techniques had been administered. Pulmonary function measures were obtained at baseline and 30-minutes posttreatment. For the actual pulmonary function measures and percent predicted values, Wilcoxon signed rank tests were used to test within-technique changes from baseline. For the percent change from baseline, Friedman tests were used to test for between-technique differences. Results Twenty-five subjects were enrolled in the study. All four tested osteopathic techniques were associated with adverse posttreatment changes in pulmonary function measures; however, different techniques changed different measures. TLP with activation increased posttreatment residual volume compared to baseline, while TLP without activation did not. Side effects were mild, mostly posttreatment chest wall soreness. Surprisingly, the majority of subjects believed they could breathe better after receiving osteopathic manipulation. Conclusion In persons with COPD, TLP with activation, TLP without activation, rib raising, and myofascial release mildly worsened pulmonary function measures immediately posttreatment relative to baseline measurements. The activation component of the TLP technique appears to increase posttreatment residual volume. Despite adverse changes in pulmonary function measures, persons with COPD subjectively reported they benefited from osteopathic manipulation. PMID:19814829

The immediate effect of individual manipulation techniques on pulmonary function measures in persons with chronic obstructive pulmonary disease.

PubMed

Noll, Donald R; Johnson, Jane C; Baer, Robert W; Snider, Eric J

2009-10-08

The use of manipulation has long been advocated in the treatment of chronic obstructive pulmonary disease (COPD), but few randomized controlled clinical trials have measured the effect of manipulation on pulmonary function. In addition, the effects of individual manipulative techniques on the pulmonary system are poorly understood. Therefore, the purpose of this study was to determine the immediate effects of four osteopathic techniques on pulmonary function measures in persons with COPD relative to a minimal-touch control protocol. Persons with COPD aged 50 and over were recruited for the study. Subjects received five, single-technique treatment sessions: minimal-touch control, thoracic lymphatic pump (TLP) with activation, TLP without activation, rib raising, and myofascial release. There was a 4-week washout period between sessions. Protocols were given in random order until all five techniques had been administered. Pulmonary function measures were obtained at baseline and 30-minutes posttreatment. For the actual pulmonary function measures and percent predicted values, Wilcoxon signed rank tests were used to test within-technique changes from baseline. For the percent change from baseline, Friedman tests were used to test for between-technique differences. Twenty-five subjects were enrolled in the study. All four tested osteopathic techniques were associated with adverse posttreatment changes in pulmonary function measures; however, different techniques changed different measures. TLP with activation increased posttreatment residual volume compared to baseline, while TLP without activation did not. Side effects were mild, mostly posttreatment chest wall soreness. Surprisingly, the majority of subjects believed they could breathe better after receiving osteopathic manipulation. In persons with COPD, TLP with activation, TLP without activation, rib raising, and myofascial release mildly worsened pulmonary function measures immediately posttreatment relative to baseline measurements. The activation component of the TLP technique appears to increase posttreatment residual volume. Despite adverse changes in pulmonary function measures, persons with COPD subjectively reported they benefited from osteopathic manipulation.

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). ...

Decreased expression of monocarboxylate transporter 1 and 4 in the branching airway epithelium of nitrofen-induced congenital diaphragmatic hernia.

PubMed

Takahashi, Toshiaki; Friedmacher, Florian; Zimmer, Julia; Puri, Prem

2016-06-01

Monocarboxylate transporters (MCTs) are crucial for the maintenance of intracellular pH homeostasis in developing fetal lungs. MCT1/4 is strongly expressed by epithelial airway cells throughout lung branching morphogenesis. Functional inhibition of MCT1/4 in fetal rat lung explants has been shown to result in airway defects similar to pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH). We hypothesized that pulmonary expression of MCT1/4 is decreased during lung branching morphogenesis in the nitrofen model of CDH-associated PH. Timed-pregnant rats received nitrofen or vehicle on gestational day 9 (D9). Fetuses were harvested on D15, D18, and D21, and divided into control and nitrofen-exposed group. Pulmonary gene expression levels of MCT1/4 were analyzed by qRT-PCR. Immunofluorescence staining for MCT1/4 was combined with E-cadherin in order to evaluate protein expression in branching airway tissue. Relative mRNA levels of MCT1/4 were significantly reduced in lungs of nitrofen-exposed fetuses on D15, D18, and D21 compared to controls. Confocal laser scanning microscopy confirmed markedly decreased immunofluorescence of MCT1/4 in distal bronchial and primitive alveolar epithelium of nitrofen-exposed fetuses on D15, D18, and D21 compared to controls. Decreased expression of MCT1/4 in distal airway epithelium may disrupt lung branching morphogenesis and thus contribute to the development of PH in the nitrofen-induced CDH model. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Survival Analysis of Patients with End Stage Renal Disease

NASA Astrophysics Data System (ADS)

Urrutia, J. D.; Gayo, W. S.; Bautista, L. A.; Baccay, E. B.

2015-06-01

This paper provides a survival analysis of End Stage Renal Disease (ESRD) under Kaplan-Meier Estimates and Weibull Distribution. The data were obtained from the records of V. L. MakabaliMemorial Hospital with respect to time t (patient's age), covariates such as developed secondary disease (Pulmonary Congestion and Cardiovascular Disease), gender, and the event of interest: the death of ESRD patients. Survival and hazard rates were estimated using NCSS for Weibull Distribution and SPSS for Kaplan-Meier Estimates. These lead to the same conclusion that hazard rate increases and survival rate decreases of ESRD patient diagnosed with Pulmonary Congestion, Cardiovascular Disease and both diseases with respect to time. It also shows that female patients have a greater risk of death compared to males. The probability risk was given the equation R = 1 — e-H(t) where e-H(t) is the survival function, H(t) the cumulative hazard function which was created using Cox-Regression.

Experimental evidence of age-related adaptive changes in human acinar airways

PubMed Central

Quirk, James D.; Sukstanskii, Alexander L.; Woods, Jason C.; Lutey, Barbara A.; Conradi, Mark S.; Gierada, David S.; Yusen, Roger D.; Castro, Mario

2015-01-01

The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized 3He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized 3He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger. PMID:26542518

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.

Pulmonary function of children with acute leukemia in maintenance phase of chemotherapy☆

PubMed Central

de Macêdo, Thalita Medeiros Fernandes; Campos, Tania Fernandes; Mendes, Raquel Emanuele de França; França, Danielle Corrêa; Chaves, Gabriela Suéllen da Silva; de Mendonça, Karla Morganna Pereira Pinto

2014-01-01

OBJECTIVE: The aim of this study was to assess the pulmonary function of children with acute leukemia. METHODS: Cross-sectional observational analytical study that enrolled 34 children divided into groups A (17 with acute leukemia in the maintenance phase of chemotherapy) and B (17 healthy children). The groups were matched for sex, age and height. Spirometry was measured using a spirometer Microloop Viasys(r) in accordance with American Thoracic Society and European Respiratory Society guidelines. Maximal respiratory pressures were measured with an MVD300 digital manometer (Globalmed(r)). Maximal inspiratory pressures and maximal expiratory pressures were measured from residual volume and total lung capacity, respectively. RESULTS: Group A showed a significant decrease in maximal inspiratory pressures when compared to group B. No significant difference was found between the spirometric values of the two groups, nor was there any difference between maximal inspiratory pressure and maximal expiratory pressure values in group A compared to the lower limit values proposed as reference. CONCLUSION: Children with acute leukemia, myeloid or lymphoid, during the maintenance phase of chemotherapy exhibited unchanged spirometric variables and maximal expiratory pressure; However, there was a decrease in inspiratory muscle strength. PMID:25510995

Inspiratory and expiratory computed tomographic volumetry for lung volume reduction surgery.

PubMed

Morimura, Yuki; Chen, Fengshi; Sonobe, Makoto; Date, Hiroshi

2013-06-01

Three-dimensional (3D) computed tomographic (CT) volumetry has been introduced into the field of thoracic surgery, and a combination of inspiratory and expiratory 3D-CT volumetry provides useful data on regional pulmonary function as well as the volume of individual lung lobes. We report herein a case of a 62-year-old man with severe emphysema who had undergone lung volume reduction surgery (LVRS) to assess this technique as a tool for the evaluation of regional lung function and volume before and after LVRS. His postoperative pulmonary function was maintained in good condition despite a gradual slight decrease 2 years after LVRS. This trend was also confirmed by a combination of inspiratory and expiratory 3D-CT volumetry. We confirm that a combination of inspiratory and expiratory 3D-CT volumetry might be effective for the preoperative assessment of LVRS in order to determine the amount of lung tissue to be resected as well as for postoperative evaluation. This novel technique could, therefore, be used more widely to assess local lung function.

Inspiratory and expiratory computed tomographic volumetry for lung volume reduction surgery

PubMed Central

Morimura, Yuki; Chen, Fengshi; Sonobe, Makoto; Date, Hiroshi

2013-01-01

Three-dimensional (3D) computed tomographic (CT) volumetry has been introduced into the field of thoracic surgery, and a combination of inspiratory and expiratory 3D-CT volumetry provides useful data on regional pulmonary function as well as the volume of individual lung lobes. We report herein a case of a 62-year-old man with severe emphysema who had undergone lung volume reduction surgery (LVRS) to assess this technique as a tool for the evaluation of regional lung function and volume before and after LVRS. His postoperative pulmonary function was maintained in good condition despite a gradual slight decrease 2 years after LVRS. This trend was also confirmed by a combination of inspiratory and expiratory 3D-CT volumetry. We confirm that a combination of inspiratory and expiratory 3D-CT volumetry might be effective for the preoperative assessment of LVRS in order to determine the amount of lung tissue to be resected as well as for postoperative evaluation. This novel technique could, therefore, be used more widely to assess local lung function. PMID:23460599

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

Respiratory complications in the postanesthesia care unit: A review of pathophysiological mechanisms

PubMed Central

Karcz, Marcin; Papadakos, Peter J

2013-01-01

General anesthesia and mechanical ventilation impair pulmonary function, even in normal individuals, and result in decreased oxygenation in the postanesthesia period. They also cause a reduction in functional residual capacity of up to 50% of the preanesthesia value. It has been shown that pulmonary atelectasis is a common finding in anesthetized individuals because it occurs in 85% to 90% of healthy adults. Furthermore, there is substantial evidence that atelectasis, in combination with alveolar hypoventilation and ventilation-perfusion mismatch, is the core mechanism responsible for postoperative hypoxemic events in the majority of patients in the postanesthesia care unit (PACU). Many concomitant factors also must be considered, such as respiratory depression from the type and anatomical site of surgery altering lung mechanics, the consequences of hemodynamic impairment and the residual effects of anesthetic drugs, most notably residual neuromuscular blockade. The appropriate use of anesthetic and analgesic techniques, when combined with meticulous postoperative care, clearly influences pulmonary outcomes in the PACU. The present review emphasizes the major pathophysiological mechanisms and treatment strategies of critical respiratory events in the PACU to provide health care workers with the knowledge needed to prevent such potentially adverse outcomes from occurring. PMID:26078599

Effects of High-Flux versus Low-Flux Membranes on Pulmonary Function Tests in Hemodialysis Patients.

PubMed

Momeni, Ali; Rouhi, Hamid; Kiani, Glareh; Amiri, Masoud

2013-01-01

Several studies have been carried out to evaluate the effects of dialysis on pulmonary function tests (PFT). Dialysis procedure may reduce lung volumes and capacities or cause hypoxia; however, to the best of our knowledge, there is no previous study evaluating the effects of membrane type (high flux vs. low flux) on PFT in these patients. The aim of this study was the evaluation of this relationship. In this cross-sectional study, 43 hemodialysis patients without pulmonary disease were enrolled. In these patients dialysis was conducted by low-and high-flux membranes and before and after the procedure, spirometry was done and the results were evaluated by t-test and chi square test. The mean age of patients was 56.34 years. Twenty-three of them were female (53.5%). Type of membrane (high flux vs. low flux) had no effect on spirometry results of patients despite the significant decrease in the body weight during the dialysis session. High flux membrane had no advantage over low flux membrane in terms of improvement in spirometry findings; thus, we could not offer these expensive membranes for this purpose.

Balloon pulmonary angioplasty relieves haemodynamic stress towards untreated-side pulmonary vasculature and improves its resistance in patients with chronic thromboembolic pulmonary hypertension.

PubMed

Hosokawa, Kazuya; Abe, Kohtaro; Horimoto, Koshin; Yamasaki, Yuzo; Nagao, Michinobu; Tsutsui, Hiroyuki

2018-04-20

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by organised thrombotic obliteration of major vessels and small-vessel arteriopathy in the non-thrombosed vessels. The aim of this study was to investigate the impact of balloon pulmonary angioplasty (BPA) on the non-BPA-side pulmonary vasculature in patients with CTEPH. This study explored the outcomes of 20 unilateral BPA sessions in 13 CTEPH patients. We measured the pulmonary vascular resistance (PVR), pulmonary artery (PA) flow in the BPA-side and non-BPA-side lungs, respectively, using phase contrast MRI and cardiac catheterisation. The interval from BPA to the follow-up evaluation was 92.8±52.0 days. A single session of BPA decreased mean PA pressure from 37.4±6.2 to 30.9±6.5 mmHg (p<0.001). In the BPA side, BPA increased the PA flow from 1.58±0.65 to 1.95±0.62 L/min (p=0.001) and decreased the PVR from 27.3±27.4 to 14.4±9.0 Wood units (p=0.004). In contrast, it decreased both the non-BPA-side PA flow from 2.25±0.64 to 1.90±0.23 L/min (p=0.008) and the non-BPA-side PVR from 14.8±6.6 to 12.8±3.9 Wood units (p=0.01). BPA could relieve haemodynamic stress towards the non-BPA-side vasculature and decrease its PVR in patients with CTEPH, suggesting that it can suppress or regress the progression of the small-vessel arteriopathy in non-BPA-side vasculature, presumably due to haemodynamic unloading.

Pulmonary involvement in Fabry disease: effect of plasma globotriaosylsphingosine and time to initiation of enzyme replacement therapy.

PubMed

Franzen, Daniel; Haile, Sarah R; Kasper, David C; Mechtler, Thomas P; Flammer, Andreas J; Krayenbühl, Pierre A; Nowak, Albina

2018-01-01

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by mutations of GLA gene leading to reduced α-galactosidase activity and resulting in a progressive accumulation of globotriaosylceramide (Gb3) and its deacylated derivative, globotriaosyl-sphingosine (Lyso-Gb3). Plasma Lyso-Gb3 levels serve as a disease severity and treatment monitoring marker during enzyme replacement therapy (ERT). Adult patients with AFD who had yearly pulmonary function tests between 1999 and 2015 were eligible for this observational study. Primary outcome measures were the change in z-score of forced expiratory volume in the first second (FEV 1 ) and FEV 1 /FVC over time. Plasma Lyso-Gb3 levels and the age of ERT initiation were investigated for their association with lung function decline. Fifty-three patients (42% male, median (range) age at diagnosis of AFD 34 (6-61) years in men, 34 (13-67) in women) were included. The greatest decrease of FEV 1 /FVC z-scores was observed in Classic men (-0.048 per year, 95% CI -0.081 to -0.014), compared with the Later-Onset men (+0.013,95% CI -0.055 to 0.082), Classic women (-0.008, 95% CI -0.035 to +0.020) and Later-Onset women (-0.013, 95% CI -0.084 to +0.058). Cigarette smoking (P=0.022) and late ERT initiation (P=0.041) were independently associated with faster FEV 1 decline. FEV 1 /FVC z-score decrease was significantly reduced after initiation of ERT initiation (-0.045 compared with -0.015, P=0.014). Furthermore, there was a trend towards a relevant influence of Lyso-Gb3 (P=0.098) on airflow limitation with age. Early ERT initiation seems to preserve pulmonary function. Plasma Lyso-Gb3 is maybe a useful predictor for airflow limitation. Classic men need a closer monitoring of the lung function.

Oxygen dependence of endothelium-dependent vasodilation: importance in chronic obstructive pulmonary disease.

PubMed

Keymel, Stefanie; Schueller, Benedikt; Sansone, Roberto; Wagstaff, Rabea; Steiner, Stephan; Kelm, Malte; Heiss, Christian

2018-03-01

Epidemiological studies have shown increased morbidity and mortality in patients with coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD). We aimed to characterize the oxygen dependence of endothelial function in patients with CAD and coexisting COPD. In CAD patients with and without COPD ( n = 33), we non-invasively measured flow-mediated dilation (FMD) and intima-media thickness (IMT) of the brachial artery (BA), forearm blood flow (FBF), and perfusion of the cutaneous microcirculation with laser Doppler perfusion imaging (LDPI). In an experimental setup, vascular function was assessed in healthy volunteers ( n = 5) breathing 12% oxygen or 100% oxygen in comparison to room air. COPD was associated with impaired FMD (3.4 ±0.5 vs. 4.2 ±0.6%; p < 0.001) and increased IMT (0.49 ±0.04 vs. 0.44 ±0.04 mm; p <0.01), indicating functional and structural alterations of the BA in COPD. Forearm blood flow and LDPI were comparable between the groups. Flow-mediated dilation correlated with capillary oxygen pressure (pO 2 , r = 0.608). Subgroup analysis in COPD patients with pO 2 > 65 mm Hg and pO 2 ≤ 65 mm Hg revealed even lower FMD in patients with lower pO 2 (3.0 ±0.5 vs. 3.7 ±0.4%; p < 0.01). Multivariate analysis showed that pO 2 was a predictor of FMD independent of the forced expiratory volume and pack years. Exposure to hypoxic air led to an acute decrease in FMD, whereby exposure to 100% oxygen did not change vascular function. Our data suggest that in CAD patients with COPD, decreased systemic oxygen levels lead to endothelial dysfunction, underlining the relevance of cardiopulmonary interaction and the potential importance of pulmonary treatment in secondary prevention of vascular disease.

The effect of ACE inhibition on the pulmonary vasculature in combined model of chronic hypoxia and pulmonary arterial banding in Sprague Dawley rats

NASA Astrophysics Data System (ADS)

Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert

2010-03-01

Microfocal CT was used to image the pulmonary arterial (PA) tree in rodent models of pulmonary hypertension (PH). CT images were used to measure the arterial tree diameter along the main arterial trunk at several hydrostatic intravascular pressures and calculate distensibility. High-resolution planar angiographic imaging was also used to examine distal PA microstructure. Data on pulmonary artery tree morphology improves our understanding of vascular remodeling and response to treatments. Angiotensin II (ATII) has been identified as a mediator of vasoconstriction and proliferative mitotic function. ATII has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia as well as stimulate synthesis of extracellular matrix proteins. Available ATII is targeted through angiotensin converting enzyme inhibitors (ACEIs), a method that has been used in animal models of PH to attenuate vascular remodeling and decrease pulmonary vascular resistance. In this study, we used rat models of chronic hypoxia to induce PH combined with partial left pulmonary artery occlusion (arterial banding, PLPAO) to evaluate effects of the ACEI, captopril, on pulmonary vascular hemodynamic and morphology. Male Sprague Dawley rats were placed in hypoxia (FiO2 0.1), with one group having underwent PLPAO three days prior to the chronic hypoxia. After the twenty-first day of hypoxia exposure, treatment was started with captopril (20 mg/kg/day) for an additional twenty-one days. At the endpoint, lungs were excised and isolated to examine: pulmonary vascular resistance, ACE activity, pulmonary vessel morphology and biomechanics. Hematocrit and RV/LV+septum ratio was also measured. CT planar images showed less vessel dropout in rats treated with captopril versus the non-treatment lungs. Distensibility data shows no change in rats treated with captopril in both chronic hypoxia (CH) and CH with PLPAO (CH+PLPAO) models. Hemodynamic measurements also show no change in the pulmonary vascular resistance with captopril treatment in both CH and CH+PLPAO.

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.

Sox17 is required for normal pulmonary vascular morphogenesis

PubMed Central

Lange, Alexander W.; Haitchi, Hans Michael; LeCras, Timothy D.; Sridharan, Anusha; Xu, Yan; Wert, Susan E.; James, Jeanne; Udell, Nicholas; Thurner, Philipp J.; Whitsett, Jeffrey A.

2015-01-01

The SRY-box containing transcription factor Sox17 is required for endoderm formation and vascular morphogenesis during embryonic development. In the lung, Sox17 is expressed in mesenchymal progenitors of the embryonic pulmonary vasculature and is restricted to vascular endothelial cells in the mature lung. Conditional deletion of Sox17 in splanchnic mesenchyme-derivatives using Dermo1-Cre resulted in substantial loss of Sox17 from developing pulmonary vascular endothelial cells and caused pulmonary vascular abnormalities before birth, including pulmonary vein varices, enlarged arteries, and decreased perfusion of the microvasculature. While survival of Dermo1-Cre;Sox17Δ/Δ mice (herein termed Sox17Δ/Δ) was unaffected at E18.5, most Sox17Δ/Δ mice died by 3 weeks of age. After birth, the density of the pulmonary microvasculature was decreased in association with alveolar simplification, biventricular cardiac hypertrophy, and valvular regurgitation. The severity of the postnatal cardiac phenotype was correlated with the severity of pulmonary vasculature abnormalities. Sox17 is required for normal formation of the pulmonary vasculature and postnatal cardiovascular homeostasis. PMID:24418654

Lack of sensitivity of measurements of Vd/Vt at rest and during exercise in detection of hemodynamically significant pulmonary vascular abnormalities in collagen vascular disease.

PubMed

Mohsenifar, Z; Tashkin, D P; Levy, S E; Bjerke, R D; Clements, P J; Furst, D

1981-05-01

Wasted ventilation fraction (Vd/Vt) normally declines substantially during exercise in persons without lung disease. Failure of Vd/Vt to decrease during exercise has been reported to be one of the earliest abnormalities in patients with dyspnea caused by pulmonary vaso-occlusive disease, suggesting that measurement of Vd/Vt at rest and during exercise are useful in the diagnosis of pulmonary vascular disorders. We studied pulmonary hemodynamic and Vd/Vt responses to exercise in 11 patients in the supine position with suspected pulmonary vascular involvement caused by progressive systemic sclerosis, systemic lupus erythematosus, or recurrent pulmonary emboli, 10 of whom had dyspnea at rest and/or on exertion. In contrast to previous reports of no change or an increase in Vd/Vt during exercise in patients with pulmonary vascular disease, we found Vd/Vt to decrease significantly during exercise in 8 of 9 patients in whom mean pulmonary artery pressures were abnormally elevated at rest and/or during exercise. Our findings suggest that normal responses of Vd/Vt to exercise do not exclude hemodynamically significant pulmonary vaso-occlusive disease.

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.

The β2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.

