Assessment of lung function in a large cohort of patients with acromegaly.

PubMed

Störmann, Sylvère; Gutt, Bodo; Roemmler-Zehrer, Josefine; Bidlingmaier, Martin; Huber, Rudolf M; Schopohl, Jochen; Angstwurm, Matthias W

2017-07-01

Acromegaly is associated with increased mortality due to respiratory disease. To date, lung function in patients with acromegaly has only been assessed in small studies, with contradicting results. We assessed lung function parameters in a large cohort of patients with acromegaly. Lung function of acromegaly patients was prospectively assessed using spirometry, blood gas analysis and body plethysmography. Biochemical indicators of acromegaly were assessed through measurement of growth hormone and IGF-I levels. This study was performed at the endocrinology outpatient clinic of a tertiary referral center in Germany. We prospectively tested lung function of 109 acromegaly patients (53 male, 56 female; aged 24-82 years; 80 with active acromegaly) without severe acute or chronic pulmonary disease. We compared lung volume, air flow, airway resistance and blood gases to normative data. Acromegaly patients had greater lung volumes (maximal vital capacity, intra-thoracic gas volume and residual volume: P  < 0.001, total lung capacity: P  = 0.006) and showed signs of small airway obstruction (reduced maximum expiratory flow when 75% of the forced vital capacity (FVC) has been exhaled: P  < 0.001, lesser peak expiratory flow: P  = 0.01). There was no significant difference between active and inactive acromegaly. Female patients had significantly altered lung function in terms of subclinical airway obstruction. In our cross-sectional analysis of lung function in 109 patients with acromegaly, lung volumes were increased compared to healthy controls. Additionally, female patients showed signs of subclinical airway obstruction. There was no difference between patients with active acromegaly compared with patients biochemically in remission. © 2017 European Society of Endocrinology.

Association of generic health-related quality of life (EQ-5D dimensions) and inactivity with lung function in lung-healthy German adults: results from the KORA studies F4L and Age.

PubMed

Luzak, Agnes; Karrasch, Stefan; Wacker, Margarethe; Thorand, Barbara; Nowak, Dennis; Peters, Annette; Schulz, Holger

2018-03-01

Among patients with lung disease, decreased lung function is associated with lower health-related quality of life. However, whether this association is detectable within the physiological variability of respiratory function in lung-healthy populations is unknown. We analyzed the association of each EQ-5D-3L dimension (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and self-reported physical inactivity with spirometric indices in lung-healthy adults. Modulating effects between inactivity and EQ-5D dimensions were considered. 1132 non-smoking, apparently lung-healthy participants (48% male, aged 64 ± 12 years) from the population-based KORA F4L and Age surveys in Southern Germany were analyzed. Associations of each EQ-5D dimension and inactivity with spirometric indices serving as outcomes (forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC, and mid-expiratory flow) were examined by linear regression, considering possible confounders. Interactions between EQ-5D dimensions (no problems/any problems) and inactivity (four categories of time spent engaging in exercise: inactive to most active) were assessed. Among all participants 42% reported no problems in any EQ-5D dimension, 24% were inactive and 32% exercised > 2 h/week. After adjustment, FEV 1 was - 99 ml (95% CI - 166; - 32) and FVC was - 109 ml (95% CI - 195; - 24) lower among subjects with mobility problems. Comparable estimates were observed for usual activities. Inactivity was negatively associated with FVC (β-coefficient: - 83 ml, 95% CI - 166; 0), but showed no interactions with EQ-5D. Problems with mobility or usual activities, and inactivity were associated with slightly lower spirometric parameters in lung-healthy adults, suggesting a relationship between perceived physical functioning and volumetric lung function.

[Clinical and functional characteristics of patients prior to lung transplantation: report of experience at the Clínica Puerta de Hierro].

PubMed

Laporta, Rosalía; Ussetti, Piedad; Mora, Gema; López, Cristina; Gómez, David; de Pablo, Alicia; Lázaro, M Teresa; Carreño, M Cruz; Ferreiro, M José

2008-08-01

The time at which lung transplantation is indicated is determined by clinical and functional criteria that vary according to the particular disease. The aim of our study was to present the criteria according to which patients were placed on waiting lists for lung transplantation in our hospital. We analyzed retrospectively the clinical characteristics, lung function, heart function, and 6-minute walk test results of patients who had received a lung transplant in our hospital from January 2002 through September 2005. During the study period 100 lung transplants were performed. The mean age of the patients was 45 years (range, 15-67 years) and 57% were men. The diseases that most often led to a lung transplant were chronic obstructive pulmonary disease (COPD) (35%), pulmonary fibrosis (29%), and bronchiectasis (21%). Lung function values differed by disease: mean (SD) forced expiratory volume in 1 second (FEV1) was 20% (11%) and forced vital capacity (FVC) was 37% (15%) in patients with COPD; FEV1 was 41% (15%) and FVC, 40% (17%) in patients with pulmonary fibrosis; and FEV1 was 23% (7%) and FVC, 37% (10%) in patients with bronchiectasis. The patients who received lung transplants in our hospital were in advanced phases of their disease and met the inclusion criteria accepted by the various medical associations when they were placed on the waiting list.

Lung function, functional capacity, and respiratory symptoms at discharge from hospital in patients with acute pulmonary embolism: A cross-sectional study.

PubMed

Danielsbacka, Jenny S; Olsén, Monika Fagevik; Hansson, Per-Olof; Mannerkorpi, Kaisa

2018-03-01

Acute pulmonary embolism (PE) is a cardiovascular disease with symptoms including respiratory associated chest pain (RACP) and dyspnea. No previous studies exist focusing on lung function, functional capacity, and respiratory symptoms at discharge after PE. The aim was to examine and describe lung function, functional capacity, and respiratory symptoms at discharge in patients with PE and compare to reference values. Fifty consecutive patients with PE admitted to the Acute Medical Unit, Sahlgrenska University Hospital, were included. Size of PE was calculated by Qanadli score (QS) percentage (mean QS 33.4% (17.6)). FVC and FEV 1 were registered and 6-minute walk test (6MWT) performed at the day of discharge. RACP was rated before and after spirometry/6MWT with the Visual Analogue Scale. Perceived exertion was rated with Borg CR-10 scale. Spirometry and 6MWT results were compared with reference values. This study shows that patients with PE have significantly reduced lung function (p < 0.05) and functional capacity (p < 0.001) at discharge compared with reference values. Patients with higher QS percentage were more dyspneic after 6MWT, no other significant differences in lung function or functional capacity were found between the groups. The patients still suffer from RACP (30%) and dyspnea (60%) at discharge. This study indicates that patients with PE have a reduced lung function, reduced functional capacity, and experience respiratory symptoms as pain and dyspnea at discharge. Further studies are needed concerning long-term follow-up of lung function, functional capacity, and symptoms after PE.

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease

PubMed Central

Malhotra, Deepti; Boezen, H. Marike; Siedlinski, Mateusz; Postma, Dirkje S.; Wong, Vivien; Akhabir, Loubna; He, Jian-Qing; Connett, John E.; Anthonisen, Nicholas R.; Paré, Peter D.; Biswal, Shyam

2012-01-01

An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function. PMID:22693272

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease.

PubMed

Sandford, Andrew J; Malhotra, Deepti; Boezen, H Marike; Siedlinski, Mateusz; Postma, Dirkje S; Wong, Vivien; Akhabir, Loubna; He, Jian-Qing; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Biswal, Shyam

2012-08-01

An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function.

Lung function in the absence of respiratory symptoms in overweight children and adolescents*

PubMed Central

de Assunção, Silvana Neves Ferraz; Daltro, Carla Hilário da Cunha; Boa Sorte, Ney Christian; Ribeiro, Hugo da Costa; Bastos, Maria de Lourdes; Queiroz, Cleriston Farias; Lemos, Antônio Carlos Moreira

2014-01-01

OBJECTIVE: To describe lung function findings in overweight children and adolescents without respiratory disease. METHODS: This was a cross-sectional study involving male and female overweight children and adolescents in the 8-18 year age bracket, without respiratory disease. All of the participants underwent anthropometric assessment, chest X-ray, pulse oximetry, spirometry, and lung volume measurements. Individuals with respiratory disease were excluded, as were those who were smokers, those with abnormal chest X-rays, and those with an SpO2 = 92%. Waist circumference was measured in centimeters. The body mass index-for-age Z score for boys and girls was used in order to classify the individuals as overweight, obese, or severely obese. Lung function variables were expressed in percentage of the predicted value and were correlated with the anthropometric indices. RESULTS: We included 59 individuals (30 males and 29 females). The mean age was 11.7 ± 2.7 years. Lung function was normal in 21 individuals (35.6%). Of the 38 remaining individuals, 19 (32.2%), 15 (25.4%), and 4 (6.7%) presented with obstructive, restrictive, and mixed ventilatory disorder, respectively. The bronchodilator response was positive in 15 individuals (25.4%), and TLC measurements revealed that all of the individuals with reduced VC had restrictive ventilatory disorder. There were significant negative correlations between the anthropometric indices and the Tiffeneau index in the individuals with mixed ventilatory disorder. CONCLUSIONS: Lung function was abnormal in approximately 65% of the individuals evaluated here, all of whom were overweight. Obstructive ventilatory disorder and positive bronchodilator response predominated. PMID:24831397

Lung inflation with hydrogen during the cold ischemia phase decreases lung graft injury in rats

PubMed Central

Liu, Rongfang; Fang, Xianhai; Meng, Chao; Xing, Jingchun; Liu, Jinfeng; Yang, Wanchao

2015-01-01

Hydrogen has antioxidant and anti-inflammatory effects on lung ischemia–reperfusion injury when it is inhaled by donor or/and recipient. This study examined the effects of lung inflation with 3% hydrogen during the cold ischemia phase on lung graft function in rats. The donor lung was inflated with 3% hydrogen, 40% oxygen, and 57% nitrogen at 5 mL/kg, and the gas was replaced every 20 min during the cold ischemia phase for 2 h. In the control group, the donor lung was inflated with 40% oxygen and 60% nitrogen at 5 mL/kg. The recipient was euthanized 2 h after orthotropic lung transplantation. The hydrogen concentration in the donor lung during the cold ischemia phase was 1.99–3%. The oxygenation indices in the arterial blood and pulmonary vein blood were improved in the hydrogen group. The inflammation response indices, including lung W/D ratio, the myeloperoxidase activity in the grafts, and the levels of IL-8 and TNF-α in serum, were significantly lower in the hydrogen group (5.2 ± 0.8, 0.76 ± 0.32 U/g, 340 ± 84 pg/mL, and 405 ± 115 pg/mL, respectively) than those in the control group (6.5 ± 0.7, 1.1 ± 0.5 U/g, 443 ± 94 pg/mL, and 657 ± 96 pg/mL, respectively (P < 0.05), and the oxidative stress indices, including the superoxide dismutase activity and the level of malonaldehyde in lung grafts were improved after hydrogen application. Furthermore, the lung injury score determined by histopathology, the cell apoptotic index, and the caspase-3 protein expression in lung grafts were decreased after hydrogen treatment, and the static pressure–volume curve of lung graft was improved by hydrogen inflation. In conclusion, lung inflation with 3% hydrogen during the cold ischemia phase alleviated lung graft injury and improved graft function. PMID:25662956

Lung volumes: measurement, clinical use, and coding.

PubMed

Flesch, Judd D; Dine, C Jessica

2012-08-01

Measurement of lung volumes is an integral part of complete pulmonary function testing. Some lung volumes can be measured during spirometry; however, measurement of the residual volume (RV), functional residual capacity (FRC), and total lung capacity (TLC) requires special techniques. FRC is typically measured by one of three methods. Body plethysmography uses Boyle's Law to determine lung volumes, whereas inert gas dilution and nitrogen washout use dilution properties of gases. After determination of FRC, expiratory reserve volume and inspiratory vital capacity are measured, which allows the calculation of the RV and TLC. Lung volumes are commonly used for the diagnosis of restriction. In obstructive lung disease, they are used to assess for hyperinflation. Changes in lung volumes can also be seen in a number of other clinical conditions. Reimbursement for measurement of lung volumes requires knowledge of current procedural terminology (CPT) codes, relevant indications, and an appropriate level of physician supervision. Because of recent efforts to eliminate payment inefficiencies, the 10 previous CPT codes for lung volumes, airway resistance, and diffusing capacity have been bundled into four new CPT codes.

Measurement of lung function using Electrical Impedance Tomography (EIT) during mechanical ventilation

NASA Astrophysics Data System (ADS)

Nebuya, Satoru; Koike, Tomotaka; Imai, Hiroshi; Noshiro, Makoto; Brown, Brian H.; Soma, Kazui

2010-04-01

The consistency of regional lung density measurements as estimated by Electrical Impedance Tomography (EIT), in eleven patients supported by a mechanical ventilator, was validated to verify the feasibility of its use in intensive care medicine. There were significant differences in regional lung densities between the normal lung and diseased lungs associated with pneumonia, atelectasis and pleural effusion (Steel-Dwass test, p < 0.05). Temporal changes in regional lung density of patients with atelectasis were observed to be in good agreement with the results of clinical diagnosis. These results indicate that it is feasible to obtain a quantitative value for regional lung density using EIT.

The problem of the treatment of sarcoidosis: Report of the Subcommittee on Therapy.

PubMed

Turiaf, J; Johns, C J; Terstein, A S; Tsuji, S; Wurm, K

1976-01-01

Stage I: Hilar Adenopathy With normal lung function observe, as it often resolves. With reduced lung function observe for 6-12 months. Treat if there is progression or persistence. With erythema nodosum use mild anti-inflammatory agents such as salicylates or like drugs. Stage II: Adenopathy + Pulmonar Infiltrates With normal or slightly reduced lung function observe; treat if it worsens. Treat if there is no remission in 6-12 months. With reduced lung function treat, possibly for many years or a lifetime. Stage III: Pulmonary Infiltrates +/- Fibrosis Without Adenopathy There is reduced lung function. Treat, demonstrate improvement, follow patients with serial measurements of vital capacity at least. Other Indications for Treatment Other indications for treatment include myocardial sarcoidosis, cerebral sarcoidosis (although the outcome is less certain), serious hepatic or renal sarcoidosis, hypercalcemia, persistent systemic symptoms, or other serious organ or functional impairment. Assess each patient individually and completely. Use good clinical judgement. It is clear that treatment that is too little or too late is of little benefit. Even the statistical results form a perfectly controlled study cannot provide absolute direction for the individual patient. As clinicians we are frequently called upon to apply considered judgements without hard data to predict the outcome. We also maintain the flexibility to change our therapeutic programs when circumstances change, either in the patient or in our knowledge. We can be grateful we have a treatment as good as corticosteroids and must try to exercise our best judgement as to when it should be instituted.

Linking microbiota and respiratory disease.

PubMed

Hauptmann, Matthias; Schaible, Ulrich E

2016-11-01

An increasing body of evidence indicates the relevance of microbiota for pulmonary health and disease. Independent investigations recently demonstrated that the lung harbors a resident microbiota. Therefore, it is intriguing that a lung microbiota can shape pulmonary immunity and epithelial barrier functions. Here, we discuss the ways how the composition of the microbial community in the lung may influence pulmonary health and vice versa, factors that determine community composition. Prominent microbiota at other body sites such as the intestinal one may also contribute to pulmonary health and disease. However, it is difficult to discriminate between influences of lung vs. gut microbiota due to systemic mutuality between both communities. With focuses on asthma and respiratory infections, we discuss how microbiota of lung and gut can determine pulmonary immunity and barrier functions. © 2016 Federation of European Biochemical Societies.

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.

Acute effects of PM2.5 on lung function parameters in schoolchildren in Nanjing, China: a panel study.

PubMed

Xu, Dandan; Zhang, Yi; Zhou, Lian; Li, Tiantian

2018-03-17

The association between exposure to ambient particulate matter (PM) and reduced lung function parameters has been reported in many works. However, few studies have been conducted in developing countries with high levels of air pollution like China, and little attention has been paid to the acute effects of short-term exposure to air pollution on lung function. The study design consisted of a panel comprising 86 children from the same school in Nanjing, China. Four measurements of lung function were performed. A mixed-effects regression model with study participant as a random effect was used to investigate the relationship between PM 2.5 and lung function. An increase in the current day, 1-day and 2-day moving average PM 2.5 concentration was associated with decreases in lung function indicators. The greatest effect of PM 2.5 on lung function was detected at 1-day moving average PM 2.5 exposure. An increase of 10 μg/m 3 in the 1-day moving average PM 2.5 concentration was associated with a 23.22 mL decrease (95% CI: 13.19, 33.25) in Forced Vital Capacity (FVC), a 18.93 mL decrease (95% CI: 9.34, 28.52) in 1-s Forced Expiratory Volume (FEV 1 ), a 29.38 mL/s decrease (95% CI: -0.40, 59.15) in Peak Expiratory Flow (PEF), and a 27.21 mL/s decrease (95% CI: 8.38, 46.04) in forced expiratory flow 25-75% (FEF 25-75% ). The effects of PM 2.5 on lung function had significant lag effects. After an air pollution event, the health effects last for several days and we still need to pay attention to health protection.

"EXHALE": exercise as a strategy for rehabilitation in advanced stage lung cancer patients: a randomized clinical trial comparing the effects of 12 weeks supervised exercise intervention versus usual care for advanced stage lung cancer patients.

PubMed

Quist, Morten; Langer, Seppo W; Rørth, Mikael; Christensen, Karl Bang; Adamsen, Lis

2013-10-14

Lung cancer is the leading cause of cancer death in North America and Western Europe. Patients with lung cancer in general have reduced physical capacity, functional capacity, poor quality of life and increased levels of anxiety and depression. Intervention studies indicate that physical training can address these issues. However, there is a lack of decisive evidence regarding the effect of physical exercise in patients with advanced lung cancer. The aim of this study is to evaluate the effects of a twelve weeks, twice weekly program consisting of: supervised, structured training in a group of advanced lung cancer patients (cardiovascular and strength training, relaxation). A randomized controlled trial will test the effects of the exercise intervention in 216 patients with advanced lung cancer (non-small cell lung cancer (NSCLC) stage IIIb-IV and small cell lung cancer (SCLC) extensive disease (ED)). Primary outcome is maximal oxygen uptake (VO₂peak). Secondary outcomes are muscle strength (1RM), functional capacity (6MWD), lung capacity (Fev1) and patient reported outcome (including anxiety, depression (HADS) and quality of life (HRQOL)). The present randomized controlled study will provide data on the effectiveness of a supervised exercise intervention in patients receiving systemic therapy for advanced lung cancer. It is hoped that the intervention can improve physical capacity and functional level, during rehabilitation of cancer patients with complex symptom burden and help them to maintain independent function for as long as possible. http://ClinicalTrials.gov, NCT01881906.

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.

Quantitative computed tomography of pulmonary emphysema and ventricular function in chronic obstructive pulmonary disease patients with pulmonary hypertension.

PubMed

Huang, Yu-Sen; Hsu, Hsao-Hsun; Chen, Jo-Yu; Tai, Mei-Hwa; Jaw, Fu-Shan; Chang, Yeun-Chung

2014-01-01

This study strived to evaluate the relationship between degree of pulmonary emphysema and cardiac ventricular function in chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH) using electrocardiographic-gated multidetector computed tomography (CT). Lung transplantation candidates with the diagnosis of COPD and PH were chosen for the study population, and a total of 15 patients were included. The extent of emphysema is defined as the percentage of voxels below -910 Hounsfield units in the lung windows in whole lung CT without intravenous contrast. Heart function parameters were measured by electrocardiographic-gated CT angiography. Linear regression analysis was conducted to examine the associations between percent emphysema and heart function indicators. Significant correlations were found between percent emphysema and right ventricular (RV) measurements, including RV end-diastolic volume (R(2) = 0.340, p = 0.023), RV stroke volume (R(2) = 0.406, p = 0.011), and RV cardiac output (R(2) = 0.382, p = 0.014); the correlations between percent emphysema and left ventricular function indicators were not observed. The study revealed that percent emphysema is correlated with RV dysfunction among COPD patients with PH. Based on our findings, percent emphysema can be considered for use as an indicator to predict the severity of right ventricular dysfunction among COPD patients.

Computed tomographic-based quantification of emphysema and correlation to pulmonary function and mechanics.

PubMed

Washko, George R; Criner, Gerald J; Mohsenifar, Zab; Sciurba, Frank C; Sharafkhaneh, Amir; Make, Barry J; Hoffman, Eric A; Reilly, John J

2008-06-01

Computed tomographic based indices of emphysematous lung destruction may highlight differences in disease pathogenesis and further enable the classification of subjects with Chronic Obstructive Pulmonary Disease. While there are multiple techniques that can be utilized for such radiographic analysis, there is very little published information comparing the performance of these methods in a clinical case series. Our objective was to examine several quantitative and semi-quantitative methods for the assessment of the burden of emphysema apparent on computed tomographic scans and compare their ability to predict lung mechanics and function. Automated densitometric analysis was performed on 1094 computed tomographic scans collected upon enrollment into the National Emphysema Treatment Trial. Trained radiologists performed an additional visual grading of emphysema on high resolution CT scans. Full pulmonary function test results were available for correlation, with a subset of subjects having additional measurements of lung static recoil. There was a wide range of emphysematous lung destruction apparent on the CT scans and univariate correlations to measures of lung function were of modest strength. No single method of CT scan analysis clearly outperformed the rest of the group. Quantification of the burden of emphysematous lung destruction apparent on CT scan is a weak predictor of lung function and mechanics in severe COPD with no uniformly superior method found to perform this analysis. The CT based quantification of emphysema may augment pulmonary function testing in the characterization of COPD by providing complementary phenotypic information.

Assessment of volume reduction effect after lung lobectomy for cancer.

PubMed

Ueda, Kazuhiro; Murakami, Junichi; Sano, Fumiho; Hayashi, Masataro; Kobayashi, Taiga; Kunihiro, Yoshie; Hamano, Kimikazu

2015-07-01

Lung lobectomy results in an unexpected improvement of the remaining lung function in some patients with moderate-to-severe emphysema. Because the lung function is the main limiting factor for therapeutic decision making in patients with lung cancer, it may be advantageous to identify patients who may benefit from the volume reduction effect, particularly those with a poor functional reserve. We measured the regional distribution of the emphysematous lung and normal lung using quantitative computed tomography in 84 patients undergoing lung lobectomy for cancer between January 2010 and December 2012. The volume reduction effect was diagnosed using a combination of radiologic and spirometric parameters. Eight patients (10%) were favorably affected by the volume reduction effect. The forced expiratory volume in one second increased postoperatively in these eight patients, whereas the forced vital capacity was unchanged, thus resulting in an improvement of the airflow obstruction postoperatively. This improvement was not due to a compensatory expansion of the remaining lung but was associated with a relative decrease in the forced end-expiratory lung volume. According to a multivariate analysis, airflow obstruction and the forced end-expiratory lung volume were independent predictors of the volume reduction effect. A combined assessment using spirometry and quantitative computed tomography helped to characterize the respiratory dynamics underlying the volume reduction effect, thus leading to the identification of novel predictors of a volume reduction effect after lobectomy for cancer. Verification of our results by a large-scale prospective study may help to extend the indications for lobectomy in patients with oncologically resectable lung cancer who have a marginal pulmonary function. Copyright © 2015 Elsevier Inc. All rights reserved.

Lung segmentation from HRCT using united geometric active contours

NASA Astrophysics Data System (ADS)

Liu, Junwei; Li, Chuanfu; Xiong, Jin; Feng, Huanqing

2007-12-01

Accurate lung segmentation from high resolution CT images is a challenging task due to various detail tracheal structures, missing boundary segments and complex lung anatomy. One popular method is based on gray-level threshold, however its results are usually rough. A united geometric active contours model based on level set is proposed for lung segmentation in this paper. Particularly, this method combines local boundary information and region statistical-based model synchronously: 1) Boundary term ensures the integrality of lung tissue.2) Region term makes the level set function evolve with global characteristic and independent on initial settings. A penalizing energy term is introduced into the model, which forces the level set function evolving without re-initialization. The method is found to be much more efficient in lung segmentation than other methods that are only based on boundary or region. Results are shown by 3D lung surface reconstruction, which indicates that the method will play an important role in the design of computer-aided diagnostic (CAD) system.

Accuracy of mini peak flow meters in indicating changes in lung function in children with asthma.

PubMed Central

Sly, P. D.; Cahill, P.; Willet, K.; Burton, P.

1994-01-01

OBJECTIVE--To assess whether mini flow meters used to measure peak expiratory flow can track changes in lung function and indicate clinically important changes. DESIGN--Comparison of measurements with a spirometer and different brands of mini flow meter; the meters were allocated to subjects haphazardly. SUBJECTS--12 boys with asthma aged 11 to 17 attending boarding school. MAIN OUTCOME MEASURES--Peak expiratory flow measured twice daily for three months with a spirometer and at least one of four brands of mini flow meter. RESULTS--The relation between changes in lung function measured with the spirometer and those measured with the mini flow meters was generally poor. In all, 26 episodes (range 1-3 in an individual child) of clinically important deterioration in lung function were detected from the records obtained with the spirometer. One mini flow meter detected six of 19 episodes, one detected six of 15, one detected six of 18, and one detected three of 21. CONCLUSIONS--Not only are the absolute values of peak expiratory flow obtained with mini flow meters inaccurate but the clinical message may also be incorrect. These findings do not imply that home monitoring of peak expiratory flow has no place in the management of childhood asthma but that the values obtained should be interpreted cautiously. PMID:8148680

Physical activity is not associated with spirometric indices in lung-healthy German youth.

PubMed

Smith, Maia P; von Berg, Andrea; Berdel, Dietrich; Bauer, Carl-Peter; Hoffmann, Barbara; Koletzko, Sibylle; Nowak, Dennis; Heinrich, Joachim; Schulz, Holger

2016-08-01

In lung disease, physical activity improves lung function and reduces morbidity. However, healthy populations are not well studied. We estimate the relationship between spirometric indices and accelerometric physical activity in lung-healthy adolescents.895 nonsmoking German adolescents without chronic lung disease (45% male, mean±sd age 15.2±0.26 years) from the GINIplus and LISAplus cohorts completed questionnaires, spirometry, 7-day accelerometry and an activity diary. Physical activity was measured as minutes, quintiles and regularity of daily moderate, vigorous and moderate-to-vigorous physical activity (MVPA), participation in sport and active commuting to school. Primary outcomes were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow at 25-75% of FVC; they were separately correlated with physical activity and adjusted for confounders of respiratory function, including early-life exposures.Adolescents averaged 40 min MVPA per day, typical for European youth. 79% participated in sports and 51% commuted actively. An association was suggested between 3% higher FVC (∼100 mL) and either extreme MVPA quintile or percentage of days with >30 min MVPA (p<0.05). However, after Bonferroni correction all associations between spirometry, active lifestyle and physical activity were nonsignificant.Spirometric indices were not significantly associated with active lifestyle or measures of activity in lung-healthy adolescents after adjustment for confounding and multiple-comparison artefacts. Copyright ©ERS 2016.

Linking lung function to structural damage of alveolar epithelium in ventilator-induced lung injury.

PubMed

Hamlington, Katharine L; Smith, Bradford J; Dunn, Celia M; Charlebois, Chantel M; Roy, Gregory S; Bates, Jason H T

2018-05-06

Understanding how the mechanisms of ventilator-induced lung injury (VILI), namely atelectrauma and volutrauma, contribute to the failure of the blood-gas barrier and subsequent intrusion of edematous fluid into the airspace is essential for the design of mechanical ventilation strategies that minimize VILI. We ventilated mice with different combinations of tidal volume and positive end-expiratory pressure (PEEP) and linked degradation in lung function measurements to injury of the alveolar epithelium observed via scanning electron microscopy. Ventilating with both high inspiratory plateau pressure and zero PEEP was necessary to cause derangements in lung function as well as visually apparent physical damage to the alveolar epithelium of initially healthy mice. In particular, the epithelial injury was tightly associated with indicators of alveolar collapse. These results support the hypothesis that mechanical damage to the epithelium during VILI is at least partially attributed to atelectrauma-induced damage of alveolar type I epithelial cells. Copyright © 2018. Published by Elsevier B.V.

Long-term ambient air pollution and lung function impairment in Chinese children from a high air pollution range area: The Seven Northeastern Cities (SNEC) study

NASA Astrophysics Data System (ADS)

Zeng, Xiao-Wen; Vivian, Elaina; Mohammed, Kahee A.; Jakhar, Shailja; Vaughn, Michael; Huang, Jin; Zelicoff, Alan; Xaverius, Pamela; Bai, Zhipeng; Lin, Shao; Hao, Yuan-Tao; Paul, Gunther; Morawska, Lidia; Wang, Si-Quan; Qian, Zhengmin; Dong, Guang-Hui

2016-08-01

Epidemiological studies have reported inconsistent and inconclusive associations between long-term exposure to ambient air pollution and lung function in children from Europe and America, where air pollution levels were typically low. The aim of the present study is to examine the relationship between air pollutants and lung function in children selected from heavily industrialized and polluted cities in northeastern China. During 2012, 6740 boys and girls aged 7-14 years were recruited in 24 districts of seven northeastern cities. Portable electronic spirometers were used to measure lung function. Four-year average concentrations of particulate matter with an aerodynamic diameter ≤10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) were measured at monitoring stations in the 24 districts. Two-staged regression models were used in the data analysis, controlling for covariates. Overall, for all subjects, the increased odds of lung function impairment associated with exposure to air pollutants, ranged from 5% (adjusted odds ratio [aOR] = 1.05; 95% confidence interval [CI] = 1.01, 1.10) for FVC < 85% predicted per 46.3 μg/m3 for O3 to 81% (aOR = 1.81; 95%CI = 1.44, 2.28) for FEV1 < 85% predicted per 30.6 μg/m3 for PM10. The linear regression models consistently showed a negative relationship between all air pollutants and lung function measures across subjects. There were significant interaction terms indicating gender differences for lung function impairment and pulmonary function from exposure to some pollutants (P < 0.10). In conclusion, long term exposure to high concentrations of ambient air pollution is associated with decreased pulmonary function and lung function impairment, and females appear to be more susceptible than males.

Lung transplantation in children. Specific aspects.

PubMed

Moreno Galdó, Antonio; Solé Montserrat, Juan; Roman Broto, Antonio

2013-12-01

Lung transplantation has become in recent years a therapeutic option for infantswith terminal lung disease with similar results to transplantation in adults.In Spain, since 1996 114 children lung transplants have been performed; this corresponds to3.9% of the total transplant number.The most common indication in children is cystic fibrosis, which represents between 70-80% of the transplants performed in adolescents. In infants common indications areinterstitial lung disease and pulmonary hypertension.In most children a sequential double lung transplant is performed, generally with the help ofextracorporeal circulation. Lung transplantation in children presents special challenges in monitoring and follow-up, especially in infants, given the difficulty in assessing lung function and performing transbronchial biopsies.There are some more specific complications in children like postransplant lymphoproliferative syndrome or a greater severity of respiratory virus infections .After lung transplantation children usually experiment a very important improvement in their quality of life. Eighty eight per cent of children have no limitations in their activity after 3 years of transplantation.According to the registry of the International Society for Heart & Lung Transplantation (ISHLT) survival at 5 years of transplantation is 54% and at 10 years is around 35%. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

LncRNA NNT-AS1 promotes the proliferation, and invasion of lung cancer cells via regulating miR-129-5p expression.

PubMed

Shen, Qin; Jiang, Yongjie

2018-05-29

Lung cancer is the leading cause of cancer related-deaths worldwide. Long non-coding RNAs (lncRNAs) are identified as important therapeutic targets in treatment of lung cancer. However, the roles of NNT-AS1 in lung cancer remain unclear. In the present study, we showed that the expression of NNT-AS1 was upregulated in non-small cell lung cancer (NSCLC) tissues and cell lines. High NNT-AS1 expression was associated with advanced tumor stage, and lymph node metastasis of NSCLC patients. In vitro function assays showed that NNT-AS1 inhibition could significantly reduce lung cancer cells proliferation and invasion ability. Then, we identified that NNT-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-129-5p in lung cancer. In addition, we showed that alteration in cell proliferation and invasion caused by NNT-AS1 downregulation could be rescued by miR-129-5p inhibitors. Thus, our study indicated that lncRNA NNT-AS1 exerted functions in NSCLC via altering NNT-AS1/miR-129-5p axis which provided a novel therapeutic target for lung cancer treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Abnormal lung sounds in patients with asthma during episodes with normal lung function.

PubMed

Schreur, H J; Vanderschoot, J; Zwinderman, A H; Dijkman, J H; Sterk, P J

1994-07-01

Even in patients with clinically stable asthma with normal lung function, the airways are characterized by inflammatory changes, including mucosal swelling. In order to investigate whether lung sounds can distinguish these subjects from normal subjects, we compared lung sound characteristics between eight normal and nine symptom-free subjects with mild asthma. All subjects underwent simultaneous recordings of airflow, lung volume changes, and lung sounds during standardized quiet breathing, and during forced maneuvers. Flow-dependent power spectra were computed using fast Fourier transform. For each spectrum we determined lung sound intensity (LSI), frequencies (Q25%, Q50%, Q75%) wheezing (W), and W%. The results were analyzed by ANOVA. During expiration, LSI was lower in patients with asthma than in healthy controls, in particular at relatively low airflow values. During quiet expiration, Q25% to Q75% were higher in asthmatics than in healthy controls, while the change of Q25% to Q75% with flow was greater in asthmatic than in normal subjects. The W and W% were not different between the subject groups. The results indicate that at given airflows, lung sounds are lower in intensity and higher in pitch in asthmatics as compared with controls. This suggests that the generation and/or transmission of lung sounds in symptom-free patients with stable asthma differ from that in normal subjects, even when lung function is within the normal range. Therefore, airflow standardized phonopneumography might reflect morphologic changes in airways of patients with asthma.

Pulmonary functions in plastic factory workers: a preliminary study.