PubMed

Neumann, Vanessa; Knies, Ralf; Seidinger, Alexander; Simon, Annika; Lorenz, Kristina; Matthey, Michaela; Breuer, Johannes; Wenzel, Daniela

2018-05-01

Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β 2 adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse. This effect was found to be independent of β ARs and the endothelium but was determined by the type of the preconstrictor. Vasodilation by β 2 AR agonists occurred after pretreatment of pulmonary arteries with phenylephrine and serotonin, both agonists of α 1 ARs, but was absent after preconstriction with the thromboxane analog U46619. These data indicated α-adrenolytic activity of β 2 AR agonists, which was confirmed by a right shift of the phenylephrine dose-response curve by TER. This effect was physiologically relevant because TER also relaxed small intrapulmonary arteries in lung slices and diminished pulmonary arterial pressure in an isolated perfused lung model under normoxia and hypoxia. Finally, TER applied as an aerosol also selectively decreased pulmonary arterial pressure without effects on systemic blood pressure and heart rate in mouse in vivo. Thus, β 2 AR agonists display α-adrenolytic activity in pulmonary arteries ex vivo and in vivo, and may provide a novel option to reduce pulmonary arterial pressure in pulmonary hypertension.-Neumann, V., Knies, R., Seidinger, A., Simon, A., Lorenz, K., Matthey, M., Breuer, J., Wenzel, D. The β 2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.

MIP-2 causes differential activation of RhoA in mouse aortic versus pulmonary artery endothelial cells

PubMed Central

Moldobaeva, Aigul; Baek, Amy; Wagner, Elizabeth M.

2008-01-01

Previously, we have shown that endothelial cell chemotaxis to the proangiogenic chemokine MIP-2 (macrophage inflammatory protein-2), is much greater in mouse aortic endothelial cells (EC) than pulmonary arterial endothelial cells (PA EC). This was true despite the observation that both cell types display comparable levels of the ligand receptor, CXCR2 (8). Since the systemic arterial circulation is proangiogenic in the adult lung and the pulmonary circulation is relatively resistant to neovascularization, we questioned whether the observed functional heterogeneity is related to inherent differences in cell signaling cascades of the two EC subtypes. Specifically, we measured activation of Rac1 and RhoA, both thought to be involved in EC cell migration. Rac1 showed inconsistent and minimal changes in both cell types after MIP-2 treatment (p>0.05). However, activated RhoA was increased upon exposure to MIP-2 only in aortic EC (61% increase; p<0.05). Decreased RhoA activation after treatment of aortic EC with specific siRNA for RhoA resulted in a functional decrease in EC chemotaxis to MIP-2 (17% increase; p<0.05). Additionally, increased RhoA activation in PA EC with adenoviral infection of RhoA caused an increase in PA EC chemotaxis to MIP-2 (46% increase; p<0.05). Inhibition of RhoA activity with the Rho kinase inhibitor, Y27632 blocked aortic EC chemotaxis and stress fiber formation. Thus, RhoA activation is increased after MIP-2 treatment in mouse aortic endothelial cells but not in pulmonary artery endothelial cells. We conclude that RhoA is part of a signaling pathway essential for aortic cell migration after CXCR2 ligation. This result provides one explanation for the difference in chemotaxis observed in these two endothelial subtypes that express similar levels of CXCR2. PMID:17662312

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.…

Prior exposure to ozone potentiates subsequent response to sulfur dioxide in adolescent asthmatic subjects

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

Koenig, J.Q.; Covert, D.S.; Hanley, Q.S.

The objective of this study was to test whether prior exposure to a low concentration of ozone (120 ppb) would condition airways in asthmatic subjects to respond to a subthreshold concentration of sulfur dioxide (100 ppb). Eight male and five female subjects 12 to 18 yr of age participated. They all had allergic asthma and exercise-induced bronchospasm. Subjects were exposed to three test atmosphere sequences during intermittent moderate exercise (a 45-min exposure to one pollutant followed by a 15-min exposure to the second pollutant). The sequences were: air followed by 100 ppb SO2, 120 ppb O3 followed by 120 ppbmore » O3, and 120 ppb O3 followed by 100 ppb SO2. The pulmonary function measurements assessed were FEV1, total respiratory resistance (RT), and maximal flow (Vmax50). Air-SO2 and O3-O3 exposures did not cause significant changes in pulmonary function. On the other hand, exposure to 100 ppb SO2 after a 45-min exposure to 120 ppb O3 caused a significant (8%) decrease in FEV1 (p = 0.046), a significant (19%) increase in RT (p = 0.048), and a significant (15%) decrease in Vmax50 (p = 0.008). It is concluded that prior O3 exposure increased bronchial hyperresponsiveness in these subjects such that they responded to an ordinarily subthreshold concentration of SO2. These data suggest that assessment of pulmonary changes to single pollutant challenges overlooks the interactive effects of common coexisting or sequentially occurring air pollutants.« less

Breakdown of lung framework and an increase in pores of Kohn as initial events of emphysema and a cause of reduction in diffusing capacity.

PubMed

Yoshikawa, Akira; Sato, Shuntaro; Tanaka, Tomonori; Hashisako, Mikiko; Kashima, Yukio; Tsuchiya, Tomoshi; Yamasaki, Naoya; Nagayasu, Takeshi; Yamamoto, Hiroshi; Fukuoka, Junya

2016-01-01

Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema.

Comparison between effects of pressure support and pressure-controlled ventilation on lung and diaphragmatic damage in experimental emphysema.

PubMed

Padilha, Gisele de A; Horta, Lucas F B; Moraes, Lillian; Braga, Cassia L; Oliveira, Milena V; Santos, Cíntia L; Ramos, Isalira P; Morales, Marcelo M; Capelozzi, Vera Luiza; Goldenberg, Regina C S; de Abreu, Marcelo Gama; Pelosi, Paolo; Silva, Pedro L; Rocco, Patricia R M

2016-12-01

In patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema. Emphysema was induced by intratracheal instillation of porcine pancreatic elastase in Wistar rats, once weekly for 4 weeks. Control animals received saline under the same protocol. Eight weeks after first instillation, control and emphysema rats were randomly assigned to PCV (n = 6/each) or PSV (n = 6/each) under protective tidal volume (6 ml/kg) for 4 h. Non-ventilated control and emphysema animals (n = 6/group) were used to characterize the model and for molecular biology analysis. Cardiorespiratory function, lung histology, diaphragm ultrastructure alterations, extracellular matrix organization, diaphragmatic proteolysis, and biological markers associated with pulmonary inflammation, alveolar stretch, and epithelial and endothelial cell damage were assessed. Emphysema animals exhibited cardiorespiratory changes that resemble human emphysema, such as increased areas of lung hyperinflation, pulmonary amphiregulin expression, and diaphragmatic injury. In emphysema animals, PSV compared to PCV yielded: no changes in gas exchange; decreased mean transpulmonary pressure (Pmean,L), ratio between inspiratory and total time (Ti/Ttot), lung hyperinflation, and amphiregulin expression in lung; increased ratio of pulmonary artery acceleration time to pulmonary artery ejection time, suggesting reduced right ventricular afterload; and increased ultrastructural damage to the diaphragm. Amphiregulin correlated with Pmean,L (r = 0.99, p < 0.0001) and hyperinflation (r = 0.70, p = 0.043), whereas Ti/Ttot correlated with hyperinflation (r = 0.81, p = 0.002) and Pmean,L (r = 0.60, p = 0.04). In the model of elastase-induced emphysema used herein, PSV reduced lung damage and improved cardiac function when compared to PCV, but worsened diaphragmatic injury.

Lack of ventilatory threshold in patients with chronic obstructive pulmonary disease.

PubMed

Midorikawa, J; Hida, W; Taguchi, O; Okabe, S; Kurosawa, H; Mizusawa, A; Ogawa, H; Ebihara, S; Kikuchi, Y; Shirato, K

1997-01-01

We investigated whether the ventilatory threshold (VET) could be detected in 25 patients with severe chronic obstructive pulmonary disease (COPD). Exercise on a treadmill was performed until symptom-limited maximum oxygen uptake (VO2SL) was obtained. VET was absent in 14 patients (56%, VET(-) group) and present in the others (44%, VET(+) group). Basal pulmonary functions and dyspnea index (VE,SL/MVV) were not different between the two groups. Endurance time and exercise tolerance (VO2SL/bw) were significantly less in VET(-) than in VET(+). In the former group, PaO2 and pH at maximal exercise decreased and PaCO2 increased significantly, but HCO3- did not change compared with the corresponding values before exercise. In the latter group, PaCO2 at maximal exercise increased significantly, and pH and HCO3- decreased significantly compared with the values before exercise, but PaO2 did not. The changes in PaO2 and PaCO2 were not different between the two groups, but changes in pH and HCO3- in VET(+) were greater than those in VET(-). These results suggest that the absence of VET in some COPD patients indicates a lower exercise capacity without producing metabolic acidosis. This may be caused by rapidly developing dyspnea.

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.

Pulmonary functions in air conditioner users.

PubMed

Khaliq, Farah; Sharma, Sameer; Tandon, O P

2006-01-01

Air conditioning may affect human health since it has profound effect on our environment, than just lowering temperature. The present study was planned to assess the effect of air conditioners (AC) on pulmonary functions in young healthy non-smoker males. The study group comprised of ten subjects who were using AC's in their cars for at least 1 hr daily since last 6 months. While ten subjects who did not use AC at all served as controls. The pulmonary functions were assessed using PK Morgan 232 spirometer in a closed room. The peak expiratory flow rate (PEFR) and Forced expiratory flow between 25-75% of vital capacity (FEF25-75) were significantly reduced in subjects using car AC's. Inspiratory flow rates also showed a trend towards decline in AC users but could not reach the level of significance. The lung volumes and capacities were not significantly different in the two groups except for forced expiratory volume in 0.5 sec (FEV 0.5 sec), which also decreased in AC users. The airway resistance and lung compliance did not show significant change. In the presence of normal FEV1, reduced FEF25-75% which is the flow rate over the middle half of vital capacity, is an evidence of mild airflow limitation. The result is suggestive of predisposition of AC users towards respiratory disorders in form of mild airflow restriction.

Respiratory function in facioscapulohumeral muscular dystrophy 1.

PubMed

Wohlgemuth, M; Horlings, C G C; van der Kooi, E L; Gilhuis, H J; Hendriks, J C M; van der Maarel, S M; van Engelen, B G M; Heijdra, Y F; Padberg, G W

2017-06-01

To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk factors for developing respiratory insufficiency in facioscapulohumeral muscular dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1 of varying degrees of severity ranging from ambulatory patients to wheelchair-bound patients. We examined the patients neurologically and by conducting pulmonary function tests: Forced Vital Capacity, Forced Expiratory Volume in 1 second, and static maximal inspiratory and expiratory mouth pressures. We did not find pulmonary function test abnormalities in ambulant facioscapulohumeral muscular dystrophy patients. Even though none of the patients complained of respiratory dysfunction, mild to severe respiratory insufficiency was found in more than one third of the wheelchair-dependent patients. Maximal inspiratory pressures and maximal expiratory pressures were decreased in most patients, with a trend that maximal expiratory pressures were more affected than maximal inspiratory pressures. Wheelchair-dependent patients with (kypho-)scoliosis showed the most restricted lung function. Wheelchair-dependent patients with (kypho-)scoliosis are at risk for developing respiratory function impairment. We advise examining this group of facioscapulohumeral muscular dystrophy patients periodically, even in the absence of symptoms of respiratory insufficiency, given its frequency and impact on daily life and the therapeutic consequences. Copyright © 2017 Elsevier B.V. All rights reserved.

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

A New Era of Therapeutic Strategies for Chronic Thromboembolic Pulmonary Hypertension by Two Different Interventional Therapies; Pulmonary Endarterectomy and Percutaneous Transluminal Pulmonary Angioplasty

PubMed Central

Ando, Motomi; Fukuda, Keiichi; Yoshino, Hideaki; Satoh, Toru

2014-01-01

Background Pulmonary endarterectomy (PEA) is established for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Recently, percutaneous transluminal pulmonary angioplasty (PTPA) has been added for peripheral-type CTEPH, whose lesions exist in segmental, subsegmental, and more distal pulmonary arteries. A shift in clinical practice of interventional therapies occurred in 2009 (first mainly PEA, later PTPA). We examined the latest clinical outcomes of patients with CTEPH. Methods and Results This study retrospectively included 136 patients with CTEPH. Twenty-nine were treated only with drug (Drug-group), and the other 107 underwent interventional therapies (Interventions-group) (39 underwent PEA [PEA-group] and 68 underwent PTPA [PTPA-group]). Total 213 PTPA sessions (failures, 0%; mortality rate, 1.47%) was performed in the PTPA-group (complications: reperfusion pulmonary edema, 7.0%; hemosputum or hemoptysis, 5.6%; vessel dissection, 2.3%; wiring perforation, 0.9%). Although baseline hemodynamic parameters were significantly more severe in the Interventions-group, the outcome after the diagnosis was much better in the Interventions-group than in the Drug-group (98% vs. 64% 5-year survival, p<0.0001). Hemodynamic improvement in the PEA-group was a 46% decrease in mean pulmonary arterial pressure (PAP) and a 49% decrease in total pulmonary resistance (TPR) (follow-up period; 74.7±32.3 months), while those in the PTPA-group were a 40% decrease in mean PAP and a 49% decrease in TPR (follow-up period; 17.4±9.3 months). The 2-year survival rate in the Drug-group was 82.0%, and the 2-year survival rate, occurrence of right heart failure, and re-vascularization rate in the PEA-group were 97.4%, 2.6%, and 2.8%, and those in the PTPA-group were 98.5%, 2.9%, and 2.9%, respectively. Conclusion The patients who underwent interventional therapies had better results than those treated only with drugs. The availability of both of these operative and catheter-based interventional therapies leads us to expect the dawn of a new era of therapeutic strategies for CTEPH. PMID:24728482

Experimental myocardial infarction

PubMed Central

Kumar, Raj; Joison, Julio; Gilmour, David P.; Molokhia, Farouk A.; Pegg, C. A. S.; Hood, William B.

1971-01-01

The hemodynamic effects of tachycardia induced by atrial pacing were investigated in left ventricular failure of acute and healing experimental myocardial infarction in 20 intact, conscious dogs. Myocardial infarction was produced by gradual inflation of a balloon cuff device implanted around the left anterior descending coronary artery 10-15 days prior to the study. 1 hr after acute myocardial infarction, atrial pacing at a rate of 180 beats/min decreased left ventricular end-diastolic pressure from 19 to 8 mm Hg and left atrial pressure from 17 to 12 mm Hg, without change in cardiac output. In the healing phase of myocardial infarction 1 wk later, atrial pacing decreased left ventricular end-diastolic pressure from 17 to 9 mm Hg and increased the cardiac output by 37%. This was accompanied by evidence of peripheral vasodilation. In two dogs with healing anterior wall myocardial infarction, left ventricular failure was enhanced by partial occlusion of the circumflex coronary artery. Both the dogs developed pulmonary edema. Pacing improved left ventricular performance and relieved pulmonary edema in both animals. In six animals propranolol was given after acute infarction, and left ventricular function deteriorated further. However the pacing-induced augmentation of cardiac function was unaltered and, hence, is not mediated by sympathetics. The results show that the spontaneous heart rate in left ventricular failure of experimental canine myocardial infarction may be less than optimal and that maximal cardiac function may be achieved at higher heart rates. Images PMID:4395910

Aclidinium bromide plus formoterol for the treatment of chronic obstructive pulmonary disease.

PubMed

Lal, Chitra; Strange, Charlie

2015-02-01

Drugs that target dynamic hyperinflation such as long-acting β-2 agonists and long-acting antimuscarinic antagonists form a cornerstone of chronic obstructive pulmonary disease (COPD) management. The idea of combining these two medications in a single formulation, which may potentially improve patient compliance, is novel and attractive. The pharmacologic profiles of aclidinium bromide and formoterol fumarate are discussed. However, studies to define drug interactions and alterations in the pharmacodynamics and pharmacokinetics of the fixed dose combination (FDC) of aclidinium bromide/formoterol fumarate in large populations remain unpublished. Results of Phase II and two Phase III pivotal trials, ACLIFORM/COPD and AUGMENT COPD, evaluating the FDC are discussed. Initial data for the aclidinium/formoterol inhaler appears to be promising for impacting the lung function. To define if this benefit translates into improved long-term outcomes of decreased exacerbation frequency, improved quality of life and decreased disease-specific mortality are important. The introduction of this combination will likely have a significant impact on the prescribing habits of physicians across the world.

[Lung dysfunction in patients with mild chronic obstructive bronchitis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2004-01-01

VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Ravt, Riin, Rex, DLCO-SS, PaO2, and PaO2 were determined in 33 patients with mild chronic obstructive lung disease (FEV1 > 70% of the normal value). All the patients were found to have impaired bronchial patency; most (63.6%) patients had lung volume and capacity changes, almost half (45.5%) the patients had pulmonary gas exchange dysfunction. Impaired bronchial patency mainly appeared as decreased MEF50, MEF15, and FEV1/VC%; altered lung volumes and capacities manifested chiefly by increased RV and decreased VC; pulmonary gas exchange dysfunction showed up primarily as lowered PaO2. The magnitude of the observed functional changes was generally slight. MEF50, MEF75, FEV1/VC%, and VC dropped to 59-20 and 79-70% of the normal value, respectively. RV increased up to 142-196% of the normal value; PaO2 reduced up to 79-60% mm Hg.

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

Effects of milrinone and epinephrine or dopamine on biventricular function and hemodynamics in right heart failure after pulmonary regurgitation.

PubMed

Hyldebrandt, Janus Adler; Agger, Peter; Sivén, Eleonora; Wemmelund, Kristian Borup; Heiberg, Johan; Frederiksen, Christian Alcaraz; Ravn, Hanne Berg

2015-09-01

Right ventricular failure (RVF) secondary to pulmonary regurgitation (PR) impairs right ventricular (RV) function and interrupts the interventricular relationship. There are few recommendations for the medical management of severe RVF after prolonged PR. PR was induced in 16 Danish landrace pigs by plication of the pulmonary valve leaflets. Twenty-three pigs served as controls. At reexamination the effect of milrinone, epinephrine, and dopamine was evaluated using biventricular conductance and pulmonary catheters. Seventy-nine days after PR was induced, RV end-diastolic volume index (EDVI) had increased by 33% (P = 0.006) and there was a severe decrease in the load-independent measurement of contractility (PRSW) (-58%; P = 0.003). Lower cardiac index (CI) (-28%; P < 0.0001), mean arterial pressure (-15%; P = 0.01) and mixed venous oxygen saturation (SvO2) (36%; P < 0.0001) were observed compared with the control group. The interventricular septum deviated toward the left ventricle (LV). Milrinone improved RV-PRSW and CI and maintained systemic pressure while reducing central venous pressure (CVP). Epinephrine and dopamine further improved biventricular PRSW and CI equally in a dose-dependent manner. Systemic and pulmonary pressures were higher in the dopamine-treated animals compared with epinephrine-treated animals. None of the treatments improved stroke volume index (SVI) despite increases in contractility. Strong correlation was detected between SVI and LV-EDVI, but not SVI and biventricular contractility. In RVF due to PR, milrinone significantly improved CI, SvO2, and CVP and increased contractility in the RV. Epinephrine and dopamine had equal inotropic effect, but a greater vasopressor effect was observed for dopamine. SV was unchanged due to inability of both treatments to increase LV-EDVI. Copyright © 2015 the American Physiological Society.

Pulmonary rehabilitation in patients with bronchiectasis: pulmonary function, arterial blood gases, and the 6-minute walk test.

PubMed

van Zeller, Mafalda; Mota, Patrícia Caetano; Amorim, Adelina; Viana, Paulo; Martins, Paula; Gaspar, Luís; Hespanhol, Venceslau; Gomes, Isabel

2012-01-01

Information regarding the effects of pulmonary rehabilitation (PR) on pulmonary function (PF), arterial blood gases (ABG), and 6-minute walk distance (6MWD) in patients with bronchiectasis is scant in the literature. To evaluate the effects of PR on these indices in this population, a retrospective evaluation of those who attended PR from 2007 to 2010, was made. Pulmonary rehabilitation lasted a mean of 12 weeks and included cycle ergometer exercise for 30 minutes, 3 times per week, with additional upper limbs and quadriceps training. PF, ABG, and 6MWD were evaluated before and after PR to determine the potential influence of gender, exacerbations, underlying cause of bronchiectasis, severity of obstruction, and colonization with bacteria. Forty-one patients (48.8% males; median age, 54 years) were included; 25 had severe obstruction and 19 were colonized with bacteria. Following PR, no significant changes were detected in PF or ABG. Median 6MWD before PR was 425 m and post-PR was 450 m (P = .431). Outcomes did not show any interaction with gender, colonization, or exacerbations. However, patients with idiopathic bronchiectasis did show a significant improvement in forced vital capacity in percent of predicted and residual volume after PR (P = .016 and .048, respectively). Patients with severe obstruction showed a statistically significant decrease in percent of predicted residual volume (P = .025). There appears to be a beneficial impact of PR on PF in certain groups of patients with bronchiectasis. In addition, PR indications and protocols for patients with bronchiectasis may need to be adapted to accommodate specific patients, so that expressive exercise capacity improvement can be achieved.

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

Indoor mold exposure associated with neurobehavioral and pulmonary impairment: a preliminary report.

PubMed

Kilburn, Kaye H

2003-07-01

Recently, patients who have been exposed indoors to mixed molds, spores, and mycotoxins have reported asthma, airway irritation and bleeding, dizziness, and impaired memory and concentration, all of which suggest the presence of pulmonary and neurobehavioral problems. The author evaluated whether such patients had measurable pulmonary and neurobehavioral impairments by comparing consecutive cases in a series vs. a referent group. Sixty-five consecutive outpatients exposed to mold in their respective homes in Arizona, California, and Texas were compared with 202 community subjects who had no known mold or chemical exposures. Balance, choice reaction time, color discrimination, blink reflex, visual fields, grip, hearing, problem-solving, verbal recall, perceptual motor speed, and memory were measured. Medical histories, mood states, and symptom frequencies were recorded with checklists, and spirometry was used to measure various pulmonary volumes and flows. Neurobehavioral comparisons were made after individual measurements were adjusted for age, educational attainment, and sex. Significant differences between groups were assessed by analysis of variance; a p value of less than 0.05 was used for all statistical tests. The mold-exposed group exhibited decreased function for balance, reaction time, blink-reflex latency, color discrimination, visual fields, and grip, compared with referents. The exposed group's scores were reduced for the following tests: digit-symbol substitution, peg placement, trail making, verbal recall, and picture completion. Twenty-one of 26 functions tested were abnormal. Airway obstructions were found, and vital capacities were reduced. Mood state scores and symptom frequencies were elevated. The author concluded that indoor mold exposures were associated with neurobehavioral and pulmonary impairments that likely resulted from the presence of mycotoxins, such as trichothecenes.

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

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.

Inhibition of nuclear factor of activated T cells (NFAT) c3 activation attenuates acute lung injury and pulmonary edema in murine models of sepsis

PubMed Central

Karpurapu, Manjula; Lee, Yong Gyu; Qian, Ziqing; Wen, Jin; Ballinger, Megan N.; Rusu, Luiza; Chung, Sangwoon; Deng, Jing; Qian, Feng; Reader, Brenda F.; Nirujogi, Teja Srinivas; Park, Gye Young; Pei, Dehua; Christman, John W.

2018-01-01

Specific therapies targeting cellular and molecular events of sepsis induced Acute Lung Injury (ALI) pathogenesis are lacking. We have reported a pivotal role for Nuclear Factors of Activated T cells (NFATc3) in regulating macrophage phenotype during sepsis induced ALI and subsequent studies demonstrate that NFATc3 transcriptionally regulates macrophage CCR2 and TNFα gene expression. Mouse pulmonary microvascular endothelial cell monolayer maintained a tighter barrier function when co-cultured with LPS stimulated NFATc3 deficient macrophages whereas wild type macrophages caused leaky monolayer barrier. More importantly, NFATc3 deficient mice showed decreased neutrophilic lung inflammation, improved alveolar capillary barrier function, arterial oxygen saturation and survival benefit in lethal CLP sepsis mouse models. In addition, survival of wild type mice subjected to the lethal CLP sepsis was not improved with broad-spectrum antibiotics, whereas the survival of NFATc3 deficient mice was improved to 40–60% when treated with imipenem. Passive adoptive transfer of NFATc3 deficient macrophages conferred protection against LPS induced ALI in wild type mice. Furthermore, CP9-ZIZIT, a highly potent, cell-permeable peptide inhibitor of Calcineurin inhibited NFATc3 activation. CP9-ZIZIT effectively reduced sepsis induced inflammatory cytokines and pulmonary edema in mice. Thus, this study demonstrates that inhibition of NFATc3 activation by CP9-ZIZIT provides a potential therapeutic option for attenuating sepsis induced ALI/pulmonary edema. PMID:29535830

Potential Benefits of Rib Fracture Fixation in Patients with Flail Chest and Multiple Non-flail Rib Fractures.

PubMed

Qiu, Meiguang; Shi, Zhanjun; Xiao, Jun; Zhang, Xuming; Ling, Shishui; Ling, Hao

2016-12-01

The purpose of this study is to evaluate the potential benefits of rib fracture fixation in patients with flail chest and multiple non-flail rib fractures versus conventional treatment modalities. A retrospective reviewed study compared 86 cases which received surgical treatment between June 2009 and May 2013 to 76 cases which received conservative treatment between January 2006 and May 2009. The patients were divided into the flail chest ( n  = 38) and multiple non-flail rib fracture groups ( n  = 124). In the flail chest group, the mechanical ventilation time, ICU monitoring time, tracheostomies, thoracic deformity, and impaired pulmonary function and return to full-time employment were compared. In the multiple non-flail rib fracture group, fracture healing, visual analog scale (VAS) pain score, inpatient length of stay, atelectatic, pulmonary complications, and normal activity-returning time were compared. Patients in the flail chest operative fixation group had significantly shorter ICU stay, decreased ventilator requirements, fewer tracheostomies, less thoracic deformity and impaired pulmonary function, and more returned to full-time employment. Patients in the multiple non-flail rib fracture operative fixation had shorter hospital stay, less pain, earlier return to normal activity, more fracture healing, less atelectasis, and fewer pulmonary infections. This study demonstrates the potential benefits of surgical stabilization of flail chest and multiple non-flail rib fractures with plate fixation. When compared with conventional conservative management, operatively managed patients demonstrated improved clinical outcomes.

miR-34a Inhibits Lung Fibrosis by Inducing Lung Fibroblast Senescence.

PubMed

Cui, Huachun; Ge, Jing; Xie, Na; Banerjee, Sami; Zhou, Yong; Antony, Veena B; Thannickal, Victor J; Liu, Gang

2017-02-01

Cellular senescence has been implicated in diverse pathologies. However, there is conflicting evidence regarding the role of this process in tissue fibrosis. Although dysregulation of microRNAs is a key mechanism in the pathogenesis of lung fibrosis, it is unclear whether microRNAs function by regulating cellular senescence in the disease. In this study, we found that miR-34a demonstrated greater expression in the lungs of patients with idiopathic pulmonary fibrosis and in mice with experimental pulmonary fibrosis, with its primary localization in lung fibroblasts. More importantly, miR-34a was up-regulated significantly in both human and mouse lung myofibroblasts. We found that mice with miR-34a ablation developed more severe pulmonary fibrosis than did wild-type animals after fibrotic lung injury. Mechanistically, we found that miR-34a induced a senescent phenotype in lung fibroblasts because this microRNA increased senescence-associated β-galactosidase activity, enhanced expression of senescence markers, and decreased cell proliferative capacities. Consistently, we found that primary lung fibroblasts from fibrotic lungs of miR-34a-deficient mice had a diminished senescent phenotype and enhanced resistance to apoptosis as compared with those from wild-type animals. We also identified multiple miR-34a targets that likely mediated its activities in inducing senescence in lung fibroblasts. In conclusion, our data suggest that miR-34a functions through a negative feedback mechanism to restrain fibrotic response in the lungs by promoting senescence of pulmonary fibroblasts.

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.

Inhaled nitric oxide, oxygen, and alkalosis: dose-response interactions in a lamb model of pulmonary hypertension.

PubMed

Heidersbach, R S; Johengen, M J; Bekker, J M; Fineman, J R

1999-07-01

Inhaled nitric oxide (NO) is currently used as an adjuvant therapy for a variety of pulmonary hypertensive disorders. In both animal and human studies, inhaled NO induces selective, dose-dependent pulmonary vasodilation. However, its potential interactions with other simultaneously used pulmonary vasodilator therapies have not been studied. Therefore, the objective of this study was to determine the potential dose-response interactions of inhaled NO, oxygen, and alkalosis therapies. Fourteen newborn lambs (age 1-6 days) were instrumented to measure vascular pressures and left pulmonary artery blood flow. After recovery, the lambs were sedated and mechanically ventilated. During steady-state pulmonary hypertension induced by U46619 (a thromboxane A2 mimic), the lambs were exposed to the following conditions: Protocol A, inhaled NO (0, 5, 40, and 80 ppm) and inspired oxygen concentrations (FiO2) of 0.21, 0.50, and 1.00; and Protocol B, inhaled NO (0, 5, 40, and 80 ppm) and arterial pH levels of 7.30, 7.40, 7.50, and 7.60. Each condition (in randomly chosen order) was maintained for 10 min, and all variables were allowed to return to baseline between conditions. Inhaled NO, oxygen, and alkalosis produced dose-dependent decreases in mean pulmonary arterial pressures (P < 0.05). Systemic arterial pressure remained unchanged. At 5 ppm of inhaled NO, alkalosis and oxygen induced further dose-dependent decreases in mean pulmonary arterial pressures (P < 0.05). At inhaled NO doses > 5 ppm, alkalosis induced further dose-independent decreases in mean pulmonary arterial pressure, while oxygen did not. We conclude that in this animal model, oxygen, alkalosis, and inhaled NO induced selective, dose-dependent pulmonary vasodilation. However, when combined, a systemic arterial pH > 7.40 augmented inhaled NO-induced pulmonary vasodilation, while an FiO2 > 0.5 did not. Therefore, weaning high FiO2 during inhaled NO therapy should be considered, since it may not diminish the pulmonary vasodilating effects. Further studies are warranted to guide the clinical weaning strategies of these pulmonary vasodilator therapies.

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.

Pharmacological treatment optimization for stable chronic obstructive pulmonary disease. Proposals from the Société de Pneumologie de Langue Française.

PubMed

Zysman, M; Chabot, F; Devillier, P; Housset, B; Morelot-Panzini, C; Roche, N

2016-12-01

The Société de Pneumologie de Langue Française proposes a decision algorithm on long-term pharmacological COPD treatment. A working group reviewed the literature published between January 2009 and May 2016. This document lays out proposals and not guidelines. It only focuses on pharmacological treatments except vaccinations, smoking cessation treatments and oxygen therapy. Any COPD diagnosis, based on pulmonary function tests, should lead to recommend smoking cessation, vaccinations, physical activity, pulmonary rehabilitation in case of activity limitation, and short-acting bronchodilators. Symptoms like dyspnea and exacerbations determine the therapeutic choices. In case of daily dyspnea and/or exacerbations, a long-acting bronchodilator should be suggested (beta-2 agonist, LABA or anticholinergics, LAMA). A clinical and lung function reevaluation is suggested 1 to 3 months after any treatment modification and every 3-12 months according to the severity of the disease. In case of persisting dyspnea, a fixed dose LABA+LAMA combination improves pulmonary function (FEV1), quality of life, dyspnea and decreases exacerbations without increasing side effects. In case of frequent exacerbations and a FEV1≤70%, a fixed dose long-acting bronchodilator combination or a LABA+ inhaled corticosteroids (ICS) combination can be proposed. A triple combination (LABA+LAMA+ICS) is indicated when exacerbations persist despite one of these combinations. Dyspnea in spite of a bronchodilator combination or exacerbations in spite of a triple combination should lead to consider other pharmacological treatments (theophylline if dyspnea, macrolides if exacerbations, low-dose opioids if refractory dyspnea). Copyright © 2016. Published by Elsevier Masson SAS.

The contribution of the sympathetic nervous system to the immunopathology of experimental pulmonary tuberculosis.

PubMed

Barrios-Payán, Jorge; Revuelta, Alberto; Mata-Espinosa, Dulce; Marquina-Castillo, Brenda; Villanueva, Enrique Becerril; Gutiérrez, María Eugenia Hernández; Pérez-Sánchez, Gilberto; Pavón, Lenin; Hernandez-Pando, Rogelio

2016-09-15

The role of norepinephrine (NE) in the immunopathology of experimental tuberculosis (TB) was studied by measuring pulmonary NE and determining its cellular sources and targets. Functional studies were performed administrating adrenergic and anti-adrenergic drugs at different TB phases. Results showed high production of NE during early infection by adrenergic nerve terminals and lymphocytes located in the lungs and mediastinal lymph nodes, these cells highly expressed β2 adreno-receptors (β2AR) which by an autocrine mechanism promote Th-1 cell differentiation favoring protection. During advanced infection, the production of NE and β2AR sharply decreased, suggesting that adrenergic activity is less important during late TB. Copyright © 2016 Elsevier B.V. All rights reserved.

Peri-operative physiotherapy.

PubMed

Makhabah, Dewi Nurul; Martino, Federica; Ambrosino, Nicolino

2013-01-23

Postoperative pulmonary complications (PPC) are a major cause of morbidity, mortality, prolonged hospital stay, and increased cost of care. Physiotherapy (PT) programs in post-surgical and critical area patients are aimed to reduce the risks of PPC due to long-term bed-rest, to improve the patient's quality of life and residual function, and to avoid new hospitalizations. At this purpose, PT programs apply advanced cost-effective therapeutic modalities to decrease complications and patient's ventilator-dependency. Strategies to reduce PPC include monitoring and reduction of risk factors, improving preoperative status, patient education, smoking cessation, intra-operative and postoperative pulmonary care. Different PT techniques, as a part of the comprehensive management of patients undergoing cardiac, upper abdominal, and thoracic surgery, may prevent and treat PPC such as secretion retention, atelectasis, and pneumonia.

Novel Goal-Directed Hemodynamic Optimization Therapy Based on Major Vasopressor during Corrective Cardiac Surgery in Patients with Severe Pulmonary Arterial Hypertension: A Pilot Study.

PubMed

Li, Shuwen; Ma, Qing; Yang, Yanwei; Lu, Jiakai; Zhang, Zhiquan; Jin, Mu; Cheng, Weiping

2016-12-22

Pulmonary arterial hypertension (PAH) is a common and fatal complication of congenital heart disease (CHD). PAH-CHD increases the risk for postoperative complications. Recent evidence suggests that perioperative goal-directed hemodynamic optimization therapy (GDHOT) significantly improves outcomes in surgery patients. Standard GDHOT is based on major solution volume, vasodilators and inotropic therapy, while novel GDHOT is based on major vasopressor and inotropic therapy. Therefore, we tested whether standard or novel GDHOT improves surgical outcomes in PAH-CHD patients. Forty PAH-CHD patients with a ventricular septal defect (VSD) and mean pulmonary arterial pressure (mPAP) >50 mmHg, who were scheduled for corrective surgery, were randomly assigned to 2 groups: SG (study group, n = 20) and CG (control group, n = 20). SG patients received perioperative hemodynamic therapy guided by novel GDHOT, while CG patients received standard GDHOT. Outcome data were recorded up to 28 days postoperatively. Ventilator time, length of ICU stay, and mortality were the primary endpoints. There were no significant differences in preoperative data, surgical procedure, and hospital mortality rates between the 2 groups. Time of mechanical ventilation and length of ICU stay were significantly shorter in SG patients compared to CG patients (P < .05, n = 20). Patients in SG showed a significantly increased systemic vascular resistance index and decreased cardiac index, but no change in pulmonary vascular resistance index at 12 and 24 hours after surgery compared to the controls (P < .05). Patients in SG had significantly decreased PAP, pulmonary arterial pressure/systemic arterial pressure (Pp/Ps), and RVSWI (right ventricular stroke work index) at 12 and 24 hours after surgery (P < .05, respectively). Patients in SG also showed significantly decreased central venous pressure at 4, 12, and 24 hours after surgery compared to those treated with standard protocol (P < .05). Our study provides clinical evidence that perioperative goal-directed hemodynamic optimization therapy based on major vasopressor is associated with reduced duration of postoperative respiratory support, and length of ICU stay in PAH-CHD patients undergoing elective surgery. These outcomes, then, may be linked to improved hemodynamics and preservation of right ventricular dynamic function.

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.

Expression of Sproutys and SPREDs is decreased during lung branching morphogenesis in nitrofen-induced pulmonary hypoplasia.

PubMed

Friedmacher, Florian; Gosemann, Jan-Hendrik; Fujiwara, Naho; Takahashi, Hiromizu; Hofmann, Alejandro; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) is a life-threatening condition associated with congenital diaphragmatic hernia (CDH), characterized by defective lung development. Sproutys and Sprouty-related proteins (SPREDs) play a key role in lung branching morphogenesis through modification of epithelial-mesenchymal interactions. During the pseudoglandular stage, Sproutys are highly expressed in distal airway epithelium, while SPREDs within the surrounding mesenchyme. Sprouty2/4 knockouts show severe defects in branching morphogenesis with reduced number of distal airways. SPRED-1 and SPRED-2 are strongly expressed in regions of new airway formation, highlighting their important function in branching pattern. We hypothesized that expression of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 is decreased during lung branching morphogenesis in nitrofen-induced PH. Timed-pregnant rats received either nitrofen or vehicle on E9.5. On E15.5 (n = 16), fetal lungs were micro-dissected and divided into controls and PH, while on E18.5 (n = 24) groups were: control, PH without CDH [CDH(-)], and PH with CDH [CDH(+)]. Pulmonary gene expression levels of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 were analyzed by qRT-PCR. Immunohistochemistry was performed to evaluate protein expression/distribution. On E18.5, relative mRNA expression levels of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 were significantly decreased in CDH(-) and CDH(+) groups compared to controls (P < 0.05). Immunoreactivity of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 was markedly diminished on E18.5 in nitrofen-induced PH. Decreased expression of Sproutys and SPREDs during the terminal pseudoglandular stage may disrupt lung branching morphogenesis by interfering with epithelial-mesenchymal interactions contributing to PH.

Respiratory Pattern and Tidal Volumes Differ for Pressure Support and Volume-assured Pressure Support in Amyotrophic Lateral Sclerosis.

PubMed

Nicholson, Trevor T; Smith, Sean B; Siddique, Teepu; Sufit, Robert; Ajroud-Driss, Senda; Coleman, John M; Wolfe, Lisa F

2017-07-01

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease resulting in respiratory failure and death. Use of noninvasive ventilation (NIV) improves survival. However, use of volume-assured pressure support (VAPS) has not been extensively studied in ALS. To explore the clinical usefulness of a detailed evaluation of device-recorded NIV data in the management of chronic respiratory failure in ALS, and to determine whether there are differences in efficacy between patients using VAPS or PS. We performed a retrospective chart review of 271 patients with ALS using either PS or VAPS, along with an evaluation of device-recorded data to explore differences in attainment of goal tidal volumes (Vt) and ratio of respiratory rate to tidal volume (f/Vt), in addition to triggering and cycling ability. Two hundred and fifteen patients were using PS, while 56 were using VAPS. There were no significant differences in demographic data, symptoms, pulmonary function, or patient compliance. Compared with VAPS, achieved Vt was significantly lower for PS while f/Vt was significantly higher. Percent spontaneous triggering was relatively preserved in both cohorts, whereas percent spontaneous cycling was considerably decreased in both. Furthermore, there was no association found between spontaneous triggering or cycling, and pulmonary function, indicating the presence of low spontaneous breath cycling or triggering ability is difficult to predict. Examination of device data for exhaled tidal volumes and f/Vt may be of use in evaluating efficacy of NIV in ALS. VAPS provides more reliable goal Vt than does PS, and is associated with decreased f/Vt. Spontaneous cycling is decreased in ALS despite preservation of triggering ability. Although a set backup rate may address decreased triggering, perhaps more importantly, setting a sufficient fixed inspiratory time would address the issue of decreased cycling.

Maternal Dietary Docosahexaenoic Acid Supplementation Attenuates Fetal Growth Restriction and Enhances Pulmonary Function in a Newborn Mouse Model of Perinatal Inflammation123

PubMed Central

Velten, Markus; Britt, Rodney D.; Heyob, Kathryn M.; Tipple, Trent E.; Rogers, Lynette K.

2014-01-01

The preterm infant is often exposed to maternal and neonatal inflammatory stimuli and is born with immature lungs, resulting in a need for oxygen therapy. Nutritional intervention with docosahexaenoic acid (DHA; 6.3 g/kg of diet) has been shown to attenuate inflammation in various human diseases. Previous studies demonstrated that maternal DHA supplementation during late gestation and lactation attenuated hyperoxic lung injury in newborn mouse pups. In the present studies, we tested the hypothesis that DHA supplementation to the dam would reduce hyperoxic lung injury and growth deficits in a more severe model of systemic maternal inflammation, including lipopolysaccharide (LPS) and neonatal hyperoxia exposure. On embryonic day 16, dams were placed on DHA (6.3 g DHA/kg diet) or control diets and injected with saline or LPS. Diets were maintained through weaning. At birth, pups were placed in room air or hyperoxia for 14 d. Improvements in birth weight (P < 0.01), alveolarization (P ≤ 0.01), and pulmonary function (P ≤ 0.03) at 2 and 8 wk of age were observed in pups exposed to perinatal inflammation and born to DHA-supplemented dams compared with control diet–exposed pups. These improvements were associated with decreases in tissue macrophage numbers (P < 0.01), monocyte chemoattractant protein-1 expression (P ≤ 0.05), and decreases in soluble receptor for advanced glycation end products concentrations (P < 0.01) at 2 and 8 wk. Furthermore, DHA supplementation attenuated pulmonary fibrosis, which was associated with the reduction of matrix metalloproteinases 2, 3, and 8 (P ≤ 0.03) and collagen mRNA (P ≤ 0.05), and decreased collagen (P < 0.01) and vimentin (P ≤ 0.03) protein concentrations. In a model of severe inflammation, maternal DHA supplementation lessened inflammation and improved lung growth in the offspring. Maternal supplementation with DHA may be a therapeutic strategy to reduce neonatal inflammation. PMID:24453131

MicroRNA-138 and MicroRNA-25 Down-regulate Mitochondrial Calcium Uniporter, Causing the Pulmonary Arterial Hypertension Cancer Phenotype

PubMed Central

Hong, Zhigang; Chen, Kuang-Hueih; DasGupta, Asish; Potus, Francois; Dunham-Snary, Kimberly; Bonnet, Sebastien; Tian, Lian; Fu, Jennifer; Breuils-Bonnet, Sandra; Provencher, Steeve; Wu, Danchen; Mewburn, Jeffrey; Ormiston, Mark L.

2017-01-01

Rationale: Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy characterized by excessive pulmonary artery smooth muscle cell (PASMC) proliferation, migration, and apoptosis resistance. This cancer-like phenotype is promoted by increased cytosolic calcium ([Ca2+]cyto), aerobic glycolysis, and mitochondrial fission. Objectives: To determine how changes in mitochondrial calcium uniporter (MCU) complex (MCUC) function influence mitochondrial dynamics and contribute to PAH’s cancer-like phenotype. Methods: PASMCs were isolated from patients with PAH and healthy control subjects and assessed for expression of MCUC subunits. Manipulation of the pore-forming subunit, MCU, in PASMCs was achieved through small interfering RNA knockdown or MCU plasmid-mediated up-regulation, as well as through modulation of the upstream microRNAs (miRs) miR-138 and miR-25. In vivo, nebulized anti-miRs were administered to rats with monocrotaline-induced PAH. Measurements and Main Results: Impaired MCUC function, resulting from down-regulation of MCU and up-regulation of an inhibitory subunit, mitochondrial calcium uptake protein 1, is central to PAH’s pathogenesis. MCUC dysfunction decreases intramitochondrial calcium ([Ca2+]mito), inhibiting pyruvate dehydrogenase activity and glucose oxidation, while increasing [Ca2+]cyto, promoting proliferation, migration, and fission. In PAH PASMCs, increasing MCU decreases cell migration, proliferation, and apoptosis resistance by lowering [Ca2+]cyto, raising [Ca2+]mito, and inhibiting fission. In normal PASMCs, MCUC inhibition recapitulates the PAH phenotype. In PAH, elevated miRs (notably miR-138) down-regulate MCU directly and also by decreasing MCU’s transcriptional regulator cAMP response element–binding protein 1. Nebulized anti-miRs against miR-25 and miR-138 restore MCU expression, reduce cell proliferation, and regress established PAH in the monocrotaline model. Conclusions: These results highlight miR-mediated MCUC dysfunction as a unifying mechanism in PAH that can be therapeutically targeted. PMID:27648837

Downregulation of insulin-like growth factor binding protein 3 and 5 in nitrofen-induced pulmonary hypoplasia.