PubMed

Khaliq, Farah; Singh, Pawan; Chandra, Prakash; Gupta, Keshav; Vaney, Neelam

2011-01-01

Exposure to long term air pollution in the work environment may result in decreased lung functions and various other health problems. A significant occupational hazard to lung functions is experienced by plastic factory workers. The present study is planned to assess the pulmonary functions of workers in the plastic factory where recycling of pastic material was done. These workers were constantly exposed to fumes of various chemicals throughout the day. Thirty one workers of plastic factory were assessed for their pulmonary functions. Parameters were compared with 31 age and sex matched controls not exposed to the same environment. The pulmonary function tests were done using Sibelmed Datospir 120 B portable spirometer. A significant decrease in most of the flow rates (MEF 25%, MEF 50%, MEF 75% and FEF 25-75%) and most of the lung volumes and capacities (FVC, FEV1, VC, TV, ERV, MVV) were observed in the workers. Smoking and duration of exposure were not affecting the lung functions as the non smokers also showed a similar decrement in pulmonary functions. Similarly the workers working for less than 5 years also had decrement in pulmonary functions indicating that their lungs are being affected even if they have worked for one year. Exposure to the organic dust in the work environment should be controlled by adequate engineering measures, complemented by effective personal respiratory protection.

Unilateral donor lung dysfunction does not preclude successful contralateral single lung transplantation.

PubMed

Puskas, J D; Winton, T L; Miller, J D; Scavuzzo, M; Patterson, G A

1992-05-01

Single lung transplantation remains limited by a severe shortage of suitable donor lungs. Potential lung donors are often deemed unsuitable because accepted criteria (both lungs clear on the chest roentgenogram, arterial oxygen tension greater than 300 mm Hg with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 5 cm H2O, and no purulent secretions) do not distinguish between unilateral and bilateral pulmonary disease. Many adequate single lung grafts may be discarded as a result of contralateral aspiration or pulmonary trauma. We have recently used intraoperative unilateral ventilation and perfusion to assess single lung function in potential donors with contralateral lung disease. In the 11-month period ending October 1, 1990, we performed 18 single lung transplants. In four of these cases (22%), the donor chest roentgenogram or bronchoscopic examination demonstrated significant unilateral lung injury. Donor arterial oxygen tension, (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) was below the accepted level in each case (246 +/- 47 mm Hg, mean +/- standard deviation). Through the sternotomy used for multiple organ harvest, the pulmonary artery to the injured lung was clamped. A double-lumen endotracheal tube or endobronchial balloon occlusion catheter was used to permit ventilation of the uninjured lung alone. A second measurement of arterial oxygen tension (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) revealed excellent unilateral lung function in all four cases (499.5 +/- 43 mm Hg; p less than 0.0004). These single lung grafts (three right, one left) were transplanted uneventfully into four recipients (three with pulmonary fibrosis and one with primary pulmonary hypertension). Lung function early after transplantation was adequate in all patients. Two patients were extubated within 24 hours. There were two late deaths, one caused by rejection and Aspergillus infection and the other caused by cytomegalovirus 6 months after transplantation. Two patients are alive and doing well. We conclude that assessment of unilateral lung function in potential lung donors is indicated in selected cases, may be quickly and easily performed, and may significantly increase the availability of single lung grafts.

Airway symptoms and lung function among male workers in an area polluted from an oil tank explosion.

PubMed

Granslo, Jens-Tore; Bråtveit, Magne; Hollund, Bjørg Eli; Lygre, Stein Håkon Låstad; Svanes, Cecilie; Moen, Bente Elisabeth

2014-09-01

To assess whether working in an industrial harbor where an oil tank exploded was associated with more airway symptoms and lower lung function in men 1.5 years later. In a cross-sectional study of 180 men, 18 to 67 years old, airway symptoms and lung function among men who worked in the industrial harbor at the time of the explosion was compared with those of working men with residence more than 20 km away. Regression analyses are adjusted for smoking, occupational exposure, atopy, recent infection, and age. Exposed men had significantly more upper (ORirritated nose = 2.89 [95% confidence interval = 1.31 to 6.37]) and lower (ORdyspnea uphill = 3.79 [95% confidence interval = 1.69 to 8.46]) airway symptoms, and some indication of more reversible airway obstruction than unexposed workers. Men working in an area with an oil tank explosion had more airway symptoms and indication of more airway obstruction 1.5 years after the event.

The Preoperative Composite Physiologic Index May Predict Mortality in Lung Cancer Patients with Combined Pulmonary Fibrosis and Emphysema.

PubMed

Ueno, Fumika; Kitaguchi, Yoshiaki; Shiina, Takayuki; Asaka, Shiho; Miura, Kentaro; Yasuo, Masanori; Wada, Yosuke; Yoshizawa, Akihiko; Hanaoka, Masayuki

2017-01-01

It remains unclear whether the preoperative pulmonary function parameters and prognostic indices that are indicative of nutritional and immunological status are associated with prognosis in lung cancer patients with combined pulmonary fibrosis and emphysema (CPFE) who have undergone surgery. The aim of this study is to identify prognostic determinants in these patients. The medical records of all patients with lung cancer associated with CPFE who had undergone surgery at Shinshu University Hospital were retrospectively reviewed to obtain clinical data, including the results of preoperative pulmonary function tests and laboratory examinations, chest high-resolution computed tomography (HRCT), and survival. Univariate Cox proportional hazards regression analysis showed that a high pathological stage of the lung cancer, a higher preoperative serum carcinoembryonic antigen level, and a higher preoperative composite physiologic index (CPI) were associated with a high risk of death. Multivariate analysis showed that a high pathological stage of the lung cancer (HR: 1.579; p = 0.0305) and a higher preoperative CPI (HR: 1.034; p = 0.0174) were independently associated with a high risk of death. In contrast, the severity of fibrosis or emphysema on chest HRCT, the individual pulmonary function parameters, the prognostic nutritional index, the neutrophil-to-lymphocyte ratio, and the platelet-to-lymphocyte ratio were not associated with prognosis. In the Kaplan-Meier analysis, the log-rank test showed significant differences in survival between the high-CPI and the low-CPI group (p = 0.0234). The preoperative CPI may predict mortality and provide more powerful prognostic information than individual pulmonary function parameters in lung cancer patients with CPFE who have undergone surgery. © 2017 S. Karger AG, Basel.

Clinical value of CT-based preoperative software assisted lung lobe volumetry for predicting postoperative pulmonary function after lung surgery

NASA Astrophysics Data System (ADS)

Wormanns, Dag; Beyer, Florian; Hoffknecht, Petra; Dicken, Volker; Kuhnigk, Jan-Martin; Lange, Tobias; Thomas, Michael; Heindel, Walter

2005-04-01

This study was aimed to evaluate a morphology-based approach for prediction of postoperative forced expiratory volume in one second (FEV1) after lung resection from preoperative CT scans. Fifteen Patients with surgically treated (lobectomy or pneumonectomy) bronchogenic carcinoma were enrolled in the study. A preoperative chest CT and pulmonary function tests before and after surgery were performed. CT scans were analyzed by prototype software: automated segmentation and volumetry of lung lobes was performed with minimal user interaction. Determined volumes of different lung lobes were used to predict postoperative FEV1 as percentage of the preoperative values. Predicted FEV1 values were compared to the observed postoperative values as standard of reference. Patients underwent lobectomy in twelve cases (6 upper lobes; 1 middle lobe; 5 lower lobes; 6 right side; 6 left side) and pneumonectomy in three cases. Automated calculation of predicted postoperative lung function was successful in all cases. Predicted FEV1 ranged from 54% to 95% (mean 75% +/- 11%) of the preoperative values. Two cases with obviously erroneous LFT were excluded from analysis. Mean error of predicted FEV1 was 20 +/- 160 ml, indicating absence of systematic error; mean absolute error was 7.4 +/- 3.3% respective 137 +/- 77 ml/s. The 200 ml reproducibility criterion for FEV1 was met in 11 of 13 cases (85%). In conclusion, software-assisted prediction of postoperative lung function yielded a clinically acceptable agreement with the observed postoperative values. This method might add useful information for evaluation of functional operability of patients with lung cancer.

SU-E-J-86: Lobar Lung Function Quantification by PET Galligas and CT Ventilation Imaging in Lung Cancer Patients

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

Eslick, E; Kipritidis, J; Keall, P

2014-06-01

Purpose: The purpose of this study was to quantify the lobar lung function using the novel PET Galligas ([68Ga]-carbon nanoparticle) ventilation imaging and the investigational CT ventilation imaging in lung cancer patients pre-treatment. Methods: We present results on our first three lung cancer patients (2 male, mean age 78 years) as part of an ongoing ethics approved study. For each patient a PET Galligas ventilation (PET-V) image and a pair of breath hold CT images (end-exhale and end-inhale tidal volumes) were acquired using a Siemens Biograph PET CT. CT-ventilation (CT-V) images were created from the pair of CT images usingmore » deformable image registration (DIR) algorithms and the Hounsfield Unit (HU) ventilation metric. A comparison of ventilation quantification from each modality was done on the lobar level and the voxel level. A Bland-Altman plot was used to assess the difference in mean percentage contribution of each lobe to the total lung function between the two modalities. For each patient, a voxel-wise Spearmans correlation was calculated for the whole lungs between the two modalities. Results: The Bland-Altman plot demonstrated strong agreement between PET-V and CT-V for assessment of lobar function (r=0.99, p<0.001; range mean difference: −5.5 to 3.0). The correlation between PET-V and CT-V at the voxel level was moderate(r=0.60, p<0.001). Conclusion: This preliminary study on the three patients data sets demonstrated strong agreement between PET and CT ventilation imaging for the assessment of pre-treatment lung function at the lobar level. Agreement was only moderate at the level of voxel correlations. These results indicate that CT ventilation imaging has potential for assessing pre-treatment lobar lung function in lung cancer patients.« less

Prolonged Injury and Altered Lung Function after Ozone Inhalation in Mice with Chronic Lung Inflammation

PubMed Central

Groves, Angela M.; Gow, Andrew J.; Massa, Christopher B.; Laskin, Jeffrey D.

2012-01-01

Surfactant protein–D (Sftpd) is a pulmonary collectin important in down-regulating macrophage inflammatory responses. In these experiments, we analyzed the effects of chronic macrophage inflammation attributable to loss of Sftpd on the persistence of ozone-induced injury, macrophage activation, and altered functioning in the lung. Wild-type (Sftpd+/+) and Sftpd−/− mice (aged 8 wk) were exposed to air or ozone (0.8 parts per million, 3 h). Bronchoalveolar lavage (BAL) fluid and tissue were collected 72 hours later. In Sftpd−/− mice, but not Sftpd+/+ mice, increased BAL protein and nitrogen oxides were observed after ozone inhalation, indicating prolonged lung injury and oxidative stress. Increased numbers of macrophages were also present in BAL fluid and in histologic sections from Sftpd−/− mice. These cells were enlarged and foamy, suggesting that they were activated. This conclusion was supported by findings of increased BAL chemotactic activity, and increased expression of inducible nitric oxide synthase in lung macrophages. In both Sftpd+/+ and Sftpd−/− mice, inhalation of ozone was associated with functional alterations in the lung. Although these alterations were limited to central airway mechanics in Sftpd+/+ mice, both central airway and parenchymal mechanics were modified by ozone exposure in Sftpd−/− mice. The most notable changes were evident in resistance and elastance spectra and baseline lung function, and in lung responsiveness to changes in positive end-expiratory pressure. These data demonstrate that a loss of Sftpd is associated with prolonged lung injury, oxidative stress, and macrophage accumulation and activation in response to ozone, and with more extensive functional changes consistent with the loss of parenchymal integrity. PMID:22878412

Production and Assessment of Decellularized Pig and Human Lung Scaffolds

PubMed Central

Niles, Jean; Riddle, Michael; Vargas, Gracie; Schilagard, Tuya; Ma, Liang; Edward, Kert; La Francesca, Saverio; Sakamoto, Jason; Vega, Stephanie; Ogadegbe, Marie; Mlcak, Ronald; Deyo, Donald; Woodson, Lee; McQuitty, Christopher; Lick, Scott; Beckles, Daniel; Melo, Esther; Cortiella, Joaquin

2013-01-01

The authors have previously shown that acellular (AC) trachea-lung scaffolds can (1) be produced from natural rat lungs, (2) retain critical components of the extracellular matrix (ECM) such as collagen-1 and elastin, and (3) be used to produce lung tissue after recellularization with murine embryonic stem cells. The aim of this study was to produce large (porcine or human) AC lung scaffolds to determine the feasibility of producing scaffolds with potential clinical applicability. We report here the first attempt to produce AC pig or human trachea-lung scaffold. Using a combination of freezing and sodium dodecyl sulfate washes, pig trachea-lungs and human trachea-lungs were decellularized. Once decellularization was complete we evaluated the structural integrity of the AC lung scaffolds using bronchoscopy, multiphoton microscopy (MPM), assessment of the ECM utilizing immunocytochemistry and evaluation of mechanics through the use of pulmonary function tests (PFTs). Immunocytochemistry indicated that there was loss of collagen type IV and laminin in the AC lung scaffold, but retention of collagen-1, elastin, and fibronectin in some regions. MPM scoring was also used to examine the AC lung scaffold ECM structure and to evaluate the amount of collagen I in normal and AC lung. MPM was used to examine the physical arrangement of collagen-1 and elastin in the pleura, distal lung, lung borders, and trachea or bronchi. MPM and bronchoscopy of trachea and lung tissues showed that no cells or cell debris remained in the AC scaffolds. PFT measurements of the trachea-lungs showed no relevant differences in peak pressure, dynamic or static compliance, and a nonrestricted flow pattern in AC compared to normal lungs. Although there were changes in content of collagen I and elastin this did not affect the mechanics of lung function as evidenced by normal PFT values. When repopulated with a variety of stem or adult cells including human adult primary alveolar epithelial type II cells both pig and human AC scaffolds supported cell attachment and cell viability. Examination of scaffolds produced using a variety of detergents indicated that detergent choice influenced human immune response in terms of T cell activation and chemokine production. PMID:23638920

Production and assessment of decellularized pig and human lung scaffolds.

PubMed

Nichols, Joan E; Niles, Jean; Riddle, Michael; Vargas, Gracie; Schilagard, Tuya; Ma, Liang; Edward, Kert; La Francesca, Saverio; Sakamoto, Jason; Vega, Stephanie; Ogadegbe, Marie; Mlcak, Ronald; Deyo, Donald; Woodson, Lee; McQuitty, Christopher; Lick, Scott; Beckles, Daniel; Melo, Esther; Cortiella, Joaquin

2013-09-01

The authors have previously shown that acellular (AC) trachea-lung scaffolds can (1) be produced from natural rat lungs, (2) retain critical components of the extracellular matrix (ECM) such as collagen-1 and elastin, and (3) be used to produce lung tissue after recellularization with murine embryonic stem cells. The aim of this study was to produce large (porcine or human) AC lung scaffolds to determine the feasibility of producing scaffolds with potential clinical applicability. We report here the first attempt to produce AC pig or human trachea-lung scaffold. Using a combination of freezing and sodium dodecyl sulfate washes, pig trachea-lungs and human trachea-lungs were decellularized. Once decellularization was complete we evaluated the structural integrity of the AC lung scaffolds using bronchoscopy, multiphoton microscopy (MPM), assessment of the ECM utilizing immunocytochemistry and evaluation of mechanics through the use of pulmonary function tests (PFTs). Immunocytochemistry indicated that there was loss of collagen type IV and laminin in the AC lung scaffold, but retention of collagen-1, elastin, and fibronectin in some regions. MPM scoring was also used to examine the AC lung scaffold ECM structure and to evaluate the amount of collagen I in normal and AC lung. MPM was used to examine the physical arrangement of collagen-1 and elastin in the pleura, distal lung, lung borders, and trachea or bronchi. MPM and bronchoscopy of trachea and lung tissues showed that no cells or cell debris remained in the AC scaffolds. PFT measurements of the trachea-lungs showed no relevant differences in peak pressure, dynamic or static compliance, and a nonrestricted flow pattern in AC compared to normal lungs. Although there were changes in content of collagen I and elastin this did not affect the mechanics of lung function as evidenced by normal PFT values. When repopulated with a variety of stem or adult cells including human adult primary alveolar epithelial type II cells both pig and human AC scaffolds supported cell attachment and cell viability. Examination of scaffolds produced using a variety of detergents indicated that detergent choice influenced human immune response in terms of T cell activation and chemokine production.

[Current state and development of artificial lungs].

PubMed

Mei, Zaoxian; Sun, Xin; Wu, Qi

2010-12-01

The artificial lung is a technical device for providing life support; it will be put in use when the natural lungs are failing and are not able to maintain sufficient oxygenation of the body's organ systems. From the viewpoint of long-term development, the artificial lung should be permanently implanted in the body, so that it will substitute for the human pulmonary function partially or completely. In this paper, four artificial lung technologies were expounded with reference to the development and research process of artificial lung. They were extracorporeal membrane oxygenation, intravascular artificial lung, implantable artificial lung, and pumpless extracorporeal lung assist. In this paper were described the structure of the four kinds of artificial lung, the working principle, and their advantages, disadvantages and indications. The prospect of artificial lung was evaluated in the light of the data from the existing animal experiments and from the clinical experience of the centers.

Clinical Validation of 4-Dimensional Computed Tomography Ventilation With Pulmonary Function Test Data

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

Brennan, Douglas; Schubert, Leah; Diot, Quentin

Purpose: A new form of functional imaging has been proposed in the form of 4-dimensional computed tomography (4DCT) ventilation. Because 4DCTs are acquired as part of routine care for lung cancer patients, calculating ventilation maps from 4DCTs provides spatial lung function information without added dosimetric or monetary cost to the patient. Before 4DCT-ventilation is implemented it needs to be clinically validated. Pulmonary function tests (PFTs) provide a clinically established way of evaluating lung function. The purpose of our work was to perform a clinical validation by comparing 4DCT-ventilation metrics with PFT data. Methods and Materials: Ninety-eight lung cancer patients withmore » pretreatment 4DCT and PFT data were included in the study. Pulmonary function test metrics used to diagnose obstructive lung disease were recorded: forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity. Four-dimensional CT data sets and spatial registration were used to compute 4DCT-ventilation images using a density change–based and a Jacobian-based model. The ventilation maps were reduced to single metrics intended to reflect the degree of ventilation obstruction. Specifically, we computed the coefficient of variation (SD/mean), ventilation V20 (volume of lung ≤20% ventilation), and correlated the ventilation metrics with PFT data. Regression analysis was used to determine whether 4DCT ventilation data could predict for normal versus abnormal lung function using PFT thresholds. Results: Correlation coefficients comparing 4DCT-ventilation with PFT data ranged from 0.63 to 0.72, with the best agreement between FEV1 and coefficient of variation. Four-dimensional CT ventilation metrics were able to significantly delineate between clinically normal versus abnormal PFT results. Conclusions: Validation of 4DCT ventilation with clinically relevant metrics is essential. We demonstrate good global agreement between PFTs and 4DCT-ventilation, indicating that 4DCT-ventilation provides a reliable assessment of lung function. Four-dimensional CT ventilation enables exciting opportunities to assess lung function and create functional avoidance radiation therapy plans. The present work provides supporting evidence for the integration of 4DCT-ventilation into clinical trials.« less

Precision-cut vibratome slices allow functional live cell imaging of the pulmonary neuroepithelial body microenvironment in fetal mice.

PubMed

Schnorbusch, Kathy; Lembrechts, Robrecht; Brouns, Inge; Pintelon, Isabel; Timmermans, Jean-Pierre; Adriaensen, Dirk

2012-01-01

We recently developed an ex vivo lung slice model that allows for confocal live cell imaging (LCI) of neuroepithelial bodies (NEBs) in postnatal mouse lungs (postnatal days 1-21 and adult). NEBs are morphologically well-characterized, extensively innervated groups of neuroendocrine cells in the airway epithelium, which are shielded from the airway lumen by 'Clara-like' cells. The prominent presence of differentiated NEBs from early embryonic development onwards, strongly suggests that NEBs may exert important functions during late fetal and neonatal life. The main goal of the present study was to adapt the current postnatal LCI lung slice model to enable functional studies of fetal mouse lungs (gestational days 17-20).In vibratome lung slices of prenatal mice, NEBs could be unequivocally identified with the fluorescent stryryl pyridinium dye 4-Di-2-ASP. Changes in the intracellular free calcium concentration and in mitochondrial membrane potential could be monitored using appropriate functional fluorescent indicators (e.g. Fluo-4).It is clear that the described fetal mouse lung slice model is suited for LCI studies of Clara cells, ciliated cells, and the NEB microenvironment, and offers excellent possibilities to further unravel the significance of NEBs during the prenatal and perinatal period.

IL4R alpha mutations are associated with asthma exacerbations and mast cell/IgE expression.

PubMed

Wenzel, Sally E; Balzar, Silvana; Ampleford, Elizabeth; Hawkins, Gregory A; Busse, William W; Calhoun, William J; Castro, Mario; Chung, K Fan; Erzurum, Serpil; Gaston, Benjamin; Israel, Elliot; Teague, W Gerald; Curran-Everett, Douglas; Meyers, Deborah A; Bleecker, Eugene R

2007-03-15

Severe asthma has been associated with severe exacerbations, lower lung function and greater tissue inflammation. Previous studies have suggested that mutations in interleukin-4 receptor alpha (IL4Ralpha) are associated with lower lung function, higher IgE, and a gain in receptor function. However, an effect on exacerbations and tissue inflammation has not been shown. Allelic substitutions in IL4Ralpha are associated with asthma exacerbations, lower lung function, and tissue inflammation, in particular to mast cells and IgE. Two well-characterized cohorts of subjects with severe asthma were analyzed for five single nucleotide polymorphisms (SNPs) in IL4Ralpha. These polymorphisms were compared with the history of severe asthma exacerbations and lung function. In the primary (National Jewish) cohort, these polymorphisms were also compared with endobronchial tissue inflammatory cells and local IgE. In both cohorts, the presence of the minor alleles at E375A and Q551R, which were more common in African Americans, was associated with a history of severe exacerbations and lower lung function. In the National Jewish cohort, the C allele at E375A was associated with higher tissue mast cells and higher levels of IgE bound to mast cells. The significance for most of these associations remained when whites (the larger racial subgroup) were analyzed separately. SNPs in IL4Ralpha, which are more common in African Americans, are associated with severe asthma exacerbations, lower lung function, and increased mast cell-related tissue inflammation. Further studies of the impact of these mutations in African Americans and on receptor function are indicated.

Acute Exacerbations of COPD Are Associated With Increased Expression of Heparan Sulfate and Chondroitin Sulfate in BAL.

PubMed

Papakonstantinou, Eleni; Klagas, Ioannis; Roth, Michael; Tamm, Michael; Stolz, Daiana

2016-03-01

Acute exacerbations of COPD (AECOPDs) are associated with accelerated aggravation of clinical symptoms and deterioration of pulmonary function. The mechanisms by which exacerbations may contribute to airway remodeling and declined lung function are poorly understood. We investigated whether AECOPDs are associated with differential expression of glycosaminoglycans in BAL in a cohort of 97 patients with COPD. Patients with COPD with either stable disease (n = 53) or AECOPD (n = 44) and undergoing diagnostic bronchoscopy were matched for demographics and lung function parameters. Levels of heparan sulfate, chondroitin sulfate, dermatan sulfate, and matrix metalloproteinases (MMPs) in BAL were measured by enzyme-linked immunosorbent assay. Heparan sulfate and chondroitin sulfate were significantly increased in BAL of patients during exacerbations. Levels of heparan sulfate were higher in the BAL of patients with microbial infections. Chondroitin sulfate was negatively correlated with FEV1 % predicted but not with diffusing capacity of lung for carbon monoxide % predicted, indicating that chondroitin sulfate is associated with airway remodeling, leading to obstruction rather than to emphysema. Furthermore, heparan sulfate and chondroitin sulfate were significantly correlated with MMP-9, MMP-2, and MMP-12 in BAL, indicating that they were cleaved from their respective proteoglycans by MMPs and subsequently washed out in BAL. During AECOPD, there is increased expression of heparan sulfate and chondroitin sulfate in BAL. These molecules are significantly correlated with MMPs in BAL, indicating that they may be associated with airway remodeling and may lead to lung function decline during exacerbations of COPD. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Growth and nutritional status, and their association with lung function: a study from the international Primary Ciliary Dyskinesia Cohort.

PubMed

Goutaki, Myrofora; Halbeisen, Florian S; Spycher, Ben D; Maurer, Elisabeth; Belle, Fabiën; Amirav, Israel; Behan, Laura; Boon, Mieke; Carr, Siobhan; Casaulta, Carmen; Clement, Annick; Crowley, Suzanne; Dell, Sharon; Ferkol, Thomas; Haarman, Eric G; Karadag, Bulent; Knowles, Michael; Koerner-Rettberg, Cordula; Leigh, Margaret W; Loebinger, Michael R; Mazurek, Henryk; Morgan, Lucy; Nielsen, Kim G; Phillipsen, Maria; Sagel, Scott D; Santamaria, Francesca; Schwerk, Nicolaus; Yiallouros, Panayiotis; Lucas, Jane S; Kuehni, Claudia E

2017-12-01

Chronic respiratory disease can affect growth and nutrition, which can influence lung function. We investigated height, body mass index (BMI), and lung function in patients with primary ciliary dyskinesia (PCD).In this study, based on the international PCD (iPCD) Cohort, we calculated z-scores for height and BMI using World Health Organization (WHO) and national growth references, and assessed associations with age, sex, country, diagnostic certainty, age at diagnosis, organ laterality and lung function in multilevel regression models that accounted for repeated measurements.We analysed 6402 measurements from 1609 iPCD Cohort patients. Height was reduced compared to WHO (z-score -0.12, 95% CI -0.17 to -0.06) and national references (z-score -0.27, 95% CI -0.33 to -0.21) in male and female patients in all age groups, with variation between countries. Height and BMI were higher in patients diagnosed earlier in life (p=0.026 and p<0.001, respectively) and closely associated with forced expiratory volume in 1 s and forced vital capacity z-scores (p<0.001).Our study indicates that both growth and nutrition are affected adversely in PCD patients from early life and are both strongly associated with lung function. If supported by longitudinal studies, these findings suggest that early diagnosis with multidisciplinary management and nutritional advice could improve growth and delay disease progression and lung function impairment in PCD. Copyright ©ERS 2017.

Lung microvascular transport properties measured by multiple indicator dilution methods in patients with adult respiratory distress syndrome. A comparison between patients reversing respiratory failure and those failing to reverse

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

Harris, T.R.; Bernard, G.R.; Brigham, K.L.

1990-02-01

We conducted indicator dilution studies on the lungs of patients in the early phases of adult respiratory distress syndrome (ARDS) to test the hypothesis that capillary permeability was increased in patients with respiratory failure. Indicator dilution studies were performed using 51Cr-erythrocytes, 125I-albumin, 14C-urea, and 3H-water as tracers. The injectate was infused as a bolus into a central venous line. Peripheral arterial blood was collected and counted for radioactivity. Mathematical analysis of the indicator curves yielded cardiac output, measures of the product of capillary permeability and surface area for urea (PS and D1/2S), the intravascular lung volume (Vv), and the extravascularmore » lung water volume (Ve). Permeability was separated from surface area by normalizing PS and D1/2S to Vv. Patients could be divided into 16 in whom blood gas determinations and radiologic criteria for ARDS were reversed and 23 in whom they were not. We examined indicator dilution and other measures of lung function in the two groups to determine whether significant differences in microvascular function existed. PS and PS/Vv were significantly higher in the nonreversal patients. Ve was above normal, but not different between groups. Linear regression analysis showed significant correlations for all of the following in the nonreversal group: Ve and all measures of permeability, pulmonary vascular resistance (PVR), and the inverse of permeability-surface area measures and AaDO2 and PVR. Only measures of Ve and PS correlated in the reversal group. These results support the hypothesis that capillary permeability is increased in patients with early ARDS and continuing respiratory failure.« less

Structural-functional lung imaging using a combined CT-EIT and a Discrete Cosine Transformation reconstruction method.

PubMed

Schullcke, Benjamin; Gong, Bo; Krueger-Ziolek, Sabine; Soleimani, Manuchehr; Mueller-Lisse, Ullrich; Moeller, Knut

2016-05-16

Lung EIT is a functional imaging method that utilizes electrical currents to reconstruct images of conductivity changes inside the thorax. This technique is radiation free and applicable at the bedside, but lacks of spatial resolution compared to morphological imaging methods such as X-ray computed tomography (CT). In this article we describe an approach for EIT image reconstruction using morphologic information obtained from other structural imaging modalities. This leads to recon- structed images of lung ventilation that can easily be superimposed with structural CT or MRI images, which facilitates image interpretation. The approach is based on a Discrete Cosine Transformation (DCT) of an image of the considered transversal thorax slice. The use of DCT enables reduction of the dimensionality of the reconstruction and ensures that only conductivity changes of the lungs are reconstructed and displayed. The DCT based approach is well suited to fuse morphological image information with functional lung imaging at low computational costs. Results on simulated data indicate that this approach preserves the morphological structures of the lungs and avoids blurring of the solution. Images from patient measurements reveal the capabilities of the method and demonstrate benefits in possible applications.

Structural-functional lung imaging using a combined CT-EIT and a Discrete Cosine Transformation reconstruction method

PubMed Central

Schullcke, Benjamin; Gong, Bo; Krueger-Ziolek, Sabine; Soleimani, Manuchehr; Mueller-Lisse, Ullrich; Moeller, Knut

2016-01-01

Lung EIT is a functional imaging method that utilizes electrical currents to reconstruct images of conductivity changes inside the thorax. This technique is radiation free and applicable at the bedside, but lacks of spatial resolution compared to morphological imaging methods such as X-ray computed tomography (CT). In this article we describe an approach for EIT image reconstruction using morphologic information obtained from other structural imaging modalities. This leads to recon- structed images of lung ventilation that can easily be superimposed with structural CT or MRI images, which facilitates image interpretation. The approach is based on a Discrete Cosine Transformation (DCT) of an image of the considered transversal thorax slice. The use of DCT enables reduction of the dimensionality of the reconstruction and ensures that only conductivity changes of the lungs are reconstructed and displayed. The DCT based approach is well suited to fuse morphological image information with functional lung imaging at low computational costs. Results on simulated data indicate that this approach preserves the morphological structures of the lungs and avoids blurring of the solution. Images from patient measurements reveal the capabilities of the method and demonstrate benefits in possible applications. PMID:27181695

Differential protein-coding gene and long noncoding RNA expression in smoking-related lung squamous cell carcinoma.

PubMed

Li, Shicheng; Sun, Xiao; Miao, Shuncheng; Liu, Jia; Jiao, Wenjie

2017-11-01

Cigarette smoking is one of the greatest preventable risk factors for developing cancer, and most cases of lung squamous cell carcinoma (lung SCC) are associated with smoking. The pathogenesis mechanism of tumor progress is unclear. This study aimed to identify biomarkers in smoking-related lung cancer, including protein-coding gene, long noncoding RNA, and transcription factors. We selected and obtained messenger RNA microarray datasets and clinical data from the Gene Expression Omnibus database to identify gene expression altered by cigarette smoking. Integrated bioinformatic analysis was used to clarify biological functions of the identified genes, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, the construction of a protein-protein interaction network, transcription factor, and statistical analyses. Subsequent quantitative real-time PCR was utilized to verify these bioinformatic analyses. Five hundred and ninety-eight differentially expressed genes and 21 long noncoding RNA were identified in smoking-related lung SCC. GO and KEGG pathway analysis showed that identified genes were enriched in the cancer-related functions and pathways. The protein-protein interaction network revealed seven hub genes identified in lung SCC. Several transcription factors and their binding sites were predicted. The results of real-time quantitative PCR revealed that AURKA and BIRC5 were significantly upregulated and LINC00094 was downregulated in the tumor tissues of smoking patients. Further statistical analysis indicated that dysregulation of AURKA, BIRC5, and LINC00094 indicated poor prognosis in lung SCC. Protein-coding genes AURKA, BIRC5, and LINC00094 could be biomarkers or therapeutic targets for smoking-related lung SCC. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

PubMed

Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

2015-11-01

Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. Copyright © 2015 by The American Association of Immunologists, Inc.

Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity

PubMed Central

Turrell, Frances K.; Kerr, Emma M.; Gao, Meiling; Thorpe, Hannah; Doherty, Gary J.; Cridge, Jake; Shorthouse, David; Speed, Alyson; Samarajiwa, Shamith; Hall, Benjamin A.; Griffiths, Meryl; Martins, Carla P.

2017-01-01

Lung adenocarcinoma accounts for ∼40% of lung cancers, the leading cause of cancer-related death worldwide, and current therapies provide only limited survival benefit. Approximately half of lung adenocarcinomas harbor mutations in TP53 (p53), making these mutants appealing targets for lung cancer therapy. As mutant p53 remains untargetable, mutant p53-dependent phenotypes represent alternative targeting opportunities, but the prevalence and therapeutic relevance of such effects (gain of function and dominant-negative activity) in lung adenocarcinoma are unclear. Through transcriptional and functional analysis of murine KrasG12D-p53null, -p53R172H (conformational), and -p53R270H (contact) mutant lung tumors, we identified genotype-independent and genotype-dependent therapeutic sensitivities. Unexpectedly, we found that wild-type p53 exerts a dominant tumor-suppressive effect on mutant tumors, as all genotypes were similarly sensitive to its restoration in vivo. These data show that the potential of p53 targeted therapies is comparable across all p53-deficient genotypes and may explain the high incidence of p53 loss of heterozygosity in mutant tumors. In contrast, mutant p53 gain of function and their associated vulnerabilities can vary according to mutation type. Notably, we identified a p53R270H-specific sensitivity to simvastatin in lung tumors, and the transcriptional signature that underlies this sensitivity was also present in human lung tumors, indicating that this therapeutic approach may be clinically relevant. PMID:28790158

Six-year trajectory of objective physical function in persons with depressive and anxiety disorders.

PubMed

Lever-van Milligen, Bianca A; Lamers, Femke; Smit, Jan H; Penninx, Brenda W J H

2017-02-01

Depression and anxiety have been related to poorer self-reported physical functioning over time; however, objective measures of physical function are less frequently examined. This study assessed the 6-year trajectory of hand-grip strength and lung function in persons with depressive and/or anxiety disorders. At four waves (baseline, 2, 4, and 6 years) hand-grip strength and lung function were assessed in 2,480 participants, aged 18-65 years, of the Netherlands Study of Depression and Anxiety. Linear mixed models were used to examine the association between baseline psychiatric status (current and remitted depression and anxiety, healthy controls) and physical function during 6-year follow-up, adjusted for sociodemographics, lifestyle, and health indicators. Although there were no differences in the rate of decline over time, women with current, but not remitted, depression and anxiety had poorer hand-grip strength (B = -1.34, P < .001) and poorer lung function (B = -11.91, P =.002) compared to healthy women during the entire 6-year follow-up. Associations with depression and anxiety severity measures confirmed dose-response relationships with objective physical function. In men, stronger 6-year decline of lung function was found in those with current disorders (current diagnosis-by-time: B = -11.72, P = .002) and even in those with remitted disorders (remitted diagnosis by time: B = -10.11, P = .04) compared to healthy men. Depression and anxiety are associated with consistently poorer hand-grip strength in women and poorer lung function in women and men over 6 years of time, implicating their long-lasting impact on physical functioning. © 2016 Wiley Periodicals, Inc.