PubMed

Ruttenstock, Elke; Doi, Takashi; Dingemann, Jens; Puri, Prem

2010-01-01

The high mortality in congenital diaphragmatic hernia (CDH) is mainly attributed to pulmonary hypoplasia. Recent studies suggest that retinoid signaling pathway (RSP) is inhibited in the nitrofen-induced hypoplastic lung. The insulin-like growth factor (IGF) system plays a crucial role in fetal lung development by interaction of IGFBP-3 and IGFBP-5 with RSP. We hypothesized that pulmonary IGFBP-3 and IGFBP-5 gene expression levels are downregulated in the nitrofen-induced pulmonary hypoplasia. Pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9.5 (D9.5) of gestation. Fetal lungs were harvested on D18 and D21 and divided into control and nitrofen groups. IGFBP-3 and IGFBP-5 pulmonary gene and protein expression were determined using real-time RT-PCR and immunohistochemistry. Relative levels of IGFBP-3 mRNA were significantly decreased in the nitrofen group (8.00 +/- 14.44) in D21 compared to controls (14.81 +/- 16.11; p < 0.05). Expression levels of IGFBP-5 mRNA were also significantly decreased in nitrofen group (10.66 +/- 4.83) on D18 compared to controls (17.92 +/- 4.77). Immunohistochemistry showed decreased IGFBP-3 expression on D21 and decreased IGFBP-5 immunoreactivity on D18 in hypoplastic lungs compared to controls. Downregulation of IGFBP-3 and IGFBP-5 gene expression may cause pulmonary hypoplasia in the nitrofen-induced CDH model by interfering with retinoid signaling pathway.

Kif7 expression is decreased in the diaphragmatic and pulmonary mesenchyme of nitrofen-induced congenital diaphragmatic hernia.

PubMed

Takahashi, Toshiaki; Friedmacher, Florian; Takahashi, Hiromizu; Hofmann, Alejandro Daniel; Puri, Prem

2015-06-01

Developmental mutations that inhibit diaphragmatic and pulmonary mesenchyme formation have been shown to cause congenital diaphragmatic hernia (CDH) and pulmonary hypoplasia (PH). Kinesin family member 7 (Kif7) plays a crucial role in diaphragmatic and pulmonary morphogenesis by controlling proliferation of mesenchymal cells. Loss of Kif7 has been reported to result in diaphragmatic defects and PH. We hypothesized that diaphragmatic and pulmonary Kif7 expression is decreased in the nitrofen-induced CDH model. Timed-pregnant rats were exposed to either nitrofen or vehicle on gestational day 9 (D9). Fetal diaphragms and lungs were microdissected on D13, D15, and D18, and divided into control and nitrofen-exposed specimens. Gene expression levels of Kif7 were analyzed by qPCR. Immunohistochemical staining was performed to evaluate Kif7 protein expression. Relative mRNA expression of Kif7 was significantly reduced in pleuroperitoneal folds (D13), developing diaphragms and lungs (D15), and fully muscularized diaphragms and differentiated lungs (D18) of nitrofen-exposed fetuses compared to controls. Immunoreactivity/immunofluorescence of Kif7 was markedly decreased in diaphragmatic and pulmonary mesenchyme of nitrofen-exposed fetuses on D13, D15, and D18 compared to controls. Decreased Kif7 expression during diaphragmatic development may interfere with mesenchymal cell proliferation, leading to defective pleuroperitoneal folds, and resulting in diaphragmatic defects and associated PH in the nitrofen-induced CDH model. Copyright © 2015 Elsevier Inc. All rights reserved.

Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

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

Malur, Anagha; Huizar, Isham; Wells, Greg

2011-11-18

Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO)more » mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by analysis of bronchoalveolar lavage fluid. Lung compliance was diminished in untreated GMCSF KO mice but improved significantly after lenti-ABCG1 treatment. Data demonstrate that in vivo instillation of lenti-ABCG1 in GM-CSF KO mice is sufficient to restore pulmonary homeostasis by: (1) upregulating ABCG1; (2) reducing intra and extracellular lipids; and (3) improving lung function. Results suggest that the ABCG1 lipid transporter is the key downstream target of GM-CSF-induced PPAR{gamma} necessary for surfactant catabolism.« less

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.

[Experts consensus on the management of the right heart function in critically ill patients].

PubMed

Wang, X T; Liu, D W; Zhang, H M; Long, Y; Guan, X D; Qiu, H B; Yu, K J; Yan, J; Zhao, H; Tang, Y Q; Ding, X; Ma, X C; Du, W; Kang, Y; Tang, B; Ai, Y H; He, H W; Chen, D C; Chen, H; Chai, W Z; Zhou, X; Cui, N; Wang, H; Rui, X; Hu, Z J; Li, J G; Xu, Y; Yang, Y; Ouyan, B; Lin, H Y; Li, Y M; Wan, X Y; Yang, R L; Qin, Y Z; Chao, Y G; Xie, Z Y; Sun, R H; He, Z Y; Wang, D F; Huang, Q Q; Jiang, D P; Cao, X Y; Yu, R G; Wang, X; Chen, X K; Wu, J F; Zhang, L N; Yin, M G; Liu, L X; Li, S W; Chen, Z J; Luo, Z

2017-12-01

To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of critical care-related pulmonary hypertension should be a priority. (11) Attention should be paid to the change of right heart function before and after implementation of mechanical ventilation and adjustment of ventilator parameter. (12) The pulmonary arterial pressure should be monitored timingly when dealing with critical care-related pulmonary hypertension accompanied with circulatory failure.(13) The elevation of pulmonary aterial pressure should be taken into account in critical patients with acute right heart dysfunction. (14) Prone position ventilation is an important measure to reduce pulmonary vascular resistance when treating acute respiratory distress syndrome patients accompanied with acute cor pulmonale. (15) Attention should be paid to right ventricle-pulmonary artery coupling during the management of right heart function. (16) Right ventricular diastolic function is more prone to be affected in critically ill patients, the application of critical ultrasound is more conducive to quantitative assessment of right ventricular diastolic function. (17) As one of the parameters to assess the filling pressure of right heart, central venous pressure can be used to assess right heart diastolic function. (18). The early and prominent manifestation of non-focal cardiac tamponade is right ventricular diastolic involvement, the elevated right atrial pressure should be noticed. (19) The effect of increased intrathoracic pressure on right heart diastolic function should be valued. (20) Ttricuspid annular plane systolic excursion (TAPSE) is an important parameter that reflects right ventricular systolic function, and it is recommended as a general indicator of critically ill patient. (21) Circulation management with right heart protection as the core strategy is the key point of the treatment of acute respiratory distress syndrome. (22) Right heart function involvement after cardiac surgery is very common and should be highly valued. (23) Right ventricular dysfunction should not be considered as a routine excuse for maintaining higher central venous pressure. (24) When left ventricular dilation, attention should be paid to the effect of left ventricle on right ventricular diastolic function. (25) The impact of left ventricular function should be excluded when the contractility of the right ventricle is decreased. (26) When the right heart load increases acutely, the shunt between the left and right heart should be monitored. (27) Attention should be paid to the increase of central venous pressure caused by right ventricular dysfunction and its influence on microcirculation blood flow. (28) When the vasoactive drugs was used to reduce the pressure of pulmonary circulation, different effects on pulmonary and systemic circulation should be evaluated. (29) Right atrial pressure is an important factor affecting venous return. Attention should be paid to the influence of the pressure composition of the right atrium on the venous return. (30) Attention should be paid to the role of the right ventricle in the acute pulmonary edema. (31) Monitoring the difference between the mean systemic filling pressure and the right atrial pressure is helpful to determine whether the infusion increases the venous return. (32) Venous return resistance is often considered to be a insignificant factor that affects venous return, but attention should be paid to the effect of the specific pathophysiological status, such as intrathoracic hypertension, intra-abdominal hypertension and so on. Consensus can promote right heart function management in critically ill patients, optimize hemodynamic therapy, and even affect prognosis.

Iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.

PubMed

Kawashima, Masahiro; Nakamura, Takayuki; Schneider, Sven; Vollmar, Brigitte; Lausberg, Henning F; Bauer, Michael; Menger, Michael D; Schäfers, Hans-Joachim

2003-07-01

Ischemia-reperfusion (I/R) injury of the lung involves increased pulmonary vascular resistance. Prostaglandins are thought to have a beneficial effect in lung transplantation, but their mechanism in I/R injury is unknown. We investigated whether iloprost, a stable prostacyclin analogue, prevents I/R-associated pulmonary vascular dysfunction and whether it affects endothelin-1 (ET-1) balance. In an isolated blood-perfusion model, we subjected lungs of Lewis rats to 45 minutes of ischemia at 37 degrees C and randomly allocated the lungs to 3 groups (n = 6 each): iloprost (33.3 nmol/liter) added to the perfusate before ischemia and reperfusion (ILO+IR), iloprost (33.3 nmol/liter) given only before reperfusion (ILO+R), and controls without iloprost treatment (ILO-). Reperfusion induced marked pulmonary edema in non-treated controls (ILO-), which was attenuated in ILO+R lungs and completely prevented in ILO+IR lungs. At 60 minutes reperfusion, arterial oxygen tension was significantly greater in both ILO+R and ILO+IR lungs compared with ILO- controls. Mean pulmonary artery pressure and pulmonary vascular resistance were slightly decreased in the ILO+R and significantly decreased in the ILO+IR group compared with the ILO- controls. Plasma levels of big ET-1, measured in both afferent and efferent blood, showed that I/R results in increased pulmonary venous levels of big ET-1. Interestingly, the increased venoarterial ET-1 gradient in ILO- lungs decreased significantly in the ILO+IR group. We demonstrated in an isolated lung perfusion model that iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.

Lung remodeling in a porcine model of cyanotic congenital heart defect with decreased pulmonary blood flow.

PubMed

Xu, Yaoqiang; Liu, Yinglong; Li, Zhiqiang; Su, Junwu; Li, Gang; Sun, Lizhong

2012-09-01

Hypoperfusion of the pulmonary vascular bed under the condition of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the mechanistic understanding of this disease, we examined the biochemical and morphological changes of the lung in a relevant animal model and provided valuable insights into the underlying mechanisms of the pathogenesis of pulmonary hypotension. A model of congenital heart defect with decreased pulmonary blood flow was implemented into 8 piglets (the cyanosis group). Another 8 piglets underwent a sham operation (the control group). Two months postoperatively, lung biopsy specimens were harvested for the measurement of the expression levels of MMP-2, MMP-9, TIMP-1, VEGF, and type I and type III collagens. Moreover, the light-microscopic morphology, morphometry, and ultrastructure of lobes were examined. Compared to the controls, the histopathological changes of the pulmonary vasculature in the cyanosis group showed evident hypoplasia and degeneration. The expression levels of MMP-2, MMP-9, TIMP-1, VEGF, and type I collagen, as well as the microvessel density, in the cyanosis group were significantly lower than those in the control group, whereas the level of type III collagen in the cyanosis group was significantly higher than that in the control group. The observed morphological changes may represent an adaptive reaction to the prolonged decrease of pulmonary blood flow. The underlying mechanism of lung remodeling may be attributed to the changes in the expression of structural proteins and cytokines in the pulmonary extracellular matrix induced by modulating factors.

The reservoir-wave approach to characterize pulmonary vascular-right ventricular interactions in humans.

PubMed

Ghimire, Anukul; Andersen, Mads J; Burrowes, Lindsay M; Bouwmeester, J Christopher; Grant, Andrew D; Belenkie, Israel; Fine, Nowell M; Borlaug, Barry A; Tyberg, John V

2016-12-01

Using the reservoir-wave approach (RWA) we previously characterized pulmonary vasculature mechanics in a normal canine model. We found reflected backward-traveling waves that decrease pressure and increase flow in the proximal pulmonary artery (PA). These waves decrease right ventricular (RV) afterload and facilitate RV ejection. With pathological alterations to the pulmonary vasculature, these waves may change and impact RV performance. Our objective in this study was to characterize PA wave reflection and the alterations in RV performance in cardiac patients, using the RWA. PA pressure, Doppler-flow velocity, and pulmonary arterial wedge pressure were measured in 11 patients with exertional dyspnea. The RWA was employed to analyze PA pressure and flow; wave intensity analysis characterized PA waves. Wave-related pressure was partitioned into two components: pressures due to forward-traveling and to backward-traveling waves. RV performance was assessed by examining the work done in raising reservoir pressure and that associated with the wave components of systolic PA pressure. Wave-related work, the mostly nonrecoverable energy expended by the RV to eject blood, tended to vary directly with mean PA pressure. Where PA pressures were lower, there were pressure-decreasing/flow-increasing backward waves that aided RV ejection. Where PA pressures were higher, there were pressure-increasing/flow-decreasing backward waves that impeded RV ejection. Pressure-increasing/flow-decreasing backward waves were responsible for systolic notches in the Doppler flow velocity profiles in patients with the highest PA pressure. Pulmonary hypertension is characterized by reflected waves that impede RV ejection and an increase in wave-related work. The RWA may facilitate the development of therapeutic strategies. Copyright © 2016 the American Physiological Society.

Work-related symptoms and dose-response relationships for personal exposures and pulmonary function among woodworkers.

PubMed

Mandryk, J; Alwis, K U; Hocking, A D

1999-05-01

Four sawmills, a wood chipping mill, and five joineries in New South Wales, Australia, were studied for the effects of personal exposure to wood dust, endotoxins. (1-->3)-beta-D-glucans, Gram-negative bacteria, and fungi on lung function among woodworkers. Personal inhalable and respirable dust sampling was carried out. The lung function tests of workers were conducted before and after a workshift. The mean percentage cross-shift decrease in lung function was markedly high for woodworkers compared with the controls. Dose-response relationships among personal exposures and percentage cross-shift decrease in lung function and percentage predicted lung function were more pronounced among joinery workers compared with sawmill and chip mill workers. Woodworkers had markedly high prevalence of regular cough, phlegm, and chronic bronchitis compared with controls. Significant associations were found between percentage cross-shift decrease in FVC and regular phlegm and blocked nose among sawmill and chip mill workers. Both joinery workers and sawmill and chip mill workers showed significant relationships between percentage predicted lung function (FVC, FEV1, FEV1/FVC, FEF25-75%) and respiratory symptoms. Wood dust and biohazards associated with wood dust are potential health hazards and should be controlled.

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

Impaired systemic oxygen extraction in treated exercise pulmonary hypertension: a new engine in an old car?

PubMed

Faria-Urbina, Mariana; Oliveira, Rudolf K F; Segrera, Sergio A; Lawler, Laurie; Waxman, Aaron B; Systrom, David M

2018-01-01

Ambrisentan in 22 patients with pulmonary hypertension diagnosed during exercise (ePH) improved pulmonary hemodynamics; however, there was only a trend toward increased maximum oxygen uptake (VO 2 max) secondary to decreased maximum exercise systemic oxygen extraction (Ca-vO 2 ). We speculate that improved pulmonary hemodynamics at maximum exercise "unmasked" a pre-existing skeletal muscle abnormality.

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.

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.

Four SNPs and Systemic Level of FOXP3 in Smokers and Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Chu, Shuyuan; Zhong, Xiaoning; Zhang, Jianquan; Lai, Xiaoying; Xie, Jiajun; Li, Yu

2016-12-01

Forkhead box P3 (FOXP3) is the essential transcription factor for the function of regulatory T-cell (Treg). However, the gene mutation of FOXP3 in patients with chronic obstructive pulmonary disease (COPD) at different stages has not been reported. We aim to investigate four single nucleotide polymorphisms (SNPs) and the mRNA expression of FOXP3 in smokers with normal lung function and smokers with COPD at different stages. FOXP3 mRNA expression and SNPs in FOXP3 were assessed in nonsmokers with normal lung function (N), smokers with normal lung function (S), smokers with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 grade (COPD 1-2), and smokers with COPD in GOLD 3 or 4 grade (COPD 3-4). In peripheral blood sample, FOXP3 mRNA was assessed using real-time quantitative PCR and SNPs were analyzed by TaqMan PCR. FOXP3 mRNA level in peripheral blood sample was decreased when COPD was aggravated. The frequency of FOXP3 rs5902434 genotype del/del and allele del are lower in COPD 1-2 and COPD 3-4 than that in N or S. The rs5902434 genotype del/del and allele del were, respectively, associated with decreased risk of COPD and lung function decline. The rs5902434 genotypic distribution was correlated with FOXP3 mRNA level. In conclusion, both FOXP3 rs5902434 genotypes and alleles were differently distributed in COPD patients and smokers with normal lung function. The distribution of del/del genotype was associated with systemic expression of FOXP3 mRNA. More research is needed to explore the role of FOXP3 gene polymorphism in immunoinflammation of COPD.

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.

Hypopnea consequent to reduced pulmonary blood flow in the dog.

PubMed

Stremel, R W; Whipp, B J; Casaburi, R; Huntsman, D J; Wasserman, K

1979-06-01

The ventilatory responses to diminished pulmonary blood flow (Qc), as a result of partial cardiopulmonary bypass (PCB), were studied in chloralose-urethan-anesthetized dogs. Qc was reduced by diverting vena caval blood through a membrane gas exchanger and returning it to the ascending aorta. PCB flows of 400--1,600 ml/min were utilized for durations of 2--3 min. Decreasing Qc, while maintaining systemic arterial blood gases and perfusion, results in a significant (P less than 0.05) decrease in expiratory ventilation (VE) (15.9%) and alveolar ventilation (VA) (31.0%). The ventilatory decreases demonstrated for this intact group persist after bilateral cervical vagotomy (Vx), carotid body and carotid sinus denervation (Cx), and combined Vx and Cx. The changes in VE and VA were significantly (P less than 0.001) correlated with VCO2 changes, r = 0.80 and r = 0.93, respectively. These ventilatory changes were associated with an overall average decrease in left ventricular PCO2 of 2.1 Torr; this decrease was significant (P less than 0.05) only in the intact and Cx groups. Decreasing pulmonary blood flow results in a decrease in ventilation that may be CO2 related; however, the exact mechanism remains obscure but must have a component that is independent of vagally mediated cardiac and pulmonary afferents and peripheral baroreceptor and chemoreceptor afferents.

Mechanisms of lung aging.

PubMed

Brandenberger, Christina; Mühlfeld, Christian

2017-03-01

Lung aging is associated with structural remodeling, a decline of respiratory function and a higher susceptibility to acute and chronic lung diseases. Individual factors that modulate pulmonary aging include basic genetic configuration, environmental exposure, life-style and biography of systemic diseases. However, the actual aging of the lung takes place in pulmonary resident cells and is closely linked to aging of the immune system (immunosenescence). Therefore, this article reviews the current knowledge about the impact of aging on pulmonary cells and the immune system, without analyzing those factors that may accelerate the aging process in depth. Hallmarks of aging include alterations at molecular, cellular and cell-cell interaction levels. Because of the great variety of cell types in the lung, the consequences of aging display a broad spectrum of phenotypes. For example, aging is associated with more collagen and less elastin production by fibroblasts, thus increasing pulmonary stiffness and lowering compliance. Decreased sympathetic airway innervation may increase the constriction status of airway smooth muscle cells. Aging of resident and systemic immune cells leads to a pro-inflammatory milieu and reduced capacity of fighting infectious diseases. The current review provides an overview of cellular changes occurring with advancing age in general and in several cell types of the lung as well as of the immune system. Thereby, this survey not only aims at providing a better understanding of the mechanisms of pulmonary aging but also to identify gaps in knowledge that warrant further investigations.

PPARδ agonist GW501516 inhibits PDGF-stimulated pulmonary arterial smooth muscle cell function related to pathological vascular remodeling.

PubMed

Liu, Guangjie; Li, Xuan; Li, Yan; Tang, Xin; Xu, Jie; Li, Ran; Hao, Peng; Sun, Yongchang

2013-01-01

Pulmonary arterial hypertension (PAH) is a severe and progressive disease, a key feature of which is pulmonary vascular remodeling. Growth factors, cytokines, and lipid mediators are involved in this remodeling process. Recent reports suggest that the peroxisome proliferator-activated receptors (PPARs) play important roles in the regulation of cell growth and differentiation as well as tissue wounding and repair. In this study, we examined the role of PPAR δ in the regulation of proliferation, migration, collagen synthesis, and chemokine production in human pulmonary arterial smooth muscle cells (HPASMCs). The data showed that PPAR δ was the most abundant isoform in HPASMCs. PPAR δ was upregulated in HPASMCs treated with PDGF, which is the major mediator in pulmonary vascular remodeling. Activation of PPAR δ by GW501516, a specific PPAR δ ligand, significantly inhibited PDGF-induced proliferation in HPASMCs. The inhibitory effect of GW501516 on HPASMCs was associated with decreased expression of cyclin D1, cyclin D3, CDK2, and CDK4 as well as increased expression of the cell cycle inhibitory genes G0S2 and P27(kip1). Pretreatment of HPASMCs with GW501516 significantly inhibited PDGF-induced cell migration and collagen synthesis. GW501516 also significantly attenuated TNF-mediated expression of MCP-1. These results suggest that PPAR δ may be a potential therapeutic target against the progression of vascular remodeling in PAH.

PPARδ Agonist GW501516 Inhibits PDGF-Stimulated Pulmonary Arterial Smooth Muscle Cell Function Related to Pathological Vascular Remodeling

PubMed Central

Liu, Guangjie; Li, Xuan; Li, Yan; Tang, Xin; Xu, Jie; Li, Ran; Hao, Peng; Sun, Yongchang

2013-01-01

Pulmonary arterial hypertension (PAH) is a severe and progressive disease, a key feature of which is pulmonary vascular remodeling. Growth factors, cytokines, and lipid mediators are involved in this remodeling process. Recent reports suggest that the peroxisome proliferator-activated receptors (PPARs) play important roles in the regulation of cell growth and differentiation as well as tissue wounding and repair. In this study, we examined the role of PPARδ in the regulation of proliferation, migration, collagen synthesis, and chemokine production in human pulmonary arterial smooth muscle cells (HPASMCs). The data showed that PPARδ was the most abundant isoform in HPASMCs. PPARδ was upregulated in HPASMCs treated with PDGF, which is the major mediator in pulmonary vascular remodeling. Activation of PPARδ by GW501516, a specific PPARδ ligand, significantly inhibited PDGF-induced proliferation in HPASMCs. The inhibitory effect of GW501516 on HPASMCs was associated with decreased expression of cyclin D1, cyclin D3, CDK2, and CDK4 as well as increased expression of the cell cycle inhibitory genes G0S2 and P27kip1. Pretreatment of HPASMCs with GW501516 significantly inhibited PDGF-induced cell migration and collagen synthesis. GW501516 also significantly attenuated TNF-mediated expression of MCP-1. These results suggest that PPARδ may be a potential therapeutic target against the progression of vascular remodeling in PAH. PMID:23607100

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.

Functional mechanism of lung mosaic CT attenuation: assessment with deep-inspiration breath-hold perfusion SPECT-CT fusion imaging and non-breath-hold Technegas SPECT.

PubMed

Suga, K; Yasuhiko, K; Iwanaga, H; Tokuda, O; Matsunaga, N

2009-01-01

The functional mechanism of lung mosaic computed tomography attenuation (MCA) in pulmonary vascular disease (PVD) and obstructive airway disease (OAD) has not yet been fully clarified. To clarify the mechanism of MCA in these diseases by assessing the relationship between regional lung function and CT attenuation change at MCA sites with the use of automated deep-inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images and non-breath-hold Technegas SPECT. Subjects were 42 PVD patients (31 pulmonary thromboembolism, four primary/two secondary pulmonary hypertension, and five Takayasu arteritis), 12 OAD patients (five acute asthma, four obliterative bronchiolitis, and three bronchiectasis), and 12 normal controls, all of whom had MCA on DIBrH CT. The relationship between regional lung function and CT attenuation change at the lung slices with MCA was assessed using DIBrH perfusion SPECT-CT fusion images and non-breath-hold Technegas SPECT. The severity of perfusion defects with or without MCA was quantified by regions-of-interest analysis. On DIBrH CT and perfusion SPECT, in contrast to no noticeable CT attenuation abnormality and fairly uniform perfusion in controls, 60 MCA and 274 perfusion defects in PVD patients, and 18 MCA and 61 defects in OAD patients were identified, with a total of 77 ventilation defects on Technegas SPECT in all patients. SPECT-CT correlation showed that, throughout the 78 MCA sites of all patients, lung perfusion was persistently decreased at low CT attenuation and preserved at intervening high CT attenuation, while lung ventilation was poorly correlated with CT attenuation change. The radioactivity ratios of reduced perfusion and the intervening preserved perfusion at the 78 perfusion defects with MCA were significantly lower than those at the remaining 257 defects without MCA (P<0.0001). Although further validation is required, our results indicate that heterogeneous pulmonary arterial perfusion may be a dominant mechanism of MCA in PVD and OAD.

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.

[Pulmonary function of children with acute leukemia in maintenance phase of chemotherapy].

PubMed

de Macêdo, Thalita Medeiros Fernandes; Campos, Tania Fernandes; Mendes, Raquel Emanuele de França; França, Danielle Corrêa; Chaves, Gabriela Suéllen da Silva; de Mendonça, Karla Morganna Pereira Pinto

2014-12-01

The aim of this study was to assess the pulmonary function of children with acute leukemia. Cross-sectional observational analytical study that enrolled 34 children divided into groups A (17 with acute leukemia in the maintenance phase of chemotherapy) and B (17 healthy children). The groups were matched for sex, age and height. Spirometry was measured using a spirometer Microloop Viasys(®) in accordance with American Thoracic Society and European Respiratory Society guidelines. Maximal respiratory pressures were measured with an MVD300 digital manometer (Globalmed(®)). Maximal inspiratory pressures and maximal expiratory pressures were measured from residual volume and total lung capacity, respectively. Group A showed a significant decrease in maximal inspiratory pressures when compared to group B. No significant difference was found between the spirometric values of the two groups, nor was there any difference between maximal inspiratory pressure and maximal expiratory pressure values in group A compared to the lower limit values proposed as reference. Children with acute leukemia, myeloid or lymphoid, during the maintenance phase of chemotherapy exhibited unchanged spirometric variables and maximal expiratory pressure; However, there was a decrease in inspiratory muscle strength. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Exercise-Induced Pulmonary Hypertension: Translating Pathophysiological Concepts Into Clinical Practice.

PubMed

Naeije, Robert; Saggar, Rajeev; Badesch, David; Rajagopalan, Sanjay; Gargani, Luna; Rischard, Franz; Ferrara, Francesco; Marra, Alberto M; D' Alto, Michele; Bull, Todd M; Saggar, Rajan; Grünig, Ekkehard; Bossone, Eduardo

2018-01-31

Exercise stress testing of the pulmonary circulation for the diagnosis of latent or early-stage pulmonary hypertension (PH) is gaining acceptance. There is emerging consensus to define exercise-induced PH by a mean pulmonary artery pressure > 30 mm Hg at a cardiac output < 10 L/min and a total pulmonary vascular resistance> 3 Wood units at maximum exercise, in the absence of PH at rest. Exercise-induced PH has been reported in association with a bone morphogenetic receptor-2 gene mutation, in systemic sclerosis, in left heart conditions, in chronic lung diseases, and in chronic pulmonary thromboembolism. Exercise-induced PH is a cause of decreased exercise capacity, may precede the development of manifest PH in a proportion of patients, and is associated with a decreased life expectancy. Exercise stress testing of the pulmonary circulation has to be dynamic and rely on measurements of the components of the pulmonary vascular equation during, not after exercise. Noninvasive imaging measurements may be sufficiently accurate in experienced hands, but suffer from lack of precision, so that invasive measurements are required for individual decision-making. Exercise-induced PH is caused either by pulmonary vasoconstriction, pulmonary vascular remodeling, or by increased upstream transmission of pulmonary venous pressure. This differential diagnosis is clinical. Left heart disease as a cause of exercise-induced PH can be further ascertained by a pulmonary artery wedge pressure above or below 20 mm Hg at a cardiac output < 10 L/min or a pulmonary artery wedge pressure-flow relationship above or below 2 mm Hg/L/min during exercise. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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.

Long-term outcomes of anterior spinal fusion for treating thoracic adolescent idiopathic scoliosis curves: average 15-year follow-up analysis.

PubMed

Sudo, Hideki; Ito, Manabu; Kaneda, Kiyoshi; Shono, Yasuhiro; Takahata, Masahiko; Abumi, Kuniyoshi

2013-05-01

Retrospective review. To assess the long-term outcomes of anterior spinal fusion (ASF) for treating thoracic adolescent idiopathic scoliosis (AIS). Although ASF is reported to provide good coronal and sagittal correction of the main thoracic (MT) AIS curves, the long-term outcomes of ASF is unknown. A consecutive series of 25 patients with Lenke 1 MT AIS were included. Outcome measures comprised radiographical measurements, pulmonary function, and Scoliosis Research Society outcome instrument (SRS-30) scores (preoperative SRS-30 scores were not documented). Postoperative surgical revisions and complications were recorded. Twenty-five patients were followed-up for 12 to 18 years (average, 15.2 yr). The average MT Cobb angle correction rate and the correction loss at the final follow-up were 56.7% and 9.2°, respectively. The average preoperative instrumented level of kyphosis was 8.3°, which significantly improved to 18.6° (P = 0.0003) at the final follow-up. The average percent-predicted forced vital capacity and forced expiratory volume in 1 second were significantly decreased during long-term follow-up measurements (73% and 69%; P = 0.0004 and 0.0016, respectively). However, no patient had complaints related to pulmonary function. The average total SRS-30 score was 4.0. Implant breakage was not observed. All patients, except 1 who required revision surgery, demonstrated solid fusion. Late instrumentation-related bronchial problems were observed in 1 patient who required implant removal and bronchial tube repair, 13 years after the initial surgery. Overall radiographical findings and patient outcome measures of ASF for Lenke 1 MT AIS were satisfactory at an average follow-up of 15 years. ASF provides significant sagittal correction of the main thoracic curve with long-term maintenance of sagittal profiles. Percent-predicted values of forced vital capacity and forced expiratory volume in 1 second were decreased in this cohort; however, no patient had complaints related to pulmonary function.

A Prospective, Cross-Sectional Survey Study of the Natural History of Niemann-Pick B Disease

PubMed Central

McGovern, Margaret M.; Wasserstein, Melissa P.; Giugliani, Roberto; Bembi, Bruno; Vanier, Marie; Mengel, Eugen; Brodie, Scott E.; Mendelson, David; Skloot, Gwen; Desnick, Robert J.; Kuriyama, Noriko; Cox, Gerald F.

2009-01-01

Objective The objective of this study was to characterize the clinical features of patients with Niemann-Pick disease Type B and to identify efficacy endpoints for future clinical trials of enzyme replacement therapy. Patients and Methods Fifty-nine patients who had Niemann-Pick disease Type B, were at least 6 years of age, and manifested at least 2 disease symptoms participated in this multicenter, multinational, cross-sectional survey study. Medical histories; physical examinations; and assessments of cardiorespiratory function, clinical laboratory data, and liver and spleen volumes; radiographic evaluation of the lungs and bone age; and quality-of-life were obtained during a 2 to 3 day period. Results Fifty-three percent of the patients were male, 92% white, and the median age was 17.6 years. The R508del mutation accounted for 25% of all disease alleles. Most patients initially presented with splenomegaly (78%) or hepatomegaly (73%). Frequent symptoms included bleeding (49%), pulmonary infections and shortness of breath (42% each), and joint/limb pain (39%). Growth was markedly delayed during adolescence. Patients commonly had low levels of platelets and high-density lipoprotein, elevated levels of LDL, VLDL, triglycerides, leukocyte sphingomyelin, and serum chitotriosidase, and abnormal liver function tests. Nearly all patients had documented splenomegaly and hepatomegaly and interstitial lung disease. Patients commonly showed restrictive lung disease physiology with impaired pulmonary gas exchange and decreased maximal exercise tolerance. Quality of life was only mildly decreased by standardized questionnaires. The degree of splenomegaly correlated with most aspects of disease, including hepatomegaly, growth, lipid profile, hematologic parameters, and pulmonary function. Conclusions This study documents the multisystem involvement and clinical variability of Niemann-Pick B disease. Several efficacy endpoints were identified for future clinical treatment studies. Because of its correlation with disease severity, spleen volume may be a useful surrogate endpoint in treatment trials, whereas biomarkers such as chitotriosidase also may play a role in monitoring treatment responses. PMID:18625664

Effect of Asian dust on pulmonary function in adult asthma patients in western Japan: A panel study.

PubMed

Watanabe, Masanari; Noma, Hisashi; Kurai, Jun; Sano, Hiroyuki; Mikami, Masaaki; Yamamoto, Hiroyuki; Ueda, Yasuto; Touge, Hirokazu; Fujii, Yoshihiro; Ikeda, Toshikazu; Tokuyasu, Hirokazu; Konishi, Tatsuya; Yamasaki, Akira; Igishi, Tadashi; Shimizu, Eiji

2016-04-01

Asian dust (AD) has become a major health concern. The concentration of AD is typically expressed in particulate matter less than 10 μm (PM10) and 2.5 μm (PM2.5). However, PM10 and PM2.5 consist of various substances besides AD. Light detection and ranging (LIDAR) systems can selectively measure the quantity of AD particles to distinguish non-spherical airborne particles from spherical airborne particles. The objective of this study was to investigate the relationship between pulmonary function in adult asthma patients and AD using LIDAR data. Subjects were 231 adult asthma patients who had their morning peak expiratory flow (PEF) measured from March to May 2012. A linear mixed model was used to estimate the association of PEF with sand dust particles detected by LIDAR. Increases in the interquartile range of AD particles (0.018 km(-1)) led to changes in PEF of -0.42 L/min (95% confidence interval [CI], -0.85 to 0.01). An increase of 11.8 μg/m(3) in suspended particulate matter and 6.9 μg/m(3) in PM2.5 led to decreases of -0.17 L/min (-0.53 to 0.21) and 0.03 L/min (-0.35 to 0.42), respectively. A heavy AD day was defined as a day with a level of AD particles >0.032 km(-1), which was the average plus one standard deviation during the study period, and six heavy AD days were identified. Change in PEF after a heavy AD day was -0.97 L/min (-1.90 to -0.04). Heavy exposure to AD particles was significantly associated with decreased pulmonary function in adult asthma patients. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

[The prevention and therapeutics effect of sodium bicarbonate with gastric lavage, atomization inhalation and intravenous injection on the patients with paraquat poisoning and pulmonary fibrosis induced by paraquat poisoning].

PubMed

Ren, Ainong; Ren, Siqing; Jian, Xiangdong; Zhang, Qing

2015-09-01

To observe the prevention effects of patients with lung exudation and pulmonary fibrosis induced by paraquat poisoning in sodium bicarbonate (SB) with gastric lavage, atomization inhalation and intravenous injection. To collect 38 patients with paraquat poisoning in hospital, after poison immediately with gastric lavage of 1.5% SB, and atomization inhalation of 5% SB 10~15 ml twice daily and intravenous injection of 5% SB twice a day, continuous application of 5~7 days. and the HRCT score and liver and kidney function was performed on patients with lung after treatment. And the extraction of 38 SB patients with previously untreated with SB for comparison. Lung HRCT average score in 72 h, 7 d, 30 d on patients with paraquat poisoning untreated with SB reached 2.87, 3.12, 2.13, HRCT display shows that the appearance of the wear glass shadow, grid shadow, honeycomb shadow, and other signs of fibrosis. Average HRCT reached 1.95, 2.20, 1.67 on patients treated with SB,signs of lung exudation and fibrosis was significantly reduced,compare two groups,there was statistically significance (P<0.01). And compared to the control group, activity of serum alanine aminotransferase (ALT) and aspartic acid transaminase (AST) decreased significantly in group of paraquat poisoning with triple application of SB, the level of serum urea nitrogen (BUN) and creatinine (Cr) significantly decreased, the difference is statistically significant (P<0.01). The triple application of SB can reduced the pulmonary fibrosis and effusion induced by paraquat poisoning,and protective effect on the function of liver and kidney is obvious, suggesting that the method for treatment of paraquat poisoning, prevention of paraquat lung and improve survival rate has the exact effect.

Simulations of Congenital Septal Defect Closure and Reactivity Testing in Patient-Specific Models of the Pediatric Pulmonary Vasculature: A 3D Numerical Study With Fluid-Structure Interaction

PubMed Central

Hunter, Kendall S.; Lanning, Craig J.; Chen, Shiuh-Yung J.; Zhang, Yanhang; Garg, Ruchira; Ivy, D. Dunbar; Shandas, Robin

2014-01-01

Clinical imaging methods are highly effective in the diagnosis of vascular pathologies, but they do not currently provide enough detail to shed light on the cause or progression of such diseases, and would be hard pressed to foresee the outcome of surgical interventions. Greater detail of and prediction capabilities for vascular hemodynamics and arterial mechanics are obtained here through the coupling of clinical imaging methods with computational techniques. Three-dimensional, patient-specific geometric reconstructions of the pediatric proximal pulmonary vasculature were obtained from x-ray angiogram images and meshed for use with commercial computational software. Two such models from hypertensive patients, one with multiple septal defects, the other who underwent vascular reactivity testing, were each completed with two sets of suitable fluid and structural initial and boundary conditions and used to obtain detailed transient simulations of artery wall motion and hemodynamics in both clinically measured and predicted configurations. The simulation of septal defect closure, in which input flow and proximal vascular stiffness were decreased, exhibited substantial decreases in proximal velocity, wall shear stress (WSS), and pressure in the post-op state. The simulation of vascular reactivity, in which distal vascular resistance and proximal vascular stiffness were decreased, displayed negligible changes in velocity and WSS but a significant drop in proximal pressure in the reactive state. This new patient-specific technique provides much greater detail regarding the function of the pulmonary circuit than can be obtained with current medical imaging methods alone, and holds promise for enabling surgical planning. PMID:16813447

Dual-energy micro-CT imaging of pulmonary airway obstruction: correlation with micro-SPECT

NASA Astrophysics Data System (ADS)

Badea, C. T.; Befera, N.; Clark, D.; Qi, Y.; Johnson, G. A.

2014-03-01

To match recent clinical dual energy (DE) CT studies focusing on the lung, similar developments for DE micro-CT of the rodent lung are required. Our group has been actively engaged in designing pulmonary gating techniques for micro- CT, and has also introduced the first DE micro-CT imaging method of the rodent lung. The aim of this study was to assess the feasibility of DE micro-CT imaging for the evaluation of airway obstruction in mice, and to compare the method with micro single photon emission computed tomography (micro-SPECT) using technetium-99m labeled macroaggregated albumin (99mTc-MAA). The results suggest that the induced pulmonary airway obstruction causes either atelectasis, or air-trapping similar to asthma or chronic bronchitis. Atelectasis could only be detected at early time points in DE micro-CT images, and is associated with a large increase in blood fraction and decrease in air fraction. Air trapping had an opposite effect with larger air fraction and decreased blood fraction shown by DE micro-CT. The decrease in perfusion to the hypoventilated lung (hypoxic vasoconstriction) is also seen in micro-SPECT. The proposed DE micro-CT technique for imaging localized airway obstruction performed well in our evaluation, and provides a higher resolution compared to micro-SPECT. Both DE micro-CT and micro-SPECT provide critical, quantitative lung biomarkers for image-based anatomical and functional information in the small animal. The methods are readily linked to clinical methods allowing direct comparison of preclinical and clinical results.

Superior Vena Cava Stent Migration into the Pulmonary Artery Causing Fatal Pulmonary Infarction

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

Anand, Girija, E-mail: gijanandm@hotmail.com; Lewanski, Conrad R.; Cowman, Steven A.

2011-02-15

Migration of superior vena cava (SVC) stents is a well-recognised complication of their deployment, and numerous strategies exist for their retrieval. To our knowledge, only three cases of migration of an SVC stent to the pulmonary vasculature have previously been reported. None of these patients developed complications that resulted in death. We report a case of SVC stent migration to the pulmonary vasculature with delayed pulmonary artery thrombosis and death from pulmonary infarction. We conclude that early retrieval of migrated stents should be performed to decrease the risk of serious complications.

Changes in right ventricular function assessed by echocardiography in dog models of mild RV pressure overload.

PubMed

Morita, Tomoya; Nakamura, Kensuke; Osuga, Tatsuyuki; Yokoyama, Nozomu; Morishita, Keitaro; Sasaki, Noboru; Ohta, Hiroshi; Takiguchi, Mitsuyoshi

2017-07-01

The assessment of hemodynamic change by echocardiography is clinically useful in patients with pulmonary hypertension. Recently, mild elevation of the mean pulmonary arterial pressure (PAP) has been shown to be associated with increased mortality. However, changes in the echocardiographic indices of right ventricular (RV) function are still unknown. The objective of this study was to validate the relationship between echocardiographic indices of RV function and right heart catheterization variables under a mild RV pressure overload condition. Echocardiography and right heart catheterization were performed in dog models of mild RV pressure overload induced by thromboxane A 2 analog (U46619) (n=7). The mean PAP was mildly increased (19.3±1.1 mm Hg), and the cardiac index was decreased. Most echocardiographic indices of RV function were significantly impaired even under a mild RV pressure overload condition. Multivariate analysis revealed that the RV free wall longitudinal strain (RVLS), standard deviation of the time-to-peak longitudinal strain of RV six segments (RV-SD) by speckle-tracking echocardiography, and Tei index were independent echocardiographic predictors of the mean PAP (free wall RVLS, β=-0.60, P<.001; RV-SD, β=0.40, P=.011), pulmonary vascular resistance (free wall RVLS, β=-0.39, P=.020; RV-SD, β=0.47, P=.0086; Tei index, β=0.34, P=.047), and cardiac index (Tei index, β=-0.65, P<.001). Free wall RVLS, RV-SD, and Tei index are useful for assessing the hemodynamic change under a mild RV pressure overload condition. © 2017, Wiley Periodicals, Inc.

[Effect of the components of the metabolic syndrome on pulmonary function. The unexpected role of high-density lipoprotein cholesterol].

PubMed

Huerta-Ramírez, Saúl; Paniagua-Pérez, Angélica; Castro-Serna, David; Ledesma-Velázquez, Andrés; Rubio-Guerra, Alberto; Vargas-Ayala, Germán

2018-01-01

Metabolic syndrome is a condition that predisposes to cardiovascular disease and diabetes mellitus. In addition, it can have effects over neoplastic pathologies, liver and pulmonary function. Our objective is to analyze the effect of the metabolic syndrome and its components on pulmonary function. 110 subjects from Mexico City were evaluated and anthropometric measurements, glucose determination, triglycerides and high-density lipoprotein (HDL) cholesterol were made. They underwent a simple spirometry. Diagnosis of metabolic syndrome was made following the NCEP-ATPIII criteria. Of 110 individuals, 90 (82%) were women and 20 men (18%); 71 subjects (65%) presented metabolic syndrome. Subjects with central obesity had a forced vital capacity (FVC) lower than subjects without central obesity (2.72 vs. 3.11 liters; p < 0.05). Those with low HDL had better spirometric results than subjects with normal HDL (FEV1 2.36 vs. 1.85 liters; p < 0.05), FVC (2.95 vs. 2.45 liters; p < 0.05) and FEV1/FVC ratio (0.78 vs.74; p < 0.05). Hypertensive subjects presented lower volumes in FEV1 (1.91 vs. 2.38; p < 0.05) and FVC (2.49 vs. 2.99; p < 0.05). There is no difference between the spirometry volumes of patients with metabolic syndrome versus the metabolically healthy subjects. The only factors associated with a decrease in FEV1 and FVC are central obesity and arterial hypertension. An unexpected finding was the negative correlation between HDL levels and lung function. Copyright: © 2018 Permanyer.

Alveolar derecruitment and collapse induration as crucial mechanisms in lung injury and fibrosis.

PubMed

Lutz, Dennis; Gazdhar, Amiq; Lopez-Rodriguez, Elena; Ruppert, Clemens; Mahavadi, Poornima; Günther, Andreas; Klepetko, Walter; Bates, Jason H; Smith, Bradford; Geiser, Thomas; Ochs, Matthias; Knudsen, Lars

2015-02-01

Idiopathic pulmonary fibrosis (IPF) and bleomycin-induced pulmonary fibrosis are associated with surfactant system dysfunction, alveolar collapse (derecruitment), and collapse induration (irreversible collapse). These events play undefined roles in the loss of lung function. The purpose of this study was to quantify how surfactant inactivation, alveolar collapse, and collapse induration lead to degradation of lung function. Design-based stereology and invasive pulmonary function tests were performed 1, 3, 7, and 14 days after intratracheal bleomycin-instillation in rats. The number and size of open alveoli was correlated to mechanical properties. Active surfactant subtypes declined by Day 1, associated with a progressive alveolar derecruitment and a decrease in compliance. Alveolar epithelial damage was more pronounced in closed alveoli compared with ventilated alveoli. Collapse induration occurred on Day 7 and Day 14 as indicated by collapsed alveoli overgrown by a hyperplastic alveolar epithelium. This pathophysiology was also observed for the first time in human IPF lung explants. Before the onset of collapse induration, distal airspaces were easily recruited, and lung elastance could be kept low after recruitment by positive end-expiratory pressure (PEEP). At later time points, the recruitable fraction of the lung was reduced by collapse induration, causing elastance to be elevated at high levels of PEEP. Surfactant inactivation leading to alveolar collapse and subsequent collapse induration might be the primary pathway for the loss of alveoli in this animal model. Loss of alveoli is highly correlated with the degradation of lung function. Our ultrastructural observations suggest that collapse induration is important in human IPF.