Which early life events or current environmental and lifestyle factors influence lung function in adolescents? - results from the GINIplus & LISAplus studies.

PubMed

Luzak, Agnes; Fuertes, Elaine; Flexeder, Claudia; Standl, Marie; von Berg, Andrea; Berdel, Dietrich; Koletzko, Sibylle; Heinrich, Joachim; Nowak, Dennis; Schulz, Holger

2017-07-12

Various factors may affect lung function at different stages in life. Since investigations that simultaneously consider several factors are rare, we examined the relative importance of early life, current environmental/lifestyle factors and allergic diseases on lung function in 15-year-olds. Best subset selection was performed for linear regression models to investigate associations between 21 diverse early life events and current factors with spirometric parameters (forced vital capacity, forced expiratory volume in 1 s and maximal mid-expiratory flow (FEF 25-75 )) in 1326 participants of the German GINIplus and LISAplus birth cohorts. To reduce model complexity, one model for each spirometric parameter was replicated 1000 times in random subpopulations (N = 884). Only those factors that were included in >70% of the replication models were retained in the final analysis. A higher peak weight velocity and early lung infections were the early life events prevalently associated with airflow limitation and FEF 25-75 . Current environmental/lifestyle factors at age 15 years and allergic diseases that were associated with lung function were: indoor second-hand smoke exposure, vitamin D concentration, body mass index (BMI) and asthma status. Sex and height captured the majority of the explained variance (>75%), followed by BMI (≤23.7%). The variance explained by early life events was comparatively low (median: 4.8%; range: 0.2-22.4%), but these events were consistently negatively associated with airway function. Although the explained variance was mainly captured by well-known factors included in lung function prediction equations, our findings indicate early life and current factors that should be considered in studies on lung health among adolescents.

Relationship between clinical signs and pulmonary function estimated by the single breath diagram for CO(2) (SBD-CO(2)) in horses with chronic obstructive pulmonary disease.

PubMed

Herholz, C; Straub, R; Gerber, V; Wampfler, B; Lüthi, S; Imhof, A; Moens, Y; Busato, A

2002-03-01

The pulmonary health of 66 horses was assessed by a clinical examination and simple supplementary diagnostic methods. Single breath diagrams for CO(2) (SBD-CO(2)) and derived lung function indices were used to determine pulmonary function. The clinical signs in different groups were related to the results of the lung function indices derived from the SBD-CO(2). In horses with moderate to severe chronic obstructive pulmonary disease (COPD), a significant relationship was found between the respiratory frequency and the ratio of Bohr's dead space to the tidal volume (VD(Bohr)/VT), and between the physiological dead space/tidal volume ratio (VD(phys)/VT) and the ratio of the alveolar dead space to the alveolar tidal volume (VD(alv)/VT(alv)), but no significant associations were found between the arterial oxygen tension (P(a)O(2)) and lung function indices derived from the SBD-CO(2). The occurrence of cough, the viscosity of tracheobronchial mucus and the amount of polynuclear neutrophils in tracheobronchial aspirates were significantly related to the expiratory tidal volume (VT), the total expired volume of CO(2) (VCO(2)), VD(Bohr)/VT, VD(phys)/VT and VD(alv)/VT(alv). We conclude that abnormal findings in these clinical parameters indicate a measurable ventilation and perfusion (V(A)/Q) mismatch which is reflected by increases in dead space, VD(Bohr)/VT and VD(phys)/VT as well as VD(alv)/VT(alv). Copyright 2002 Elsevier Science Ltd. All rights reserved.

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

PubMed

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

2017-12-19

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

The β-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22.

PubMed

Lilly, Lauren M; Gessner, Melissa A; Dunaway, Chad W; Metz, Allison E; Schwiebert, Lisa; Weaver, Casey T; Brown, Gordon D; Steele, Chad

2012-10-01

Sensitization to fungi, such as the mold Aspergillus fumigatus, is increasingly becoming linked with asthma severity. We have previously shown that lung responses generated via the β-glucan receptor Dectin-1 are required for lung defense during acute, invasive A. fumigatus infection. Unexpectedly, in an allergic model of chronic lung exposure to live A. fumigatus conidia, β-glucan recognition via Dectin-1 led to the induction of multiple proallergic (Muc5ac, Clca3, CCL17, CCL22, and IL-33) and proinflammatory (IL-1β and CXCL1) mediators that compromised lung function. Attenuated proallergic and proinflammatory responses in the absence of Dectin-1 were not associated with changes in Ido (IDO), Il12p35/Ebi3 (IL-35), IL-10, or TGF-β levels. Assessment of Th responses demonstrated that purified lung CD4(+) T cells produced IL-4, IL-13, IFN-γ, and IL-17A, but not IL-22, in a Dectin-1-dependent manner. In contrast, we observed robust, Dectin-1-dependent IL-22 production by unfractionated lung digest cells. Intriguingly, the absence of IL-22 alone mimicked the attenuated proallergic and proinflammatory responses observed in the absence of Dectin-1, suggesting that Dectin-1-mediated IL-22 production potentiated responses that led to decrements in lung function. To this end, neutralization of IL-22 improved lung function in normal mice. Collectively, these results indicate that the β-glucan receptor Dectin-1 contributes to lung inflammation and immunopathology associated with persistent fungal exposure via the production of IL-22.

Clinical utility of computed tomographic lung volumes in patients with chronic obstructive pulmonary disease.

PubMed

Lee, Jae Seung; Lee, Sang-Min; Seo, Joon Beom; Lee, Sei Won; Huh, Jin Won; Oh, Yeon-Mok; Lee, Sang-Do

2014-01-01

Published data concerning the utility of computed tomography (CT)-based lung volumes are limited to correlation with lung function. The aim of this study was to evaluate the clinical utility of the CT expiratory-to-inspiratory lung volume ratio (CT Vratio) by assessing the relationship with clinically relevant outcomes. A total of 75 stable chronic obstructive pulmonary disease (COPD) patients having pulmonary function testing and volumetric CT at full inspiration and expiration were retrospectively evaluated. Inspiratory and expiratory CT lung volumes were measured using in-house software. Correlation of the CT Vratio with patient-centered outcomes, including the modified Medical Research Council (MMRC) dyspnea score, the 6-min walk distance (6MWD), the St. George's Respiratory Questionnaire (SGRQ) score, and multidimensional COPD severity indices, such as the BMI, airflow obstruction, dyspnea, and exercise capacity index (BODE) and age, dyspnea, and airflow obstruction (ADO), were analyzed. The CT Vratio correlated significantly with BMI (r = -0.528, p < 0.001). The CT Vratio was also significantly associated with MMRC dyspnea (r = 0.387, p = 0.001), 6MWD (r = -0.459, p < 0.001), and SGRQ (r = 0.369, p = 0.001) scores. Finally, the CT Vratio had significant correlations with the BODE and ADO multidimensional COPD severity indices (r = 0.605, p < 0.001; r = 0.411, p < 0.001). The CT Vratio had significant correlations with patient-centered outcomes and multidimensional COPD severity indices. © 2013 S. Karger AG, Basel.

Improvement in lung function and functional capacity in morbidly obese women subjected to bariatric surgery.

PubMed

Campos, Elaine Cristina de; Peixoto-Souza, Fabiana Sobral; Alves, Viviane Cristina; Basso-Vanelli, Renata; Barbalho-Moulim, Marcela; Laurino-Neto, Rafael Melillo; Costa, Dirceu

2018-03-15

To determine whether weight loss in women with morbid obesity subjected to bariatric surgery alters lung function, respiratory muscle strength, functional capacity and the level of habitual physical activity and to investigate the relationship between these variables and changes in both body composition and anthropometrics. Twenty-four women with morbid obesity were evaluated with regard to lung function, respiratory muscle strength, functional capacity, body composition, anthropometrics and the level of habitual physical activity two weeks prior to and six months after bariatric surgery. Regarding lung function, mean increases of 160 mL in slow vital capacity, 550 mL in expiratory reserve volume, 290 mL in forced vital capacity and 250 mL in forced expiratory volume in the first second as well as a mean reduction of 490 mL in inspiratory capacity were found. Respiratory muscle strength increased by a mean of 10 cmH2O of maximum inspiratory pressure, and a 72-meter longer distance on the Incremental Shuttle Walk Test demonstrated that functional capacity also improved. Significant changes also occurred in anthropometric variables and body composition but not in the level of physical activity detected using the Baecke questionnaire, indicating that the participants remained sedentary. Moreover, correlations were found between the percentages of lean and fat mass and both inspiratory and expiratory reserve volumes. The present data suggest that changes in body composition and anthropometric variables exerted a direct influence on functional capacity and lung function in the women analyzed but exerted no influence on sedentarism, even after accentuated weight loss following bariatric surgery.

Use of a Doppler pulmonary artery catheter for continuous measurement of right ventricular pump function and contractility during single lung transplantation.

PubMed

Heerdt, P M; Pond, C G; Kussman, M K; Triantafillou, A N

1993-01-01

Despite numerous technologic advances in intraoperative monitoring, the only methods routinely available for assessment of right ventricular function in lung transplant recipients are continuous measurement of right heart pressures and intermittent thermodilution determination of cardiac output and ejection fraction. Additional data may now be obtained with transesophageal echocardiography, although this technology is expensive and not widely available and requires diverting attention from a potentially unstable patient for data acquisition and analysis. Recently, a Doppler pulmonary artery catheter was introduced that measures beat-to-beat pulmonary artery blood flow-velocity, cross sectional area, and volume flow. Because of data indicating that acceleration of blood in the pulmonary artery (measured as the first derivative of either the velocity or flow waveform) is a sensitive indicator of right ventricular contractility, we have used waveforms obtained with the catheter for assessment of right ventricular pump function (stroke volume and peak pulmonary artery flow rate) and contractility in heart surgery patients. We report here our experience with this method in two patients undergoing left single lung transplantation.

Robot-assisted thoracoscopic lobectomy as treatment of a giant bulla.

PubMed

Roemers, Rosa; Patberg, Kornelis; van de Wauwer, Caroline; Nguyen, Tam; Shahin, Ghada

2017-05-18

A bulla is a marked enlarged space within the parenchyma of the lung. Bullae may cause dyspnea by compressing healthy lung parenchyma and can cause a pneumothorax. Also, bullae are associated with malignancy, therefore surgical bullectomy is indicated on preventive basis. This case is unique and therefore valuable because of the remarkable presentation, innovative treatment and the spectacular improvement of lung function and socio-economic performance of the patient. In this case report we describe the presentation, minimally invasive surgical treatment by means of a robot-assisted lobectomy and postoperative outcome of a young patient with a giant congenital bulla of the left upper lobe. In this case robot-assisted lobectomy has shown spectacular improvement of lung function and fast-track recovery with beneficial socio-economic performance in a young patient with a giant congenital bulla.

[The dose response decrease of lung function associated with the urinary polycyclic aromatic hydrocarbons metabolites in coke oven workers].

PubMed

Hu, Die; Deng, Qi-fei; Huang, Su-li; He, Yun-feng; Guo, Huan; Wu, Tang-chun

2012-12-01

To analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and lung function in coke oven workers, and to provide scientific basis for further exploring the potential mechanism and developing the preventing strategies of the workers' early lung damage. We measured carbon monoxide, sulfur dioxide, benzene soluble matter, particulate matters, and PAHs at different workplaces of a coke oven plant. Detailed information on demography and occupational health condition of 912 workers were collected. We divided these workers into control group and coke oven group according to their workplaces and the different concentrations of COEs in the environment. We detected 10 urinary PAH metabolites and lung function using gas chromatography-mass spectrometry and spirometric tests, respectively. FEV(1.0) (91.12 ± 13.31) and FEV(1.0)/FVC (108.61 ± 20.37) of the coke oven group is significantly lower than the control group (94.16 ± 15.57, 113.45 ± 19.70). In the coke oven group, the hydroxyphenanthrene and 1-hydroxypyrene are negatively correlated with FEV(1.0)/FVC (β = -0.136, β = -0.100), Ptrend < 0.05 for all. The dose response decrease of lung function is associated with the urinary PAH metabolites in coke oven workers. Indicated that the long exposure to PAHs may cause the early lung damage in coke oven workers, phenanthrene and pyrene may be the main factors.

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.

Indoor molds and lung function in healthy adults.

PubMed

Hernberg, Samu; Sripaiboonkij, Penpatra; Quansah, Reginald; Jaakkola, Jouni J K; Jaakkola, Maritta S

2014-05-01

Indoor mold exposure is common worldwide and constitutes an important health problem. There are very few studies assessing the relation between mold exposure and lung function levels among non-asthmatic adults. Our objective was to assess the relations between dampness and mold exposures at home and at work and lung function. In particular, we elaborated the importance of different exposure indicators. In a population-based study, 269 non-asthmatic adults from South Finland answered a questionnaire on indoor dampness and mold exposures at home or at work and other factors potentially influencing lung function, and performed spirometry. Multiple linear regression model was applied to study the relations between exposures and spirometric lung function levels. In linear regression adjusting for confounding, FEV1 level was reduced on average 200 ml related to mold odor at home (effect estimate -0.20, 95% CI -0.60 to 0.21) and FVC level was reduced on average 460 ml (-0.46, -0.95 to 0.03) respectively. Exposure to mold odor at home or at work or both was related to reduced FEV1 (-0.15, -0.42 to 0.12) and FVC (-0.22, -0.55 to 0.11) levels. Women had on average 510 ml reduced FEV1 levels (-0.51, -1.0 to 0.03) and 820 ml reduced FVC levels (-0.82, -1.4 to -0.20) related to mold odor exposure at home. Mold odor exposure was related to lower lung function levels among non-asthmatic adults, especially among women. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sensitivity of newly defined impulse oscillometry indices in preschool children.

PubMed

Knihtilä, Hanna; Kotaniemi-Syrjänen, Anne; Pelkonen, Anna S; Kalliola, Satu; Mäkelä, Mika J; Malmberg, L Pekka

2017-05-01

Early origins of chronic obstructive pulmonary disease have been recognized. Impulse oscillometry (IOS) is suitable for assessment of lung function also in preschool children, and some novel indices have been connected to assessment of small airway function. However, limited data exist on the sensitivity of these new indices to detect lung function deficits in young symptomatic children. IOS measurements of 103 healthy preschool children were evaluated to establish reference equations for the difference between respiratory resistance at 5 and 20 Hz (R5-20), the relative difference of R5-20 (R5-20%), and area under the reactance curve (AX). Thereafter, IOS results of children with late-onset troublesome lung symptoms (n = 20), a history of early wheeze (n = 37), or a history of bronchopulmonary dysplasia (BPD, n = 8) were compared to healthy children. None of the patient groups differed from healthy regarding respiratory resistance at 5 Hz (R5), and only children with a history of BPD differed from healthy regarding respiratory reactance at 5 Hz (X5). In contrast, z-scores of R5-20, R5-20%, and AX were significantly higher in all patient groups than in healthy children (P < 0.001), showing improved sensitivity (20-55%) compared to R5 and X5 (5-6%). R5-20, R5-20%, and AX are superior to conventional IOS parameters in distinguishing children with current or past lower respiratory tract symptoms from healthy, and may prove valuable for screening early lung function deficits. Pediatr Pulmonol. 2017;52:598-605. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of ambient air pollution from municipal solid waste landfill on children's non-specific immunity and respiratory health.

PubMed

Yu, Yunjiang; Yu, Ziling; Sun, Peng; Lin, Bigui; Li, Liangzhong; Wang, Zhengdong; Ma, Ruixue; Xiang, Mingdeng; Li, Hui; Guo, Shu

2018-05-01

This cross-sectional study investigated the association between air pollutant (AP) and respiratory health of 951 children residing near a municipal solid waste (MSW) landfill in Northern China. Results showed that students in non-exposure areas had significantly higher levels of lysozyme, secretory immunoglobulin A (SIgA), and better lung capacity than students in exposure areas (p < .05). Multiple regression model analysis indicated that lysozyme levels exhibited a consistent negative association with methane (CH 4 : β = -76.3, 95% CI -105 to -47.7) and sulfuretted hydrogen (H 2 S: β = -11.7, 95% CI -20.2 to -3.19). In addition, SIgA levels were negatively associated with H 2 S (β = -68.9, 95% CI -97.9 to -39.9) and ammonia (NH 3 : β = -30.3, 95% CI -51.7 to -8.96). Among all AP, H 2 S and sulfur dioxide (SO 2 ) were the most robustly related with reduced lung function. H 2 S exposure was negatively associated with six lung function indices, 1-s forced expiratory volume (FEV1%), mean forced expiratory flow between 25% and 75% (MMF), maximum voluntary ventilation (MVV), and forced expiratory flow at 25%, 50%, and 75% of the pulmonary volume (FEF25, FEF50, FEF75); and SO 2 was negatively associated with FEV1%, MVV, FEF25, FEF50 and FEF75. Our results suggested that AP exposure was negatively associated with more lung function parameters in boys than in girls. In conclusion, our findings suggested that children living adjacent to landfill sites were more likely to have deficient non-specific immunity and impaired lung function. Copyright © 2017 Elsevier Ltd. All rights reserved.

SU-E-I-90: Characterizing Small Animal Lung Properties Using Speckle Observed with An In-Line X-Ray Phase Contrast Benchtop System

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

Garson, A; Gunsten, S; Guan, H

Purpose: We demonstrate a novel X-ray phase-contrast (XPC) method for lung imaging representing a paradigm shift in the way small animal functional imaging is performed. In our method, information regarding airway microstructure that is encoded within speckle texture of a single XPC radiograph is decoded to produce 2D parametric images that will spatially resolve changes in lung properties such as microstructure sizes and air volumes. Such information cannot be derived from conventional lung radiography or any other 2D imaging modality. By computing these images at different points within a breathing cycle, dynamic functional imaging will be readily achieved without themore » need for tomography. Methods: XPC mouse lung radiographs acquired in situ with an in-line X-ray phase contrast benchtop system. The lung air volume is varied and controlled with a small animal ventilator. XPC radiographs will be acquired for various lung air volume levels representing different phases of the respiratory cycle. Similar data will be acquired of microsphere-based lung phantoms containing hollow glass spheres with known distributions of diameters. Image texture analysis is applied to the data to investigate relationships between texture characteristics and airspace/microsphere physical properties. Results: Correlations between Fourier-based texture descriptors (FBTDs) and regional lung air volume indicate that the texture features in 2D radiographs reveal information on 3D properties of the lungs. For example, we find for a 350 × 350 πm2 lung ROI a linear relationship between injected air volume and FBTD value with slope and intercept of 8.9×10{sup 5} and 7.5, respectively. Conclusion: We demonstrate specific image texture measures related to lung speckle features are correlated with physical characteristics of refracting elements (i.e. lung air spaces). Furthermore, we present results indicating the feasibility of implementing the technique with a simple imaging system design, short exposures, and low dose which provides potential for widespread use in laboratory settings for in vivo studies. This research was supported in part by NSF Award CBET1263988.« less

Paclitaxel-induced lung injury and its amelioration by parecoxib sodium.

PubMed

Liu, Wen-jie; Zhong, Zhong-jian; Cao, Long-hui; Li, Hui-ting; Zhang, Tian-hua; Lin, Wen-qian

2015-08-10

To investigate the mechanism of paclitaxel-induced lung injury and its amelioration by parecoxib sodium. In this study, rats were randomly divided into: the control group (Con); the paclitaxel chemotherapy group (Pac); the paclitaxel+ parecoxib sodium intervention group (Pac + Pare); and the parecoxib sodium group (Pare). We observed changes in alveolar ventilation function, alveolar-capillary membrane permeability, lung tissue pathology and measured the levels of inflammatory cytokines and cyclooxygenase-2 (Cox-2) in lung tissue, the expression of tight junction proteins (Zo-1 and Claudin-4). Compared with the Con group, the lung tissue of the Pac group showed significantly increased expression of Cox-2 protein (p < 0.01), significant lung tissue inflammatory changes, significantly increased expression of inflammatory cytokines, decreased expression of Zo-1 and Claudin-4 proteins (p < 0.01), increased alveolar-capillary membrane permeability (p < 0.01), and reduced ventilation function (p < 0.01). Notably, in Pac + Pare group, intraperitoneal injection of parecoxib sodium led to decreased Cox-2 and ICAM-1 levels and reduced inflammatory responses, the recovered expression of Zo-1 and Claudin-4, reduced level of indicators reflecting the high permeability state, and close-to-normal levels of ventilation function. Intervention by the Cox-2-specific inhibitor parecoxib sodium can block this damage.

Paclitaxel-induced lung injury and its amelioration by parecoxib sodium

PubMed Central

Liu, Wen-jie; Zhong, Zhong-jian; Cao, Long-hui; Li, Hui-ting; Zhang, Tian-hua; Lin, Wen-qian

2015-01-01

To investigate the mechanism of paclitaxel-induced lung injury and its amelioration by parecoxib sodium. In this study, rats were randomly divided into: the control group (Con); the paclitaxel chemotherapy group (Pac); the paclitaxel+ parecoxib sodium intervention group (Pac + Pare); and the parecoxib sodium group (Pare). We observed changes in alveolar ventilation function, alveolar-capillary membrane permeability, lung tissue pathology and measured the levels of inflammatory cytokines and cyclooxygenase-2 (Cox-2) in lung tissue, the expression of tight junction proteins (Zo-1 and Claudin-4). Compared with the Con group, the lung tissue of the Pac group showed significantly increased expression of Cox-2 protein (p < 0.01), significant lung tissue inflammatory changes, significantly increased expression of inflammatory cytokines, decreased expression of Zo-1 and Claudin-4 proteins (p < 0.01), increased alveolar-capillary membrane permeability (p < 0.01), and reduced ventilation function (p < 0.01). Notably, in Pac + Pare group, intraperitoneal injection of parecoxib sodium led to decreased Cox-2 and ICAM-1 levels and reduced inflammatory responses, the recovered expression of Zo-1 and Claudin-4, reduced level of indicators reflecting the high permeability state, and close-to-normal levels of ventilation function. Intervention by the Cox-2-specific inhibitor parecoxib sodium can block this damage. PMID:26256764

Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury.

PubMed

Whitehead, Gregory S; Grasman, Keith A; Kimmel, Edgar C

2003-02-01

Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the lavage fluid. Increased MIP-2 levels also preceded the maximum neutrophil infiltration. The differences in the time-course and primary site of TNF-alpha, MIP-2, and IFN-gamma expression; and the differences in the temporal relationship between their expression and infiltration of inflammatory cells may have accounted for the differences in lung function between paraquat treated and ACM smoke exposed animals.

The Markers of Glutamate Metabolism in Peripheral Blood Mononuclear Cells and Neurological Complications in Lung Cancer Patients

PubMed Central

Ambrosius, Wojciech; Gazdulska, Joanna; Gołda-Gocka, Iwona; Kozubski, Wojciech; Ramlau, Rodryg

2016-01-01

Objective. To evaluate the involvement of glutamate metabolism in peripheral blood mononuclear cells (PBMC) in the development of neurological complications in lung cancer and during chemotherapy. Methods. The prospective study included 221 lung cancer patients treated with chemotherapeutics. Neurological status and cognitive functions were evaluated at baseline and after 6-month follow-up. Glutamate level, the activities of glutaminase- (GLS-) glutamate synthetizing enzyme, glutamate dehydrogenase (GDH), and glutamate decarboxylase catalyzing glutamate degradation were analyzed in PBMC and in sera of lung cancer patients by means of spectrophotometric and colorimetric methods. Results. Chemotherapy of lung neoplasms induced increase of glutamate content in PBMC and its concentration in serum increased the activity of GDH in PBMC and decreased activity of glutaminase in PBMC. The changes in glutamate metabolism markers were associated with initial manifestation of neurological deficit in lung cancer patients and with new symptoms, which appear as a complication of chemotherapy. Moreover, the analyzed parameters of glutamate control correlated with a spectrum of cognitive functions measures in lung cancer patients. Conclusion. We have demonstrated dysregulation in glutamate and glutamate metabolism controlling enzymes as promising indicators of risk for chemotherapy-induced neurological complications in lung cancer patients with particular emphasis on cognitive impairment. PMID:28044066

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.

A preclinical rodent model of acute radiation-induced lung injury after ablative focal irradiation reflecting clinical stereotactic body radiotherapy.

PubMed

Hong, Zhen-Yu; Lee, Hae-June; Choi, Won Hoon; Lee, Yoon-Jin; Eun, Sung Ho; Lee, Jung Il; Park, Kwangwoo; Lee, Ji Min; Cho, Jaeho

2014-07-01

In a previous study, we established an image-guided small-animal micro-irradiation system mimicking clinical stereotactic body radiotherapy (SBRT). The goal of this study was to develop a rodent model of acute phase lung injury after ablative irradiation. A radiation dose of 90 Gy was focally delivered to the left lung of C57BL/6 mice using a small animal stereotactic irradiator. At days 1, 3, 5, 7, 9, 11 and 14 after irradiation, the lungs were perfused with formalin for fixation and paraffin sections were stained with hematoxylin and eosin (H&E) and Masson's trichrome. At days 7 and 14 after irradiation, micro-computed tomography (CT) images of the lung were taken and lung functional measurements were performed with a flexiVent™ system. Gross morphological injury was evident 9 days after irradiation of normal lung tissues and dynamic sequential events occurring during the acute phase were validated by histopathological analysis. CT images of the mouse lungs indicated partial obstruction located in the peripheral area of the left lung. Significant alteration in inspiratory capacity and tissue damping were detected on day 14 after irradiation. An animal model of radiation-induced lung injury (RILI) in the acute phase reflecting clinical stereotactic body radiotherapy was established and validated with histopathological and functional analysis. This model enhances our understanding of the dynamic sequential events occurring in the acute phase of radiation-induced lung injury induced by ablative dose focal volume irradiation.

Microgravity and the lung

NASA Technical Reports Server (NTRS)

West, John B.

1991-01-01

Results are presented from studies of the effect of microgravity on the lungs of rats flown on the Cosmos 2044 mission, and from relevant laboratory experiments. The effects of microgravity fall into five categories: topographical structure and function, the lung volumes and mechanics, the intrathoracic blood pressures and volumes, the pulmonary deposition of aerosol, and denitrogenaton during EVA. The ultrastructure of the left lungs of rats flown for 14 days on the Cosmos 2044 spacecraft and that of some tail-suspended rats disclosed presence of red blood cells in the alveolar spaces, indicating that pulmonary hemorrhage and pulmonary edema occurred in these rats. Possible causes for this phenomenon are discussed.

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.

A new approach to assess COPD by identifying lung function break-points

PubMed Central

Eriksson, Göran; Jarenbäck, Linnea; Peterson, Stefan; Ankerst, Jaro; Bjermer, Leif; Tufvesson, Ellen

2015-01-01

Purpose COPD is a progressive disease, which can take different routes, leading to great heterogeneity. The aim of the post-hoc analysis reported here was to perform continuous analyses of advanced lung function measurements, using linear and nonlinear regressions. Patients and methods Fifty-one COPD patients with mild to very severe disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I–IV) and 41 healthy smokers were investigated post-bronchodilation by flow-volume spirometry, body plethysmography, diffusion capacity testing, and impulse oscillometry. The relationship between COPD severity, based on forced expiratory volume in 1 second (FEV1), and different lung function parameters was analyzed by flexible nonparametric method, linear regression, and segmented linear regression with break-points. Results Most lung function parameters were nonlinear in relation to spirometric severity. Parameters related to volume (residual volume, functional residual capacity, total lung capacity, diffusion capacity [diffusion capacity of the lung for carbon monoxide], diffusion capacity of the lung for carbon monoxide/alveolar volume) and reactance (reactance area and reactance at 5Hz) were segmented with break-points at 60%–70% of FEV1. FEV1/forced vital capacity (FVC) and resonance frequency had break-points around 80% of FEV1, while many resistance parameters had break-points below 40%. The slopes in percent predicted differed; resistance at 5 Hz minus resistance at 20 Hz had a linear slope change of −5.3 per unit FEV1, while residual volume had no slope change above and −3.3 change per unit FEV1 below its break-point of 61%. Conclusion Continuous analyses of different lung function parameters over the spirometric COPD severity range gave valuable information additional to categorical analyses. Parameters related to volume, diffusion capacity, and reactance showed break-points around 65% of FEV1, indicating that air trapping starts to dominate in moderate COPD (FEV1 =50%–80%). This may have an impact on the patient’s management plan and selection of patients and/or outcomes in clinical research. PMID:26508849

Radiological Evaluation of Artificial Stone Silicosis Outbreak: Emphasizing Findings in Lung Transplant Recipients.

PubMed

Grubstein, Ahuva; Shtraichman, Osnat; Fireman, Elizabeth; Bachar, Gil N; Noach-Ophir, Noa; Kramer, Mordechai R

The aim of this study was to describe the computed tomography (CT) findings and correlate pulmonary function tests (PFTs) of silicosis patients with emphasis on the findings in lung transplantation (LTX) recipients. We studied the chest CT scans from 82 marble workers exposed to artificial stone dust and who had a diagnosis of silicosis, of whom 13 patients underwent LTX. Silicosis-associated findings were graded and correlated to concomitant PFT. A statistically significant inverse relationship was found between chest CT scores and PFT including forced expired volume in the first second (r = -0.54, P < 0.0001), total lung capacity (r = -0.4, P < 0.0001), and diffusion capacity for carbon monoxide single breath % (r = -0.6, P < 0.0001) parameters. Progressive massive fibrosis indicating advanced and complicated silicosis was found in 85% of LTX patients, as compared with 40% in patients with maintained pulmonary function. Ground-glass opacities were seen in some LTX patients with or without signs of progressive massive fibrosis. Two of these patients had silicoproteinosis diagnosed within the resected lung, indicating an acute or accelerated form of silicosis. This silicosis current outbreak is important because of the worldwide use of this and similar high-silica-content, artificial stone products, which can cause progressive severe forms of silicosis. Along with standard clinical assessment and PFT, CT parameters are indicative measures of the disease severity.

Improvement in lung function and functional capacity in morbidly obese women subjected to bariatric surgery

PubMed Central

de Campos, Elaine Cristina; Peixoto-Souza, Fabiana Sobral; Alves, Viviane Cristina; Basso-Vanelli, Renata; Barbalho-Moulim, Marcela; Laurino-Neto, Rafael Melillo; Costa, Dirceu

2018-01-01

OBJECTIVE: To determine whether weight loss in women with morbid obesity subjected to bariatric surgery alters lung function, respiratory muscle strength, functional capacity and the level of habitual physical activity and to investigate the relationship between these variables and changes in both body composition and anthropometrics. METHODS: Twenty-four women with morbid obesity were evaluated with regard to lung function, respiratory muscle strength, functional capacity, body composition, anthropometrics and the level of habitual physical activity two weeks prior to and six months after bariatric surgery. RESULTS: Regarding lung function, mean increases of 160 mL in slow vital capacity, 550 mL in expiratory reserve volume, 290 mL in forced vital capacity and 250 mL in forced expiratory volume in the first second as well as a mean reduction of 490 mL in inspiratory capacity were found. Respiratory muscle strength increased by a mean of 10 cmH2O of maximum inspiratory pressure, and a 72-meter longer distance on the Incremental Shuttle Walk Test demonstrated that functional capacity also improved. Significant changes also occurred in anthropometric variables and body composition but not in the level of physical activity detected using the Baecke questionnaire, indicating that the participants remained sedentary. Moreover, correlations were found between the percentages of lean and fat mass and both inspiratory and expiratory reserve volumes. CONCLUSION: The present data suggest that changes in body composition and anthropometric variables exerted a direct influence on functional capacity and lung function in the women analyzed but exerted no influence on sedentarism, even after accentuated weight loss following bariatric surgery. PMID:29561930

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.

Automatic estimation of heart boundaries and cardiothoracic ratio from chest x-ray images

NASA Astrophysics Data System (ADS)

Dallal, Ahmed H.; Agarwal, Chirag; Arbabshirani, Mohammad R.; Patel, Aalpen; Moore, Gregory

2017-03-01

Cardiothoracic ratio (CTR) is a widely used radiographic index to assess heart size on chest X-rays (CXRs). Recent studies have suggested that also two-dimensional CTR might contain clinical information about the heart function. However, manual measurement of such indices is both subjective and time consuming. This study proposes a fast algorithm to automatically estimate CTR indices based on CXRs. The algorithm has three main steps: 1) model based lung segmentation, 2) estimation of heart boundaries from lung contours, and 3) computation of cardiothoracic indices from the estimated boundaries. We extended a previously employed lung detection algorithm to automatically estimate heart boundaries without using ground truth heart markings. We used two datasets: a publicly available dataset with 247 images as well as clinical dataset with 167 studies from Geisinger Health System. The models of lung fields are learned from both datasets. The lung regions in a given test image are estimated by registering the learned models to patient CXRs. Then, heart region is estimated by applying Harris operator on segmented lung fields to detect the corner points corresponding to the heart boundaries. The algorithm calculates three indices, CTR1D, CTR2D, and cardiothoracic area ratio (CTAR). The method was tested on 103 clinical CXRs and average error rates of 7.9%, 25.5%, and 26.4% (for CTR1D, CTR2D, and CTAR respectively) were achieved. The proposed method outperforms previous CTR estimation methods without using any heart templates. This method can have important clinical implications as it can provide fast and accurate estimate of cardiothoracic indices.

Lung function in asphalt pavers: a longitudinal study.

PubMed

Ulvestad, Bente; Randem, Britt Grethe; Skare, Øivind; Aaløkken, Trond Mogens; Myranek, Georg Karl; Elihn, Karine; Lund, May Brit

2017-01-01

To study longitudinal changes in lung function in asphalt pavers and a reference group of road maintenance workers, and to detect possible signs of lung disease by high-resolution computed tomography (HRCT) scans. Seventy-five asphalt pavers and 71 road maintenance workers were followed up with questionnaires and measurements of lung function. Not every worker was tested every year, but most of them had four or more measurement points. The 75 asphalt pavers were also invited to have HRCT scans of the lungs at the end of the follow-up period. Mean annual decline in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ) of the asphalt pavers was 58 and 35 ml, respectively. Adjusted for age at baseline, packyears of smoking and BMI, the asphalt pavers had a significant excess annual decline in FVC and FEV 1 compared to the references. The screedmen, the most exposed group of the asphalt pavers, showed a significantly larger decline in FVC than the other asphalt pavers (P = 0.029). Fine intralobular fibrosis without evident cysts was identified with HRCT in three subjects (4 %). We conclude that our findings may indicate an excess annual decline in FVC and FEV 1 related to exposure to asphalt fumes. The screedmen, who carry out their work behind and close to the paving machine, had the largest decline in lung function. The finding of adverse pulmonary effects in asphalt pavers calls for better technological solutions to prevent exposure.

Validation of the plain chest radiograph for epidemiologic studies of airflow obstruction

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

Musk, A.W.

The chest radiographs of 125 industrial workers from rural New South Wales were examined for overinflated lungs, with and without attenuated midzonal vessels. Although the mean values of a comprehensive range of pulmonary function tests in the whole group were within normal limits, the nine subjects whose radiographs showed overinflated lungs and attenuated vessels had significantly impaired pulmonary function in comparison with 85 subjects with normal radiographs. The mean values for these nine subjects, expressed as a percentage of the mean value for subjects with normal radiographs, were: forced expiratory volume in 1 second, 75%; total lung capacity, 107%; residualmore » volume, 143%; transpulmonary pressure at maximum inspiration, 60%; static deflation compliance, 158%; lung volume at transpulmonary pressure 10 cm H/sub 2/O, 132%; transfer factor, 79%; and transfer factor/alveolar volume, 77%. Similar results were obtained by a second observer. Those subjects with overinflation but no vascular attenuation had significantly larger mean values for vital capacity and alveolar volume but no significant difference in total lung capacity or other tests of the mechanical properties of the lungs. Agreement on the presence of a positive sign between the two observers expressed as a percentage of those considered positive by either was 81% for overinflation and 62% for attenuated midzonal vessels. The results indicate that in groups of subjects with normal-average values of pulmonary function, the plain chest radiograph may provide information concerning pulmonary structure that is reflected in tests of function.« less

The association between endotoxin and lung function among children and adolescents living in a rural area

PubMed Central

Lawson, Joshua A; Dosman, James A; Rennie, Donna C; Beach, Jeremy; Newman, Stephen C; Senthilselvan, Ambikaipakan

2011-01-01

BACKGROUND/OBJECTIVES: Knowledge of the effects of domestic endotoxin on children’s lung function is limited. The association between domestic endotoxin and asthma or wheeze and lung function among school-age children (six to 18 years of age) was examined. The interaction between endotoxin and other personal and environmental characteristics and lung function was also assessed. METHODS: A case-control study was conducted in and around the rural community of Humboldt, Saskatchewan, between 2005 and 2007. Parents of cases reported either doctor-diagnosed asthma or wheeze in the previous year. Controls were randomly selected from those not reporting these conditions. Data were collected by questionnaire to ascertain symptoms and conditions, while spirometry was used to measure lung function including forced vital capacity and forced expiratory volume in 1 s. Dust collected from the child’s play area floor and the child’s mattress was used to quantify endotoxin, and saliva was collected to quantify cotinine levels and assess tobacco smoke exposure. RESULTS: There were 102 cases and 207 controls included in the present study. Lower forced expiratory volume in 1 s was associated with higher mattress endotoxin load among female cases (beta=−0.25, SE=0.07 [P<0.01]). There was a trend toward lower forced vital capacity, which was associated with higher play area endotoxin load among cases with high tobacco smoke exposure (beta=−0.17, SE=0.09 [P<0.10]). CONCLUSIONS: Findings indicated that high endotoxin levels present in common household areas of rural children with asthma or wheeze may also affect their lung function. These associations may be potentiated by tobacco smoke exposure and female sex. PMID:22187693

Influence of Lung Function and Sleep-disordered Breathing on All-Cause Mortality. A Community-based Study.

PubMed

Putcha, Nirupama; Crainiceanu, Ciprian; Norato, Gina; Samet, Jonathan; Quan, Stuart F; Gottlieb, Daniel J; Redline, Susan; Punjabi, Naresh M

2016-10-15

Whether sleep-disordered breathing (SDB) severity and diminished lung function act synergistically to heighten the risk of adverse health outcomes remains a topic of significant debate. The current study sought to determine whether the association between lower lung function and mortality would be stronger in those with increasing severity of SDB in a community-based cohort of middle-aged and older adults. Full montage home sleep testing and spirometry data were analyzed on 6,173 participants of the Sleep Heart Health Study. Proportional hazards models were used to calculate risk for all-cause mortality, with FEV 1 and apnea-hypopnea index (AHI) as the primary exposure indicators along with several potential confounders. All-cause mortality rate was 26.9 per 1,000 person-years in those with SDB (AHI ≥5 events/h) and 18.2 per 1,000 person-years in those without (AHI <5 events/h). For every 200-ml decrease in FEV 1 , all-cause mortality increased by 11.0% in those without SDB (hazard ratio, 1.11; 95% confidence interval, 1.08-1.13). In contrast, for every 200-ml decrease in FEV 1 , all-cause mortality increased by only 6.0% in participants with SDB (hazard ratio, 1.06; 95% confidence interval, 1.04-1.09). Additionally, the incremental influence of lung function on all-cause mortality was less with increasing severity of SDB (P value for interaction between AHI and FEV 1 , 0.004). Lung function was associated with risk for all-cause mortality. The incremental contribution of lung function to mortality diminishes with increasing severity of SDB.

Influence of Lung Function and Sleep-disordered Breathing on All-Cause Mortality. A Community-based Study

PubMed Central

Putcha, Nirupama; Crainiceanu, Ciprian; Norato, Gina; Samet, Jonathan; Quan, Stuart F.; Gottlieb, Daniel J.; Redline, Susan

2016-01-01

Rationale: Whether sleep-disordered breathing (SDB) severity and diminished lung function act synergistically to heighten the risk of adverse health outcomes remains a topic of significant debate. Objectives: The current study sought to determine whether the association between lower lung function and mortality would be stronger in those with increasing severity of SDB in a community-based cohort of middle-aged and older adults. Methods: Full montage home sleep testing and spirometry data were analyzed on 6,173 participants of the Sleep Heart Health Study. Proportional hazards models were used to calculate risk for all-cause mortality, with FEV1 and apnea–hypopnea index (AHI) as the primary exposure indicators along with several potential confounders. Measurements and Main Results: All-cause mortality rate was 26.9 per 1,000 person-years in those with SDB (AHI ≥5 events/h) and 18.2 per 1,000 person-years in those without (AHI <5 events/h). For every 200-ml decrease in FEV1, all-cause mortality increased by 11.0% in those without SDB (hazard ratio, 1.11; 95% confidence interval, 1.08–1.13). In contrast, for every 200-ml decrease in FEV1, all-cause mortality increased by only 6.0% in participants with SDB (hazard ratio, 1.06; 95% confidence interval, 1.04–1.09). Additionally, the incremental influence of lung function on all-cause mortality was less with increasing severity of SDB (P value for interaction between AHI and FEV1, 0.004). Conclusions: Lung function was associated with risk for all-cause mortality. The incremental contribution of lung function to mortality diminishes with increasing severity of SDB. PMID:27105053

Treatment of acute lung injury by targeting MG53-mediated cell membrane repair

PubMed Central

Lieber, Gissela; Nishi, Miyuki; Yan, Rosalie; Wang, Zhen; Yao, Yonggang; Li, Yu; Whitson, Bryan A.; Duann, Pu; Li, Haichang; Zhou, Xinyu; Zhu, Hua; Takeshima, Hiroshi; Hunter, John C.; McLeod, Robbie L.; Weisleder, Noah; Zeng, Chunyu; Ma, Jianjie

2014-01-01

Injury to lung epithelial cells has a role in multiple lung diseases. We previously identified mitsugumin 53 (MG53) as a component of the cell membrane repair machinery in striated muscle cells. Here we show that MG53 also has a physiological role in the lung and may be used as a treatment in animal models of acute lung injury. Mice lacking MG53 show increased susceptibility to ischemia-reperfusion and over-ventilation induced injury to the lung when compared with wild type mice. Extracellular application of recombinant human MG53 (rhMG53) protein protects cultured lung epithelial cells against anoxia/reoxygenation-induced injuries. Intravenous delivery or inhalation of rhMG53 reduces symptoms in rodent models of acute lung injury and emphysema. Repetitive administration of rhMG53 improves pulmonary structure associated with chronic lung injury in mice. Our data indicate a physiological function for MG53 in the lung and suggest that targeting membrane repair may be an effective means for treatment or prevention of lung diseases. PMID:25034454

In vitro particulate matter exposure causes direct and lung-mediated indirect effects on cardiomyocyte function.

PubMed

Gorr, Matthew W; Youtz, Dane J; Eichenseer, Clayton M; Smith, Korbin E; Nelin, Timothy D; Cormet-Boyaka, Estelle; Wold, Loren E

2015-07-01

Particulate matter (PM) exposure induces a pathological response from both the lungs and the cardiovascular system. PM is capable of both manifestation into the lung epithelium and entrance into the bloodstream. Therefore, PM has the capacity for both direct and lung-mediated indirect effects on the heart. In the present studies, we exposed isolated rat cardiomyocytes to ultrafine particulate matter (diesel exhaust particles, DEP) and examined their contractile function and calcium handling ability. In another set of experiments, lung epithelial cells (16HBE14o- or Calu-3) were cultured on permeable supports that allowed access to both the basal (serosal) and apical (mucosal) media; the basal media was used to culture cardiomyocytes to model the indirect, lung-mediated effects of PM on the heart. Both the direct and indirect treatments caused a reduction in contractility as evidenced by reduced percent sarcomere shortening and reduced calcium handling ability measured in field-stimulated cardiomyocytes. Treatment of cardiomyocytes with various anti-oxidants before culture with DEP was able to partially prevent the contractile dysfunction. The basal media from lung epithelial cells treated with PM contained several inflammatory cytokines, and we found that monocyte chemotactic protein-1 was a key trigger for cardiomyocyte dysfunction. These results indicate the presence of both direct and indirect effects of PM on cardiomyocyte function in vitro. Future work will focus on elucidating the mechanisms involved in these separate pathways using in vivo models of air pollution exposure. Copyright © 2015 the American Physiological Society.

Effect of a smoking ban on respiratory health in nonsmoking hospitality workers: a prospective cohort study.

PubMed

Rajkumar, Sarah; Stolz, Daiana; Hammer, Jürg; Moeller, Alexander; Bauer, Georg F; Huynh, Cong Khanh; Röösli, Martin

2014-10-01

The aim of this study was to examine the effect of a smoking ban on lung function, fractional exhaled nitric oxide, and respiratory symptoms in nonsmoking hospitality workers. Secondhand smoke exposure at the workplace, spirometry, and fractional exhaled nitric oxide were measured in 92 nonsmoking hospitality workers before as well as twice after a smoking ban. At baseline, secondhand smoke-exposed hospitality workers had lung function values significantly below the population average. After the smoking ban, the covariate-adjusted odds ratio for cough was 0.59 (95% confidence interval, 0.36 to 0.93) and for chronic bronchitis 0.75 (95% confidence interval, 0.55 to 1.02) compared with the preban period. The below-average lung function before the smoking ban indicates chronic damages from long-term exposure. Respiratory symptoms such as cough decreased within 12 months after the ban.

Respiratory muscle adaptations: a comparison between bodybuilders and endurance athletes.

PubMed

Hackett, D A; Johnson, N; Chow, C

2013-04-01

The purpose of this study was to compare the respiratory muscle and lung function measures of bodybuilders (BB) and endurance athletes (EA). Forty-two male subjects (22 BB and 20 EA) aged 20-35 years underwent respiratory muscle strength measurements (MIP and MEP), lung function testing (FEV1, FVC, FEV1/FVC%, IC, ERV, FRC, RV, and TLC), hydrostatic weighing and VO2max testing. One-repetition maximum (1RM) for bench press, squat and deadlift was performed by BB. BB had significantly greater MIP and MEP compared to EA by 43% and 53% respectively (P<0.01). Moderate correlation was found for MEP and 1RM bench press (P<0.01), and weak correlations found for the squat and deadlift (P<0.01). Fat-free mass was significantly greater for BB compared with EA (P<0.01), while VO2max was significantly greater for EA compared with BB (P<0.01). No differences in lung function indices were observed between groups. When compared to EA, BB exhibited significantly greater respiratory muscle strength. The maximal load lifted for bench press predicted expiratory muscle strength gain. Lung function measures did not differ between the groups.

Respiratory function in wind instrument players.

PubMed

Zuskin, Eugenija; Mustajbegovic, Jadranka; Schachter, E N; Kern, Josipa; Vitale, Ksenija; Pucarin-Cvetkovic, Jasna; Chiarelli, A; Milosevic, M; Jelinic, Jagoda Doko

2009-01-01

The playing of wind instruments has been associated with changes in respiratory function. To investigate the effect of playing wind instruments on lung function and respiratory symptoms. The present study included 99 wind instrument players and a group of 41 string instrument players as a control from 3 major orchestras in Zagreb, Croatia. Data on chronic respiratory symptoms were recorded in all studied subjects. Lung function was measured in wind instrument players by recording maximum expiratory flow-volume curves. Wind instrument players demonstrated significantly higher prevalences of sinusitis, nasal catarrh and hoarseness compared to control musicians. One wind instrument player developed asthma associated with his work. Odds ratios for wind instrument players were significant for chronic cough, chronic phlegm and chronic bronchitis by smoking habit (p<0.05 or p<0.01) but not for length of employment. Ventilatory capacity data indicate that wind instrument players had significantly greater FEV1 (smokers and nonsmokers) as well as FEF50 (nonsmokers) (p<0.05) compared to predicted values. Regression analysis of pulmonary function tests in wind instrument players demonstrate a significant link between FEV1 and FEF50 and length of employment. Those wind instrument players with longer employment had the greatest increases in lung function. Our data suggest that musicians playing wind instruments may be susceptible to chronic upper airway symptoms. Interestingly wind instrument playing may be associated with higher than expected lung function parameters.

WE-AB-202-04: Statistical Evaluation of Lung Function Using 4DCT Ventilation Imaging: Proton Therapy VS IMRT

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

Huang, Q; Zhang, M; Chen, T

Purpose: Variation in function of different lung regions has been ignored so far for conventional lung cancer treatment planning, which may lead to higher risk of radiation induced lung disease. 4DCT based lung ventilation imaging provides a novel yet convenient approach for lung functional imaging as 4DCT is taken as routine for lung cancer treatment. Our work aims to evaluate the impact of accounting for spatial heterogeneity in lung function using 4DCT based lung ventilation imaging for proton and IMRT plans. Methods: Six patients with advanced stage lung cancer of various tumor locations were retrospectively evaluated for the study. Protonmore » and IMRT plans were designed following identical planning objective and constrains for each patient. Ventilation images were calculated from patients’ 4DCT using deformable image registration implemented by Velocity AI software based on Jacobian-metrics. Lung was delineated into two function level regions based on ventilation (low and high functional area). High functional region was defined as lung ventilation greater than 30%. Dose distribution and statistics in different lung function area was calculated for patients. Results: Variation in dosimetric statistics of different function lung region was observed between proton and IMRT plans. In all proton plans, high function lung regions receive lower maximum dose (100.2%–108.9%), compared with IMRT plans (106.4%–119.7%). Interestingly, three out of six proton plans gave higher mean dose by up to 2.2% than IMRT to high function lung region. Lower mean dose (lower by up to 14.1%) and maximum dose (lower by up to 9%) were observed in low function lung for proton plans. Conclusion: A systematic approach was developed to generate function lung ventilation imaging and use it to evaluate plans. This method hold great promise in function analysis of lung during planning. We are currently studying more subjects to evaluate this tool.« less

Extraction of immune and inflammatory cells from human lung parenchyma: evaluation of an enzymatic digestion procedure.

PubMed Central

Holt, P G; Robinson, B W; Reid, M; Kees, U R; Warton, A; Dawson, V H; Rose, A; Schon-Hegrad, M; Papadimitriou, J M

1986-01-01

The inflammatory and immune cell populations of the human lung parenchyma have not been characterized in detail. This report describes a novel and efficient procedure for their extraction. Histologically normal human lung tissue samples from pneumonectomy specimens were sliced to 0.5 mm, and digested in collagenase/DNAse. Viable mononuclear cell yields ranged from 15-48 X 10(6)/g, and were markedly in excess of reported methods employing mechanical tissue disruption, which normally yield populations containing almost exclusively macrophages. The lung digest population was examined by flow cytometry using monoclonal antibodies against cell surface receptors, and found to comprise up to 40% T lymphocytes, 10% B lymphocytes and 30% macrophages, contaminated by less than 1% peripheral blood cells. Based upon these figures, the recoverable lung parenchymal lymphoid cell pool appears considerably larger than previously recognized, being of the same order as the peripheral blood pool. Initial functional studies suggest that such cellular activities as antigen-specific T cell proliferation, antigen-presentation, interleukin 1 production and natural killer cell activity survive the extraction process, and controlled enzymatic digestion experiments with peripheral blood cells indicate that the degree of enzyme-mediated damage to these functions and to cell-surface structures, was minimal. The extraction method thus appears suitable for studying the types and functions of human parenchymal lung cells in health and disease. Images Fig. 2 p195-a PMID:3026698

Bronchoscopic Lung Volume Reduction with Endobronchial Valves in Low-FEV1 Patients.

PubMed

Darwiche, Kaid; Karpf-Wissel, Rüdiger; Eisenmann, Stephan; Aigner, Clemens; Welter, Stefan; Zarogoulidis, Paul; Hohenforst-Schmidt, Wolfgang; Freitag, Lutz; Oezkan, Filiz

2016-01-01

Bronchoscopic lung volume reduction (BLVR) with valves has been shown to improve lung function, exercise capacity, and quality of life in patients with emphysema, but only few patients with forced expiratory volume in 1 s (FEV1) ≤20% predicted have been included in former studies. Although the procedure can be performed safely, pneumothorax is a frequent complication, which can be critical for these very severely diseased patients. The aim of the study was to assess the safety of BLVR in patients with a very advanced stage of emphysema, as indicated by FEV1 ≤20% predicted. Patients in whom BLVR was performed between January 2013 and August 2015 were included in this analysis if their baseline predicted FEV1 was ≤20%. BLVR, performed only if collateral ventilation was absent, achieved complete occlusion of the target lobe. All patients were closely monitored and were not discharged before the fourth day after BLVR. Twenty patients with FEV1 ≤20% predicted were included in the analysis. Lung volume reduction was achieved in 65% of the cases. Pneumothorax occurred in 4 cases (20%). No patient died. Lung function and exercise tolerance improved after 1 and 3 months, respectively. BLVR with valves can be safely performed in patients with FEV1 ≤20% predicted when close postprocedural monitoring is provided. Improvement in lung function and exercise capacity can be achieved. © 2016 S. Karger AG, Basel.

Reduced Lung Function and Cerebral Small Vessel Disease in Japanese Men: the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).

PubMed

Seto-Yukimura, Ruriko; Ogawa, Emiko; Hisamatsu, Takashi; Torii, Sayuki; Shiino, Akihiko; Nozaki, Kazuhiko; Fujiyoshi, Akira; Miura, Katsuyuki; Nakano, Yasutaka; Ueshima, Hirotsugu

2018-02-16

We aimed to investigate the association between reduced lung function and cerebral small vessel diseases via cranial magnetic resonance imaging (MRI) in the cross-sectional study of the general Japanese population. We recruited participants aged ≥40 years from the general population of a single city in Japan. We clarified the comorbidities and treatments, smoking habits, second-hand smoke exposure, current alcohol consumption, education level, exercise habits, and occupation. The pulmonary function test was performed to assess the forced expiratory volume in 1 second (FEV 1 ) % predicted and forced vital capacity (FVC) % predicted values. Cranial MRI was performed to evaluate the white matter lesions (WMLs) and lacunar infarcts. We examined the association of the WMLs and lacunar infarcts with a 1-standard deviation (SD) lower in the FEV 1 % predicted and FVC % predicted, on the basis of the smoking status. A total of 473 men were examined. The association of WMLs and lacunar infarcts with the spirometry-based indices were significant only in never smokers. The association between lung function impairment and cerebral small vessel disease did not change after further adjusting for second-hand smoke exposure. In a community-based sample of Japanese men, we found an association between reduced lung function and WMLs and lacunar infarcts in never smokers.

Adenovirus vector expressing keratinocyte growth factor using CAG promoter impairs pulmonary function of mice with elastase-induced emphysema.

PubMed

Oki, Hiroshi; Yazawa, Takuya; Baba, Yasuko; Kanegae, Yumi; Sato, Hanako; Sakamoto, Seiko; Goto, Takahisa; Saito, Izumu; Kurahashi, Kiyoyasu

2017-07-01

Pulmonary emphysema impairs quality of life and increases mortality. It has previously been shown that administration of adenovirus vector expressing murine keratinocyte growth factor (KGF) before elastase instillation prevents pulmonary emphysema in mice. We therefore hypothesized that therapeutic administration of KGF would restore damage to lungs caused by elastase instillation and thus improve pulmonary function in an animal model. KGF expressing adenovirus vector, which prevented bleomycin-induced pulmonary fibrosis in a previous study, was constructed. Adenovirus vector (1.0 × 10 9 plaque-forming units) was administered intratracheally one week after administration of elastase into mouse lungs. One week after administration of KGF-vector, exercise tolerance testing and blood gas analysis were performed, after which the lungs were removed under deep anesthesia. KGF-positive pneumocytes were more numerous, surfactant protein secretion in the airspace greater and mean linear intercept of lungs shorter in animals that had received KGF than in control animals. Unexpectedly, however, arterial blood oxygenation was worse in the KGF group and maximum running speed, an indicator of exercise capacity, had not improved after KGF in mice with elastase-induced emphysema, indicating that KGF-expressing adenovirus vector impaired pulmonary function in these mice. Notably, vector lacking KGF-expression unit did not induce such impairment, implying that the KGF expression unit itself may cause the damage to alveolar cells. Possible involvement of the CAG promoter used for KGF expression in impairing pulmonary function is discussed. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment.

PubMed

Winkler-Heil, R; Hussain, M; Hofmann, W

2015-05-01

Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM(-1). If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas.

Sterilization of Lung Matrices by Supercritical Carbon Dioxide

PubMed Central

Balestrini, Jenna L.; Liu, Angela; Gard, Ashley L.; Huie, Janet; Blatt, Kelly M.S.; Schwan, Jonas; Zhao, Liping; Broekelmann, Tom J.; Mecham, Robert P.; Wilcox, Elise C.

2016-01-01

Lung engineering is a potential alternative to transplantation for patients with end-stage pulmonary failure. Two challenges critical to the successful development of an engineered lung developed from a decellularized scaffold include (i) the suppression of resident infectious bioburden in the lung matrix, and (ii) the ability to sterilize decellularized tissues while preserving the essential biological and mechanical features intact. To date, the majority of lungs are sterilized using high concentrations of peracetic acid (PAA) resulting in extracellular matrix (ECM) depletion. These mechanically altered tissues have little to no storage potential. In this study, we report a sterilizing technique using supercritical carbon dioxide (ScCO2) that can achieve a sterility assurance level 10−6 in decellularized lung matrix. The effects of ScCO2 treatment on the histological, mechanical, and biochemical properties of the sterile decellularized lung were evaluated and compared with those of freshly decellularized lung matrix and with PAA-treated acellular lung. Exposure of the decellularized tissue to ScCO2 did not significantly alter tissue architecture, ECM content or organization (glycosaminoglycans, elastin, collagen, and laminin), observations of cell engraftment, or mechanical integrity of the tissue. Furthermore, these attributes of lung matrix did not change after 6 months in sterile buffer following sterilization with ScCO2, indicating that ScCO2 produces a matrix that is stable during storage. The current study's results indicate that ScCO2 can be used to sterilize acellular lung tissue while simultaneously preserving key biological components required for the function of the scaffold for regenerative medicine purposes. PMID:26697757

Effect of gas cooking on lung function in adolescents: modifying role of sex and immunoglobulin E.

PubMed

Corbo, G M; Forastiere, F; Agabiti, N; Dell'Orco, V; Pistelli, R; Aebischer, M L; Valente, S; Perucci, C A

2001-07-01

A study was undertaken to investigate the effect of gas cooking on the lung function of adolescents while considering serum IgE level as a possible effect modifier. The cross sectional study was performed in 702 subjects aged 11-13 years from primary and secondary schools in Civitavecchia and Viterbo ( Latium region in Central Italy), categorised according to how often they were in the kitchen while the mother cooked (never, sometimes, often). Data were collected by questionnaire and lung function was measured by spirometric tests. Bronchial hyperresponsiveness was evaluated by the methacholine test, atopic status by a skin prick test, and a blood sample was collected to determine serum IgE levels. The results were analysed separately for boys and girls. Multiple regression analysis was performed, taking functional parameters (FEV(1), FEV(1)/FVC, FEF(25-75), FEF(50), FEF(75)) as the dependent variables and age, height, parental smoking, and father's education as independent variables. There was no association between time spent in the kitchen and lung function level in boys, but a reduction in lung function was detected in girls which was statistically significant for FEF(75) (sometimes -10.3%, often -11.1%). After stratifying boys and girls into four groups on the basis of the IgE serum level (below and above the median value of IgE), the reduction in lung function was significant in girls with a high IgE value whereas no significant deleterious effects were evident in girls with a low IgE value or in boys with either a low or high IgE. The results remained substantially unchanged after excluding girls with a response to methacholine below the concentration of 4 mg/ml, asthmatic patients, and those with positive skin prick tests. Gas cooking has a harmful effect on the lung function of girls with a high serum level of IgE. We do not know whether serum IgE, a marker of allergic susceptibility, is a simple indicator that an inflammatory process is in progress or whether it is involved in the pathogenesis of injury leading to bronchial obstruction.

Radioaerosol lung imaging in chronic obstructive pulmonary disease. Comparison with pulmonary function tests and roentgenography. [/sup 113m/In, /sup 99m/Tc, /sup 133/Xe tracer techniques

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

Ramanna, L.; Tashkin, D.P.; Taplin, G.V.

1975-11-01

Seventy subjects with either no, mild, or definite evidence of pulmonary abnormality on screening studies volunteered to have detailed pulmonary function tests (PFTs), respiratory questionnaires, physical examinations, and /sup 113m/indium aerosol-inhalation lung imaging performed. Also, 22 and 52 of these subjects underwent /sup 133/xenon ventilation and lung perfusion imaging with /sup 99m/technetium-labelled macroaggregated albumin, and 56 had chest x-ray examinations performed. Results of the radionuclide lung-imaging procedures were compared with those of conventional PFTs and other clinical diagnostic procedures used to identify chronic obstructive pulmonary disease (COPD). Abnormal radioaerosol patterns were found in 32 of 33 subjects with abnormal findingsmore » on PFTs, whereas results of PFTs were abnormal in only 32 of 46 subjects with abnormal aerosol deposition. Aerosol lung images were abnormal more frequently than respiratory questionnaire responses, findings on physical examination, chest x-ray films, and perfusion lung images and with approximately the same frequency as /sup 133/xenon ventilation scintiscans. These results suggest that radioaerosol lung imaging may be a more sensitive indicator of early COPD than other diagnostic procedures, including maximal midexpiratory flow rates, single-breath nitrogen washout, and closing volume. Further studies are required to determine the physiologic and pathologic significance of isolated aerosol lung-imaging abnormalities.« less

IL-22 Is Essential for Lung Epithelial Repair following Influenza Infection

PubMed Central

Pociask, Derek A.; Scheller, Erich V.; Mandalapu, Sivanarayana; McHugh, Kevin J.; Enelow, Richard I.; Fattman, Cheryl L.; Kolls, Jay K.; Alcorn, John F.

2014-01-01

Influenza infection is widespread in the United States and the world. Despite low mortality rates due to infection, morbidity is common and little is known about the molecular events involved in recovery. Influenza infection results in persistent distal lung remodeling, and the mechanism(s) involved are poorly understood. Recently IL-22 has been found to mediate epithelial repair. We propose that IL-22 is critical for recovery of normal lung function and architecture after influenza infection. Wild-type and IL-22−/− mice were infected with influenza A PR8/34 H1N1 and were followed up for up to 21 days post infection. IL-22 receptor was localized to the airway epithelium in naive mice but was expressed at the sites of parenchymal lung remodeling induced by influenza infection. IL-22−/− mice displayed exacerbated lung injury compared with wild-type mice, which correlated with decreased lung function 21 days post infection. Epithelial metaplasia was observed in wild-type mice but was not evident in IL-22−/− animals that were characterized with an increased fibrotic phenotype. Gene expression analysis revealed aberrant expression of epithelial genes involved in repair processes, among changes in several other biological processes. These data indicate that IL-22 is required for normal lung repair after influenza infection. IL-22 represents a novel pathway involved in interstitial lung disease. PMID:23490254

Which prognostic indicator should we use for clinical practice in the initial evaluation and follow-up of IIP: should we depend on PFT, HRCT or...what?

PubMed

Caminati, Antonella; Harari, Sergio

2005-12-01

Idiopathic interstitial pneumonias are a group of diffuse, inflammatory and fibrotic disorders of the lung parenchyma that cause restrictive physiology and impair gas exchange. Usual interstitial pneumonia and non-specific interstitial pneumonia comprise the majority of idiopathic interstitial pneumonia cases. Previous studies have identified the histopathologic pattern as the most important baseline factor in determining prognosis. The non-invasive diagnosis of these diseases is sometimes uncertain but histological evaluation is an imperfect gold-standard. In some cases, the biopsy specimen may not be representative of the entire lung. In other cases, there may be differences in interpretation of the histological findings. HRCT has also assumed a greater role in the diagnosis and management of patients with idiopathic interstitial pneumonia. Factors affecting prognosis are discussed controversially. Histological criteria, clinical features, or lung function parameters are not clear prognostic indicators. Increased interstitial abnormalities in the HRCT, parameters indicating restrictive lung function, desaturation at 6MWT and abnormal gas exchange are possible determinants of survival. The prognostic value of pulmonary function trends over time may prove more useful. Longitudinal behavior is a more accurate determinant of outcome than evaluation at a single point in time. It is important to remember that no predictor of survival can ever reliably predict an individual patient's prognosis. Physicians should realize this limitation, and use predictor tools as general prognostic guides, not crystal balls. However, due to the great variability in the natural history of the disease, close monitoring of the patients may be necessary to evaluate the individual course of each patient.

A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients with Severe Lung Disease

PubMed Central

Bacci, Giovanni; Fiscarelli, Ersilia; Taccetti, Giovanni; Dolce, Daniela; Paganin, Patrizia; Morelli, Patrizia; Tuccio, Vanessa; De Alessandri, Alessandra; Lucidi, Vincenzina

2017-01-01

In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which specific genes are associated with various stages of CF lung disease. In the present study, we aimed to identify the microbial gene repertoire of CF microbiota in twelve patients with severe and normal/mild lung disease by performing sputum shotgun metagenome sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF airways was reconstructed from the metagenome. We identified a set of metabolic pathways differently distributed in patients with different pulmonary function; namely, pathways related to bacterial chemotaxis and flagellar assembly, as well as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence-related genes. The results indicated that the microbiome of CF patients with low pulmonary function is enriched in virulence-related genes and in genes encoding efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of severely affected adults with CF seems to encode different mechanisms for the facilitation of microbial colonization and persistence in the lung, consistent with the characteristics of multidrug-resistant microbial communities that are commonly observed in patients with severe lung disease. PMID:28758937

A Combination RNAi-Chemotherapy Layer-by-Layer Nanoparticle for Systemic Targeting of KRAS/P53 with Cisplatin to Treat Non-small Cell Lung Cancer

PubMed Central

Gu, Li; Deng, Zhou J.; Roy, Sweta; Hammond, Paula T.

2017-01-01

Purpose Mutation of the Kirsten ras sarcoma viral oncogene homolog (KRAS) and loss of p53 function are commonly seen in non-small cell lung cancer (NSCLC). Combining therapeutics targeting these tumor defensive pathways with cisplatin in a single nanoparticle platform are rarely developed in clinic. Experimental Design Cisplatin was encapsulated in liposomes which multiple polyelectrolyte layers including siKRAS and miR-34a were built on to generate multifunctional layer-by-layer nanoparticle. Structure, size, and surface charge were characterized, in addition to in vitro toxicity studies. In vivo tumor targeting and therapy was investigated in an orthotopic lung cancer model by microCT, fluorescence imaging, and immunohistochemistry. Results The singular nanoscale formulation, incorporating oncogene siKRAS, tumor suppressor stimulating miR-34a, and cisplatin, has shown enhanced toxicity against lung cancer cell line, KP cell. In vivo, systemic delivery of the nanoparticles indicated a preferential uptake in lung of the tumor-bearing mice. Efficacy studies indicated prolonged survival of mice from the combination treatment. Conclusion The combination RNA-chemotherapy in an LbL formulation provides an enhanced treatment efficacy against NSCLC, indicating promising potential in clinic. PMID:28912139

Developing Physiologic Models for Emergency Medical Procedures Under Microgravity

NASA Technical Reports Server (NTRS)

Parker, Nigel; O'Quinn, Veronica

2012-01-01

Several technological enhancements have been made to METI's commercial Emergency Care Simulator (ECS) with regard to how microgravity affects human physiology. The ECS uses both a software-only lung simulation, and an integrated mannequin lung that uses a physical lung bag for creating chest excursions, and a digital simulation of lung mechanics and gas exchange. METI s patient simulators incorporate models of human physiology that simulate lung and chest wall mechanics, as well as pulmonary gas exchange. Microgravity affects how O2 and CO2 are exchanged in the lungs. Procedures were also developed to take into affect the Glasgow Coma Scale for determining levels of consciousness by varying the ECS eye-blinking function to partially indicate the level of consciousness of the patient. In addition, the ECS was modified to provide various levels of pulses from weak and thready to hyper-dynamic to assist in assessing patient conditions from the femoral, carotid, brachial, and pedal pulse locations.