[Impaired lung function in patients with moderate chronic obstructive bronchitis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2004-01-01

VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, RV, Raw, Rin, Rex, DLCO-SS, paO2 and paCO2 were determined in 22 patients with moderate chronic obstructive bronchitis (FEV1, 79-50% of the normal value). All the patients were found to have impaired bronchial patency, 90.9% of the patients had lung volume and capacity changes; pulmonary gas exchange dysfunction was present in 72.7%. Bronchial patency impairments were manifested by a decrease in FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, and an increase in Raw, Rin, Rex. Changes in the lung volumes and capacities appeared as higher RV, TGV, TLC, lower VC and FVC. Pulmonary gas exchange dysfunction showed up as a reduction in pO2 and DLCO-SS a reduction and an increase in paCO2. The magnitude of the functional changes observed in most patients was low. Significant and pronounced disorders were seen in one third of the patients.

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.

Implantation of the Medtronic Harmony Transcatheter Pulmonary Valve Improves Right Ventricular Size and Function in an Ovine Model of Postoperative Chronic Pulmonary Insufficiency.

PubMed

Schoonbeek, Rosanne C; Takebayashi, Satoshi; Aoki, Chikashi; Shimaoka, Toru; Harris, Matthew A; Fu, Gregory L; Kim, Timothy S; Dori, Yoav; McGarvey, Jeremy; Litt, Harold; Bouma, Wobbe; Zsido, Gerald; Glatz, Andrew C; Rome, Jonathan J; Gorman, Robert C; Gorman, Joseph H; Gillespie, Matthew J

2016-10-01

Pulmonary insufficiency is the nexus of late morbidity and mortality after transannular patch repair of tetralogy of Fallot. This study aimed to establish the feasibility of implantation of the novel Medtronic Harmony transcatheter pulmonary valve (hTPV) and to assess its effect on pulmonary insufficiency and ventricular function in an ovine model of chronic postoperative pulmonary insufficiency. Thirteen sheep underwent baseline cardiac magnetic resonance imaging, surgical pulmonary valvectomy, and transannular patch repair. One month after transannular patch repair, the hTPV was implanted, followed by serial magnetic resonance imaging and computed tomography imaging at 1, 5, and 8 month(s). hTPV implantation was successful in 11 animals (85%). There were 2 procedural deaths related to ventricular fibrillation. Seven animals survived the entire follow-up protocol, 5 with functioning hTPV devices. Two animals had occlusion of hTPV with aneurysm of main pulmonary artery. A strong decline in pulmonary regurgitant fraction was observed after hTPV implantation (40.5% versus 8.3%; P=0.011). Right ventricular end diastolic volume increased by 49.4% after transannular patch repair (62.3-93.1 mL/m 2 ; P=0.028) but was reversed to baseline values after hTPV implantation (to 65.1 mL/m 2 at 8 months, P=0.045). Both right ventricular ejection fraction and left ventricular ejection fraction were preserved after hTPV implantation. hTPV implantation is feasible, significantly reduces pulmonary regurgitant fraction, facilitates right ventricular volume improvements, and preserves biventricular function in an ovine model of chronic pulmonary insufficiency. This percutaneous strategy could potentially offer an alternative for standard surgical pulmonary valve replacement in dilated right ventricular outflow tracts, permitting lower risk, nonsurgical pulmonary valve replacement in previously prohibitive anatomies. © 2016 American Heart Association, Inc.

Effect of laryngeal anesthesia on pulmonary function testing in normal subjects.

PubMed

Kuna, S T; Woodson, G E; Sant'Ambrogio, G

1988-03-01

Pulmonary function tests (PFT) were performed on 11 normal subjects before and after topical anesthesia of the larynx. The PFT consisted of flow volume loops and body box determinations of functional residual capacity and airway resistance, each performed in triplicate. After the first set of tests, cotton pledgets soaked in 4% lidocaine were held in the pyriform sinuses for 2 min to block the superior laryngeal nerves. In addition, 1.5 ml of 10% cocaine was dropped on the vocal cords via indirect laryngoscopy. PFT were repeated 5 min after anesthesia. Besides routine analysis of the flow volume loops, areas under the inspiratory (Area I) and expiratory (Area E) portions of the loops were calculated by planimetry. Area I, peak inspiratory flow (PIF), as well as forced inspiratory flow at 25, 50, and 75% forced vital capacity (FVC), decreased after anesthesia. Peak expiratory flow decreased after anesthesia, but Area E and forced expiratory flow at 25, 50, and 75% FVC were unchanged. This protocol also was performed in 12 normal subjects with isotonic saline being substituted for the lidocaine and cocaine. In this group, no significant differences were observed when flow volume loop parameters were compared before and after topical application of saline. In 5 spontaneously breathing anesthetized dogs, posterior cricoarytenoid muscle and afferent superior laryngeal nerve activity were recorded before and after laryngeal anesthesia performed with the same procedure used in the human subjects. Laryngeal anesthesia resulted in a substantial decrease or a complete disappearance of afferent SLN activity recorded during unobstructed and obstructed respiration. The data suggest that laryngeal receptors help modulate upper airway patency in man.

Deficiency of Kruppel-like factor KLF4 in mammary tumor cells inhibits tumor growth and pulmonary metastasis and is accompanied by compromised recruitment of myeloid-derived suppressor cells

PubMed Central

Yu, Fang; Shi, Ying; Wang, Junfeng; Li, Juan; Fan, Daping; Ai, Walden

2013-01-01

Increasing evidence indicates that myeloid-derived suppressor cells (MDSCs) negatively regulate immune responses during tumor progression, inflammation and infection. However, the underlying molecular mechanisms of their development and mobilization remain to be fully delineated. Kruppel-like factor KLF4 is a transcription factor that has an oncogenic function in breast cancer development, but its function in tumor microenvironment, a critical component for tumorigenesis, has not been examined. By using a spontaneously metastatic 4T1 breast cancer mouse model and an immunodeficient NOD/SCID mouse model, we demonstrated that KLF4 knockdown delayed tumor development and inhibited pulmonary metastasis, which was accompanied by decreased accumulation of MDSCs in bone marrow, spleens and primary tumors. Mechanistically, we found that KLF4 knockdown resulted in a significant decrease of circulating GM-CSF, an important cytokine for MDSC biology. Consistently, recombinant GM-CSF restored the frequency of MDSCs in purified bone marrow cells incubated with conditioned medium from KLF4 deficient cells. In addition, we identified CXCL5 as a critical mediator to enhance the expression and function of GM-CSF. Reduced CXCL5 expression by KLF4 knockdown in primary tumors and breast cancer cells was correlated with a decreased GM-CSF expression in our mouse models. Finally, we found that CXCL5/CXCR2 axis facilitated MDSC migration and that anti-GM-CSF antibodies neutralized CXCL5-induced accumulation of MDSCs. Taken together, our data suggest that KLF4 modulates maintenance of MDSCs in bone marrow by inducing GM-CSF production via CXCL5 and regulates recruitment of MDSCs into the primary tumors through the CXCL5/CXCR2 axis, both of which contribute to KLF4-mediated mammary tumor development. PMID:23737434

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.

Time Trends in Pulmonary Embolism in the United States: Evidence of Overdiagnosis

PubMed Central

Wiener, Renda Soylemez; Schwartz, Lisa M.; Woloshin, Steven

2011-01-01

Background Computed tomography pulmonary angiography (CTPA) may improve detection of life-threatening pulmonary embolism. But this sensitive test may have a downside: overdiagnosis and overtreatment (finding clinically unimportant emboli and exposing patients to harms from unnecessary treatment). Methods To assess the impact of CTPA on national pulmonary embolism incidence, mortality, and treatment complications, we conducted a time trend analysis using the Nationwide Inpatient Sample and Multiple Cause-of-Death databases. We compared age-adjusted incidence, mortality, and treatment complications (in-hospital gastrointestinal or intracranial hemorrhage or secondary thrombocytopenia) of pulmonary embolism among United States adults before (1993–1998) and after (1998–2006) CTPA was introduced. Results Pulmonary embolism incidence was unchanged before CTPA (p=0.63), but increased substantially after CTPA (81% increase: from 62.1 to 112.3 per 100,000, p<0.001). Pulmonary embolism mortality decreased during both periods: more so before CTPA (8% reduction: from 13.4 to 12.3 per 100,000, p<0.001) than after (3% reduction: from 12.3 to 11.9 per 100,000, p=0.02). Case-fatality improved slightly before (8% decrease, from 13.2% to 12.1%, p=0.02) and substantially after CTPA (36% decrease: from 12.1% to 7.8%, p<0.001). Meanwhile, CTPA was associated with an increase in presumed complications of anticoagulation for pulmonary embolism: pre-CTPA, the complication rate was stable (p=0.24), but post-CTPA it increased by 71% (from 3.1 to 5.3 per 100,000, p<0.001). Conclusions The introduction of CTPA was associated with changes consistent with overdiagnosis: rising incidence, minimal change in mortality, and lower case-fatality. Better technology allows us to diagnose more emboli, but to minimize harms of overdiagnosis we must learn which ones matter. PMID:21555660

Cardiopulmonary protective effects of the selective FXR agonist obeticholic acid in the rat model of monocrotaline-induced pulmonary hypertension.

PubMed

Vignozzi, Linda; Morelli, Annamaria; Cellai, Ilaria; Filippi, Sandra; Comeglio, Paolo; Sarchielli, Erica; Maneschi, Elena; Vannelli, Gabriella Barbara; Adorini, Luciano; Maggi, Mario

2017-01-01

Farnesoid X receptor (FXR) activation by obeticholic acid (OCA) has been demonstrated to inhibit inflammation and fibrosis development and even induce fibrosis regression in liver, kidney and intestine in multiple disease models. OCA also inhibits liver fibrosis in nonalcoholic steatohepatitis patients. FXR activation has also been demonstrated to suppress the inflammatory response and to promote lung repair after lung injury. This study investigated the effects of OCA treatment (3, 10 or 30mg/kg, daily for 5days a week, for 7 and/or 28 days) on inflammation, tissue remodeling and fibrosis in the monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) rat model. Treatment with OCA attenuated MCT-induced increased pulmonary arterial wall thickness and right ventricular hypertrophy, by i) blunting pathogenic inflammatory mechanisms (downregulation of interleukin 6, IL-6, and monocyte chemoattractant protein-1, MCP-1) and ii) enhancing protective mechanisms counteracting fibrosis and endothelial/mesenchymal transition. MCT-injected rats also showed a marked decrease of pulmonary artery responsiveness to both endothelium-dependent and independent relaxant stimuli, such as acetylcholine and a nitric oxide donor, sodium nitroprusside. Administration of OCA (30mg/kg) normalized this decreased responsiveness. Accordingly, OCA treatment induced profound beneficial effects on lung histology. In particular, both OCA doses markedly reduced the MCT-induced medial wall thickness increase in small pulmonary arteries. To evaluate the objective functional improvement by OCA treatment of MCT-induced PAH, we performed a treadmill test and measured duration of exercise. MCT significantly reduced, and OCA normalized treadmill endurance. Results with OCA were similar, or even superior, to those obtained with tadalafil, a well-established treatment of PAH. In conclusion, OCA treatment demonstrates cardiopulmonary protective effects, modulating lung vascular remodeling, reducing right ventricular hypertrophy and significantly improving exercise capacity. Thus, OCA can restore the balance between relaxant and contractile pathways in the lung, promoting cardiopulmonary protective actions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decreased Pulmonary Function in School Children in Western Japan after Exposures to Asian Desert Dusts and Its Association with Interleukin-8

PubMed Central

Watanabe, Masanari; Kurai, Jun; Sano, Hiroyuki; Saito, Rumiko; Kimura, Yutaka; Aiba, Setsuya; Oshimura, Mitsuo; Yamasaki, Akira; Shimizu, Eiji

2015-01-01

The objective of the study was to investigate the influence of Asian dust storms (ADS) on pulmonary function of school children and the relationship of this effect with interleukin-8. Morning peak expiratory flow (PEF) was measured daily in 399 children from April to May 2012 and in 384 of these children from March to May 2013. The data were analyzed for an association between ADS events and PEF by linear mixed models. Interleukin-8 transcriptional activity was assessed in THP-G8 cells stimulated by airborne particles collected on ADS days. Seven ADS days were identified: April 23 and 24, 2012; March 8 to 10, 2013; and March 19 and 20, 2013. Changes in PEF after ADS exposure were −8.17 L/min (95% confidence interval, −11.40 to −4.93) in 2012 and −1.17 L/min (−4.07 to 1.74) in 2013, and there was a significant difference between 2012 and 2013. Interleukin-8 transcriptional activity was significantly higher in 2012 at 10.6 ± 2.9-fold compared to 3.7 ± 0.4 in March 8 to 10, 2013, and 2.3 ± 0.2 in March 19 and 20, 2013. The influence of ADS events on pulmonary function of children differs with each ADS event and may be related to interleukin-8 production. PMID:26060816

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis.

PubMed

Lancaster, Lisa H; de Andrade, Joao A; Zibrak, Joseph D; Padilla, Maria L; Albera, Carlo; Nathan, Steven D; Wijsenbeek, Marlies S; Stauffer, John L; Kirchgaessler, Klaus-Uwe; Costabel, Ulrich

2017-12-31

Pirfenidone is one of two approved therapies for the treatment of idiopathic pulmonary fibrosis (IPF). Randomised controlled clinical trials and subsequent post hoc analyses have demonstrated that pirfenidone reduces lung function decline, decreases mortality and improves progression-free survival. Long-term extension trials, registries and real-world studies have also shown similar treatment effects with pirfenidone. However, for patients with IPF to obtain the maximum benefits of pirfenidone treatment, the potential adverse events (AEs) associated with pirfenidone need to be managed. This review highlights the well-known and established safety profile of pirfenidone based on randomised controlled clinical trials and real-world data. Key strategies for preventing and managing the most common pirfenidone-related AEs are described, with the goal of maximising adherence to pirfenidone with minimal AEs. Copyright ©ERS 2017.

Alterations in chemically induced tissue injury related to all-trans-retinol pretreatment in rodents.

PubMed

Sauer, J M; Hooser, S B; Badger, D A; Baines, A; Sipes, I G

1995-01-01

Retinol (vitamin A) is an essential nutrient which has many physiological effects throughout the body. Our studies have demonstrated that retinol modulation of immune response, through alteration of macrophage and neutrophil function, can have dramatic effects on the toxicity of some compounds. Based on these studies, our current hypothesis for retinol potentiation of chemical-induced liver injury is that retinol administered to rats prior to the hepatotoxicant (CCl4 and AA in rats; and AA, APAP, and GalN in mice) primes the Kupffer cells to a more active state. This may occur in part as a result of increases in chemical mediators such as TNF from these Kupffer cells. Following hepatocyte damage by a toxicant, Kupffer cells are activated to release reactive oxygen species, immune mediators, and chemotactic factors which all serve to enhance the inflammatory response. This increased inflammatory response then results in increased injury to the already toxicant-damaged hepatocytes. In addition, retinol modulation of toxicant activation and detoxification may also make important contributions to the potentiation of some toxicants such as AA. Retinol protection of CCl4 hepatotoxicity in mice is more difficult to explain at this time but is possibly related to alterations in CCl4 metabolism in this species. Differences in response between pulmonary and liver macrophages (Kupffer cells) may explain the retinol protection from 1-NN pulmonary toxicity. Retinol may decrease the inflammatory response through downregulation of pulmonary macrophage function, thus resulting in decreased pulmonary injury. Finally, since retinol protection of cadmium toxicity in the liver and testis requires 7 days of retinol pretreatment, we suspect that retinol is inducing protective protein(s) in these organs. Aside from its normal biological role in rhe body, clinical medicine has found new uses for retinol in the treatment and prevention of some cancers, and in the treatment of certain dermatologic conditions. Since these patients are frequently administered or exposed to other potentially toxic compounds, it is obviously prudent and necessary to continue research into the effects of retinol on immune modulation and interaction with other compounds. More importantly, these studies demonstrate the modulation of immune function is one mechanism by which one chemical can influence the toxicity of another.

The Changes of Pulmonary Function in COPD During Four-Year Period

PubMed Central

Cukic, Vesna; Lovre, Vladimir; Ustamujic, Aida

2013-01-01

Conflict of interest: none declared. Introduction COPD (chronic obstructive pulmonary disease) is characterized by airflow limitation that is not fully reversible. OBJECTIVE: to show the changes of pulmonary function in COPD during the 4 -year evolution of illness. Material and Methods The research was done on patients suffering from COPD treated at the Clinic “Podhrastovi” during 2006 and 2007. The tested parameters were examined from the date of receiving patient with COPD to hospital treatment in 2006 and 2007 and then followed prospectively until 2010 or 2011 (the follow-up period was 4 years). There were total 199 treated patients who were chosen at random and regularly attended the control examinations. The study was conducted on adult patients of both sexes, different age group. In each patient the duration of illness was recorded so is sex, age, data of smoking habits, information about the regularity of taking bronchodilator therapy during remissions of disease, about the treatment of disease exacerbations, results of pulmonary functional tests as follows: FVC (forced vital capacity), FEV1 (forced expiratory volume in one second) and bronchodilator reversibility testing. All these parameters were measured at the beginning and at the end of each hospital treatment on the apparatuses of Clinic “Podhrastovi”. We took in elaboration those data obtained in the beginning of the first hospitalization and at the end of the last hospitalization or at the last control in outpatient department when patient was in stable state. Patients were divided into three groups according to the number of exacerbations per year. Results airflow limitation in COPD is progressive; both FVC and FEV1 shows the statistically significant decrease during follow-up period of 4 years (p values / for both parameters/ =0.05) . But in patients regularly treated in phases of remission and exacerbations of illness the course of illness is slower. The fall of FVC and FEV1 is statistically significantly smaller in those received regular treatment in phases of remissions and exacerbations of illness (p values / for both parameters/ =0.01). The number of patients responding properly to bronchodilators decreased statistically significantly in patients with COPD during follow-up period (p=0.05). Conclusion COPD is characterized with airflow limitation which is progressive in the course of illness, but that course may be made slower using appropriate treatment during remission and exacerbations of diseases. PMID:24082829

Validation of geometric measurements of the left atrium and pulmonary veins for analysis of reverse structural remodeling following ablation therapy

NASA Astrophysics Data System (ADS)

Rettmann, M. E.; Holmes, D. R., III; Gunawan, M. S.; Ge, X.; Karwoski, R. A.; Breen, J. F.; Packer, D. L.; Robb, R. A.

2012-03-01

Geometric analysis of the left atrium and pulmonary veins is important for studying reverse structural remodeling following cardiac ablation therapy. It has been shown that the left atrium decreases in volume and the pulmonary vein ostia decrease in diameter following ablation therapy. Most analysis techniques, however, require laborious manual tracing of image cross-sections. Pulmonary vein diameters are typically measured at the junction between the left atrium and pulmonary veins, called the pulmonary vein ostia, with manually drawn lines on volume renderings or on image cross-sections. In this work, we describe a technique for making semi-automatic measurements of the left atrium and pulmonary vein ostial diameters from high resolution CT scans and multi-phase datasets. The left atrium and pulmonary veins are segmented from a CT volume using a 3D volume approach and cut planes are interactively positioned to separate the pulmonary veins from the body of the left atrium. The cut plane is also used to compute the pulmonary vein ostial diameter. Validation experiments are presented which demonstrate the ability to repeatedly measure left atrial volume and pulmonary vein diameters from high resolution CT scans, as well as the feasibility of this approach for analyzing dynamic, multi-phase datasets. In the high resolution CT scans the left atrial volume measurements show high repeatability with approximately 4% intra-rater repeatability and 8% inter-rater repeatability. Intra- and inter-rater repeatability for pulmonary vein diameter measurements range from approximately 2 to 4 mm. For the multi-phase CT datasets, differences in left atrial volumes between a standard slice-by-slice approach and the proposed 3D volume approach are small, with percent differences on the order of 3% to 6%.

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

Effects of an Antioxidant-enriched Multivitamin in Cystic Fibrosis: Randomized, Controlled, Multicenter Trial.

PubMed

Sagel, Scott D; Khan, Umer; Jain, Raksha; Graff, Gavin; Daines, Cori L; Dunitz, Jordan M; Borowitz, Drucy; Orenstein, David M; Abdulhamid, Ibrahim; Noe, Julie; Clancy, John P; Slovis, Bonnie; Rock, Michael J; McCoy, Karen S; Strausbaugh, Steven; Livingston, Floyd R; Papas, Konstantinos A; Shaffer, Michele L

2018-04-24

Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant-antioxidant imbalance and oxidative stress. Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidative stress, and clinical outcomes. In this investigator-initiated, multicenter, randomized, double-blind, controlled trial, 73 pancreatic insufficient CF subjects 10 years of age and older with an FEV1 between 40-100% predicted were randomized to 16 weeks of an antioxidant-enriched multivitamin or control multivitamin without antioxidant enrichment. Endpoints included systemic antioxidant concentrations, markers of inflammation and oxidative stress, clinical outcomes (pulmonary exacerbations, anthropometric measures, pulmonary function), safety and tolerability. Change in sputum myeloperoxidase concentration over 16 weeks, the primary efficacy endpoint, was not significantly different between the treated and control groups. Systemic antioxidant concentrations (β-carotene, CoQ10, γ-tocopherol, lutein) significantly increased in the antioxidant treated group (p<0.001 for each), while circulating calprotectin and myeloperoxidase decreased in the treated group compared to the control group at week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio=0.50, p=0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01859390.