Developing Physiologic Models for Emergency Medical Procedures Under Microgravity

NASA Technical Reports Server (NTRS)

Parker, Nigel; OQuinn, Veronica

2012-01-01

Several technological enhancements have been made to METI's commercial Emergency Care Simulator (ECS) with regard to how microgravity affects human physiology. The ECS uses both a software-only lung simulation, and an integrated mannequin lung that uses a physical lung bag for creating chest excursions, and a digital simulation of lung mechanics and gas exchange. METI's patient simulators incorporate models of human physiology that simulate lung and chest wall mechanics, as well as pulmonary gas exchange. Microgravity affects how O2 and CO2 are exchanged in the lungs. Procedures were also developed to take into affect the Glasgow Coma Scale for determining levels of consciousness by varying the ECS eye-blinking function to partially indicate the level of consciousness of the patient. In addition, the ECS was modified to provide various levels of pulses from weak and thready to hyper-dynamic to assist in assessing patient conditions from the femoral, carotid, brachial, and pedal pulse locations.

Circular RNA circMAN2B2 facilitates lung cancer cell proliferation and invasion via miR-1275/FOXK1 axis.

PubMed

Ma, Xuemei; Yang, Xiaodong; Bao, Wenhua; Li, Shumin; Liang, Shanshan; Sun, Yunhui; Zhao, Yunwei; Wang, Jing; Zhao, Chenxu

2018-04-15

Lung cancer remains a leading cause of cancer-related deaths worldwide. In the past years, increasing reports indicate that circular RNAs (circRNAs) exert a great important role in human cancers, including lung cancer. However, the knowledge about circRNA in lung cancer remains very little so far. In the present study, we screened out a highly expressed novel circRNA named circMAN2B2 in lung cancer tissues. We investigated the function of circMAN2B2 and found that circMAN2B2 knockdown significantly inhibited cell proliferation and invasion in both H1299 and A549 lung cancer cells. Mechanistically, we found that circMAN2B2 could sponge miR-1275 to inhibit its level. Through a series of functional experiments, we dissected the role of miR-1275 in lung cancer and proved the anti-tumor role of miR-1275. Furthermore, we found that miR-1275 exerted its role in lung cancer by regulating FOXK1 expression. In addition, we demonstrated that restoration of FOXK1 could rescue circMAN2B2 knockdown-induced repression of cell proliferation and invasion. Taken together, our study demonstrated that circMAN2B2 acts as an oncogenic role in lung cancer through promoting FOXK1 expression by sponging miR-1275. Copyright © 2018 Elsevier Inc. All rights reserved.

Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections.

PubMed

Hisert, Katherine B; Heltshe, Sonya L; Pope, Christopher; Jorth, Peter; Wu, Xia; Edwards, Rachael M; Radey, Matthew; Accurso, Frank J; Wolter, Daniel J; Cooke, Gordon; Adam, Ryan J; Carter, Suzanne; Grogan, Brenda; Launspach, Janice L; Donnelly, Seamas C; Gallagher, Charles G; Bruce, James E; Stoltz, David A; Welsh, Michael J; Hoffman, Lucas R; McKone, Edward F; Singh, Pradeep K

2017-06-15

Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established. To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections. We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans. Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging. Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.

Lung clearance index is a repeatable and sensitive indicator of radiological changes in bronchiectasis.

PubMed

Rowan, Stephen A; Bradley, Judy M; Bradbury, Ian; Lawson, John; Lynch, Tom; Gustafsson, Per; Horsley, Alex; O'Neill, Katherine; Ennis, Madeleine; Elborn, J Stuart

2014-03-01

In bronchiectasis there is a need for improved markers of lung function to determine disease severity and response to therapy. To assess whether the lung clearance index is a repeatable and more sensitive indicator of computed tomography (CT) scan abnormalities than spirometry in bronchiectasis. Thirty patients with stable bronchiectasis were recruited and lung clearance index, spirometry, and health-related quality of life measures were assessed on two occasions, 2 weeks apart when stable (study 1). A separate group of 60 patients with stable bronchiectasis was studied on a single visit with the same measurements and a CT scan (study 2). In study 1, the intervisit intraclass correlation coefficient for the lung clearance index was 0.94 (95% confidence interval, 0.89 to 0.97; P < 0.001). In study 2, the mean age was 62 (10) years, FEV1 76.5% predicted (18.9), lung clearance index 9.1 (2.0), and total CT score 14.1 (10.2)%. The lung clearance index was abnormal in 53 of 60 patients (88%) and FEV1 was abnormal in 37 of 60 patients (62%). FEV1 negatively correlated with the lung clearance index (r = -0.51, P < 0.0001). Across CT scores, there was a relationship with the lung clearance index, with little evidence of an effect of FEV1. There were no significant associations between the lung clearance index or FEV1 and health-related quality of life. The lung clearance index is repeatable and a more sensitive measure than FEV1 in the detection of abnormalities demonstrated on CT scan. The lung clearance index has the potential to be a useful clinical and research tool in patients with bronchiectasis.

Effect of short-term stainless steel welding fume inhalation exposure on lung inflammation, injury, and defense responses in rats.

PubMed

Antonini, James M; Stone, Sam; Roberts, Jenny R; Chen, Bean; Schwegler-Berry, Diane; Afshari, Aliakbar A; Frazer, David G

2007-09-15

Many welders have experienced bronchitis, metal fume fever, lung function changes, and an increase in the incidence of lung infection. Questions remain regarding the possible mechanisms associated with the potential pulmonary effects of welding fume exposure. The objective was to assess the early effects of stainless steel (SS) welding fume inhalation on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to gas metal arc-SS welding fume at a concentration of 15 or 40 mg/m(3) x 3 h/day for 1, 3, or 10 days. The control group was exposed to filtered air. To assess lung defense responses, some animals were intratracheally inoculated with 5x10(4) Listeria monocytogenes 1 day after the last exposure. Welding particles were collected during exposure, and elemental composition and particle size were determined. At 1, 4, 6, 11, 14, and 30 days after the final exposure, parameters of lung injury (lactate dehydrogenase and albumin) and inflammation (PMN influx) were measured in the bronchoalveolar lavage fluid. In addition, particle-induced effects on pulmonary clearance of bacteria and macrophage function were assessed. SS particles were composed of Fe, Cr, Mn, and Ni. Particle size distribution analysis indicated the mass median aerodynamic diameter of the generated fume to be 0.255 microm. Parameters of lung injury were significantly elevated at all time points post-exposure compared to controls except for 30 days. Interestingly, no significant difference in lung PMNs was observed between the SS and control groups at 1, 4, and 6 days post-exposure. After 6 days post-exposure, a dramatic increase in lung PMNs was observed in the SS group compared to air controls. Lung bacteria clearance and macrophage function were reduced and immune and inflammatory cytokines were altered in the SS group. In summary, short-term exposure of rats to SS welding fume caused significant lung damage and suppressed lung defense responses to bacterial infection, but had a delayed effect on pulmonary inflammation. Additional chronic inhalation studies are needed to further examine the lung effects associated with SS welding fume exposure.

Effect of short-term stainless steel welding fume inhalation exposure on lung inflammation, injury, and defense responses in rats

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

Antonini, James M.; Stone, Sam; Roberts, Jenny R.

Many welders have experienced bronchitis, metal fume fever, lung function changes, and an increase in the incidence of lung infection. Questions remain regarding the possible mechanisms associated with the potential pulmonary effects of welding fume exposure. The objective was to assess the early effects of stainless steel (SS) welding fume inhalation on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to gas metal arc-SS welding fume at a concentration of 15 or 40 mg/m{sup 3} x 3 h/day for 1, 3, or 10 days. The control group was exposed to filtered air. To assess lung defense responses,more » some animals were intratracheally inoculated with 5 x 10{sup 4}Listeria monocytogenes 1 day after the last exposure. Welding particles were collected during exposure, and elemental composition and particle size were determined. At 1, 4, 6, 11, 14, and 30 days after the final exposure, parameters of lung injury (lactate dehydrogenase and albumin) and inflammation (PMN influx) were measured in the bronchoalveolar lavage fluid. In addition, particle-induced effects on pulmonary clearance of bacteria and macrophage function were assessed. SS particles were composed of Fe, Cr, Mn, and Ni. Particle size distribution analysis indicated the mass median aerodynamic diameter of the generated fume to be 0.255 {mu}m. Parameters of lung injury were significantly elevated at all time points post-exposure compared to controls except for 30 days. Interestingly, no significant difference in lung PMNs was observed between the SS and control groups at 1, 4, and 6 days post-exposure. After 6 days post-exposure, a dramatic increase in lung PMNs was observed in the SS group compared to air controls. Lung bacteria clearance and macrophage function were reduced and immune and inflammatory cytokines were altered in the SS group. In summary, short-term exposure of rats to SS welding fume caused significant lung damage and suppressed lung defense responses to bacterial infection, but had a delayed effect on pulmonary inflammation. Additional chronic inhalation studies are needed to further examine the lung effects associated with SS welding fume exposure.« less

[Lung and heart-lung transplantation in respiratory tract diseases. Evaluation and development of the indications based on our first 15 cases].

PubMed

Couraud, L; Baudet, E; Martigne, C; Roques, X; Velly, J F; Laborde, N; Clerc, P

1989-01-01

Since January 1988, the Bordeaux group has performed 15 transplantations for lung disease: 9 heart-lung transplants, 1 heart + left lung, 1 double lung, 2 right lungs and 2 left lungs. The transplantations were performed for pulmonary emphysema (10 cases), pulmonary artery hypertension (2 cases), cystic fibrosis (1 case), pulmonary fibrosis (2 cases). Cardiopulmonary transplantation was not always performed because of associated heart failure but sometimes because of large intrahilar adenopathy or intractable bronchial infection. Pulmonary transplantation is recommended on the right side in cases of pulmonary fibrosis. One patient died postoperatively (ischaemia of the transplant). Four others died during the 2nd and 3rd months from poorly defined but probably infectious pulmonary syndromes. The tracheobronchial patency of the 10 survivors was 80% or 100% of the predicted value. The respiratory functional result was excellent in the short and intermediate term. Specific difficulties essentially consisted of pleural symphyses, hilar adenopathy, bronchial infection, steroid dependence of certain subjects, the difficulty of identifying the cause and treating lung opacities during the 2nd and 3rd months.

Disruption of miR-29 Leads to Aberrant Differentiation of Smooth Muscle Cells Selectively Associated with Distal Lung Vasculature.

PubMed

Cushing, Leah; Costinean, Stefan; Xu, Wei; Jiang, Zhihua; Madden, Lindsey; Kuang, Pingping; Huang, Jingshu; Weisman, Alexandra; Hata, Akiko; Croce, Carlo M; Lü, Jining

2015-05-01

Differentiation of lung vascular smooth muscle cells (vSMCs) is tightly regulated during development or in response to challenges in a vessel specific manner. Aberrant vSMCs specifically associated with distal pulmonary arteries have been implicated in the pathogenesis of respiratory diseases, such as pulmonary arterial hypertension (PAH), a progressive and fatal disease, with no effective treatment. Therefore, it is highly relevant to understand the underlying mechanisms of lung vSMC differentiation. miRNAs are known to play critical roles in vSMC maturation and function of systemic vessels; however, little is known regarding the role of miRNAs in lung vSMCs. Here, we report that miR-29 family members are the most abundant miRNAs in adult mouse lungs. Moreover, high levels of miR-29 expression are selectively associated with vSMCs of distal vessels in both mouse and human lungs. Furthermore, we have shown that disruption of miR-29 in vivo leads to immature/synthetic vSMC phenotype specifically associated with distal lung vasculature, at least partially due to the derepression of KLF4, components of the PDGF pathway and ECM-related genes associated with synthetic phenotype. Moreover, we found that expression of FBXO32 in vSMCs is significantly upregulated in the distal vasculature of miR-29 null lungs. This indicates a potential important role of miR-29 in smooth muscle cell function by regulating FBXO32 and SMC protein degradation. These results are strongly supported by findings of a cell autonomous role of endogenous miR-29 in promoting SMC differentiation in vitro. Together, our findings suggested a vessel specific role of miR-29 in vSMC differentiation and function by targeting several key negative regulators.

The Association of Normal Range Glycated Hemoglobin with Restrictive Lung Pattern in the General Population

PubMed Central

Oh, Il Hwan; Park, Jung Hwan; Lee, Chang Hwa; Park, Joon-Sung

2015-01-01

Glycated hemoglobin (HbA1c) is an important diagnostic indicator of diabetes mellitus, and some authors have argued that it is related to impaired lung function in the diabetic population. However, there was rare study for association between lung function and HbA1c in the non-diabetic population. We investigated whether HbA1c below the diagnostic threshold is related to deficits in lung function. We analyzed biochemical and spirometry data from a nation-wide, population-based, case-control study (the KNHANES IV and V). Eligible as cases were all native Koreans aged 40 years or more with no medical illness. A total of 3670 participants were divided into 4 groups according to HbA1c (%) as follows: Group I (n = 842), ≥ 4.0 and ≤ 5.3; Group II (n = 833), > 5.3 and ≤ 5.5; Group III (n = 898), > 5.5 and ≤ 5.7; and Group IV (n = 1097), > 5.7 and ≤ 6.4. Group I had the greatest forced vital capacity (FVC, 96.3 ± 0.5% pred, P < 0.0001), forced expiratory volume per second (FEV1, 93.8 ± 0.5% pred, P < 0.0001) and FEV1/FVC (0.792 ± 0.003, P < 0.0001) compared with the other groups. Linear regression showed that HbA1c was closely related to FVC (β = -6.972154, P < 0.0001) and FEV1 (β = -5.591589, P < 0.0001), but not to FEV1/FVC. Logistic regression analysis revealed a significant association between HbA1c and a restrictive spirometric pattern (FVC < 80% pred., FEV1/FVC ≥ 0.70; OR = 3.772, 95% CI = 1.234-11.53), indicating that elevated HbA1c is closely associated with lung impairment in the non-diabetic population. In the healthy population, relatively high HbA1c level is associated with decrements of FVC and FEV1 and may be a reliable predictor of poor lung function, especially the restrictive pattern. PMID:25658743

Predicting the response of the injured lung to the mechanical breath profile

PubMed Central

Smith, Bradford J.; Lundblad, Lennart K. A.; Kollisch-Singule, Michaela; Satalin, Joshua; Nieman, Gary; Habashi, Nader

2015-01-01

Mechanical ventilation is a crucial component of the supportive care provided to patients with acute respiratory distress syndrome. Current practice stipulates the use of a low tidal volume (Vt) of 6 ml/kg ideal body weight, the presumptive notion being that this limits overdistension of the tissues and thus reduces volutrauma. We have recently found, however, that airway pressure release ventilation (APRV) is efficacious at preventing ventilator-induced lung injury, yet APRV has a very different mechanical breath profile compared with conventional low-Vt ventilation. To gain insight into the relative merits of these two ventilation modes, we measured lung mechanics and derecruitability in rats before and following Tween lavage. We fit to these lung mechanics measurements a computational model of the lung that accounts for both the degree of tissue distension of the open lung and the amount of lung derecruitment that takes place as a function of time. Using this model, we predicted how tissue distension, open lung fraction, and intratidal recruitment vary as a function of ventilator settings both for conventional low-Vt ventilation and for APRV. Our predictions indicate that APRV is more effective at recruiting the lung than low-Vt ventilation, but without causing more overdistension of the tissues. On the other hand, low-Vt ventilation generally produces less intratidal recruitment than APRV. Predictions such as these may be useful for deciding on the relative benefits of different ventilation modes and thus may serve as a means for determining how to ventilate a given lung in the least injurious fashion. PMID:25635004

Effect of hyperinflation on inspiratory function of the diaphragm.

PubMed

Minh, V D; Dolan, G F; Konopka, R F; Moser, K M

1976-01-01

The inspiratory efficiency of the diaphragm during unilateral and bilateral phrenic stimulation (UEPS and BEPS) with constant stimulus was studied in seven dogs from FRC to 120% TLC. Alveolar pressures (PAl) were recorded during relaxation, BEPS and UEPS at each lung volume in the closed respiratory system. From the PAl-lung volume curves, tidal volume (VT), and pressure developed by the diaphragm (Pmus) were derived. Results are summarized below. a) Hyperinflation impaired the inspiratory efficiency of the diaphragm which behaved as an expiratory muscle beyond the lung volume of 103.7% TLC (Vinef). b) The diaphragm during UEPS became expiratory at the same Vinef as during (BEPS. C) The VT-lung volume relationship was linear during BEPS, allowing simple quantitation of VT loss with hyperinflation and prediction of Vinef. d) With only one phrenic nerve stimulated, the functional loss is less pronounced in VT than in Pmus, as compared to BEPS, indicating that the respiratory system was more compliant during UEPS than BEPS. This compliance difference from UEPS to BEPS diminished with severe hyperinflation.

Poster - Thur Eve - 16: Four-dimensional x-ray computed tomography and hyperpolarized 3 He magnetic resonance imaging of gas distribution in lung cancer.

PubMed

Mathew, L; Castillo, R; Castillo, E; Yaremko, B; Rodrigues, G; Etemad-Rezai, R; Guerrero, T; Parraga, G

2012-07-01

Dynamic imaging methods such as four-dimensional computed tomography (4DCT) and static imaging methods such as noble gas magnetic resonance imaging (MRI) deliver direct and regional measurements of lung function even in lung cancer patients in whom global lung function measurements are dominated by tumour burden. The purpose of this study was to directly compare quantitative measurements of gas distribution from static hyperpolarized 3 He MRI and dynamic 4DCT in a small group of lung cancer patients. MRI and 4DCT were performed in 11 subjects prior to radiation therapy. MRI was performed at 3.0T in breath-hold after inhalation 1L of hyperpolarized 3 He gas. Gas distribution in 3 He MRI was quantified using a semi-automated segmentation algorithm to generate percent-ventilated volume (PVV), reflecting the volume of gas in the lung normalized to the thoracic cavity volume. 4DCT pulmonary function maps were generated using deformable image registration of six expiratory phase images. The correspondence between identical tissue elements at inspiratory and expiratory phases was used to estimate regional gas distribution and PVV was quantified from these images. After accounting for differences in lung volumes between 3 He MRI (1.9±0.5L ipsilateral, 2.3±0.7 contralateral) and 4DCT (1.2±0.3L ipsilateral, 1.3±0.4L contralateral) during image acquisition, there was no statistically significant difference in PVV between 3 He MRI (72±11% ipsilateral, 79±12% contralateral) and 4DCT (74±3% ipsilateral, 75±4% contralateral). Our results indicate quantitative agreement in the regional distribution of inhaled gas in both static and dynamic imaging methods. PVV may be considered as a regional surrogate measurement of lung function or ventilation. © 2012 American Association of Physicists in Medicine.

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

Sunil, Vasanthi R., E-mail: sunilvr@eohsi.rutgers.edu; Patel-Vayas, Kinal, E-mail: kinalv5@gmail.com; Shen, Jianliang, E-mail: jianliangs@gmail.com

Lung toxicity induced by sulfur mustard is associated with inflammation and oxidative stress. To elucidate mechanisms mediating pulmonary damage, we used 2-chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant. Male mice (B6129) were treated intratracheally with CEES (3 or 6 mg/kg) or control. Animals were sacrificed 3, 7 or 14 days later and bronchoalveolar lavage (BAL) fluid and lung tissue collected. Treatment of mice with CEES resulted in an increase in BAL protein, an indication of alveolar epithelial damage, within 3 days. Expression of Ym1, an oxidative stress marker also increased in the lung, along with inducible nitric oxidemore » synthase, and at 14 days, cyclooxygenase-2 and monocyte chemotactic protein-1, inflammatory proteins implicated in tissue injury. These responses were attenuated in mice lacking the p55 receptor for TNF{alpha} (TNFR1-/-), demonstrating that signaling via TNFR1 is key to CEES-induced injury, oxidative stress, and inflammation. CEES-induced upregulation of CuZn-superoxide dismutase (SOD) and MnSOD was delayed or absent in TNFR1-/- mice, relative to WT mice, suggesting that TNF{alpha} mediates early antioxidant responses to lung toxicants. Treatment of WT mice with CEES also resulted in functional alterations in the lung including decreases in compliance and increases in elastance. Additionally, methacholine-induced alterations in total lung resistance and central airway resistance were dampened by CEES. Loss of TNFR1 resulted in blunted functional responses to CEES. These effects were most notable in the airways. These data suggest that targeting TNF{alpha} signaling may be useful in mitigating lung injury, inflammation and functional alterations induced by vesicants.« less

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.

Deviations from Haber’s Law for Multiple Measures of Acute Lung Injury in Chlorine-Exposed Mice

PubMed Central

Hoyle, Gary W.; Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.; Rando, Roy J.

2010-01-01

Chlorine gas is considered a chemical threat agent that can cause acute lung injury. Studies in the early 20th century on war gases led Haber to postulate that the dose of an inhaled chemical expressed as the product of gas concentration and exposure time leads to a constant toxicological effect (Haber’s Law). In the present work, mice were exposed to a constant dose of chlorine (100 ppm-h) delivered using different combinations of concentration and time (800 ppm/7.5 min, 400 ppm/15 min, 200 ppm/30 min, and 100 ppm/60 min). Significant effects of exposure protocol on survival evaluated 6 h after exposure were observed, ranging from 0% for the 7.5-min exposure to 100% for the 30- and 60-min exposures. Multiple parameters indicative of lung injury were examined to determine if any aspects of lung injury were differentially affected by the exposure protocols. Most parameters (pulmonary edema, neutrophil influx, and levels of protein, immunoglobulin M, and the chemokine KC [Cxcl1] in lavage fluid) indicated that lung injury was most pronounced for the 15-min exposure and least for the 60-min exposure. In contrast, changes in pulmonary function at baseline and in response to inhaled methacholine were similar following the three exposure regimens. The results indicate that the extent of lung injury following chlorine inhalation depends not only on total dose but also on the specifics of exposure concentration and time, and they suggest that evaluation of countermeasures against chlorine-induced lung injury should be performed using multiple types of exposure scenarios. PMID:20819911

Role of epithelial-mesenchymal transition (EMT) and fibroblast function in cerium oxide nanoparticles-induced lung fibrosis

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

Ma, Jane

The emission of cerium oxide nanoparticles (CeO{sub 2}) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO{sub 2} induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO{sub 2}-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO{sub 2} (0.15 to 7 mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure. The results show that at 28 days after CeO{sub 2} (3.5 mg/kg)more » exposure, lung fibrosis was evidenced by increased soluble collagen in bronchoalveolar lavage fluid, elevated hydroxyproline content in lung tissues, and enhanced sirius red staining for collagen in the lung tissue. Lung fibroblasts and alveolar type II (ATII) cells isolated from CeO{sub 2}-exposed rats at 28 days post-exposure demonstrated decreasing proliferation rate when compare to the controls. CeO{sub 2} exposure was cytotoxic and altered cell function as demonstrated by fibroblast apoptosis and aggregation, and ATII cell hypertrophy and hyperplasia with increased surfactant. The presence of stress fibers, expressed as α-smooth muscle actin (SMA), in CeO{sub 2}-exposed fibroblasts and ATII cells was significantly increased compared to the control. Immunohistofluorescence analysis demonstrated co-localization of TGF-β or α-SMA with prosurfactant protein C (SPC)-stained ATII cells. These results demonstrate that CeO{sub 2} exposure affects fibroblast function and induces EMT in ATII cells that play a role in lung fibrosis. These findings suggest potential adverse health effects in response to CeO{sub 2} nanoparticle exposure. - Highlights: • CeO{sub 2} exposure induced lung fibrosis. • CeO{sub 2} were detected in lung tissue, alveolar type II (ATII) cells and fibroblasts. • CeO{sub 2} caused ATII cell hypertrophy and hyperplasia and altered fibroblast function. • Increased α-SMA in CeO{sub 2}-exposed lung fibroblasts indicating myofibroblast formation. • CeO{sub 2} induced EMT in ATII cells demonstrated as increased α-SMA expression.« less

Exponential analysis of the lung pressure-volume curve in patients with chronic pigeon-breeder's lung.

PubMed

Sansores, R; Perez-Padilla, R; Paré, P D; Selman, M

1992-05-01

Pigeon-breeder's lung (PBL) is extremely common in Mexico City and often progresses to irreversible pulmonary fibrosis. The exponential analysis of the lung pressure-volume (PV) curve (V = A - Be-kp) has been suggested as a method to separate the lung restriction caused by inflammation from that caused by pulmonary fibrosis; a significantly decreased value for the exponential constant, k, suggests a change in the mechanical properties of the functioning lung parenchyma, while a normal value accompanied by restriction suggests subtraction of lung units without a change in the mechanical properties of the functioning units. We measured lung volumes and static PV curves in 29 patients who had persistent lung restriction following a biopsy-proven diagnosis of PBL. Mean values in the 29 subjects were as follows: age, 43 +/- 13 years; TLC, 61 +/- 15 percent of predicted; VC, 46 +/- 19 percent of predicted; and k, 55 +/- 17 percent of predicted. Twenty-four of the 29 patients had values for k that were below the 95 percent confidence level, and five had "normal" values. There was no difference in TLC and VC (percent of predicted) between those with or without a decreased value for k. Four of five patients with a normal value for k improved subsequent to diagnosis, while only one of 21 patients with a decreased k improved. We conclude that increased lung elasticity manifested by a low value for k is common in patients with chronic PBL. These results support the observation of frequent irreversible lung fibrosis in these patients. Measurements of k could prove a good prognostic indicator at the time of initial diagnosis.

MiR-564 functions as a tumor suppressor in human lung cancer by targeting ZIC3

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

Yang, Bin; Jia, Lin; Guo, Qiaojuan

2015-11-27

Although miR-564 was reported to be dysregulated in human malignancy, the function and mechanism of miR-564 in tumorigenesis remains unknown. In the present study, we found that miR-564 frequently downregulated in lung cancer cells and significantly inhibited cell proliferation, cell cycle progression, motility, and the tumorigenicity of lung cancer cells. Moreover, we identified zic family member 3 (ZIC3) as a direct target of miR-564. ZIC3 overexpression impaired the suppressive effects of miR-564 on the capacity of lung cancer cells for proliferation and motility. Finally, we detected the expression level of miR-564 and ZIC3 protein in tissue specimens, and found amore » significant negative correlation between them. Patients with low levels of miR-564 showed a poorer overall survival. Taken together, our present study revealed the tumor suppressor role of miR-564, indicating restoration of miR-564 as a potential therapeutic strategy for the treatment of lung cancer. - Highlights: • MiR-564 inhibits cancer cell proliferation, cell cycle progression, migration, and invasion. • miR-564 suppresses the tumorigenicity of lung cancer cell in vivo. • ZIC3 is a direct and functional target of miR-564. • The expression of miR-564 was negatively correlated with ZIC3 protein in tumors. • Both low miR-564 and high ZIC3 was associated with tumor stage and prognosis.« less

Alpha 1-protease inhibitor moderates human neutrophil elastase-induced emphysema and secretory cell metaplasia in hamsters.

PubMed

Stone, P J; Lucey, E C; Virca, G D; Christensen, T G; Breuer, R; Snider, G L

1990-06-01

A study was undertaken to determine whether emphysema and airway secretory cell metaplasia, induced in hamsters by intratracheal treatment with human neutrophil elastase (HNE), could be moderated by pretreatment with human alpha 1-protease inhibitor (API). API (4.9 mg) was given intratracheally to hamsters 1 h before 0.3 mg HNE. Eight weeks later, lung volumes and pressure-volume relationships were measured in the anaesthetized animals. Mean linear intercepts and secretory cell indices were measured in lung sections. API given 1 h before HNE moderated the development of bronchial secretory cell metaplasia. The severity of emphysema was reduced by 75%. Clearance studies indicated that 80% of the functional activity of instilled API could be lavaged from the lungs after 1 h, indicating a 4 h half-life in the lavageable compartment of the lungs. We calculate that for 50% protection from emphysema the molar ratio of lavageable API to HNE at the time of HNE instillation was 4.8 as compared with 0.78 for 50% inhibition of elastolytic activity in vitro, indicating that API is only 16% as efficient in vivo as compared with its in vitro HNE inhibitory effectiveness. Nevertheless, we conclude that human API given intratracheally is efficacious against HNE-induced emphysema and secretory cell metaplasia.

Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis.

PubMed

Adam, Martin; Schikowski, Tamara; Carsin, Anne Elie; Cai, Yutong; Jacquemin, Benedicte; Sanchez, Margaux; Vierkötter, Andrea; Marcon, Alessandro; Keidel, Dirk; Sugiri, Dorothee; Al Kanani, Zaina; Nadif, Rachel; Siroux, Valérie; Hardy, Rebecca; Kuh, Diana; Rochat, Thierry; Bridevaux, Pierre-Olivier; Eeftens, Marloes; Tsai, Ming-Yi; Villani, Simona; Phuleria, Harish Chandra; Birk, Matthias; Cyrys, Josef; Cirach, Marta; de Nazelle, Audrey; Nieuwenhuijsen, Mark J; Forsberg, Bertil; de Hoogh, Kees; Declerq, Christophe; Bono, Roberto; Piccioni, Pavilio; Quass, Ulrich; Heinrich, Joachim; Jarvis, Deborah; Pin, Isabelle; Beelen, Rob; Hoek, Gerard; Brunekreef, Bert; Schindler, Christian; Sunyer, Jordi; Krämer, Ursula; Kauffmann, Francine; Hansell, Anna L; Künzli, Nino; Probst-Hensch, Nicole

2015-01-01

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO₂, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m(-3) increase in NO₂ exposure was associated with lower levels of FEV₁ (-14.0 mL, 95% CI -25.8 to -2.1) and FVC (-14.9 mL, 95% CI -28.7 to -1.1). An increase of 10 μg·m(-3) in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV₁ (-44.6 mL, 95% CI -85.4 to -3.8) and FVC (-59.0 mL, 95% CI -112.3 to -5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe. Copyright ©ERS 2015.

Lung Function in Pregnancy in Langerhans Cell Histiocytosis.

PubMed

Radzikowska, Elżbieta; Wiatr, Elżbieta; Franczuk, Monika; Bestry, Iwona; Roszkowski-Śliż, Kazimierz

2018-01-01

Pulmonary Langerhans cell histiocytosis (LCH) is a rare disease, affecting usually young people. The course of the disease is variable. In some pulmonary LCH patients a severe lung destruction and progression in spite of chemotherapy is observed, but in others just a cessation of smoking induces a regression of the disease. In the present study we seek to determine the influence of pregnancy on pulmonary function in LCH patients, an unchartered area of research. We addressed the issue by investigating eight pregnant women out of the 45 women hospitalized with the diagnosis of pulmonary LCH in the period from 2000 to 2015. For five of the eight pregnant women it was the second gestation. The median follow-up period was 120 months (range 72-175 months). Ten healthy children were born by a C-section. Two spontaneous miscarriages in the seventh week of gestation, and one tubal ectopic pregnancy were recorded. We found that pregnancy did not significantly influence pulmonary function assessed by the following indices: forced expiratory volume in 1 s (FEV1), lung vital capacity (VC), total lung capacity (TLC), residual volume (RV), diffusing capacity of the lungs for carbon monoxide (DLCO), and the distance and arterial oxygen saturation in 6-min walk test. Only one patient in the third trimester of pregnancy experienced bilateral pneumothorax, with persistent air leak. In all patients, delivery and postpartum period were uneventful. We conclude that pregnancy in pulmonary LCH patients is safe and not associated with deterioration of pulmonary function or blood oxygenation.

Risk Factors Associated with Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-infected Cohort

PubMed Central

Leader, Joseph K.; Crothers, Kristina; Huang, Laurence; King, Mark A.; Morris, Alison; Thompson, Bruce W.; Flores, Sonia C.; Drummond, M. Bradley; Rom, William N.; Diaz, Philip T.

2015-01-01

Introduction The disease spectrum for HIV-infected individuals has shifted towards co-morbid non-AIDS conditions including chronic lung disease, but quantitative image analysis of lung disease has not been performed. Objectives To quantify the prevalence of structural changes of the lung indicating emphysema or fibrosis on radiographic examination. Methods A cross-sectional analysis of 510 HIV-infected participants in the multi-center Lung-HIV study was performed. Data collected included: demographics, biological markers of HIV, pulmonary function testing, and chest CT examinations. Emphysema and fibrosis-like changes were quantified on CT images based on threshold approaches. Results In our cohort: 69% was on antiretroviral therapy, 13% had a current CD4 cell count less than 200 cells/μL, 39% had an HIV viral load greater than 500 copies/mL, 25% had at least a trace level of emphysema (defined as >2.5% of voxels <-950HU). Trace emphysema was significantly correlated with age, smoking, and pulmonary function. Neither current CD4 cell count nor HIV viral load was significantly correlated with emphysema. Fibrosis-like changes were detected in 29% of the participants and were significantly correlated with HIV viral load (Pearson correlation coefficient = 0.210, p<0.05); current CD4 cell count was not associated with fibrosis. In multivariable analyses including age, race, and smoking status, HIV viral load remained significantly correlated with fibrosis-like changes (coefficient = 0.107, P = 0.03). Conclusion A higher HIV viral load was significantly associated with fibrosis-like changes possibly indicating early interstitial lung disease, but emphysematous changes were not related to current CD4 cell count or HIV viral load. PMID:26914911

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

PubMed

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

2015-04-01

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

Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury.

PubMed

Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Suratt, Benjamin T; Kallen, Caleb B; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; Summer, Ross

2015-06-12

Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans.

Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury

PubMed Central

Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Suratt, Benjamin T.; Kallen, Caleb B.; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; Summer, Ross

2015-01-01

Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans. PMID:26068229

Corticosteroids and fetal intervention interact to alter lung maturation in preterm lambs.

PubMed

Tabor, B L; Lewis, J F; Ikegami, M; Polk, D; Jobe, A H

1994-04-01

The relationship between cortisol infusion and time of fetal catheterization on postnatal lung function of prematurely delivered lambs was investigated with the hypothesis that the intervention of catheterization would alter fetal responsiveness to the maturational effects of corticosteroids. Fetal catheterization was performed on d 117 or on d 122 of gestation. Cortisol or saline control infusions were begun on d 126, with delivery 60 h later on d 128. The animals were ventilated for 1.25 h after delivery, and compliance, the ventilation efficiency index, labeled albumin leak into and out of the lungs, alveolar and lung saturated phosphatidylcholine and surfactant protein A were measured to evaluate lung performance and biochemical indicators of maturation. Cortisol improved compliance and ventilation efficiency and decreased labeled albumin recovery without changing alveolar saturated phosphatidylcholine or surfactant protein A in the animals catheterized at 122 d relative to 122-d saline-infused animals. However, the animals catheterized at 117 d and infused with saline were as mature as assessed by compliance and ventilation efficiency as the 122-d cortisol-treated animals. The 117-d cortisol-infused animals had significantly augmented lung function relative to either 117-d saline-infused or 122-d cortisol-treated lambs and were the only group that had increased alveolar surfactant protein A and lung saturated phosphatidylcholine pool sizes. This study demonstrates that the response of the fetal lung to a maturational agent such as cortisol is dependent on the history of previous fetal interventions.

Associations of children's lung function with ambient air pollution: joint effects of regional and near-roadway pollutants.

PubMed

Urman, Robert; McConnell, Rob; Islam, Talat; Avol, Edward L; Lurmann, Frederick W; Vora, Hita; Linn, William S; Rappaport, Edward B; Gilliland, Frank D; Gauderman, W James

2014-06-01

Previous studies have reported adverse effects of either regional or near-roadway air pollution (NRAP) on lung function. However, there has been little study of the joint effects of these exposures. To assess the joint effects of NRAP and regional pollutants on childhood lung function in the Children's Health Study. Lung function was measured on 1811 children from eight Southern Californian communities. NRAP exposure was assessed based on (1) residential distance to the nearest freeway or major road and (2) estimated near-roadway contributions to residential nitrogen dioxide (NO2), nitric oxide (NO) and total nitrogen oxides (NOx). Exposure to regional ozone (O3), NO2, particulate matter with aerodynamic diameter <10 µm (PM10) and 2.5 µm (PM2.5) was measured continuously at community monitors. An increase in near-roadway NOx of 17.9 ppb (2 SD) was associated with deficits of 1.6% in forced vital capacity (FVC) (p=0.005) and 1.1% in forced expiratory volume in 1 s (FEV1) (p=0.048). Effects were observed in all communities and were similar for NO2 and NO. Residential proximity to a freeway was associated with a reduction in FVC. Lung function deficits of 2-3% were associated with regional PM10 and PM2.5 (FVC and FEV1) and with O3 (FEV1), but not NO2 across the range of exposure between communities. Associations with regional pollution and NRAP were independent in models adjusted for each. The effects of NRAP were not modified by regional pollutant concentrations. The results indicate that NRAP and regional air pollution have independent adverse effects on childhood lung function. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Matrix composition and mechanics of decellularized lung scaffolds.

PubMed

Petersen, Thomas H; Calle, Elizabeth A; Colehour, Maegen B; Niklason, Laura E

2012-01-01

The utility of decellularized native tissues for tissue engineering has been widely demonstrated. Here, we examine the production of decellularized lung scaffolds from native rodent lung using two different techniques, principally defined by use of either the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) or sodium dodecyl sulfate (SDS). All viable cellular material is removed, including at least 99% of DNA. Histochemical staining and mechanical testing indicate that collagen and elastin are retained in the decellularized matrices with CHAPS-based decellularization, while SDS-based decellularization leads to loss of collagen and decline in mechanical strength. Quantitative assays confirm that most collagen is retained with CHAPS treatment but that about 80% of collagen is lost with SDS treatment. In contrast, for both detergent methods, at least 60% of elastin content is lost along with about 95% of native proteoglycan content. Mechanical testing of the decellularized scaffolds indicates that they are mechanically similar to native lung using CHAPS decellularization, including retained tensile strength and elastic behavior, demonstrating the importance of collagen and elastin in lung mechanics. With SDS decellularization, the mechanical integrity of scaffolds is significantly diminished with some loss of elastic function as well. Finally, a simple theoretical model of peripheral lung matrix mechanics is consonant with our experimental findings. This work demonstrates the feasibility of producing a decellularized lung scaffold that can be used to study lung matrix biology and mechanics, independent of the effects of cellular components. Copyright © 2011 S. Karger AG, Basel.

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.

Early lung retrieval from traumatic brain-dead donors does not compromise outcomes following lung transplantation.

PubMed

Moreno, Paula; Alvarez, Antonio; Illana, Jennifer; Espinosa, Dionisio; Baamonde, Carlos; Cerezo, Francisco; Algar, Francisco Javier; Salvatierra, Angel

2013-06-01

To determine whether lung retrieval from traumatic donors performed within 24 h of brain death has a negative impact on early graft function and survival after lung transplantation (LT), when compared with those retrieved after 24 h. Review of lung transplants performed from traumatic donors over a 17-year period. Recipients were distributed into two groups: transplants from traumatic donor lungs retrieved within 24 h of brain death (Group A), and transplants from traumatic donor lungs retrieved after 24 h of brain death (Group B). Demographic data of donors and recipients, early graft function, perioperative complications and mortality were compared between both groups. Among 356 lung transplants performed at our institution, 132 were from traumatic donors (70% male, 30% female). Group A: 73 (55%); Group B: 59 (45%). There were 53 single, 77 double, and 2 combined LT. Indications were emphysema in 41 (31%), pulmonary fibrosis in 31 (23%), cystic fibrosis in 38 (29%), bronchiectasis in 9 (7%) and other indications in 13 patients (10%). Donor and recipient demographic data, need or cardiopulmonary bypass, postoperative complications and Intensive Care Unit and hospital stay did not differ between groups. Primary graft dysfunction (A vs B): 9 (16%) vs 13 (26%) P = 0.17. PaO2/FiO2 24 h post-transplant (A vs B): 303 mmHg vs 288 mmHg (P = 0.57). Number of acute rejection episodes (A vs B): 0.93 vs 1.49 (P = 0.01). Postoperative intubation time (A vs B): 99 vs 100 h (P = 0.99). 30-day mortality (A vs B): 7 (10%) vs 2 (3.5%) (P = 0.13). Freedom from bronchiolitis obliterans syndrome (A vs B): 82, 72, 37, 22 vs 78, 68, 42, 15%, at 3, 5, 10 and 15 years, respectively (P = 0.889). Survival (A vs B): 65, 54, 46, 42 and 27 vs 60, 50, 45, 43 and 29% at 3, 5, 7, 10 and 15 years, respectively (P = 0.937). In our experience, early lung retrieval after brain death from traumatic donors does not adversely affect early and long-term outcomes after LT.

The D prostanoid receptor agonist BW245C [(4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid] inhibits fibroblast proliferation and bleomycin-induced lung fibrosis in mice.

PubMed

van den Brule, Sybille; Wallemme, Laurent; Uwambayinema, Francine; Huaux, François; Lison, Dominique

2010-11-01

Prostaglandin (PG) D(2) exerts contrasting activities in the inflamed lung via two receptors, the D prostanoid receptor (DP) and the chemoattractant receptor-homologous molecule expressed on T helper 2 lymphocytes. DP activation is known mainly to inhibit proinflammatory cell functions. We tested the effect of a DP-specific agonist, (4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid (BW245C), on pulmonary fibroblast functions in vitro and in a mouse model of lung fibrosis induced by bleomycin. DP mRNA expression was detected in cultured mouse lung primary fibroblasts and human fetal lung fibroblasts and found to be up- and down-regulated by interleukin-13 and transforming growth factor (TGF)-β, respectively. Although micromolar concentrations of BW245C and PGD(2) did not affect mouse fibroblast collagen synthesis or differentiation in myofibroblasts, they both inhibited fibroblast basal and TGF-β-induced proliferation in vitro. The repeated administration of BW245C (500 nmol/kg body weight instilled transorally in the lungs 2 days before and three times per week for 3 weeks) in bleomycin-treated mice significantly decreased both inflammatory cell recruitment and collagen accumulation in the lung (21 days). Our results indicate that BW245C can reduce lung fibrosis in part via its activity on fibroblast proliferation and suggest that DP activation should be considered as a new therapeutic target in fibroproliferative lung diseases.

Fine mapping in TERT-CLPTM1L region identified three independent lung cancer susceptibility signals: a large-scale multi-ethnic population study.

PubMed

Li, Zhihua; Fan, Jingyi; Li, Ni; Zhu, Meng; Zhang, Jiahui; Wang, Yuzhuo; Geng, Liguo; Cheng, Yang; Ma, Hongxia; Jin, Guangfu; Dai, Juncheng; Hu, Zhibin; Shen, Hongbing

2018-05-29

Genome-wide association studies (GWAS) and fine mapping studies have identified multiple lung cancer susceptibility variants in TERT-CLPTM1L region. However, it is still unclear about the relationship between these risk variants and the independent lung cancer risk signals in this region. Therefore, we evaluated the independent susceptibility signals for lung cancer and explored the potential functional variants in this region. Sequential conditional analysis was used to detect the independent susceptibility loci based on four lung cancer GWAS datasets with 12,843 lung cases and 12,639 controls. Comprehensively functional annotations were performed for each independent signal. Three independent susceptibility signals were identified in multi-ethnic population. For the first signal, rs2736100 showed the most significant association with lung cancer risk (C > A, OR = 0.82, 95%CI: 0.79-0.85, P = 1.98 × 10 -25 ). Rs36019446 was the top-ranked site (A > G, OR = 0.88, 95%CI: 0.84-0.92, P = 1.74 × 10 -9 ) in the second signal. For the third signal, rs326048 was the leading SNP (A > G, OR = 0.91, 95%CI: 0.87-0.95, P = 1.38 × 10 -5 ). The following subgroup analysis found the same three loci among Asian population. Further, we compared the difference between various subgroup populations. Functional annotations revealed that rs2736100, rs27996 (r 2  = 0.85 with rs36019446) and rs326049 (r 2  = 0.73 with rs326048) could be potential functional variants in these three risk signals, respectively. In conclusion, although multiple variants have been found associated with lung cancer risk in TERT-CLPTM1L region, our findings indicated that there are three independent lung cancer susceptibility signals in this region. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Essential mechanisms of differential activation of eosinophils by IL-3 compared to GM-CSF and IL-5

PubMed Central

Esnault, Stephane; Kelly, Elizabeth A.

2017-01-01

There is compelling evidence that the eosinophils bring negative biological outcomes in several diseases, including eosinophilic asthma and hypereosinophilic syndromes. Eosinophils produce and store a broad range of toxic proteins and other mediators that enhance the inflammatory response and lead to tissue damage. For instance, in asthma, there is a close relationship between increased lung eosinophilia, asthma exacerbation, and loss of lung function. The use of an anti-IL-5 therapy in severe eosinophilic asthmatic patients is efficient to reduce exacerbations. However, anti-IL-5-treated patients still display a relatively high amount of functional lung tissue eosinophils, indicating that supplemental therapies are required to damper the eosinophil functions. Our recent published works, suggest that compared to IL-5, IL-3 can more strongly and differentially affect eosinophil functions. In this review, we will summarize our and other investigations that have compared the effects of the three β-chain receptor cytokines (IL-5, GM-CSF and IL-3) on eosinophil biology. We will focus on how IL-3 differentially activates eosinophils compared to IL-5 or GM-CSF. PMID:28605348

The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer

PubMed Central

2011-01-01

The role of vitamin D (VitD) in calcium and bone homeostasis is well described. In the last years, it has been recognized that in addition to this classical function, VitD modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair. VitD deficiency appears to be frequent in industrialized countries. Especially patients with lung diseases have often low VitD serum levels. Epidemiological data indicate that low levels of serum VitD is associated with impaired pulmonary function, increased incidence of inflammatory, infectious or neoplastic diseases. Several lung diseases, all inflammatory in nature, may be related to activities of VitD including asthma, COPD and cancer. The exact mechanisms underlying these data are unknown, however, VitD appears to impact on the function of inflammatory and structural cells, including dendritic cells, lymphocytes, monocytes, and epithelial cells. This review summarizes the knowledge on the classical and newly discovered functions of VitD, the molecular and cellular mechanism of action and the available data on the relationship between lung disease and VitD status. PMID:21418564

Effect of gamma interferon on lung function of mustard gas exposed patients, after 15 years.

PubMed

Ghanei, Mostafa; Panahi, Yoones; Mojtahedzadeh, Mojtaba; Khalili, Ali Reza Hosseini; Aslani, Jafar

2006-01-01

Bronchiolitis has been known to be among the main the pathological features of lung lesions in Mustard Gas (MG) exposed patients. The purpose of this research was to evaluate the efficacy of interferon gamma-1b on the lung function in MG exposed patients with bronchiolitis. Thirty-six bronchiolitis patients, whose lung lesion had been diagnosed through High Resolution Computerized Tomography (HRCT) of the chest and also pathological study, were divided into two 18-member case and control groups. Both groups were receiving their conventional treatment (inhaled Felixotide and Servent). The case group were treated for 6 months with a combination of 200 microg of interferon gamma-1b (given three times per week subcutaneously) plus 7.5 mg of prednisolone (given once a day), while the control group received their previous conventional medications. Lung function was measured at base line and after 1, 3 and 6 months of treatment. In case and control groups, Forced Expiratory Volume in first second (FEV1) did not have statistical differences at the base line (49.3 +/- 2.9 and 48.7 +/- 4.1, respectively = 0.6), whereas a significant increase was seen in the case group (66.3 +/- 5.4) compared control group (57.3 +/- 8.6) at the subsequent months (P = 0.001 for the difference between the groups). Similar pattern of increase was observed in Forced Vital Capacity (FVC). The findings of this study indicate that a 6-month treatment with interferon gamma-1b plus a low-dose prednisolone is associated with an improvement in the lung function in mustard-gas exposed patients with bronchiolitis.

Derivation of lung mesenchymal lineages from the fetal mesothelium requires hedgehog signaling for mesothelial cell entry

PubMed Central

Dixit, Radhika; Ai, Xingbin; Fine, Alan

2013-01-01

Recent studies have shown that mesothelial progenitors contribute to mesenchymal lineages of developing organs. To what extent the overlying mesothelium contributes to lung development remains unknown. To rigorously address this question, we employed Wt1CreERT2/+ mice for high-fidelity lineage tracing after confirming that Cre recombinase was mesothelial specific and faithfully recapitulated endogenous Wilms’ tumor 1 (Wt1) gene expression. We visualized WT1+ mesothelial cell entry into the lung by live imaging and identified their progenies in subpopulations of bronchial smooth muscle cells, vascular smooth muscle cells and desmin+ fibroblasts by lineage tagging. Derivation of these lineages was only observed with Cre recombinase activation during early lung development. Using loss-of-function assays in organ cultures, and targeted mesothelial-restricted hedgehog loss-of-function mice, we demonstrated that mesothelial cell movement into the lung requires the direct action of hedgehog signaling. By contrast, hedgehog signaling was not required for fetal mesothelial heart entry. These findings further support a paradigm wherein the mesothelium is a source of progenitors for mesenchymal lineages during organogenesis and indicate that signals controlling mesothelial cell entry are organ specific. PMID:24130328

Derivation of lung mesenchymal lineages from the fetal mesothelium requires hedgehog signaling for mesothelial cell entry.

PubMed

Dixit, Radhika; Ai, Xingbin; Fine, Alan

2013-11-01

Recent studies have shown that mesothelial progenitors contribute to mesenchymal lineages of developing organs. To what extent the overlying mesothelium contributes to lung development remains unknown. To rigorously address this question, we employed Wt1(CreERT2/+) mice for high-fidelity lineage tracing after confirming that Cre recombinase was mesothelial specific and faithfully recapitulated endogenous Wilms' tumor 1 (Wt1) gene expression. We visualized WT1(+) mesothelial cell entry into the lung by live imaging and identified their progenies in subpopulations of bronchial smooth muscle cells, vascular smooth muscle cells and desmin(+) fibroblasts by lineage tagging. Derivation of these lineages was only observed with Cre recombinase activation during early lung development. Using loss-of-function assays in organ cultures, and targeted mesothelial-restricted hedgehog loss-of-function mice, we demonstrated that mesothelial cell movement into the lung requires the direct action of hedgehog signaling. By contrast, hedgehog signaling was not required for fetal mesothelial heart entry. These findings further support a paradigm wherein the mesothelium is a source of progenitors for mesenchymal lineages during organogenesis and indicate that signals controlling mesothelial cell entry are organ specific.

Constrictive Bronchiolitis in Cystic Fibrosis Adolescents with Refractory Pulmonary Decline.

PubMed

Harris, William T; Boyd, J Todd; McPhail, Gary L; Brody, Alan S; Szczesniak, Rhonda D; Korbee, Leslie L; Baker, Michael L; Clancy, John P

2016-12-01

Refractory lung function decline in association with recurrent pulmonary exacerbations is a common, yet poorly explained finding in cystic fibrosis (CF). To investigate the histopathologic mechanisms of pulmonary deterioration during adolescence and early adulthood, we reviewed clinically-indicated lung biopsy specimens obtained during a period of persistent decline. To determine if peribronchiolar remodeling is prominent in lung biopsy specimens obtained in adolescents with CF refractory to conventional therapy. Six adolescents with CF (mean age, 16.2 y; mean FEV 1 , 52% predicted at biopsy) with significant pulmonary deterioration over 12-24 months (mean FEV 1 decline of 14% predicted/year) despite aggressive intervention underwent computed tomography imaging and ultimately lung biopsy to aid clinical management. In addition to routine clinical evaluation, histopathologic investigation included staining for transforming growth factor-β (TGF-β, a genetic modifier of CF lung disease), collagen deposition (a marker of fibrosis), elastin (to evaluate for bronchiectasis), and α-smooth muscle actin (to identify myofibroblasts). All computed tomography scans demonstrated a mix of bronchiectasis and hyperinflation that was variable across lung regions and within patients. Lung biopsy revealed significant peribronchiolar remodeling, particularly in patients with more advanced disease, with near complete obliteration of the peribronchiolar lumen (constrictive bronchiolitis). Myofibroblast differentiation (a TGF-β-dependent process) was prominent in specimens with significant airway remodeling. Constrictive bronchiolitis is widely present in the lung tissue of adolescents with CF with advanced disease and may contribute to impaired lung function that is refractory to conventional therapy (antibiotics, antiinflammatories, and mucolytics). TGF-β-dependent myofibroblast differentiation is prominent in areas of active fibrogenesis and may foster small airway remodeling in CF lung disease.

Pediatric lung transplantation

PubMed Central

2017-01-01

Pediatric lung transplantation has been undertaken since the 1980s, and it is today considered an accepted therapy option in carefully selected children with end-stage pulmonary diseases, providing carefully selected children a net survival benefit and improved health-related quality of life. Nowadays, >100 pediatric lung transplants are done worldwide every year. Here, specific pediatric aspects of lung transplantation are reviewed such as the surgical challenge, effects of immunosuppression on the developing pediatric immune system, and typical infections of childhood, as it is vital to comprehend that children undergoing lung transplants present a real challenge as children are not ‘just small adults’. Further, an update on the management of the pediatric lung transplant patient is provided in this review, and future challenges outlined. Indications for lung transplantation in children are different compared to adults, the most common being cystic fibrosis (CF). However, the primary diagnoses leading to pediatric lung transplantation vary considerably by age group. Furthermore, there are regional differences regarding the primary indication for lung transplantation in children. Overall, early referral, careful patient selection and appropriate timing of listing are crucial to achieve real survival benefit. Although allograft function is to be preserved, immunosuppressant-related side effects are common in children post-transplantation. Strategies need to be put into practice to reduce drug-related side effects through careful therapeutic drug monitoring and lowering of target levels of immunosuppression, to avoid acute-reversible and chronic-irreversible renal damage. Instead of a “one fits all approach”, tailored immunosuppression and a personalized therapy is to be advocated, particularly in children. Further, infectious complications are a common in children of all ages, accounting for almost 50% of death in the first year post-transplantation. However, chronic lung allograft dysfunction (CLAD) remains the major obstacle for improved long-term survival. PMID:28932575

Upregulation of autophagy decreases chlorine-induced mitochondrial injury and lung inflammation.

PubMed

Jurkuvenaite, Asta; Benavides, Gloria A; Komarova, Svetlana; Doran, Stephen F; Johnson, Michelle; Aggarwal, Saurabh; Zhang, Jianhua; Darley-Usmar, Victor M; Matalon, Sadis

2015-08-01

The mechanisms of toxicity during exposure of the airways to chlorinated biomolecules generated during the course of inflammation and to chlorine (Cl2) gas are poorly understood. We hypothesized that lung epithelial cell mitochondria are damaged by Cl2 exposure and activation of autophagy mitigates this injury. To address this, NCI-H441 (human lung adenocarcinoma epithelial) cells were exposed to Cl2 (100 ppm/15 min) and bioenergetics were assessed. One hour after Cl2, cellular bioenergetic function and mitochondrial membrane potential were decreased. These changes were associated with increased MitoSOX signal, and treatment with the mitochondrial redox modulator MitoQ attenuated these bioenergetic defects. At 6h postexposure, there was significant increase in autophagy, which was associated with an improvement of mitochondrial function. Pretreatment of H441 cells with trehalose (an autophagy activator) improved bioenergetic function, whereas 3-methyladenine (an autophagy inhibitor) resulted in increased bioenergetic dysfunction 1h after Cl2 exposure. These data indicate that Cl2 induces bioenergetic dysfunction, and autophagy plays a protective role in vitro. Addition of trehalose (2 vol%) to the drinking water of C57BL/6 mice for 6 weeks, but not 1 week, before Cl2 (400 ppm/30 min) decreased white blood cells in the bronchoalveolar lavage fluid at 6h after Cl2 by 70%. Acute administration of trehalose delivered through inhalation 24 and 1h before the exposure decreased alveolar permeability but not cell infiltration. These data indicate that Cl2 induces bioenergetic dysfunction associated with lung inflammation and suggests that autophagy plays a protective role. Published by Elsevier Inc.

Imaging Phenotype of Occupational Endotoxin-Related Lung Function Decline.

PubMed

Lai, Peggy S; Hang, Jing-Qing; Zhang, Feng-Ying; Sun, J; Zheng, Bu-Yong; Su, Li; Washko, George R; Christiani, David C

2016-09-01

Although occupational exposures contribute to a significant proportion of obstructive lung disease, the phenotype of obstructive lung disease associated with work-related organic dust exposure independent of smoking remains poorly defined. We identified the relative contributions of smoking and occupational endotoxin exposure to parenchymal and airway remodeling as defined by quantitative computed tomography (CT). The Shanghai Textile Worker Study is a longitudinal study of endotoxin-exposed cotton workers and endotoxin-unexposed silk workers that was initiated in 1981. Spirometry, occupational endotoxin exposure, and smoking habits were assessed at 5-year intervals. High-resolution computed tomography (CT) was performed in 464 retired workers in 2011, along with quantitative lung densitometric and airway analysis. Significant differences in all CT measures were noted across exposure groups. Occupational endotoxin exposure was associated with a decrease (-1.3%) in percent emphysema (LAAI-950), a 3.3-Hounsfield unit increase in 15th percentile density, an 18.1-g increase in lung mass, and a 2.3% increase in wall area percent. Current but not former smoking was associated with a similar CT phenotype. Changes in LAAI-950 were highly correlated with 15th percentile density (correlation -1.0). Lung mass was the only measure associated with forced expiratory volume in 1 sec (FEV1) decline, with each 10-g increase in lung mass associated with an additional loss (-6.1 mL) of FEV1 (p = 0.001) between 1981 and 2011. There are many similarities between the effects of occupational endotoxin exposure and those of tobacco smoke exposure on lung parenchyma and airway remodeling. The effects of occupational endotoxin exposure appear to persist even after the cessation of exposure. LAAI-950 may not be a reliable indicator of emphysema in subjects without spirometric impairment. Lung mass is a CT-based biomarker of accelerated lung function decline. Lai PS, Hang J, Zhang F, Sun J, Zheng BY, Su L, Washko GR, Christiani DC. 2016. Imaging phenotype of occupational endotoxin-related lung function decline. Environ Health Perspect 124:1436-1442; http://dx.doi.org/10.1289/EHP195.

Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection

PubMed Central

Cui, Ye; Liu, Kaifeng; Monzon-Medina, Maria E.; Padera, Robert F.; Wang, Hao; George, Gautam; Toprak, Demet; Abdelnour, Elie; D’Agostino, Emmanuel; Goldberg, Hilary J.; Perrella, Mark A.; Forteza, Rosanna Malbran; Rosas, Ivan O.; Visner, Gary; El-Chemaly, Souheil

2015-01-01

Lung transplantation is the only viable option for patients suffering from otherwise incurable end-stage pulmonary diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Despite aggressive immunosuppression, acute rejection of the lung allograft occurs in over half of transplant recipients, and the factors that promote lung acceptance are poorly understood. The contribution of lymphatic vessels to transplant pathophysiology remains controversial, and data that directly address the exact roles of lymphatic vessels in lung allograft function and survival are limited. Here, we have shown that there is a marked decline in the density of lymphatic vessels, accompanied by accumulation of low-MW hyaluronan (HA) in mouse orthotopic allografts undergoing rejection. We found that stimulation of lymphangiogenesis with VEGF-C156S, a mutant form of VEGF-C with selective VEGFR-3 binding, alleviates an established rejection response and improves clearance of HA from the lung allograft. Longitudinal analysis of transbronchial biopsies from human lung transplant recipients demonstrated an association between resolution of acute lung rejection and decreased HA in the graft tissue. Taken together, these results indicate that lymphatic vessel formation after lung transplantation mediates HA drainage and suggest that treatments to stimulate lymphangiogenesis have promise for improving graft outcomes. PMID:26485284

STUDIES ON LUNG INJURIES FOLLOWING ROENTGEN TREATMENT OF BREAST CANCER

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

Ichikawa, H.; Arai, T.

1960-01-01

Of 102 cases of breast cancer treated by x rays, 46 (45%) showed rcentgenographic evidence of lung flbrosis. A special chest phantom was constructed to measure the dose distribution within the lungs. The highest dose in the lung, by McWhirter's technique of radiation, was 150-160% of the surface. The parts of the lung where the tlssue received the highest dose were the upper, anterior, and outside parts of the radiated lung. This result was the same as indicated in the roentgenographic study. The lung radiation reaction was parallel to the skin reaction. The age had no relation to the fibrosis,more » but 4 cases, who had marked tuberculous calcification in their lung fields, seemed to have a tendency to produce considerable fibrosis by radiation. The sympton of pneumonitis was generally slight, and the general condition of the patients was not greatly influenced as a rule. The functional lung test showed almost normal results in the cases of grade I and grade II, but considerable injury in the cases of grade III, independent of their subjective symptoms. (Abstr. Japan Med., 1: No. 10, 1961)« less

Lung adenocarcinoma mimicking pulmonary fibrosis-a case report.

PubMed

Mehić, Bakir; Duranović Rayan, Lina; Bilalović, Nurija; Dohranović Tafro, Danina; Pilav, Ilijaz

2016-09-13

Lung cancer is usually presented with cough, dyspnea, pain and weight loss, which is overlapping with symptoms of other lung diseases such as pulmonary fibrosis. Pulmonary fibrosis shows characteristic reticular and nodular pattern, while lung cancers are mostly presented with infiltrative mass, thick-walled cavitations or a solitary nodule with spiculated borders. If the diagnosis is established based on clinical symptoms and CT findings, it would be a misapprehension. We report a case of lung adenocarcinoma whose symptoms as well as clinical images overlapped strongly with pulmonary fibrosis. The patient's non-productive cough, progressive dyspnea, restrictive pattern of pulmonary function test and CT scans (showing reticular interstitial opacities) were all indicative of pulmonary fibrosis. The patient underwent a treatment consisting of corticosteroids and antibiotics, to no avail. Histopathology of the lung showed that the patient suffered from mucinous adenocarcinoma. Albeit the immunohistochemical staining was not consistent with lung adenocarcinoma, tumor's morphological characteristics were consistent, and were used to make the definitive diagnosis. Given the fact that radiography cannot always make a clear-cut difference between pulmonary fibrosis and lung adenocarcinomas, and that clinical symptoms often overlap, histological examination should be considered as gold standard for diagnosis of lung adenocarcinoma.

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.

Aging effects on airflow dynamics and lung function in human bronchioles.

PubMed

Kim, JongWon; Heise, Rebecca L; Reynolds, Angela M; Pidaparti, Ramana M

2017-01-01

The mortality rate for patients requiring mechanical ventilation is about 35% and this rate increases to about 53% for the elderly. In general, with increasing age, the dynamic lung function and respiratory mechanics are compromised, and several experiments are being conducted to estimate these changes and understand the underlying mechanisms to better treat elderly patients. Human tracheobronchial (G1 ~ G9), bronchioles (G10 ~ G22) and alveolar sacs (G23) geometric models were developed based on reported anatomical dimensions for a 50 and an 80-year-old subject. The aged model was developed by altering the geometry and material properties of the model developed for the 50-year-old. Computational simulations using coupled fluid-solid analysis were performed for geometric models of bronchioles and alveolar sacs under mechanical ventilation to estimate the airflow and lung function characteristics. The airway mechanical characteristics decreased with aging, specifically a 38% pressure drop was observed for the 80-year-old as compared to the 50-year-old. The shear stress on airway walls increased with aging and the highest shear stress was observed in the 80-year-old during inhalation. A 50% increase in peak strain was observed for the 80-year-old as compared to the 50-year-old during exhalation. The simulation results indicate that there is a 41% increase in lung compliance and a 35%-50% change in airway mechanical characteristics for the 80-year-old in comparison to the 50-year-old. Overall, the airway mechanical characteristics as well as lung function are compromised due to aging. Our study demonstrates and quantifies the effects of aging on the airflow dynamics and lung capacity. These changes in the aging lung are important considerations for mechanical ventilation parameters in elderly patients. Realistic geometry and material properties need to be included in the computational models in future studies.

Aging effects on airflow dynamics and lung function in human bronchioles

PubMed Central

Kim, JongWon; Heise, Rebecca L.; Reynolds, Angela M.; Pidaparti, Ramana M.

2017-01-01

Background and objective The mortality rate for patients requiring mechanical ventilation is about 35% and this rate increases to about 53% for the elderly. In general, with increasing age, the dynamic lung function and respiratory mechanics are compromised, and several experiments are being conducted to estimate these changes and understand the underlying mechanisms to better treat elderly patients. Materials and methods Human tracheobronchial (G1 ~ G9), bronchioles (G10 ~ G22) and alveolar sacs (G23) geometric models were developed based on reported anatomical dimensions for a 50 and an 80-year-old subject. The aged model was developed by altering the geometry and material properties of the model developed for the 50-year-old. Computational simulations using coupled fluid-solid analysis were performed for geometric models of bronchioles and alveolar sacs under mechanical ventilation to estimate the airflow and lung function characteristics. Findings The airway mechanical characteristics decreased with aging, specifically a 38% pressure drop was observed for the 80-year-old as compared to the 50-year-old. The shear stress on airway walls increased with aging and the highest shear stress was observed in the 80-year-old during inhalation. A 50% increase in peak strain was observed for the 80-year-old as compared to the 50-year-old during exhalation. The simulation results indicate that there is a 41% increase in lung compliance and a 35%-50% change in airway mechanical characteristics for the 80-year-old in comparison to the 50-year-old. Overall, the airway mechanical characteristics as well as lung function are compromised due to aging. Conclusion Our study demonstrates and quantifies the effects of aging on the airflow dynamics and lung capacity. These changes in the aging lung are important considerations for mechanical ventilation parameters in elderly patients. Realistic geometry and material properties need to be included in the computational models in future studies. PMID:28846719

Pleural plaques and their effect on lung function in Libby vermiculite miners.

PubMed

Clark, Kathleen A; Flynn, J Jay; Goodman, Julie E; Zu, Ke; Karmaus, Wilfried J J; Mohr, Lawrence C

2014-09-01

Multiple studies have investigated the relationship between asbestos-related pleural plaques (PPs) and lung function, with disparate and inconsistent results. Most use chest radiographs to identify PPs and simple spirometry to measure lung function. High-resolution CT (HRCT) scanning improves the accuracy of PP identification. Complete pulmonary function tests (PFTs), including spirometry, lung volumes, and diffusing capacity of the lung for carbon monoxide, provide a more definitive assessment of lung function. The goal of this study was to determine, using HRCT scanning and complete PFTs, the effect of PPs on lung function in Libby vermiculite miners. The results of HRCT scanning and complete PFTs performed between January 2000 and August 2012 were obtained from the medical records of 166 Libby vermiculite miners. Multivariate regression analyses with Tukey multivariate adjustment were used to assess statistical associations between the presence of PPs and lung function. Adjustments were made for age, BMI, smoking history, duration of employment, and years since last occupational asbestos exposure. Nearly 90% of miners (n = 149) had evidence of PPs on HRCT scan. No significant differences in spirometry results, lung volumes, or diffusing capacity of the lung for carbon monoxide were found between miners with PPs alone and miners with normal HRCT scans. Miners with both interstitial fibrosis and the presence of PPs had a significantly decreased total lung capacity in comparison with miners with normal HRCT scans (P = .02). Age, cumulative smoking history, and BMI were significant covariates that contributed to abnormal lung function. Asbestos-related PPs alone have no significant effect on lung function in Libby vermiculite miners.

Identification and Structural Basis of Binding to Host Lung Glycogen by Streptococcal Virulence Factors

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

Lammerts van Bueren,A.; Higgins, M.; Wang, D.

2007-01-01

The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basismore » for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal {alpha}-glucan-metabolizing machinery as virulence factors.« less

Impact of airway morphological changes on pulmonary flows in scoliosis

NASA Astrophysics Data System (ADS)

Farrell, James; Garrido, Enrique; Valluri, Prashant

2016-11-01

The relationship between thoracic deformity in scoliosis and lung function is poorly understood. In a pilot study, we reviewed computed tomography (CT) routine scans of patients undergoing scoliosis surgery. The CT scans were processed to segment the anatomy of the airways, lung and spine. A three-dimensional model was created to study the anatomical relationship. Preliminary analysis showed significant airway morphological differences depending on the anterior position of the spine. A computational fluid dynamics (CFD) study was also conducted on the airway geometry using the inspiratory scans. The CFD model assuming non-compliant airway walls was capable of showing pressure drops in areas of high airway resistance, but was unable to predict regional ventilation differences. Our results indicate a dependence between the dynamic deformation of the airway during breathing and lung function. Dynamic structural deformation must therefore be incorporated within any modelling approaches to guide clinicians on the decision to perform surgical correction of the scoliosis.

Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis

PubMed Central

Adam, Martin; Schikowski, Tamara; Carsin, Anne Elie; Cai, Yutong; Jacquemin, Benedicte; Sanchez, Margaux; Vierkötter, Andrea; Marcon, Alessandro; Keidel, Dirk; Sugiri, Dorothee; Al Kanani, Zaina; Nadif, Rachel; Siroux, Valérie; Hardy, Rebecca; Kuh, Diana; Rochat, Thierry; Bridevaux, Pierre-Olivier; Eeftens, Marloes; Tsai, Ming-Yi; Villani, Simona; Phuleria, Harish Chandra; Birk, Matthias; Cyrys, Josef; Cirach, Marta; de Nazelle, Audrey; Nieuwenhuijsen, Mark J.; Forsberg, Bertil; de Hoogh, Kees; Declerq, Christophe; Bono, Roberto; Piccioni, Pavilio; Quass, Ulrich; Heinrich, Joachim; Jarvis, Deborah; Pin, Isabelle; Beelen, Rob; Hoek, Gerard; Brunekreef, Bert; Schindler, Christian; Sunyer, Jordi; Krämer, Ursula; Kauffmann, Francine; Hansell, Anna L.; Künzli, Nino; Probst-Hensch, Nicole

2015-01-01

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO2, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m−3 increase in NO2 exposure was associated with lower levels of FEV1 (−14.0 mL, 95% CI −25.8 to −2.1) and FVC (−14.9 mL, 95% CI −28.7 to −1.1). An increase of 10 μg·m−3 in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV1 (−44.6 mL, 95% CI −85.4 to −3.8) and FVC (−59.0 mL, 95% CI −112.3 to −5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe. PMID:25193994

Prevalence and determinants of airflow limitation in urban and rural children exposed to cooking fuels in South-East Nigeria.

PubMed

Oguonu, Tagbo; Obumneme-Anyim, Ijeoma N; Eze, Joy N; Ayuk, Adaeze C; Okoli, Chinyere V; Ndu, Ikenna K

2018-05-01

Background Biofuels and other cooking fuels are used in households in low- and middle-income countries. Aim To investigate the impact of cooking fuels on lung function in children in urban and rural households in South-East Nigeria. Methods The multi-stage sampling method was used to enroll children exposed to cooking fuel in the communities. Lung function values FEV1, FVC and the FEV1/FVC ratio, were measured with ndd EasyOne R spirometer. Airflow limitation was determined with FEV1/FVC Z-score values at -1.64 as the lower limit of normal (LLN5). The Global Lung Function Initiative 2012 software was used to calculate the lung function indices. Results The median age (range) of the 912 children enrolled was 10.6 years (6-18). Altogether, 468 (51.6%) children lived in rural areas. Seven hundred and thirty-seven (80.7%) were directly exposed to cooking fuels (418/737, 56.5% in rural areas). Wood and kerosene were the dominant fuels in rural and urban households. The respective mean Z-scores of the exposed children in rural and urban were zFEV1 -0.62, FVC -0.21, FEV1/FVC -0.83 and zFEV1 -0.57, zFVC -0.14, FEV1/FVC -0.75. Few (5.2%, 38/737) of the children had airflow limitation. Most of them (60.5%, 25/38) lived in the rural community; the lowest FEV1/FVC Z-scores were those of exposed to a combination of fuels. Conclusion Exposure to cooking fuels affects lung function in children with airway limitation in a small proportion, Control measures are advocated to reduce the morbidity related to cooking fuels exposure.

Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma

PubMed Central

Yates, Katherine P.; Zhou, Xiaobo; Guo, Feng; Sternberg, Alice L.; Van Natta, Mark L.; Wise, Robert A.; Szefler, Stanley J.; Sharma, Sunita; Kho, Alvin T.; Cho, Michael H.; Croteau-Chonka, Damien C.; Castaldi, Peter J.; Jain, Gaurav; Sanyal, Amartya; Zhan, Ye; Lajoie, Bryan R.; Dekker, Job; Stamatoyannopoulos, John; Covar, Ronina A.; Zeiger, Robert S.; Adkinson, N. Franklin; Williams, Paul V.; Kelly, H. William; Grasemann, Hartmut; Vonk, Judith M.; Koppelman, Gerard H.; Postma, Dirkje S.; Raby, Benjamin A.; Houston, Isaac; Lu, Quan; Fuhlbrigge, Anne L.; Tantisira, Kelan G.; Silverman, Edwin K.; Tonascia, James; Strunk, Robert C.; Weiss, Scott T.

2016-01-01

Rationale: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease. Objectives: To determine the genetic underpinnings of lung function patterns in subjects with childhood asthma. Methods: We performed a genome-wide association study of 581 non-Hispanic white individuals with asthma that were previously classified by patterns of lung function growth and decline (normal growth, normal growth with early decline, reduced growth, and reduced growth with early decline). The strongest association was also measured in two additional cohorts: a small asthma cohort and a large chronic obstructive pulmonary disease metaanalysis cohort. Interaction between the genomic region encompassing the most strongly associated single-nucleotide polymorphism and nearby genes was assessed by two chromosome conformation capture assays. Measurements and Main Results: An intergenic single-nucleotide polymorphism (rs4445257) on chromosome 8 was strongly associated with the normal growth with early decline pattern compared with all other pattern groups (P = 6.7 × 10−9; odds ratio, 2.8; 95% confidence interval, 2.0–4.0); replication analysis suggested this variant had opposite effects in normal growth with early decline and reduced growth with early decline pattern groups. Chromosome conformation capture experiments indicated a chromatin interaction between rs4445257 and the promoter of the distal CSMD3 gene. Conclusions: Early decline in lung function after normal growth is associated with a genetic polymorphism that may also protect against early decline in reduced growth groups. Clinical trial registered with www.clinicaltrials.gov (NCT00000575). PMID:27367781

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.

Comparison of the behavior of stainless and mild steel manual metal arc welding fumes in rat lung.

PubMed

Kalliomäki, P L; Junttila, M L; Kalliomäki, K K; Lakomaa, E L; Kivelä, R

1983-04-01

The lung retention and clearance of manual metal arc (MMA) stainless steel and mild steel welding fumes were determined in the rat. The exposure simulated the actual welding situation. The duration of exposure in the "nose-only" exposure chamber was 1 h/workday for one, two, three, or four weeks in the retention study and for four weeks in the clearance study. The concentration of exogenous iron was determined by the magnetic measuring method. Instrumental neutron activation analysis was applied to determine the concentration of total iron, chromium, and nickel in the lungs. The results indicated that the lung retention and clearance patterns for the two types of welding fumes were different. A linear relationship was observed between the amount of stainless steel MMA welding fume retained in the lungs and the duration of exposure, whereas the retention of mild steel MMA welding fume in the lung was saturated as a function of the cumulative exposure time rates. The maximum amount of lung-retained contaminants was 880 micrograms for stainless steel MMA welding fume and 220 micrograms for mild steel MMA fume.

Association between pulmonary function and renal function: findings from China and Australia.

PubMed

Yu, Dahai; Chen, Tao; Cai, Yamei; Zhao, Zhanzheng; Simmons, David

2017-05-01

The relationship between obstructive lung function and impaired renal function is unclear. This study investigated the dose-response relationship between obstructive lung function and impaired renal function. Two independent cross-sectional studies with representative sampling were applied. 1454 adults from rural Victoria, Australia (1298 with normal renal function, 156 with impaired renal function) and 5824 adults from Nanjing, China (4313 with normal renal function, 1511 with impaired renal function). Pulmonary function measurements included forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Estimated glomerular filtration rate (eGFR), and impaired renal function marked by eGFR <60 mL/min/1.73m 2 were used as outcome. eGFR increased linearly with FEV1 in Chinese participants and with FVC in Australians. A non-linear relationship with peaked eGFR was found for FEV1 at 2.65 L among Australians and for FVC at 2.78 L among Chinese participants, respectively. A non-linear relationship with peaked eGFR was found for the predicted percentage value of forced expiratory volume in 1 s (PFEV1) at 81-82% and for the predicted percentage value of forced vital capacity (PFVC) at 83-84% among both Chinese and Australian participants, respectively. The non-linear dose-response relationships between lung capacity measurements (both for FEV1 and FVC) and risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 3.05 L both for FEV1 and FVC, respectively. The non-linear relationship between PFEV and PVC and the risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 76-77% for PFEV1 and 79-80% for PFVC, respectively. In both Australian and Chinese populations, the risk of impaired renal function increased both with FEV1 and FVC below 3.05 L, with PFEV1 below 76-77% or with PFVC below 79-80%, respectively. Obstructive lung function was associated with increased risk of reduced renal function. The screen for impaired renal function in patients with obstructive lung disease might be useful to ensure there was no impaired renal function before the commencement of potentially nephrotoxic medication where indicated (eg diuretics).

Breast milk polyunsaturated fatty acids: associations with adolescent allergic disease and lung function.

PubMed

Waidyatillake, N T; Stoney, R; Thien, F; Lodge, C J; Simpson, J A; Allen, K J; Abramson, M J; Erbas, B; Svanes, C; Dharmage, S C; Lowe, A J

2017-08-01

It has been hypothesized that n-3 PUFA in breast milk may assist immune and lung development. There are very limited data on possible long-term effects on allergic disease and lung function. The aim was to investigate associations of n-3 and n-6 PUFA levels in colostrum and breast milk with allergic disease and lung function at ages 12 and 18 years. Polyunsaturated fatty acids were measured in 194 colostrum samples and in 118 three-month expressed breast milk samples from mothers of children enrolled in the Melbourne Atopy Cohort (MACS) Study, a high-risk birth cohort study. Associations with allergic diseases, skin prick tests and lung function assessed at 12 and 18 years were estimated using multivariable regression. Higher levels of n-3 but not n-6 PUFAs in colostrum were associated with a trend towards increased odds of allergic diseases, with strong associations observed for allergic rhinitis at 12 (OR = 5.69[95% CI: 1.83,17.60] per weight%) and 18 years (4.43[1.46,13.39]) and eczema at 18 years (9.89[1.44, 68.49]). Higher levels of colostrum n-3 PUFAs were associated with reduced sensitization (3.37[1.18, 9.6]), mean FEV 1 (-166 ml [-332, -1]) and FEV 1 /FVC ratio (-4.6%, [-8.1, -1.1]) at 12 years. Higher levels of colostrum n-3 PUFAs were associated with increased risks of allergic rhinitis and eczema up to 18 years, and sensitization and reduced lung function at 12 years. As residual confounding may have caused these associations, they should be replicated, but these results could indicate that strategies that increase maternal n-3 PUFA intake may not aid in allergic disease prevention. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stochastic dosimetry model for radon progeny in the rat lung.

PubMed

Winkler-HeiI, R; Hofmann, W; Hussain, M

2014-07-01

The stochastic dosimetry model presented here considers the distinctly asymmetric, stochastic branching pattern reported in morphometric measurements. This monopodial structure suggests that an airway diameter is a more appropriate morphometric parameter to classify bronchial dose distributions for inhaled radon progeny than the commonly assigned airway generation numbers. Bronchial doses were calculated for the typical exposure conditions reported for the Pacific Northwest National Laboratory rat inhalation studies, yielding an average bronchial dose of 7.75 mGy WLM(-1). If plotted as functions of airway generations, the resulting dose distributions are highest in the central bronchial airways, while significantly decreasing towards peripheral generations. However, if plotted as functions of airway diameters, doses are much more uniformly distributed among bronchial airways. The comparison between rat and human lungs indicates that dose conversion coefficients for the rat lung are higher than the corresponding values for the human lung by a factor of 1.34 for the experimental PNNL exposure conditions, and of 1.25 for typical human indoor conditions. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

HOXA5 plays tissue-specific roles in the developing respiratory system.

PubMed

Landry-Truchon, Kim; Houde, Nicolas; Boucherat, Olivier; Joncas, France-Hélène; Dasen, Jeremy S; Philippidou, Polyxeni; Mansfield, Jennifer H; Jeannotte, Lucie

2017-10-01

Hoxa5 is essential for development of several organs and tissues. In the respiratory system, loss of Hoxa5 function causes neonatal death due to respiratory distress. Expression of HOXA5 protein in mesenchyme of the respiratory tract and in phrenic motor neurons of the central nervous system led us to address the individual contribution of these Hoxa5 expression domains using a conditional gene targeting approach. Hoxa5 does not play a cell-autonomous role in lung epithelium, consistent with lack of HOXA5 expression in this cell layer. In contrast, ablation of Hoxa5 in mesenchyme perturbed trachea development, lung epithelial cell differentiation and lung growth. Further, deletion of Hoxa5 in motor neurons resulted in abnormal diaphragm innervation and musculature, and lung hypoplasia. It also reproduced the neonatal lethality observed in null mutants, indicating that the defective diaphragm is the main cause of impaired survival at birth. Thus, Hoxa5 possesses tissue-specific functions that differentially contribute to the morphogenesis of the respiratory tract. © 2017. Published by The Company of Biologists Ltd.

Characterization of lung inflammation and its impact on macrophage function in aging

PubMed Central

Canan, Cynthia H.; Gokhale, Nandan S.; Carruthers, Bridget; Lafuse, William P.; Schlesinger, Larry S.; Torrelles, Jordi B.; Turner, Joanne

2014-01-01

Systemic inflammation that occurs with increasing age (inflammaging) is thought to contribute to the increased susceptibility of the elderly to several disease states. The elderly are at significant risk for developing pulmonary disorders and infectious diseases, but the contribution of inflammation in the pulmonary environment has received little attention. In this study, we demonstrate that the lungs of old mice have elevated levels of proinflammatory cytokines and a resident population of highly activated pulmonary macrophages that are refractory to further activation by IFN-γ. The impact of this inflammatory state on macrophage function was determined in vitro in response to infection with M.tb. Macrophages from the lungs of old mice secreted more proinflammatory cytokines in response to M.tb infection than similar cells from young mice and also demonstrated enhanced M.tb uptake and P-L fusion. Supplementation of mouse chow with the NSAID ibuprofen led to a reversal of lung and macrophage inflammatory signatures. These data indicate that the pulmonary environment becomes inflammatory with increasing age and that this inflammatory environment can be reversed with ibuprofen. PMID:24935957

Hydrostatic weighing at residual volume and functional residual capacity.

PubMed

Thomas, T R; Etheridge, G L

1980-07-01

Hydrostatic weighing (HW) was performed at both residual volume (RV) and functional residual capacity (FRC) to determine if underwater weighing at different lung volumes affected the measurement of body density. Subjects were 43 males, 18-25 yr. Subjects were submerged in the prone position, and the lung volume was measured by helium dilution at the time of the underwater weighing. Underwater weight was first assessed at FRC followed by assessment at RV. Changes in lung volume were accurately reflected in the underwater weight. Body density (D) was not different with the use of the FRC (mean D = 1.0778) or RV (mean D = 1.0781) data. Percent fat values for the FRC and RV data were 9.3 +/- 5.4 and 9.2 +/- 5.1%, respectively, and were not statistically different. The results indicate that the difference between percent fat determinations by HW in the prone position at FRC and RV is negligible. Because measurement of underwater weight at FRC is more comfortable for the subject, this may be the method of choice when the lung volume can be measured during the underwater weighing.

Assessment of quality of life in patients with advanced non-small cell lung carcinoma treated with a combination of carboplatin and paclitaxel*

PubMed Central

Avelino, Camila Uanne Resende; Cardoso, Rafael Marques; de Aguiar, Suzana Sales; da Silva, Mário Jorge Sobreira

2015-01-01

OBJECTIVE: Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. Most patients are diagnosed at an advanced stage, palliative chemotherapy therefore being the only treatment option. This study was aimed at evaluating the health-related quality of life (HRQoL) of advanced-stage NSCLC patients receiving palliative chemotherapy with carboplatin and paclitaxel. METHODS: This was a multiple case study of advanced-stage NSCLC outpatients receiving chemotherapy at a public hospital in Rio de Janeiro, Brazil. The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire was used in conjunction with its supplemental lung cancer-specific module in order to assess HRQoL. RESULTS: Physical and cognitive functioning scale scores differed significantly among chemotherapy cycles, indicating improved and worsened HRQoL, respectively. The differences regarding the scores for pain, loss of appetite, chest pain, and arm/shoulder pain indicated improved HRQoL. CONCLUSIONS: Chemotherapy was found to improve certain aspects of HRQoL in patients with advanced-stage NSCLC. PMID:25972967

A prospective study of the impact of diabetes mellitus on restrictive and obstructive lung function impairment: The Saku study.

PubMed

Sonoda, Nao; Morimoto, Akiko; Tatsumi, Yukako; Asayama, Kei; Ohkubo, Takayoshi; Izawa, Satoshi; Ohno, Yuko

2018-05-01

To assess the impact of diabetes on restrictive and obstructive lung function impairment. This 5-year prospective study included 7524 participants aged 40-69years without lung function impairment at baseline who underwent a comprehensive medical check-up between April 2008 and March 2009 at Saku Central Hospital. Diabetes was defined by fasting plasma glucose ≥7.0mmol/l (126mg/dl), HbA1c≥6.5% (48mmol/mol), or a history of diabetes, as determined by interviews conducted by the physicians. Restrictive and obstructive lung function impairment were defined as forced vital capacity (FVC) <80% predicted and forced expiratory volume in 1s (FEV 1 ) to FVC ratio (FEV 1 /FVC) <0.70, respectively. Participants were screened until they developed restrictive or obstructive lung function impairment or until March 2014. During the follow-up period, 171 and 639 individuals developed restrictive and obstructive lung function impairment, respectively. Individuals with diabetes had a 1.6-fold higher risk of restrictive lung function impairment than those without diabetes after adjusting for sex, age, height, abdominal obesity, smoking status, exercise habits, systolic blood pressure, HDL-cholesterol, log-transformed high-sensitivity C-reactive protein, and baseline lung function [multivariable-adjusted HR and 95% CI; 1.57 (1.04-2.36)]. In contrast, individuals with diabetes did not have a significantly higher risk of obstructive lung function impairment [multivariable-adjusted HR and 95% CI; 0.93 (0.72-1.21)]. Diabetes was associated with restrictive lung function impairment but not obstructive lung function impairment. Copyright © 2017. Published by Elsevier Inc.

Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats.

PubMed

Kawamura, Tomohiro; Huang, Chien-Sheng; Tochigi, Naobumi; Lee, Sungsoo; Shigemura, Norihisa; Billiar, Timothy R; Okumura, Meinoshin; Nakao, Atsunori; Toyoda, Yoshiya

2010-12-27

Successful abrogation of ischemia/reperfusion (I/R) injury of lung grafts could significantly improve short- and long-term outcomes for lung transplant (LTx) recipients. Hydrogen gas has potent antioxidant and antiapoptotic properties and has been recently used in number of experimental and clinical studies. The purpose of this research was to investigate whether inhaled hydrogen gas could reduce graft I/R injury during lung transplantation. Orthotopic left LTxs were performed in syngenic Lewis rats. Grafts were perfused with and stored in low potassium dextran solution at 4°C for 6 hr. The recipients received 100% O2 or 98% O2 with 2% N2, 2% He, or 2% H2 during surgery and 1 hr after reperfusion. The effects of hydrogen were assessed by functional, pathologic, and molecular analysis. Gas exchange was markedly impaired in animals exposed to 100% O2, 2% N2, or 2% He. Hydrogen inhalation attenuated graft injury as indicated by significantly improved gas exchange 2 hr after reperfusion. Graft lipid peroxidation was significantly reduced in the presence of hydrogen, demonstrating antioxidant effects of hydrogen in the transplanted lungs. Lung cold I/R injury causes the rapid production and release of several proinflammatory mediators and epithelial apoptosis. Exposure to 2% H2 significantly blocked the production of several proinflammatory mediators and reduced apoptosis with induction of the antiapoptotic molecules B-cell lymphoma-2 and B-cell lymphoma-extra large. Treatment of LTx recipients with inhaled hydrogen can prevent lung I/R injury and significantly improve the function of lung grafts after extended cold preservation, transplant, and reperfusion.

HOX genes in human lung: altered expression in primary pulmonary hypertension and emphysema.

PubMed

Golpon, H A; Geraci, M W; Moore, M D; Miller, H L; Miller, G J; Tuder, R M; Voelkel, N F

2001-03-01

HOX genes belong to the large family of homeodomain genes that function as transcription factors. Animal studies indicate that they play an essential role in lung development. We investigated the expression pattern of HOX genes in human lung tissue by using microarray and degenerate reverse transcriptase-polymerase chain reaction survey techniques. HOX genes predominantly from the 3' end of clusters A and B were expressed in normal human adult lung and among them HOXA5 was the most abundant, followed by HOXB2 and HOXB6. In fetal (12 weeks old) and diseased lung specimens (emphysema, primary pulmonary hypertension) additional HOX genes from clusters C and D were expressed. Using in situ hybridization, transcripts for HOXA5 were predominantly found in alveolar septal and epithelial cells, both in normal and diseased lungs. A 2.5-fold increase in HOXA5 mRNA expression was demonstrated by quantitative reverse transcriptase-polymerase chain reaction in primary pulmonary hypertension lung specimens when compared to normal lung tissue. In conclusion, we demonstrate that HOX genes are selectively expressed in the human lung. Differences in the pattern of HOX gene expression exist among fetal, adult, and diseased lung specimens. The altered pattern of HOX gene expression may contribute to the development of pulmonary diseases.

HOX Genes in Human Lung

PubMed Central

Golpon, Heiko A.; Geraci, Mark W.; Moore, Mark D.; Miller, Heidi L.; Miller, Gary J.; Tuder, Rubin M.; Voelkel, Norbert F.

2001-01-01

HOX genes belong to the large family of homeodomain genes that function as transcription factors. Animal studies indicate that they play an essential role in lung development. We investigated the expression pattern of HOX genes in human lung tissue by using microarray and degenerate reverse transcriptase-polymerase chain reaction survey techniques. HOX genes predominantly from the 3′ end of clusters A and B were expressed in normal human adult lung and among them HOXA5 was the most abundant, followed by HOXB2 and HOXB6. In fetal (12 weeks old) and diseased lung specimens (emphysema, primary pulmonary hypertension) additional HOX genes from clusters C and D were expressed. Using in situ hybridization, transcripts for HOXA5 were predominantly found in alveolar septal and epithelial cells, both in normal and diseased lungs. A 2.5-fold increase in HOXA5 mRNA expression was demonstrated by quantitative reverse transcriptase-polymerase chain reaction in primary pulmonary hypertension lung specimens when compared to normal lung tissue. In conclusion, we demonstrate that HOX genes are selectively expressed in the human lung. Differences in the pattern of HOX gene expression exist among fetal, adult, and diseased lung specimens. The altered pattern of HOX gene expression may contribute to the development of pulmonary diseases. PMID:11238043

Peroxiredoxin 6 gene-targeted mice show increased lung injury with paraquat-induced oxidative stress.

PubMed

Wang, Yan; Feinstein, Sheldon I; Manevich, Yefim; Ho, Ye-Shih; Fisher, Aron B

2006-01-01

Mice with knock-out of peroxiredoxin 6 (Prdx6), a recently described antioxidant enzyme, were evaluated for susceptibility to lung injury with paraquat (PQ) administration. With high dose PQ (30 mg/kg i.p.), all Prdx6-/- mice died (LT50 54 +/- 2.05 h, mean +/- SE) by 4 days, whereas 86% of the wild-type (WT) mice (C57BL/6) survived (n = 14). At 2 days after PQ, lung wet/dry weight ratio increased significantly (p < 0.05) to 7.57 +/- 0.37 in Prdx6-/- mice vs. 5.42 +/- 0.25 in WT mice. Total protein and nucleated cells in bronchoalveolar lavage fluid and TBARS and protein carbonyls in lung homogenate also showed more marked increases in Prdx6-/- mice. At 2.5 days after PQ, light microscopy of WT lungs showed mild injury while Prdx6-/- lungs showed epithelial cell necrosis, perivascular edema, and inflammatory cells. With low dose PQ (12.5 mg/kg), mortality and lung injury were less marked but were significantly greater with Prdx6-/- compared to WT mice. These results show that Prdx6-/- mice have increased susceptibility to lung injury with PQ administration. Thus, Prdx6 protects lungs against PQ toxicity as shown previously for hyperoxia, indicating that it functions as an important lung antioxidant enzyme.

Salivary Telomere Length and Lung Function in Adolescents Born Very Preterm: A Prospective Multicenter Study.

PubMed

Hadchouel, Alice; Marchand-Martin, Laetitia; Franco-Montoya, Marie-Laure; Peaudecerf, Laetitia; Ancel, Pierre-Yves; Delacourt, Christophe

2015-01-01

Preterm birth is associated with abnormal respiratory functions throughout life. The mechanisms underlying these long-term consequences are still unclear. Shortening of telomeres was associated with many conditions, such as chronic obstructive pulmonary disease. We aimed to search for an association between telomere length and lung function in adolescents born preterm. Lung function and telomere length were measured in 236 adolescents born preterm and 38 born full-term from the longitudinal EPIPAGE cohort. Associations between telomere length and spirometric indices were tested in univariate and multivariate models accounting for confounding factors in the study population. Airflows were significantly lower in adolescents born preterm than controls; forced expiratory volume in one second was 12% lower in the extremely preterm born group than controls (p<0.001). Lower birth weight, bronchopulmonary dysplasia and postnatal sepsis were significantly associated with lower airflow values. Gender was the only factor that was significantly associated with telomere length. Telomere length correlated with forced expiratory flow 25-75 in the extremely preterm adolescent group in univariate and multivariate analyses (p = 0.01 and p = 0.02, respectively). We evidenced an association between telomere length and abnormal airflow in a population of adolescents born extremely preterm. There was no evident association with perinatal events. This suggests other involved factors, such as a continuing airway oxidative stress leading to persistent inflammation and altered lung function, ultimately increasing susceptibility to chronic obstructive pulmonary disease.

K-ras p21 expression and activity in lung and lung tumors.

PubMed

Ramakrishna, G; Sithanandam, G; Cheng, R Y; Fornwald, L W; Smith, G T; Diwan, B A; Anderson, L M

2000-12-01

Although K-ras is mutated in many human and mouse lung adenocarcinomas, the function of K-ras p21 in lung is not known. We sought evidence for the prevalent hypothesis that K-ras p21 activates raf, which in turn passes the signal through the extracellular signal regulated kinases (Erks) to stimulate cell division, and that this pathway is upregulated when K-ras is mutated. Results from both mouse lung tumors and immortalized cultured E10 and C10 lung type II cells failed to substantiate this hypothesis. Lung tumors did not have more total K-ras p21 or K-ras p21 GTP than normal lung tissue, nor were high levels of these proteins found in tumors with mutant K-ras. Activated K-ras p21-GTP levels did not correlate with proliferating cell nuclear antigen. Special features of tumors with mutant K-ras included small size of carcinomas compared with carcinomas lacking this mutation, and correlation of proliferating cell nuclear antigen with raf-1. In nontransformed type II cells in culture, both total and activated K-ras p21 increased markedly at confluence but not after serum stimulation, whereas both Erk1/2 and the protein kinase Akt were rapidly activated by the serum treatment. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays of K-ras mRNA indicated an increase in confluent and especially in postconfluent cells. Together the findings indicate that normal K-ras p21 activity is associated with growth arrest of lung type II cells, and that the exact contribution of mutated K-ras p21 to tumor development remains to be discovered.

A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis.

PubMed

Taroni, Jaclyn N; Greene, Casey S; Martyanov, Viktor; Wood, Tammara A; Christmann, Romy B; Farber, Harrison W; Lafyatis, Robert A; Denton, Christopher P; Hinchcliff, Monique E; Pioli, Patricia A; Mahoney, J Matthew; Whitfield, Michael L

2017-03-23

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. Our results suggest that the innate immune system is central to SSc disease processes but that subtle distinctions exist between tissues. Our approach provides a framework for examining molecular signatures of disease in fibrosis and autoimmune diseases and for leveraging publicly available data to understand common and tissue-specific disease processes in complex human diseases.

Human Oncoprotein MDM2 Up-regulates Expression of NF-κB2 Precursor p100 Conferring a Survival Advantage to Lung Cells

PubMed Central

Vaughan, Catherine; Mohanraj, Lathika; Singh, Shilpa; Dumur, Catherine I.; Ramamoorthy, Mahesh; Garrett, Carleton T.; Windle, Brad; Yeudall, W. Andrew; Deb, Sumitra

2011-01-01

The current model predicts that MDM2 is primarily overexpressed in cancers with wild-type (WT) p53 and contributes to oncogenesis by degrading p53. Following a correlated expression of MDM2 and NF-κB2 transcripts in human lung tumors, we have identified a novel transactivation function of MDM2. Here, we report that in human lung tumors, overexpression of MDM2 was found in approximately 30% of cases irrespective of their p53 status, and expression of MDM2 and NF-κB2 transcripts showed a highly significant statistical correlation in tumors with WT p53. We investigated the significance of this correlated expression in terms of mechanism and biological function. Increase in MDM2 expression from its own promoter in transgenic mice remarkably enhanced expression of NF-κB2 compared with its non-transgenic littermates. Knockdown or elimination of endogenous MDM2 expression in cultured non-transformed or lung tumor cells drastically reduced expression of NF-κB2 transcripts, suggesting a normal physiological role of MDM2 in regulating NF-κB2 transcription. MDM2 could up-regulate expression of NF-κB2 transcripts when its p53-interaction domain was blocked with Nutlin-3, indicating that the MDM2-p53 interaction is dispensable for up-regulation of NF-κB2 expression. Consistently, analysis of functional domains of MDM2 indicated that although the p53-interaction domain of MDM2 contributes to the up-regulation of the NFκB2 promoter, MDM2 does not require direct interactions with p53 for this function. Accordingly, MDM2 overexpression in non-transformed or lung cancer cells devoid of p53 also generated a significant increase in the expression of NF-κB2 transcript and its targets CXCL-1 and CXCL-10, whereas elimination of MDM2 expression had the opposite effects. MDM2-mediated increase in p100/NF-κB2 expression reduced cell death mediated by paclitaxel. Furthermore, knockdown of NF-κB2 expression retarded cell proliferation. Based on these data, we propose that MDM2-mediated NF-κB2 up-regulation is a combined effect of p53-dependent and independent mechanisms and that it confers a survival advantage to lung cancer cells. PMID:22701761

Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function

PubMed Central

Ostadkarampour, Mahyar; Müller, Malin; Öckinger, Johan; Kullberg, Susanna; Lindén, Anders; Eklund, Anders; Grunewald, Johan; Wahlström, Jan

2016-01-01

Smoking influences the immune system in different ways and, hypothetically, effects on pulmonary effector and regulatory T cells emerge as potentially detrimental. Therefore, we characterized the frequencies and characteristics of CD4+ and CD8+ T cell subsets in the blood and lungs of young tobacco smokers. Bronchoalveolar lavage (BAL) and peripheral blood were obtained from healthy moderate smokers (n = 18; 2–24 pack-years) and never-smokers (n = 15), all with normal lung function. Cells were stimulated ex vivo and key intracellular cytokines (IFNγ, IL-17, IL-10 and TNFα) and transcription factors (Foxp3, T-bet and Helios) were analyzed using flow cytometry. Our results indicate that smoking is associated with a decline in lung IL-17+ CD4+ T cells, increased IFNγ+ CD8+ T cells and these alterations relate to the history of daily cigarette consumption. There is an increased fraction of Foxp3+ regulatory T cells being Helios- in the lungs of smokers. Cytokine production is mainly confined to the Helios- T cells, both in regulatory and effector subsets. Moreover, we detected a decline of Helios+Foxp3- postulated regulatory CD8+ T cells in smokers. These alterations in the immune system are likely to increase risk for infection and may have implications for autoimmune processes initiated in the lungs among tobacco smokers. PMID:27798682

The Anoikis Effector Bit1 Inhibits EMT through Attenuation of TLE1-Mediated Repression of E-Cadherin in Lung Cancer Cells

PubMed Central

Yao, Xin; Pham, Tri; Temple, Brandi; Gray, Selena; Cannon, Cornita; Chen, Renwei; Abdel-Mageed, Asim B.; Biliran, Hector

2016-01-01

The mitochondrial Bcl-2 inhibitor of transcription 1 (Bit1) protein is part of an anoikis-regulating pathway that is selectively dependent on integrins. We previously demonstrated that the caspase-independent apoptotic effector Bit1 exerts tumor suppressive function in lung cancer in part by inhibiting anoikis resistance and anchorage-independent growth in vitro and tumorigenicity in vivo. Herein we show a novel function of Bit1 as an inhibitor cell migration and epithelial–mesenchymal transition (EMT) in the human lung adenocarcinoma A549 cell line. Suppression of endogenous Bit1 expression via siRNA and shRNA strategies promoted mesenchymal phenotypes, including enhanced fibroblastoid morphology and cell migratory potential with concomitant downregulation of the epithelial marker E-cadherin expression. Conversely, ectopic Bit1 expression in A549 cells promoted epithelial transition characterized by cuboidal-like epithelial cell phenotype, reduced cell motility, and upregulated E-cadherin expression. Specific downregulation of E-cadherin in Bit1-transfected cells was sufficient to block Bit1-mediated inhibition of cell motility while forced expression of E-cadherin alone attenuated the enhanced migration of Bit1 knockdown cells, indicating that E-cadherin is a downstream target of Bit1 in regulating cell motility. Furthermore, quantitative real-time PCR and reporter analyses revealed that Bit1 upregulates E-cadherin expression at the transcriptional level through the transcriptional regulator Amino-terminal Enhancer of Split (AES) protein. Importantly, the Bit1/AES pathway induction of E-cadherin expression involves inhibition of the TLE1-mediated repression of E-cadherin, by decreasing TLE1 corepressor occupancy at the E-cadherin promoter as revealed by chromatin immunoprecipitation assays. Consistent with its EMT inhibitory function, exogenous Bit1 expression significantly suppressed the formation of lung metastases of A549 cells in an in vivo experimental metastasis model. Taken together, our studies indicate Bit1 is an inhibitor of EMT and metastasis in lung cancer and hence can serve as a molecular target in curbing lung cancer aggressiveness. PMID:27655370

A combined pulmonary function and emphysema score prognostic index for staging in Chronic Obstructive Pulmonary Disease.