Effect of oral nitrate supplementation on pulmonary hemodynamics during exercise and time trial performance in normoxia and hypoxia: a randomized controlled trial

PubMed Central

Bourdillon, Nicolas; Fan, Jui-Lin; Uva, Barbara; Müller, Hajo; Meyer, Philippe; Kayser, Bengt

2015-01-01

Background: Hypoxia-induced pulmonary vasoconstriction increases pulmonary arterial pressure (PAP) and may impede right heart function and exercise performance. This study examined the effects of oral nitrate supplementation on right heart function and performance during exercise in normoxia and hypoxia. We tested the hypothesis that nitrate supplementation would attenuate the increase in PAP at rest and during exercise in hypoxia, thereby improving exercise performance. Methods: Twelve trained male cyclists [age: 31 ± 7 year (mean ± SD)] performed 15 km time-trial cycling (TT) and steady-state submaximal cycling (50, 100, and 150 W) in normoxia and hypoxia (11% inspired O2) following 3-day oral supplementation with either placebo or sodium nitrate (0.1 mmol/kg/day). We measured TT time-to-completion, muscle tissue oxygenation during TT and systolic right ventricle to right atrium pressure gradient (RV-RA gradient: index of PAP) during steady state cycling. Results: During steady state exercise, hypoxia elevated RV-RA gradient (p > 0.05), while oral nitrate supplementation did not alter RV-RA gradient (p > 0.05). During 15 km TT, hypoxia lowered muscle tissue oxygenation (p < 0.05). Nitrate supplementation further decreased muscle tissue oxygenation during 15 km TT in hypoxia (p < 0.05). Hypoxia impaired time-to-completion during TT (p < 0.05), while no improvements were observed with nitrate supplementation in normoxia or hypoxia (p > 0.05). Conclusion: Our findings indicate that oral nitrate supplementation does not attenuate acute hypoxic pulmonary vasoconstriction nor improve performance during time trial cycling in normoxia and hypoxia. PMID:26528189

Evidence for local dendritic cell activation in pulmonary sarcoidosis

PubMed Central

2012-01-01

Background Sarcoidosis is a granulomatous disease characterized by a seemingly exaggerated immune response against a difficult to discern antigen. Dendritic cells (DCs) are pivotal antigen presenting cells thought to play an important role in the pathogenesis. Paradoxically, decreased DC immune reactivity was reported in blood samples from pulmonary sarcoidosis patients. However, functional data on lung DCs in sarcoidosis are lacking. We hypothesized that at the site of disease DCs are mature, immunocompetent and involved in granuloma formation. Methods We analyzed myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in broncho-alveolar lavage (BAL) and blood from newly diagnosed, untreated pulmonary sarcoidosis patients and healthy controls using 9-color flowcytometry. DCs, isolated from BAL using flowcytometric sorting (mDCs) or cultured from monocytes (mo-DCs), were functionally assessed in a mixed leukocyte reaction with naïve allogeneic CD4+ T cells. Using Immunohistochemistry, location and activation status of CD11c+DCs was assessed in mucosal airway biopsies. Results mDCs in BAL, but not in blood, from sarcoidosis patients were increased in number when compared with mDCs from healthy controls. mDCs purified from BAL of sarcoidosis patients induced T cell proliferation and differentiation and did not show diminished immune reactivity. Mo-DCs from patients induced increased TNFα release in co-cultures with naïve allogeneic CD4+ T cells. Finally, immunohistochemical analyses revealed increased numbers of mature CD86+ DCs in granuloma-containing airway mucosal biopsies from sarcoidosis patients. Conclusion Taken together, these finding implicate increased local DC activation in granuloma formation or maintenance in pulmonary sarcoidosis. PMID:22513006

A novel swine model of ricin-induced acute respiratory distress syndrome

PubMed Central

Katalan, Shahaf; Falach, Reut; Rosner, Amir; Goldvaser, Michael; Brosh-Nissimov, Tal; Dvir, Ayana; Mizrachi, Avi; Goren, Orr; Cohen, Barak; Gal, Yoav; Sapoznikov, Anita; Ehrlich, Sharon; Kronman, Chanoch

2017-01-01

ABSTRACT Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS) following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS. PMID:28067630

Percutaneous pulmonary valve implantation in patients with dysfunction of a "native" right ventricular outflow tract - Mid-term results.

PubMed

Georgiev, Stanimir; Tanase, Daniel; Ewert, Peter; Meierhofer, Christian; Hager, Alfred; von Ohain, Jelena Pabst; Eicken, Andreas

2018-05-01

To investigate the feasibility and mid-term results of percutaneous pulmonary valve implantation (PPVI) in patients with conduit free or "native" right ventricular outflow tracts (RVOT). We identified all 18 patients with conduit free or "native" right ventricular outflow tract, who were treated with percutaneous pulmonary valve implantation (PPVI) in our institution. They were divided into two groups - these in whom the central pulmonary artery was used as an anchoring point for the preparation of the landing zone (n=10) for PPVI and these, in whom a pulmonary artery branch was used for this purpose (n=8). PPVI was performed successfully in all patients with significant immediate RVOT gradient and pulmonary regurgitation grade reduction. Four patients had insignificant paravalvular regurgitation. In one patient the valve was explanted after 4months because of bacterial endocarditis. A follow-up of 19 (4-60) months showed sustained good function of the other implanted valves. The MRI indexed right ventricular end diastolic volume significantly decreased from 108(54-174) ml/m 2 before the procedure to 76(60-126) ml/m 2 six months after PPVI, p=0.01. PPVI is feasible with good mid-term results in selected patients with a "native" RVOT without a previously implanted conduit. Creating a stable landing zone with a diameter less than the largest available valve (currently 29mm) is crucial for the technical success of the procedure. Further studies and the development of new devices could widen the indications for this novel treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

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 capacity before and after an 8-week multidisciplinary inpatient rehabilitation program in lung cancer patients: a pilot study.

PubMed

Spruit, Martijn A; Janssen, Paul P; Willemsen, Sonja C P; Hochstenbag, Monique M H; Wouters, Emiel F M

2006-05-01

Although lung cancer is a highly prevalent type of cancer, the effects of an inpatient multidisciplinary rehabilitation program on pulmonary function and exercise capacity have never been studied in these patients. Pulmonary function, 6-min walking distance and peak exercise capacity of 10 patients with a severely impaired pulmonary function following treatment of lung cancer were assessed in this pilot study before and after an 8-week inpatient multidisciplinary rehabilitation program. At baseline, patients had a restrictive pulmonary function and an apparent exercise intolerance (median 6-min walking distance: 63.6% predicted; median peak cycling load: 58.5% predicted). Despite the lack of change in median pulmonary function [FEV1: -0.01L, p = 0.5469], functional exercise capacity [145 m; 43.2% of the initial values, p=0.0020] and peak exercise capacity [26 W; 34.4% of the initial values, p = 0.0078] improved significantly compared to baseline. Future trials have to corroborate the present findings. Nevertheless, patients with lung cancer have a clear indication to start a comprehensive rehabilitation program following intensive treatment of their disease. In fact, based on the results of the present pilot study it appears that these patients are good candidates for pulmonary rehabilitation programs.

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.

[Special beds. Pulmonary therapy system].

PubMed

Calixto Rodríguez, Joaquín; Rodríguez Martínez, Xavier; Marín i Vivó, Gemma; Paunellas Albert, Josep

2008-10-01

To be bedridden reduces one's capacity to move and produces muscular debility that affects the respiratory system leading to a decreased effectiveness in expectoration, the ability to spit up sputum. The pulmonary therapy system integrated in a bed is the result of applying motorized elements to the articulation points of the bad in order to achieve safe positions at therapeutic angles, which improve the breathing-perfusion (blood flow) relationship. This system also makes it possible to apply vibration waves to the patient which favor the elimination of bronchial-pulmonary secretions, the rehabilitation of the bedridden patient and decrease the work load for nursing personnel.

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.

[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.

Dust is in the air. Part II: Effects of occupational exposure to welding fumes on lung function in a 9-year study.

PubMed

Haluza, Daniela; Moshammer, Hanns; Hochgatterer, Karl

2014-02-01

Adverse health effects of work-related contact with respirable hazardous substances are of great public interest. Because related prospective and long-term follow-up studies are rare, the extent of acute and chronic pulmonary health risks of occupational exposure to welding fumes is discussed controversially in the scientific literature. The objective of the present longitudinal study during a 9-year period was to investigate the annual changes of lung function in welders. Anthropometric measures and smoking behaviour, and spirometric tests (FVC, FEV1, and MEF50) obtained during routine occupational health checkups of female and male workers (n = 1,982) in Austria during the years 2002-2010 were analyzed. The study participants displayed average lung function values lower than the age- and sex-specific norm. Decrease in respiratory capacity was dependent on smoking habits and duration of occupational exposure. Specifically for welders (n = 1,326), decrease of pulmonary function was significantly associated with heavy smoking (FVC -70.7 ml, p = 0.07; FEV1 -167.4 ml, p < 0.001; MEF50 -356.2 ml/s, p < 0.001), but not with moderate smoking habits, and also with duration of occupational exposure to welding fumes per year (FVC -0.89 ml, p = 0.36; FEV1 -2.91 ml, p < 0.001; MEF50 -4.7 ml/s, p = 0.047). Individual smoking habits as well as duration of occupational exposure to welding fumes showed a negative impact on lung function parameters. To reduce the risk of work-associated respiratory morbidity, smoking cessation is highly recommended to personnel engaged in welding fumes- and dust-exposed occupations.

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.

Adverse ventricular-ventricular interactions in right ventricular pressure load: Insights from pediatric pulmonary hypertension versus pulmonary stenosis.

PubMed

Driessen, Mieke M P; Hui, Wei; Bijnens, Bart H; Dragulescu, Andreea; Mertens, Luc; Meijboom, Folkert J; Friedberg, Mark K

2016-06-01

Right ventricular (RV) pressure overload has a vastly different clinical course in children with idiopathic pulmonary arterial hypertension (iPAH) than in children with pulmonary stenosis (PS). While RV function is well recognized as a key prognostic factor in iPAH, adverse ventricular-ventricular interactions and LV dysfunction are less well characterized and the pathophysiology is incompletely understood. We compared ventricular-ventricular interactions as hypothesized drivers of biventricular dysfunction in pediatric iPAH versus PS Eighteen iPAH, 16 PS patients and 18 age- and size-matched controls were retrospectively studied. Cardiac cycle events were measured by M-mode and Doppler echocardiography. Measurements were compared between groups using ANOVA with post hoc Dunnet's or ANCOVA including RV systolic pressure (RVSP; iPAH 96.8 ± 25.4 mmHg vs. PS 75.4 ± 18.9 mmHg; P = 0.011) as a covariate. RV-free wall thickening was prolonged in iPAH versus PS, extending beyond pulmonary valve closure (638 ± 76 msec vs. 562 ± 76 msec vs. 473 ± 59 msec controls). LV and RV isovolumetric relaxation were prolonged in iPAH (P < 0.001; LV 102.8 ± 24.1 msec vs. 63.1 ± 13.7 msec; RV 95 [61-165] vs. 28 [0-43]), associated with adverse septal kinetics; characterized by rightward displacement in early systole and leftward displacement in late RV systole (i.e., early LV diastole). Early LV diastolic filling was decreased in iPAH (73 ± 15.9 vs. PS 87.4 ± 14.4 vs. controls 95.8 ± 12.5 cm/sec; P = 0.004). Prolonged RVFW thickening, prolonged RVFW isovolumetric times, and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in pediatric iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency in iPAH and may form the basis for worse clinical outcomes. We used clinically derived data to study the pathophysiology of ventricular-ventricular interactions in right ventricular pressure overload, demonstrating distinct differences between pediatric pulmonary arterial hypertension (iPAH) and pulmonary stenosis (PS). Altered timing of right ventricular free wall contraction and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency, independent of right ventricular systolic pressure. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Nitric oxide decreases coagulation protein function in rabbits as assessed by thromboelastography.

PubMed

Nielsen, V G

2001-02-01

Nitric oxide (NO) is administered via infusion of donors such as nitroglycerin or in inhaled form for treatment of ischemia and pulmonary hypertension, respectively. In rabbits, the NO donor, DETANONOate, decreases whole blood clotting function as assessed by thromboelastographic variables (R, reaction time; alpha, angle; and G, a measure of clot strength). I hypothesized that DETANONOate-derived NO would adversely affect coagulation protein and platelet function. Blood obtained from ear arteries of conscious rabbits (n = 8) anticoagulated with sodium citrate. The blood was then incubated with 0 or 10mM DETANONOate for 30 min. After incubation and recalcification, thromboelastography was performed for 60 min under four conditions: 1) 0mM DETANONOate, 2) 0mM DETANONOate with platelet inhibition with cytochalasin D, 3) 10mM DETANONOate, and 4) 10mM DETANONOate with platelet inhibition. DETANONOate significantly (P < 0.05) increased R and decreased alpha and G in samples with or without platelet inhibition, compared with samples not exposed to DETANONOate. Lastly, the percentage of total G (G(T)) attributable to platelet function (G(P)) was significantly more in the absence of DETANONOate (G(P) = 92.3% +/- 1.6%; mean +/- SD) than after exposure to DETANONOate (G(P) = 90.2% +/- 2.3%). DETANONOate-derived NO significantly decreased coagulation protein function and platelet function. Coagulation protein function may be similarly affected in clinical situations involving the administration of NO or NO donors.

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.

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.

Immediate- and medium-term effects of simultaneous percutaneous corrections of secundum type atrial septal defect combined with pulmonary valve stenosis in local anesthesia and without transesophageal echocardiography guidance.

PubMed

Xu, Xu-Dong; Ding, Xue-Yan; Liu, Su-Xuan; Bai, Yuan; Zhao, Xian-Xian; Qin, Yong-Wen

2015-01-01

The feasibility and efficacy of simultaneous percutaneous treatment of secundum type atrial septal defect (ASD) combined with pulmonary valve stenosis (PS) have not been proved. To evaluate the safety and efficacy on the clinical benefit of simultaneous percutaneous correction of these two pathologies under local anesthesia and without transesophageal echocardiography guidance. Transpulmonary gradient, functional status, pulmonary regurgitation (PR), and tricuspid regurgitation (TR) were studied in 35 patients undergoing percutaneous balloon pulmonary valvuloplasty and ASD closure from March 2004 to July 2012. All patients were followed up until January 2013, an average of 39 months. According to color Doppler transthoracic echocardiography (TTE) before the intervention, the ASD defect size and transpulmonary gradient were 17±8.4 mm and 88±37.8 mmHg, respectively. Post-interventionally, the peak-to-peak transpulmonary gradient decreased from 77±37.6 mmHg to 20±16.2 mmHg (p<0.001) and the ASD occluder size was 23±10.5 mm. In all those patients, there was no residual shunt detected, and moderate and severe TR decreased from 45.7% (16/35) and 20% (7/35) to 8.6% (3/35) and 5.7% (2/35) before and after intervention detected by TTE, respectively. Eight patients had mild PR after procedure and two of them recovered at 6 months and no patient encountered severe adverse events at the latest follow-up. Simultaneous percutaneous corrections of ASD combined with PS are feasible, safe, and effective with satisfactory results. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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.

Oxygen With Cold Bubble Humidification Is No Better Than Dry Oxygen in Preventing Mucus Dehydration, Decreased Mucociliary Clearance, and Decline in Pulmonary Function.

PubMed

Franchini, Michelle Lisidati; Athanazio, Rodrigo; Amato-Lourenço, Luis Fernando; Carreirão-Neto, Waldir; Saldiva, Paulo Hilario Nascimento; Lorenzi-Filho, Geraldo; Rubin, Bruce K; Nakagawa, Naomi Kondo

2016-08-01

Little is known about the effects of long-term nasal low-flow oxygen (NLFO) on mucus and symptoms and how this variable is affected by dry or cold humidified gas. The aim of this study was to investigate the effects of dry-NLFO and cold bubble humidified-NLFO on nasal mucociliary clearance (MCC), mucus properties, inflammation, and symptoms in subjects with chronic hypoxemia requiring long-term domiciliary oxygen therapy. Eighteen subjects (mean age, 68 years; 7 male; 66% with COPD) initiating NLFO were randomized to receive dry-NLFO (n = 10) or humidified-NLFO (n = 8). Subjects were assessed at baseline, 12 h, 7 days, 30 days, 12 months, and 24 months by measuring nasal MCC using the saccharin transit test, mucus contact angle (surface tension), inflammation (cells and cytokine concentration in nasal lavage), and symptoms according to the Sino-Nasal Outcome Test-20. Nasal MCC decreased significantly (40% longer saccharin transit times) and similarly in both groups over the study period. There was a significant association between impaired nasal MCC and decline in lung function. Nasal lavage revealed an increased proportion of macrophages, interleukin-8, and epidermal growth factor concentrations with decreased interleukin-10 during the study. No changes in the proportion of ciliated cells or contact angle were observed. Coughing and sleep symptoms decreased similarly in both groups. There were no outcome differences comparing dry vs cold bubble humidified NLFO. In subjects receiving chronic NLFO, cold bubble humidification does not adequately humidify inspired oxygen to prevent deterioration of MCC, mucus hydration, and pulmonary function. The unheated bubble humidification performed no better than no humidification. ClinicalTrials.gov; No.: NCT02515786; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Effect of small hairpin RNA targeting endothelin-converting enzyme-1 in monocrotaline-induced pulmonary hypertensive rats.

PubMed

Son, Jae Sung; Kim, Kwan Chang; Kim, Bo Kyung; Cho, Min-Sun; Hong, Young Mi

2012-12-01

The purpose of this study was to investigate the therapeutic effects of small hairpin RNA (shRNA) targeting endothelin-converting enzyme (ECE)-1 in monocrotaline (MCT)-induced pulmonary hypertensive rats. Ninty-four Sprague-Dawley rats were divided into three groups: control (n = 24), MCT (n = 35) and shRNA (n = 35). Four-week survival rate in the shRNA group was significantly increased compared to that in the MCT group. The shRNA group showed a significant improvement of right ventricular (RV) pressure compared with the MCT group. The MCT and shRNA groups also showed an increase in RV/(left ventricle + septum) ratio and lung/body weight. Plasma endothelin (ET)-1 concentrations in the shRNA group were lower than those in the MCT group. Medial wall thickness of pulmonary arterioles were increased after MCT injection and was significantly decreased in the shRNA group. The number of intra-acinar muscular pulmonary arteries was decreased in the shRNA group. The mRNA expressions of ET-1 and ET receptor A (ET(A)) were significantly decreased in the shRNA group in week 4. The protein levels of ET(A) were decreased in the shRNA group in week 2. The protein levels of tumor necrosis factor-α and vascular endothelial growth factor were decreased in the shRNA group in week 4. In conclusion, the gene silencing with lentiviral vector targeting ECE-1 could be effective against hemodynamic, histopathological and gene expression changes in pulmonary hypertension.

Decrease of pulmonary blood flow detected by phase contrast MRI is correlated with a decrease in lung volume and increase of lung fibrosis area determined by computed tomography in interstitial lung disease.

PubMed

Tsuchiya, Nanae; Yamashiro, Tsuneo; Murayama, Sadayuki

2016-09-01

Lung volume and pulmonary blood flow decrease in patients with interstitial lung disease (ILD). The purpose of this study was to assess the relationship between pulmonary blood flow and lung volume in ILD patients. This research was approved by the institutional review board. Twenty-seven patients (9 men, 18 women; mean age, 59 years; range, 24-79 years) with ILD were included. Blood flow was assessed in the pulmonary trunk and the left and right pulmonary arteries by phase contrast magnetic resonance imaging (MRI). Lung volume and the computed tomography (CT) visual score that indicates the severity of ILD were assessed on the left and right sides by thin-section CT scanning. Lung volume was automatically measured by lung analysis software (VINCENT Ver. 4). The CT visual score was measured by averaging the proportion of abnormal lung area at five anatomic levels. Pearson's correlation coefficient was used to determine the relationship between pulmonary blood flow and lung volume. Pulmonary blood flow showed a significant correlation with lung volume (both: r=0.52, p=0.006; left: r=0.61, p=0.001; right: r=0.54, p=0.004) and CT visual score (both: r=-0.39, p=0.04; left: r=-0.48, p=0.01; right: r=-0.38, p=0.04). Partial correlation analysis, controlled for age, height and weight, showed a significant correlation between pulmonary blood flow and lung volume (both: r=0.43, p=0.03; left: r=0.55, p=0.005; right: r=0.48, p=0.01) and CT visual score (both: r=-0.58, p=0.003; left: r=-0.51, p=0.01; right: r=-0.64, p=0.001). In ILD, reduced pulmonary blood flow is associated with reduced lung volume and increased abnormal lung area. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[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.

Downregulation of MicroRNA-126 Contributes to the Failing Right Ventricle in Pulmonary Arterial Hypertension.

PubMed

Potus, François; Ruffenach, Grégoire; Dahou, Abdellaziz; Thebault, Christophe; Breuils-Bonnet, Sandra; Tremblay, Ève; Nadeau, Valérie; Paradis, Renée; Graydon, Colin; Wong, Ryan; Johnson, Ian; Paulin, Roxane; Lajoie, Annie C; Perron, Jean; Charbonneau, Eric; Joubert, Philippe; Pibarot, Philippe; Michelakis, Evangelos D; Provencher, Steeve; Bonnet, Sébastien

2015-09-08

Right ventricular (RV) failure is the most important factor of both morbidity and mortality in pulmonary arterial hypertension (PAH). However, the underlying mechanisms resulting in the failed RV in PAH remain unknown. There is growing evidence that angiogenesis and microRNAs are involved in PAH-associated RV failure. We hypothesized that microRNA-126 (miR-126) downregulation decreases microvessel density and promotes the transition from a compensated to a decompensated RV in PAH. We studied RV free wall tissues from humans with normal RV (n=17), those with compensated RV hypertrophy (n=8), and patients with PAH with decompensated RV failure (n=14). Compared with RV tissues from patients with compensated RV hypertrophy, patients with decompensated RV failure had decreased miR-126 expression (quantitative reverse transcription-polymerase chain reaction; P<0.01) and capillary density (CD31(+) immunofluorescence; P<0.001), whereas left ventricular tissues were not affected. miR-126 downregulation was associated with increased Sprouty-related EVH1 domain-containing protein 1 (SPRED-1), leading to decreased activation of RAF (phosphorylated RAF/RAF) and mitogen-activated protein kinase (MAPK); (phosphorylated MAPK/MAPK), thus inhibiting the vascular endothelial growth factor pathway. In vitro, Matrigel assay showed that miR-126 upregulation increased angiogenesis of primary cultured endothelial cells from patients with decompensated RV failure. Furthermore, in vivo miR-126 upregulation (mimic intravenous injection) improved cardiac vascular density and function of monocrotaline-induced PAH animals. RV failure in PAH is associated with a specific molecular signature within the RV, contributing to a decrease in RV vascular density and promoting the progression to RV failure. More importantly, miR-126 upregulation in the RV improves microvessel density and RV function in experimental PAH. © 2015 American Heart Association, Inc.

Comparison of fenspiride with beclomethasone as adjunctive anti-inflammatory treatment in patients with chronic obstructive pulmonary disease.

PubMed

Shmelev, E I; Kunicina, Yu L

2006-01-01

This study aimed to compare the clinical efficacy of two anti-inflammatory medications (fenspiride and inhaled beclomethasone [beclomethasone dipropionate]) in patients with stable chronic obstructive pulmonary disease (COPD) over 6 months. DESIGN, METHODS AND PATIENTS: This was a randomised comparison of 58 patients with COPD, divided into five treatment groups: fenspiride (stages 1 and 2), beclomethasone (stage 2), and two control groups (stages 1 and 2). In addition, 64 patients with exacerbations of COPD were evaluated over a 2-week treatment period during which they received either fenspiride or prednisolone. Clinical signs and symptoms of COPD were evaluated every 2 months (aggregated numerical index of signs and symptoms), as were lung function tests (forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], FEV1/FVC) and a 6-minute walking test. Statistically significant reductions in all evaluated COPD signs and symptoms were achieved with fenspiride in stage 1 COPD. Fenspiride therapy significantly reduced the indices of sputum parameters (8-fold decrease), incidence of dry rales (6-fold decrease), dyspnoea (4-fold decrease) and cough (2.5-fold decrease). In comparison with beclomethasone, fenspiride was superior in stage 2 COPD. In patients with stage 2 COPD, reductions were less marked, but remained significantly superior in the fenspiride group in comparison with the beclomethasone group and the control groups. In patients with exacerbations of COPD, fenspiride had equivalent efficacy to that of systemic corticosteroids. Anti-inflammatory therapy with fenspiride in addition to bronchodilators significantly improved clinical signs and symptoms, external respiratory function tests and physical activity tests in patients with stage 1 COPD. Adjunctive fenspiride therapy was superior to inhaled beclomethasone in stage 2 COPD. Anti-inflammatory therapy in COPD may be more effective at an early stage of this disease.

Effect of cervical epidural blockade with 2% lidocaine plus epinephrine on respiratory function.

PubMed

Huang, Chih-Hung

2007-12-01

Cervical epidural anesthesia has been used widely for surgery of upper limbs. Although cervical epidural anesthesia with local anesthetic of 2% lidocaine (plain) has demonstrated the safety in respiratory function in spite of unavoidable phrenic and intercostal palsies to certain extent, the replacement of local anesthetics with 2% lidocaine plus epinephrine has not been investigated yet. I conducted this study to look into the effect of 2% lidocaine plus epinephrine on respiratory function. I collected data from 50 patients with mean age of 24 +/- 3 yrs, mean weight of 65 +/- 10 kg, ASA status: I-II without preoperative pulmonary dysfunction undergoing orthropedic open-reduction with internal fixation because of fractures of upper limbs. Cervical epidural space (C7-T1) was approached by hanging-drop method, using a 17G Tuohy needle. A catheter was inserted craniad to a distance of 12 cm. Pulmonary function measurement and arterial blood gas data were obstained before, 20 min, 50 min and 105 min after injection of 12 mL 2% lidocaine with 1:200,000 epinephrine. The anesthesia levels were between C3-T3 and obtained 15 +/- 2 min after injection. Mean arterial blood gas analysis showed mild respiratory acidosis at 20 min (PaCO2: 48 +/- 3 mmHg) and 50 min (PaCO2: 44 +/- 2 mmHg). The measured values of inspiratory vital capacity (IVC), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF) when compaired with control values, were decreased about 18.0% and 12.1% of the control values at 20 min and 50 min respectively. The ratios of FEV1/VC, FEV1/FVC were still within normal limits (> 80%). The results were significantly compatible with the criteria of mild restrictive type of pulmonary function. Cervical epidural anesthesia with 2% lidocaine plus epinephrine could reduce lung volumes and capacities, resulting from partially paralytic intercostal muscles and diaphragm innervated respectively by thoracic intercostal nerve and phrenic nerve. Without inadvertant total spinal or intravenous anesthesia or pre-existing pulmonary dysfunction, the patients with normal lungs could tolerate these changes well with the procedure.

Pulmonary function in children and adolescents with sickle cell disease: have we paid proper attention to this problem?

PubMed

Vieira, Ana Karine; Alvim, Cristina Gonçalves; Carneiro, Maria Cristina Marquez; Ibiapina, Cássio da Cunha

2016-01-01

To evaluate pulmonary function and functional capacity in children and adolescents with sickle cell disease. This was a cross-sectional study involving 70 children and adolescents (8-15 years of age) with sickle cell disease who underwent pulmonary function tests (spirometry) and functional capacity testing (six-minute walk test). The results of the pulmonary function tests were compared with variables related to the severity of sickle cell disease and history of asthma and of acute chest syndrome. Of the 64 patients who underwent spirometry, 15 (23.4%) showed abnormal results: restrictive lung disease, in 8 (12.5%); and obstructive lung disease, in 7 (10.9%). Of the 69 patients who underwent the six-minute walk test, 18 (26.1%) showed abnormal results regarding the six-minute walk distance as a percentage of the predicted value for age, and there was a ≥ 3% decrease in SpO2 in 36 patients (52.2%). Abnormal pulmonary function was not significantly associated with any of the other variables studied, except for hypoxemia and restrictive lung disease. In this sample of children and adolescents with sickle cell disease, there was a significant prevalence of abnormal pulmonary function. The high prevalence of respiratory disorders suggests the need for a closer look at the lung function of this population, in childhood and thereafter. Avaliar a função pulmonar e a capacidade funcional em crianças e adolescentes com doença falciforme. Estudo transversal com 70 crianças e adolescentes com doença falciforme (8-15 anos), submetidos a testes de função respiratória (espirometria) e de capacidade funcional (teste de caminhada de seis minutos). Os resultados da avaliação da função pulmonar foram comparados com variáveis relacionadas à gravidade da doença falciforme e à presença de história de asma e de síndrome torácica aguda. Dos 64 pacientes submetidos à espirometria, 15 (23,4%) apresentaram resultados alterados: distúrbio ventilatório restritivo, em 8; (12,5%) e distúrbio respiratório obstrutivo, em 7 (10,9%). Dos 69 pacientes submetidos ao teste de caminhada de seis minutos, 18 (26,1%) apresentaram resultados alterados na distância em % do previsto para a idade, e houve uma queda ≥ 3% na SpO2 em 36 (52,2%) dos pacientes. Não houve associações significativas entre função pulmonar alterada e as outras variáveis analisadas, exceto para hipoxemia e distúrbio ventilatório restritivo. Observou-se uma significativa prevalência de alterações na função pulmonar nesta amostra de crianças e adolescentes com doença falciforme. A elevada prevalência de distúrbios ventilatórios sugere a necessidade de um olhar mais atento à função pulmonar desde a infância nessa população.

Mitochondrial Complex IV Subunit 4 Isoform 2 Is Essential for Acute Pulmonary Oxygen Sensing.

PubMed

Sommer, Natascha; Hüttemann, Maik; Pak, Oleg; Scheibe, Susan; Knoepp, Fenja; Sinkler, Christopher; Malczyk, Monika; Gierhardt, Mareike; Esfandiary, Azadeh; Kraut, Simone; Jonas, Felix; Veith, Christine; Aras, Siddhesh; Sydykov, Akylbek; Alebrahimdehkordi, Nasim; Giehl, Klaudia; Hecker, Matthias; Brandes, Ralf P; Seeger, Werner; Grimminger, Friedrich; Ghofrani, Hossein A; Schermuly, Ralph T; Grossman, Lawrence I; Weissmann, Norbert

2017-08-04

Acute pulmonary oxygen sensing is essential to avoid life-threatening hypoxemia via hypoxic pulmonary vasoconstriction (HPV) which matches perfusion to ventilation. Hypoxia-induced mitochondrial superoxide release has been suggested as a critical step in the signaling pathway underlying HPV. However, the identity of the primary oxygen sensor and the mechanism of superoxide release in acute hypoxia, as well as its relevance for chronic pulmonary oxygen sensing, remain unresolved. To investigate the role of the pulmonary-specific isoform 2 of subunit 4 of the mitochondrial complex IV (Cox4i2) and the subsequent mediators superoxide and hydrogen peroxide for pulmonary oxygen sensing and signaling. Isolated ventilated and perfused lungs from Cox4i2 -/- mice lacked acute HPV. In parallel, pulmonary arterial smooth muscle cells (PASMCs) from Cox4i2 -/- mice showed no hypoxia-induced increase of intracellular calcium. Hypoxia-induced superoxide release which was detected by electron spin resonance spectroscopy in wild-type PASMCs was absent in Cox4i2 -/- PASMCs and was dependent on cysteine residues of Cox4i2. HPV could be inhibited by mitochondrial superoxide inhibitors proving the functional relevance of superoxide release for HPV. Mitochondrial hyperpolarization, which can promote mitochondrial superoxide release, was detected during acute hypoxia in wild-type but not Cox4i2 -/- PASMCs. Downstream signaling determined by patch-clamp measurements showed decreased hypoxia-induced cellular membrane depolarization in Cox4i2 -/- PASMCs compared with wild-type PASMCs, which could be normalized by the application of hydrogen peroxide. In contrast, chronic hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling were not or only slightly affected by Cox4i2 deficiency, respectively. Cox4i2 is essential for acute but not chronic pulmonary oxygen sensing by triggering mitochondrial hyperpolarization and release of mitochondrial superoxide which, after conversion to hydrogen peroxide, contributes to cellular membrane depolarization and HPV. These findings provide a new model for oxygen-sensing processes in the lung and possibly also in other organs. © 2017 American Heart Association, Inc.

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.

[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.

Experience with perioperative pirfenidone for lung cancer surgery in patients with idiopathic pulmonary fibrosis.

PubMed

Iwata, Takekazu; Yoshida, Shigetoshi; Nagato, Kaoru; Nakajima, Takahiro; Suzuki, Hidemi; Tagawa, Tetsuzo; Mizobuchi, Teruaki; Ota, Satoshi; Nakatani, Yukio; Yoshino, Ichiro

2015-10-01

Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse lung disease associated with an increased risk of lung cancer. Patients with IPF sometimes develop a life-threatening acute exacerbation of IPF (AE-IPF) after lung cancer surgery. In this retrospective study, pirfenidone, an antifibrotic agent, was perioperatively administered to IPF patients with lung cancer with the aim of preventing postoperative AE-IPF, and the feasibility and clinical outcomes were investigated. Twelve IPF patients with concomitant lung cancer who received perioperative pirfenidone treatment (PPT) for lung cancer surgery were retrospectively investigated. Sixteen IPF patients undergoing lung cancer surgery without PPT were analyzed as historical controls. Compared to the controls, the PPT patients had a more severely impaired preoperative pulmonary function and a larger number of limited pulmonary resections. There was a significant preoperative decrease in the serum KL-6 levels of the PPT patients. No severe pirfenidone-related complications or IPF-related events occurred in the PPT patients, while six control patients developed AE-IPF (P = 0.0167). A quantitative histopathological evaluation of resected lung specimens found that tissue changes associated with IPF were significantly fewer in the PPT patients (P = 0.021). PPT is a feasible perioperative treatment for IPF patients with lung cancer. Its effectiveness in preventing postoperative AE-IPF thus warrants prospective verification.

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

The IDO-AhR Axis Controls Th17/Treg Immunity in a Pulmonary Model of Fungal Infection.

PubMed

de Araújo, Eliseu Frank; Feriotti, Claudia; Galdino, Nayane Alves de Lima; Preite, Nycolas Willian; Calich, Vera Lúcia Garcia; Loures, Flávio Vieira

2017-01-01

In infectious diseases, the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) that catalyzes the tryptophan (Trp) degradation along the kynurenines (Kyn) pathway has two main functions, the control of pathogen growth by reducing available Trp and immune regulation mediated by the Kyn-mediated expansion of regulatory T (Treg) cells via aryl hydrocarbon receptor (AhR). In pulmonary paracoccidioidomycosis (PCM) caused by the dimorphic fungus Paracoccidioides brasiliensis , IDO1 was shown to control the disease severity of both resistant and susceptible mice to the infection; however, only in resistant mice, IDO1 is induced by TGF-β signaling that confers a stable tolerogenic phenotype to dendritic cells (DCs). In addition, in pulmonary PCM, the tolerogenic function of plasmacytoid dendritic cells was linked to the IDO1 activity. To further evaluate the function of IDO1 in pulmonary PCM, IDO1-deficient (IDO1 -/- ) C57BL/6 mice were intratracheally infected with P. brasiliensis yeasts and the infection analyzed at three postinfection periods regarding several parameters of disease severity and immune response. The fungal loads and tissue pathology of IDO1 -/- mice were higher than their wild-type controls resulting in increased mortality rates. The evaluation of innate lymphoid cells showed an upregulated differentiation of the innate lymphoid cell 3 phenotype accompanied by a decreased expansion of ILC1 and NK cells in the lungs of infected IDO1 -/- mice. DCs from these mice expressed elevated levels of costimulatory molecules and cytokine IL-6 associated with reduced production of IL-12, TNF-α, IL-1β, TGF-β, and IL-10. This response was concomitant with a marked reduction in AhR production. The absence of IDO1 expression caused an increased influx of activated Th17 cells to the lungs with a simultaneous reduction in Th1 and Treg cells. Accordingly, the suppressive cytokines IL-10, TGF-β, IL-27, and IL-35 appeared in reduced levels in the lungs of IDO1 -/- mice. In conclusion, the immunological balance mediated by the axis IDO/AhR is fundamental to determine the balance between Th17/Treg cells and control the severity of pulmonary PCM.

Effect of inhaled nitric oxide on pulmonary hemodynamics after acute lung injury in dogs

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

Romand, J.A.; Pinsky, M.R.; Firestone, L.

Increased pulmonary vascular resistance (PVR) and mismatch in ventilation-to-perfusion ratio characterize acute lung injury (ALI). Pulmonary arterial pressure (Ppa) decreases when nitric oxide (NO) is inhaled during hypoxic pulmonary vasoconstriction (HPV); thus NO inhalation may reduce PVR and improve gas exchange in ALI. The authors studied the hemodynamic and gas exchange effects of NO inhalation during HPV and then ALI in eight anesthetized open-chest mechanically ventilated dogs. Right atrial pressure, Ppa, and left ventricular and arterial pressures were measured, and cardiac output was estimated by an aortic flow probe. Shunt and dead space were also estimated. The effect of 5-minmore » exposures to 0, 17, 28, 47, and 0 ppm inhaled NO was recorded during hyperoxia, hypoxia, and oleic acid-induced ALI. During ALI, partial [beta]-adrenergic blockage (propanolol, 0.15 mg/kg iv) was induced and 74 ppm NO was inhaled. Nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) levels were measured. During hyperoxia, NO inhalation had no measurable effects. Hypoxia increased Ppa and calculated PVR, both of which decreased with 17 ppm NO. ALI decreased arterial Po[sub 2] and increased airway pressure, shunt, and dead space ventilation. Ppa and PVR were greater during ALI than during hyperoxia. NO inhalation had no measurable effect during ALI before or after [beta]-adrenergic blockage. MetHb remained low, and NO-Hb was unmeasurable. Bolus infusion of nitroglycerin (15 [mu]g) induced an immediate decrease in Ppa and PVR during ALI. Short-term NO inhalation does not affect PVR or gas exchange in dogs with oleic acid-induced ALI, nor does it increase NO-Hb or MetHb. In contrast, NO can diminish hypoxia-induced elevations in pulmonary vascular tone. These data suggest that NO inhalation selectively dilates the pulmonary circulation and specifically reduces HPV but not oleic acid-induced increases in pulmonary vasomotor tone. 28 refs., 3 figs., 2 tabs.« less

Lung damage and pulmonary uptake of serotonin in intact dogs

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

Dawson, C.A.; Christensen, C.W.; Rickaby, D.A.

1985-06-01

The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of (/sup 3/H)serotonin and the extravascular volume accessible to (/sup 14/C)antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as withmore » embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage.« less

Bronchodilator effects of prostacyclin (PGI2) in dogs and guinea pigs.

PubMed

Wasserman, M A; Ducharme, D W; Wendling, M G; Griffin, R L; Degraaf, G L

1980-08-22

prostacyclin (PGI2), a recently discovered unstable product in the biosynthetic conversion of prostaglandin endoperoxides, was examined for bronchopulmonary actions. in anesthetized dogs, PGI2 given i.v. (0.3-30.0 microgram/kg) and by aerosol (0.002-0.2%) inhibited significantly PGF2 alpha-induced increases in pulmonary resistance and decreases in dynamic lung compliance in a dose-related fashion. Intrinsically, PGI2 affected resting bronchopulmonary and cardiac functions minimally, but decreased peripheral and pulmonary vascular pressures. PGI2 (0.1-10 mg/kg, i.p.) afforded protection against histamine-induced asphyxial collapse in normal guinea pigs and ovalbumin-induced anaphylaxis in sensitized animals. Cumulative concentrations of PGI2 (1.0 x 10(-9)--3.0 x 10(-4) M) relaxed contractions of the isolated guine pig trachea produced by carbachol. These bronchodilator and hemodynamic effects could not be ascribed to the stable metabolic product of PGI2, because 6-keto-PGF1 alpha was inactive or markedly less active than PGI2 in these test systems. The results of this investigation suggest that PGI2 possesses considerable bronchodilator and vasodilator activity in experimental animal systems.

Acute effects of exercise on the inflammatory state in patients with idiopathic pulmonary arterial hypertension.

PubMed

Harbaum, Lars; Renk, Emilia; Yousef, Sara; Glatzel, Antonia; Lüneburg, Nicole; Hennigs, Jan K; Oqueka, Tim; Baumann, Hans J; Atanackovic, Djordje; Grünig, Ekkehard; Böger, Rainer H; Bokemeyer, Carsten; Klose, Hans

2016-11-11

Exercise training positively influences exercise tolerance and functional capacity of patients with idiopathic pulmonary arterial hypertension (IPAH). However, the underlying mechanisms are unclear. We hypothesized that exercise modulates the activated inflammatory state found in IPAH patients. Single cardiopulmonary exercise testing was performed in 16 IPAH patients and 10 healthy subjects. Phenotypic characterization of peripheral blood mononuclear cells and circulating cytokines were assessed before, directly after and 1 h after exercise. Before exercise testing, IPAH patients showed elevated Th2 lymphocytes, regulatory T lymphocytes, IL-6, and TNF-alpha, whilst Th1/Th17 lymphocytes and IL-4 were reduced. In IPAH patients but not in healthy subject, exercise caused an immediate relative decrease of Th17 lymphocytes and a sustained reduction of IL-1-beta and IL-6. The higher the decrease of IL-6 the higher was the peak oxygen consumption of IPAH patients. Exercise seems to be safe from an immune and inflammatory point of view in IPAH patients. Our results demonstrate that exercise does not aggravate the inflammatory state and seems to elicit an immune-modulating effect in IPAH patients.

[The satisfaction of personal needs in patients with pulmonary tuberculosis].

PubMed

Sukhova, E V

2005-01-01

The founder of humanistic psychology A. Maslow divided the needs of a personality into several levels--from the lowest to the highest ones. Higher-leveled needs rise when the lower-leveled needs are satisfied. A great deal of factors affect the origination and satisfaction of needs, but they are always interrelated with social values. The extent to which personality needs are satisfied in patients with pulmonary tuberculosis has not been studied. A special questionnaire has been drawn up to study the extent to which personality needs are met. Its suitability has been determined, by using a group of patients with bronchial asthma. The extent to which personality needs are satisfied in patients with pulmonary tuberculosis was studied in 178 patients with infiltrative pulmonary tuberculosis and 253 patients with fibrocavernous pulmonary tuberculosis. The results have shown that the extent to which personality needs are satisfied in patients with tuberculosis is lower than that in apparently healthy individuals of the same social status. In females with infiltrative pulmonary tuberculosis, the needs for safety are satisfied to a lesser extent. In those with fibrocavernous pulmonary tuberculosis, the extent to which the physiological, safety, and self-realization needs is decreased. In males with infiltrative pulmonary tuberculosis, the physiological, noetic, and self-realization needs are satisfied to a lesser extent. In those with fibrocavernous pulmonary tuberculosis, the extent to which the physiological, safety, group decision-making, noetic and self-realization needs is decreased.

Ventilatory function in rubber processing workers: acute changes over the workshift.

PubMed

Governa, M; Comai, M; Valentino, M; Antonicelli, L; Rinaldi, F; Pisani, E

1987-02-01

When considering rubber tyre manufacturing from an occupational health viewpoint, three areas may be identified in which exposure to respirable materials are potentially harmful: the processing, curing, and talc areas. A study of the ventilatory function of the entire work force employed in the processing area in a rubber tyre manufacturing plant was undertaken to determine whether an acute reduction in lung function occurs over the course of their working shift (the plant worked a three shift system) and whether a chronic exposure to the occupational airborne contaminants causes permanent changes in lung function. The ventilatory function was measured at the worksite at the beginning and immediately after the end of the workshift. No evidence of chronic obstructive pulmonary disease was found and in most cases no significant decline in FEV1 was observed. Only one of the 79 individuals showed a moderate obstruction, measured by the ratio FEV1/FVC which gave the value of 0.55, with no variation over the shift. For non-smokers, the FVC, FEV1, and FEF25-75% were lower in those exposed for more than five years than in those exposed for five years or less. A similar pattern was also observed in the FVC and FEV1 of the smokers. None of these differences was statistically significant. Within each exposure group the pulmonary function of the smokers was lower than that of the non-smokers, but the only significant difference was found in the values of FEF25-75%. Only one man showed a decline in the FEV1/FVC ratio over the shift, but during each shift, a decrease in all the lung function tests was observed. The decrease was smallest during the first of the three shifts. These results are thought to support the hypothesis that there are acute adverse effects over an eight hour shift. Further investigations are needed to discover whether these acute changes in lung function result from a chemical stimulation or irritant receptors in the airways.

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.

[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.

Effect of indoor air pollution on the respiratory system of women using different fuels for cooking in an urban slum of Pondicherry.

PubMed

Dutt, D; Srinivasa, D K; Rotti, S B; Sahai, A; Konar, D

1996-01-01

Some of the highest exposures to air pollutants in developing countries occur inside homes where biofuels are used for daily cooking. Inhalation of these pollutants may cause deleterious effects on health. We studied the effects of exposure to indoor air pollution from the use of cooking fuels on lung functions and respiratory symptoms in women aged 15-60 years. The study was conducted in Kuruchikuppam, an urban slum in Pondicherry. The study participants were 105 women using biofuels, 105 using kerosene and 105 using liquid petroleum gas (LPG), selected from among 1117 women aged 15-60 years, by a stratified random sampling technique. These women were interviewed at home to collect information about exposure to fuel smoke and presence of respiratory symptoms. Lung functions were assessed by measuring forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and peak expiratory flow rate (PEFR). Occurrence of respiratory symptoms over six months was noted by making monthly follow up visits. Women using biofuels experienced more respiratory symptoms (23%) than those using kerosene (13%;p > 0.05) or LPG (8%; p < 0.05). Lung functions-FVC, FEV1, FEV1% and PEFR-were significantly lower in biofuel users compared with both kerosene (p < 0.01) and LPG users (p < 0.001). Lung functions in kerosene users also were significantly poorer when compared with LPG users (p < 0.01). Predicted pulmonary functions using multiple regression equations, derived from the data set of the present study, indicated that women using biofuels were more liable to have reduced pulmonary functions than women using kerosene or LPG. Women exposed to biofuel smoke suffer more from respiratory illnesses and have decreased pulmonary functions compared with women exposed to kerosene or LPG smoke. To reduce pollutant exposures we recommend the use of smokeless chullas or cleaner fuels such as charcoal, biogas and kerosene.