PubMed

Boutou, Afroditi K; Nair, Arjun; Douraghi-Zadeh, Dariush; Sandhu, Ranbir; Hansell, David M; Wells, Athol U; Polkey, Michael I; Hopkinson, Nicholas S

2014-01-01

Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity and mortality. Lung computed tomography parameters, individually or as part of a composite index, may provide more prognostic information than pulmonary function tests alone. To investigate the prognostic value of emphysema score and pulmonary artery measurements compared with lung function parameters in COPD and construct a prognostic index using a contingent staging approach. Predictors of mortality were assessed in COPD outpatients whose lung computed tomography, spirometry, lung volumes and gas transfer data were collected prospectively in a clinical database. Univariate and multivariate Cox proportional hazard analysis models with bootstrap techniques were used. 169 patients were included (59.8% male, 61.1 years old; Forced Expiratory Volume in 1 second % predicted: 40.5±19.2). 20.1% died; mean survival was 115.4 months. Age (HR = 1.098, 95% Cl = 1.04-1.252) and emphysema score (HR = 1.034, 95% CI = 1.007-1.07) were the only independent predictors of mortality. Pulmonary artery dimensions were not associated with survival. An emphysema score of 55% was chosen as the optimal threshold and 30% and 65% as suboptimals. Where emphysema score was between 30% and 65% (intermediate risk) the optimal lung volume threshold, a functional residual capacity of 210% predicted, was applied. This contingent staging approach separated patients with an intermediate risk based on emphysema score alone into high risk (Functional Residual Capacity ≥210% predicted) or low risk (Functional Residual Capacity <210% predicted). This approach was more discriminatory for survival (HR = 3.123; 95% CI = 1.094-10.412) than either individual component alone. Although to an extent limited by the small sample size, this preliminary study indicates that the composite Emphysema score-Functional Residual Capacity index might provide a better separation of high and low risk patients with COPD, than other individual predictors alone.

The role of the ataxia telangiectasia mutated gene in lung cancer: recent advances in research.

PubMed

Xu, Yanling; Gao, Peng; Lv, Xuejiao; Zhang, Lin; Zhang, Jie

2017-09-01

Lung cancer is the leading cause of death due to cancer worldwide. It is estimated that approximately 1.2 million new cases of lung cancer are diagnosed each year. Early detection and treatment are crucial for improvements in both prognosis and quality of life of lung cancer patients. The ataxia telangiectasia mutated (ATM) gene is a cancer-susceptibility gene that encodes a key apical kinase in the DNA damage response pathway. It has recently been shown to play an important role in the development of lung cancer. The main functions of the ATM gene and protein includes participation in cell cycle regulation, and identification and repair of DNA damage. ATM gene mutation can lead to multiple system dysfunctions as well as a concomitant increase in tumor tendency. In recent years, many studies have indicated that single nucleotide polymorphism of the ATM gene is associated with increased incidence of lung cancer. At the same time, the ATM gene and its encoding product ATM protein predicts the response to radiotherapy, chemotherapy, and prognosis of lung cancer, thus suggesting that the ATM gene may be a new potential target for the diagnosis and treatment of lung cancer.

Handgrip strength is associated with improved spirometry in adolescents

PubMed Central

Standl, Marie; Berdel, Dietrich; von Berg, Andrea; Bauer, Carl-Peter; Schikowski, Tamara; Koletzko, Sibylle; Lehmann, Irina; Krämer, Ursula; Heinrich, Joachim; Schulz, Holger

2018-01-01

Introduction Pulmonary rehabilitation, including aerobic exercise and strength training, improves function, such as spirometric indices, in lung disease. However, we found spirometry did not correlate with physical activity (PA) in healthy adolescents (Smith ERJ: 42(4), 2016). To address whether muscle strength did, we measured these adolescents’ handgrip strength and correlated it with spirometry. Methods In 1846 non-smoking, non-asthmatic Germans (age 15.2 years, 47% male), we modeled spirometric indices as functions of handgrip strength by linear regression in each sex, corrected for factors including age, height, and lean body mass. Results Handgrip averaged 35.4 (SD 7.3) kg in boys, 26.6 (4.2) in girls. Spirometric volumes and flows increased linearly with handgrip. In boys each kg handgrip was associated with about 28 mL greater FEV1 and FVC; 60 mL/sec faster PEF; and 38 mL/sec faster FEF2575. Effects were 10–30% smaller in girls (all p<0.0001) and stable when Z-scores for spirometry and grip were modeled, after further correction for environment and/or other exposures, and consistent across stages of puberty. Conclusions Grip strength was associated with spirometry in a cohort of healthy adolescents whose PA was not. Thus, research into PA’s relationship with lung function should consider strength as well as total PA. Strength training may benefit healthy lungs; interventions are needed to prove causality. PMID:29641533

Ex Vivo Adenoviral Vector Gene Delivery Results in Decreased Vector-associated Inflammation Pre- and Post–lung Transplantation in the Pig

PubMed Central

Yeung, Jonathan C; Wagnetz, Dirk; Cypel, Marcelo; Rubacha, Matthew; Koike, Terumoto; Chun, Yi-Min; Hu, Jim; Waddell, Thomas K; Hwang, David M; Liu, Mingyao; Keshavjee, Shaf

2012-01-01

Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function. PMID:22453765

Brain-Derived Neurotrophic Factor in the Airways

PubMed Central

Prakash, Y.S.; Martin, Richard J.

2014-01-01

In addition to their well-known roles in the nervous system, there is increasing recognition that neurotrophins such as brain derived neurotrophic factor (BDNF) as well as their receptors are expressed in peripheral tissues including the lung, and can thus potentially contribute to both normal physiology and pathophysiology of several diseases. The relevance of this family of growth factors lies in emerging clinical data indicating altered neurotrophin levels and function in a range of diseases including neonatal and adult asthma, sinusitis, influenza, and lung cancer. The current review focuses on 1) the importance of BDNF expression and signaling mechanisms in early airway and lung development, critical to both normal neonatal lung function and also its disruption in prematurity and insults such as inflammation and infection; 2) how BDNF, potentially derived from airway nerves modulate neurogenic control of airway tone, a key aspect of airway reflexes as well as dysfunctional responses to allergic inflammation; 3) the emerging idea that local BDNF production by resident airway cells such as epithelium and airway smooth muscle can contribute to normal airway structure and function, and to airway hyperreactivity and remodeling in diseases such as asthma. Furthermore, given its pleiotropic effects in the airway, BDNF may be a novel and appealing therapeutic target. PMID:24560686

The significance of the choice of radiobiological (NTCP) models in treatment plan objective functions.

PubMed

Miller, J; Fuller, M; Vinod, S; Suchowerska, N; Holloway, L

2009-06-01

A Clinician's discrimination between radiation therapy treatment plans is traditionally a subjective process, based on experience and existing protocols. A more objective and quantitative approach to distinguish between treatment plans is to use radiobiological or dosimetric objective functions, based on radiobiological or dosimetric models. The efficacy of models is not well understood, nor is the correlation of the rank of plans resulting from the use of models compared to the traditional subjective approach. One such radiobiological model is the Normal Tissue Complication Probability (NTCP). Dosimetric models or indicators are more accepted in clinical practice. In this study, three radiobiological models, Lyman NTCP, critical volume NTCP and relative seriality NTCP, and three dosimetric models, Mean Lung Dose (MLD) and the Lung volumes irradiated at 10Gy (V10) and 20Gy (V20), were used to rank a series of treatment plans using, harm to normal (Lung) tissue as the objective criterion. None of the models considered in this study showed consistent correlation with the Radiation Oncologists plan ranking. If radiobiological or dosimetric models are to be used in objective functions for lung treatments, based on this study it is recommended that the Lyman NTCP model be used because it will provide most consistency with traditional clinician ranking.

[Clinical laboratory tests supporting respiratory disease treatment--chairman's introductory remarks].

PubMed

Takai, Daiya

2014-12-01

The symposium consisted of four parts: history of lung function tests, nitric oxide for diagnosis and monitoring of bronchial asthma, radiological and functional changes of the lung in COPD, and combined pulmonary fibrosis and emphysema (CPFE) occasionally showing almost normal results in lung function tests. The history of lung function tests was presented by Dr. Naoko Tojo of the Tokyo Medical and Dental University. Nitric oxide tests in clinical use for diagnosis and monitoring of bronchial asthma were presented by Dr. Hiroyuki Nagase of Teikyo University. Radiological and functional changes of the lung in COPD were presented by Dr. Shigeo Muro of Kyoto University. Clinical features of combined pulmonary fibrosis and emphysema and their associated lung function were presented by Dr. Daiya Takai of the University of Tokyo. I hope that discussing the history of lung function tests until the present was useful for many medical technologists. (Review).

Dose-response relationships between occupational exposure to potash, diesel exhaust and nitrogen oxides and lung function: cross-sectional and longitudinal study in two salt mines.

PubMed

Lotz, Gabriele; Plitzko, Sabine; Gierke, Erhardt; Tittelbach, Ulrike; Kersten, Norbert; Schneider, W Dietmar

2008-08-01

Several studies have shown that underground salt miners may have an increased incidence of chest symptoms and sometimes decreased lung function. Miners of two salt mines were investigated to evaluate relationships between the lung function and the workplace exposure. The effect of nitrogen monoxide (NO) and nitrogen dioxide (NO(2)) was investigated in view of the recent debate on European occupational exposure limits. A total of 410/463 miners (mine A/mine B) were examined cross-sectional and 75/64% of the first cohort were examined after a 5-year period. Exposure was measured by personal sampling. Personal lifetime exposure doses of salt dust, diesel exhaust, NO(2) and NO were calculated for all miners. Dose-response relationships were calculated by multiple regression analysis. Each exposure component acted as an indicator for the complex exposure. Exposure response relationships were shown in the cross-sectional and longitudinal investigations in both mines. In the 5-year period, the adjusted (age, smoking, etc.) effect of the exposure indicators resulted in a mean decrease of FEV(1) between -18 ml/year (mine A) and -10 ml/year (mine B). The personal concentrations related to this effect were 12.6/7.1 mg/m(3) inhalable dust, 2.4/0.8 mg/m(3) respirable dust, 0.09/0.09 mg/m(3) diesel exhaust, 0.4/0.5 ppm NO(2) and 1.7/1.4 ppm NO (mine A/B). Exposure was related to symptoms of chronic bronchitis only in mine B. The effects found in both mines indicate that the mixed exposure can cause lung function disorders in salt miners exposed over a long time. Because of the high correlation of the concentrations it was not possible to determine the effects of a single exposure component separately or to recommend a specific occupational exposure limit. However, possible maximum effects associated with the mixed exposure can be evaluated in the ranges of concentrations of the individual substances in the mines.

Quantification of heterogeneity in lung disease with image-based pulmonary function testing.

PubMed

Stahr, Charlene S; Samarage, Chaminda R; Donnelley, Martin; Farrow, Nigel; Morgan, Kaye S; Zosky, Graeme; Boucher, Richard C; Siu, Karen K W; Mall, Marcus A; Parsons, David W; Dubsky, Stephen; Fouras, Andreas

2016-07-27

Computed tomography (CT) and spirometry are the mainstays of clinical pulmonary assessment. Spirometry is effort dependent and only provides a single global measure that is insensitive for regional disease, and as such, poor for capturing the early onset of lung disease, especially patchy disease such as cystic fibrosis lung disease. CT sensitively measures change in structure associated with advanced lung disease. However, obstructions in the peripheral airways and early onset of lung stiffening are often difficult to detect. Furthermore, CT imaging poses a radiation risk, particularly for young children, and dose reduction tends to result in reduced resolution. Here, we apply a series of lung tissue motion analyses, to achieve regional pulmonary function assessment in β-ENaC-overexpressing mice, a well-established model of lung disease. The expiratory time constants of regional airflows in the segmented airway tree were quantified as a measure of regional lung function. Our results showed marked heterogeneous lung function in β-ENaC-Tg mice compared to wild-type littermate controls; identified locations of airway obstruction, and quantified regions of bimodal airway resistance demonstrating lung compensation. These results demonstrate the applicability of regional lung function derived from lung motion as an effective alternative respiratory diagnostic tool.

Association between lung function and mental health problems among adults in the United States: findings from the First National Health and Nutrition Examination Survey.

PubMed

Goodwin, Renee D; Chuang, Shirley; Simuro, Nicole; Davies, Mark; Pine, Daniel S

2007-02-15

The objective of this study was to determine the association between lung function and mental health problems among adults in the United States. Data were drawn from the First National Health and Nutrition Examination Survey (1971-1975), with available information on a representative sample of US adults aged 25-74 years. Lung function was assessed by spirometry, and provisional diagnoses of restrictive and obstructive airway disease were assigned based on percentage of expected forced expiratory volume. Mental health problems were assessed with the General Well-Being scales. Restrictive lung function and obstructive lung function, compared with normal lung function, were each associated with a significantly increased likelihood of mental health problems. After adjustment for differences in demographic characteristics, obstructive lung function was associated with significantly lower overall well-being (p = 0.025), and restrictive lung function was associated with significantly lower overall well-being (p < 0.001), general health (p < 0.0001), vitality (p < 0.0001), and self-control (p = 0.001) and with higher depression (p = 0.002) subscale scores compared with no lung function problems. Consistent with previous findings from clinical and community-based studies, these results extend available data by providing evidence of a link between objectively measured lung function and self-reported mental health problems in a representative sample of community adults. Future studies are needed to determine the mechanisms of these associations.

[Sputum viscosity and pulmonary function measurements during a one-week parenteral treatment with a standardized oxidation product of oil of turpentine and terpin hydrate].

PubMed

Löllgen-Horres, I; Löllgen, H

1976-01-01

In 23 patients with chronic obstructive lung diseases, viscosity, airway resistance, arterial blood gases and acid-base balance, and sputum aspect were measured before and after one-week treatment with Ozothin, a substance from oxidation products of ol. terebinth. and terpinum hydratum. Within this time, viscosity of the sputum was reduced, airway resistance decreased, and arterial oxygen pressure slightly increased, whereas arterial carbon dioxide tension obvious change of sputum aspect could be observed. Correlation calculations revealed no significant relations between viscosity and the above cited lung function values. The results indicate that administration of Ozothin may liquefy viscous secretion and reduce sputum viscosity.

miR-138 suppresses the proliferation, metastasis and autophagy of non-small cell lung cancer by targeting Sirt1.

PubMed

Ye, Zaiting; Fang, Bingmu; Pan, Jiongwei; Zhang, Ning; Huang, Jinwei; Xie, Congying; Lou, Tianzheng; Cao, Zhuo

2017-06-01

The present study determined the role and mechanism of miR-138 in non-small cell lung cancer (NSCLC). In total, 45 freshly resected clinical NSCLC tissues were collected. The expression of miR-138 in tissues and cell lines were determined by real-time quantitative PCR. miR-138 mimics were transfected into A549 and Calu-3 cells in vitro, and then the effects of miR-138 on lung cancer cell proliferation, cell cycle, invasion and metastasis were investigated by CCK-8 assay, Transwell and flow cytometry, respectively. The protein expression of the potential target gene Sirt1 in lung cancer cells were determined by western blot analysis. Dual-luciferase reporter assay was performed to further confirm whether Sirt1 was the target gene of miR-138. The expression of miR-138 was significantly lower in lung cancer tissues and was negatively correlated to the differentiation degree and lymph node metastasis of lung cancer. In vitro experiment results showed that miR-138 inhibited lung cancer cell proliferation, invasion and migration. It was verified that miR-138 could downregulate Sirt1 protein expression, inhibit epithelial-mesenchymal transition (EMT), decrease the activity of AMPK signaling pathway and elevate mTOR phosphorylation level. Dual-luciferase reporter assay demonstrated that miR-138 could directly regulate Sirt1. Downregulation of Sirt1 alone can also cause the same molecular and biological function changes. Western blot analysis and confocal microscopy results indicated that overexpression of miR-138 or interference of Sirt1 expression could inhibit lung cancer cell autophagy activity possibly through AMPK-mTOR signaling pathway. miR-138 plays a tumor suppressor function in lung cancer. It may inhibit the proliferation, invasion and migration of lung cancer through downregulation of Sirt1 expression and activation of cell autophagy. The downregulation of miR-138 is closely related to the development of lung cancer.

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

PubMed

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

2015-11-01

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

Respiratory and general health impairments of workers employed in a municipal solid waste disposal at an open landfill site in Delhi.

PubMed

Ray, Manas Ranjan; Roychoudhury, Sanghita; Mukherjee, Gopeshwar; Roy, Senjuti; Lahiri, Twisha

2005-01-01

The objective of this study was to examine the respiratory and general health of workers employed in a municipal solid waste (MSW) disposal at an open landfill site in India. Ninety-six landfill workers of Okhla landfill site, Delhi, and 90 controls matched for age, sex, and socioeconomic conditions were enrolled. Health data was obtained from questionnaire surveys, clinical examination and laboratory investigations. Lung function was evaluated by spirometry. Compared with matched controls, landfill workers had significantly higher prevalences of both upper and lower respiratory symptoms, and they suffered more often from diarrhea, fungal infection and ulceration of the skin, burning sensation in the extremities, tingling or numbness, transient loss of memory, and depression. Spirometry revealed impairment of lung function in 62% of the landfill workers compared to 27% of the controls. Sputum cytology showed squamous metaplasia, abundance of inflammatory cells, alveolar macrophages (AM) and siderophages (macrophages with iron deposits), and high elastase enzyme activity in neutrophils and AM of a majority of landfill workers, indicating adverse cellular lung reaction. Hematological profiles of these workers depicted low hemoglobin and erythrocyte levels with high total leukocyte, eosinophil and monocyte counts. Erythrocytes with target cell morphology were abundant in 42% of the landfill workers compared to 10% of the controls. Toxic granulation in neutrophils, an indication of infection and inflammation, was recorded in 94% of the landfill workers and in 49% of the controls. The results demonstrated higher prevalence of respiratory symptoms, inflammation of the airways, lung function decrement and a wide range of general health problems in MSW disposal workers.

Quantifying lung morphology with respiratory-gated micro-CT in a murine model of emphysema

NASA Astrophysics Data System (ADS)

Ford, N. L.; Martin, E. L.; Lewis, J. F.; Veldhuizen, R. A. W.; Holdsworth, D. W.; Drangova, M.

2009-04-01

Non-invasive micro-CT imaging techniques have been developed to investigate lung structure in free-breathing rodents. In this study, we investigate the utility of retrospectively respiratory-gated micro-CT imaging in an emphysema model to determine if anatomical changes could be observed in the image-derived quantitative analysis at two respiratory phases. The emphysema model chosen was a well-characterized, genetically altered model (TIMP-3 knockout mice) that exhibits a homogeneous phenotype. Micro-CT scans of the free-breathing, anaesthetized mice were obtained in 50 s and retrospectively respiratory sorted and reconstructed, providing 3D images representing peak inspiration and end expiration with 0.15 mm isotropic voxel spacing. Anatomical measurements included the volume and CT density of the lungs and the volume of the major airways, along with the diameters of the trachea, left bronchus and right bronchus. From these measurements, functional parameters such as functional residual capacity and tidal volume were calculated. Significant differences between the wild-type and TIMP-3 knockout groups were observed for measurements of CT density over the entire lung, indicating increased air content in the lungs of TIMP-3 knockout mice. These results demonstrate retrospective respiratory-gated micro-CT, providing images at multiple respiratory phases that can be analyzed quantitatively to investigate anatomical changes in murine models of emphysema.

Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic Fibrosis.

PubMed

Blue, Elizabeth; Louie, Tin L; Chong, Jessica X; Hebbring, Scott J; Barnes, Kathleen C; Rafaels, Nicholas M; Knowles, Michael R; Gibson, Ronald L; Bamshad, Michael J; Emond, Mary J

2018-04-01

Cystic fibrosis, like primary ciliary dyskinesia, is an autosomal recessive disorder characterized by abnormal mucociliary clearance and obstructive lung disease. We hypothesized that genes underlying the development or function of cilia may modify lung disease severity in persons with cystic fibrosis. To test this hypothesis, we compared variants in 93 candidate genes in both upper and lower tertiles of lung function in a large cohort of children and adults with cystic fibrosis with those of a population control dataset. Variants within candidate genes were tested for association using the SKAT-O test, comparing cystic fibrosis cases defined by poor (n = 127) or preserved (n = 127) lung function with population controls (n = 3,269 or 3,148, respectively). Associated variants were then tested for association with related phenotypes in independent datasets. Variants in DNAH14 and DNAAF3 were associated with poor lung function in cystic fibrosis, whereas variants in DNAH14 and DNAH6 were associated with preserved lung function in cystic fibrosis. Associations between DNAH14 and lung function were replicated in disease-related phenotypes characterized by obstructive lung disease in adults. Genetic variants within DNAH6, DNAH14, and DNAAF3 are associated with variation in lung function among persons with cystic fibrosis.

Conservation of small-airway function by tacrolimus/cyclosporine conversion in the management of bronchiolitis obliterans following lung transplantation.

PubMed

Revell, M P; Lewis, M E; Llewellyn-Jones, C G; Wilson, I C; Bonser, R S

2000-12-01

We studied serial lung function in 11 patients with bronchiolitis obliterans syndrome who were treated with tacrolimus conversion following lung or heart-lung transplantation. Our results show that tacrolimus conversion slows the decline of lung function in bronchiolitis obliterans syndrome. The attenuation continues for at least 1 year following conversion.

Silymarin suppressed lung cancer growth in mice via inhibiting myeloid-derived suppressor cells.

PubMed

Wu, Tiancong; Liu, Wen; Guo, Wenjie; Zhu, Xixu

2016-07-01

In this study, we investigated the antitumor activity of Silymarin in a mouse model of colon cancer xenograft of Lewis lung cancer (LLC) cells. Silymarin significantly suppressed tumor growth and induced apoptosis of cells in tumor tissues at a dose of 25 and 50mg/kg. Silymarin treatment enhanced the infiltration and function of CD8(+) T cells. In the meantime, Silymarin decreased the level of IL-10 while elevated the level of IL-2 and IFN-γ in the serum of tumor-bearing mice. Finally, Silymarin reduced the proportion of myeloid-derived suppressor cells (MDSC) in the tumor tissue and also the mRNA expressions of inducible nitric oxide synthases-2 (iNOS2), arginase-1 (Arg-1) and MMP9, which indicated that the function of MDSC in tumor tissues were suppressed. Altogether, our data here showed that Silymarin inhibited the MDSC and promoted the infiltration and function of CD8(+) T cells thus suppressed the growth of LLC xenografts, which provides evidence for the possible use of Silymarin against lung cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

lncRNA-HIT promotes cell proliferation of non-small cell lung cancer by association with E2F1.

PubMed

Yu, L; Fang, F; Lu, S; Li, X; Yang, Y; Wang, Z

2017-05-01

Lung cancer is the leading cause of cancer-related death around the world. Long noncoding RNA (lncRNA) has pivotal roles in cancer occurrence and development. However, only a few lncRNAs have been functionally characterized. In the present study, we investigated the effects of lncRNA-HIT (HOXA transcript induced by TGFβ) expression on non-small cell lung cancer (NSCLC) cell phenotype with the gain-of-function and loss-of-function assays. We found that ectopic expression or knockdown of lncRNA-HIT markedly increased or decreased NSCLC cell proliferation, respectively. Moreover, we also showed that lncRNA-HIT interacted with E2F1 to regulate its target genes, such as Survivin, FOXM1, SKP2, NELL2 and DOK1. Collectively, our findings indicated that lncRNA-HIT affected the proliferation of NSCLC cells at least in part via regulating the occupancy of E2F1 in the promoter regions of its target genes. The lncRNA-HIT-E2F1 complex may be a potential target for NSCLC treatment.

Effects of environmental ozone on the lung function of senior citizens

NASA Astrophysics Data System (ADS)

Höppe, Peter; Lindner, Jutta; Praml, Georg; Brönner, Norman

1995-09-01

Measurements with a body plethysmograph of lung function parameters and reports of unusual complaints or irritations were taken from 41 senior citizens in the situations where they usually spend their daytime hours. The subjects belonged to a group commonly assumed to be at risk from ozone. Each subject was examined on 8 days both in the morning and in the afternoon. The object was to obtain for every subject an equal distribution of measuring days between those with elevated ozone concentrations (maximum 0.5 h mean values between 1.00 and 4.00 p.m. of at least 0.050 ppm) and those with low ozone concentrations (maximum 0.5 h mean values between 1.00 and 4.00 p.m. of at most 0.040 ppm). The results showed no relevant ozone related effects on the lung function parameters or the subjective reports of irritations. Thus there was no indication that senior citizens represent a group at particular risk with respect to moderately elevated concentrations of environmental ozone, as occur in central Europe.

Comparative analysis of the mechanical signals in lung development and compensatory growth.

PubMed

Hsia, Connie C W

2017-03-01

This review compares the manner in which physical stress imposed on the parenchyma, vasculature and thorax and the thoraco-pulmonary interactions, drive both developmental and compensatory lung growth. Re-initiation of anatomical lung growth in the mature lung is possible when the loss of functioning lung units renders the existing physiologic-structural reserves insufficient for maintaining adequate function and physical stress on the remaining units exceeds a critical threshold. The appropriate spatial and temporal mechanical interrelationships and the availability of intra-thoracic space, are crucial to growth initiation, follow-on remodeling and physiological outcome. While the endogenous potential for compensatory lung growth is retained and may be pharmacologically augmented, supra-optimal mechanical stimulation, unbalanced structural growth, or inadequate remodeling may limit functional gain. Finding ways to optimize the signal-response relationships and resolve structure-function discrepancies are major challenges that must be overcome before the innate compensatory ability could be fully realized. Partial pneumonectomy reproducibly removes a known fraction of functioning lung units and remains the most robust model for examining the adaptive mechanisms, structure-function consequences and plasticity of the remaining functioning lung units capable of regeneration. Fundamental mechanical stimulus-response relationships established in the pneumonectomy model directly inform the exploration of effective approaches to maximize compensatory growth and function in chronic destructive lung diseases, transplantation and bioengineered lungs.

Comparative Analysis of the Mechanical Signals in Lung Development and Compensatory Growth

PubMed Central

Hsia, Connie C.W.

2017-01-01

This review compares the manner in which physical stress imposed on the parenchyma, vasculature and thorax, and the thoraco-pulmonary interactions, drive both developmental and compensatory lung growth. Re-initiation of anatomical lung growth in the mature lung is possible when the loss of functioning lung units renders the existing physiologic-structural reserves insufficient for maintaining adequate function and physical stress on the remaining units exceeds a critical threshold. The appropriate spatial and temporal mechanical interrelationships, and the availability of intra-thoracic space, are crucial to growth initiation, follow-on remodeling and physiological outcome. While the endogenous potential for compensatory lung growth is retained and may be pharmacologically augmented, supra-optimal mechanical stimulation, unbalanced structural growth, or inadequate remodeling, may limit functional gain. Finding ways to optimize the signal-response relationships and resolve structure-function discrepancies are major challenges that must be overcome before the innate compensatory ability could be fully realized. Partial pneumonectomy reproducibly removes a known fraction of functioning lung units and remains the most robust model for examining the adaptive mechanisms, structure-function consequences, and plasticity of the remaining functioning lung units capable of regeneration. Fundamental mechanical stimulus-response relationships established in the pneumonectomy model directly inform the exploration of effective approaches to maximize compensatory growth and function in chronic destructive lung diseases, transplantation and bioengineered lungs. PMID:28084523

Classification of interstitial lung disease patterns with topological texture features

NASA Astrophysics Data System (ADS)

Huber, Markus B.; Nagarajan, Mahesh; Leinsinger, Gerda; Ray, Lawrence A.; Wismüller, Axel

2010-03-01

Topological texture features were compared in their ability to classify morphological patterns known as 'honeycombing' that are considered indicative for the presence of fibrotic interstitial lung diseases in high-resolution computed tomography (HRCT) images. For 14 patients with known occurrence of honey-combing, a stack of 70 axial, lung kernel reconstructed images were acquired from HRCT chest exams. A set of 241 regions of interest of both healthy and pathological (89) lung tissue were identified by an experienced radiologist. Texture features were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM), Minkowski Dimensions (MDs), and three Minkowski Functionals (MFs, e.g. MF.euler). A k-nearest-neighbor (k-NN) classifier and a Multilayer Radial Basis Functions Network (RBFN) were optimized in a 10-fold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions and the significance thresholds were adjusted for multiple comparisons by the Bonferroni correction. The best classification results were obtained by the MF features, which performed significantly better than all the standard GLCM and MD features (p < 0.005) for both classifiers. The highest accuracy was found for MF.euler (97.5%, 96.6%; for the k-NN and RBFN classifier, respectively). The best standard texture features were the GLCM features 'homogeneity' (91.8%, 87.2%) and 'absolute value' (90.2%, 88.5%). The results indicate that advanced topological texture features can provide superior classification performance in computer-assisted diagnosis of interstitial lung diseases when compared to standard texture analysis methods.

The relationship between different diet quality indices and severity of airflow obstruction among COPD patients

PubMed Central

Yazdanpanah, Leila; Paknahad, Zamzam; Moosavi, Ali Javad; Maracy, Mohammad Reza; Zaker, Mohammad Masoud

2016-01-01

Background: Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide. Smoking is the number one cause of COPD; however, genetic, environmental and dietary factors contribute to the etiology of this disease. In this study, we assessed the association between three diet quality indices -the Healthy Eating Index-2005 (HEI-2005), the Healthy Eating Index-2010 (HEI-2010), and Mediterranean Diet Score (MED)- and the severity of disease in COPD patients. Methods: This cross-sectional study was performed at Rasul-e-Akram Hospital in Tehran on 121 COPD patients with the mean age of (SD) of 66.1(10.9) years. A pulmonary specialist diagnosed all participants based on a spirometry test. They were categorized into four groups (1, 2, 3, 4 stages of disease). Three diet quality indices, spirometry test and determination of disease severity were performed for all the participants. ANCOVA and Kruskal-Wallis test were used to assess the relationship between dietary quality indices and severity of the disease. The relationship between HEI-2010, HEI-2005, MED score, their components and lung function was assessed using a multiple linear regression analysis. All analyses were done using SPSS 18. Results: Reduction of the Healthy Eating Index-2010 and MED score were observed along with the increase in disease severity, but they were not significant. The relationship between the three diet quality indices and lung function showed a significant association between MED score and Forced expiratory volume in one second (FEV1), The Forced Vital Capacity (FVC) (β=2.9, 95% CI (1.1, 4.8), p=0.002), (β=2.8, 95% CI (0.9, 4.8), p=0.007), respectively. Conclusion: Mediterranean dietary pattern and obtaining a better score on HEI-2010 diet were associated with a better lung function test. PMID:27493924

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.

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.

Respiratory system mechanics in acute respiratory distress syndrome.

PubMed

Kallet, Richard H; Katz, Jeffrey A

2003-09-01

Respiratory mechanics research is important to the advancement of ARDS management. Twenty-eight years ago, research on the effects of PEEP and VT indicated that the lungs of ARDS patients did not behave in a manner consistent with homogenously distributed lung injury. Both Suter and colleagues] and Katz and colleagues reported that oxygenation continued to improve as PEEP increased (suggesting lung recruitment), even though static Crs decreased and dead-space ventilation increased (suggesting concurrent lung overdistension). This research strongly suggested that without VT reduction, the favorable effects of PEEP on lung recruitment are offset by lung overdistension at end-inspiration. The implications of these studies were not fully appreciated at that time, in part because the concept of ventilator-associated lung injury was in its nascent state. Ten years later. Gattinoni and colleagues compared measurements of static pressure-volume curves with FRC and CT scans of the chest in ARDS. They found that although PEEP recruits collapsed (primarily dorsal) lung segments, it simultaneously causes overdistension of non-dependent, inflated lung regions. Furthermore, the specific compliance of the aerated, residually healthy lung tissue is essentially normal. The main implication of these findings is that traditional mechanical ventilation practice was injecting excessive volumes of gas into functionally small lungs. Therefore, the emblematic low static Crs measured in ARDS reflects not only surface tension phenomena and recruitment of collapsed airspaces but also overdistension of the remaining healthy lung. The studies reviewed in this article support the concept that lung injury in ARDS is heterogeneously distributed, with resulting disparate mechanical stresses, and indicate the additional complexity from alterations in chest wall mechanics. Most of these studies, however, were published before lung-protective ventilation. Therefore, further studies are needed to refine the understanding of the mechanical effects of lung-protective ventilation. Although low-VT ventilation is becoming a standard of care for ARDS patients, many issues remain unresolved; among them are the role of PEEP and recruitment maneuvers in either preventing or promoting lung injury and the effects of respiratory rate and graded VT reduction on mechanical stress in the lungs. The authors believe that advances in mechanical ventilation that may further improve patient outcomes are likely to come from more sophisticated monitoring capabilities (ie, the ability to measure P1 or perhaps Cslice) than from the creation of new modes of ventilatory support.

Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells.

PubMed

Zhang, Yu; Zhu, Chenyang; Sun, Bangyao; Lv, Jiawei; Liu, Zhonghua; Liu, Shengwang; Li, Hai

2017-01-01

p53 dysfunction is frequently observed in lung cancer. Although restoring the tumour suppressor function of p53 is recently approved as a putative strategy for combating cancers, the lack of understanding of the molecular mechanism underlying p53-mediated lung cancer suppression has limited the application of p53-based therapies in lung cancer. Using RNA sequencing, we determined the transcriptional profile of human non-small cell lung carcinoma A549 cells after treatment with two p53-activating chemical compounds, nutlin and RITA, which could induce A549 cell cycle arrest and apoptosis, respectively. Bioinformatics analysis of genome-wide gene expression data showed that distinct transcription profiles were induced by nutlin and RITA and 66 pathways were differentially regulated by these two compounds. However, only two of these pathways, 'Adherens junction' and 'Axon guidance', were found to be synthetic lethal with p53 re-activation, as determined via integrated analysis of genome-wide gene expression profile and short hairpin RNA (shRNA) screening. Further functional protein association analysis of significantly regulated genes associated with these two synthetic lethal pathways indicated that GSK3 played a key role in p53-mediated A549 cell apoptosis, and then gene function study was performed, which revealed that GSK3 inhibition promoted p53-mediated A549 cell apoptosis in a p53 post-translational activity-dependent manner. Our findings provide us with new insights regarding the mechanism by which p53 mediates A549 apoptosis and may cast light on the development of more efficient p53-based strategies for treating lung cancer. © 201 The Author(s). Published by S. Karger AG, Basel.

The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis

PubMed Central

Huang, Long Shuang; Mathew, Biji; Zhao, Yutong; Noth, Imre; Reddy, Sekhar P.; Harijith, Anantha; Usatyuk, Peter V.; Berdyshev, Evgeny V.; Kaminski, Naftali; Zhou, Tong; Zhang, Wei; Zhang, Yanmin; Rehman, Jalees; Kotha, Sainath R.; Gurney, Travis O.; Parinandi, Narasimham L.; Lussier, Yves A.; Garcia, Joe G. N.

2014-01-01

Rationale: Lysocardiolipin acyltransferase (LYCAT), a cardiolipin-remodeling enzyme regulating the 18:2 linoleic acid pattern of mammalian mitochondrial cardiolipin, is necessary for maintaining normal mitochondrial function and vascular development. We hypothesized that modulation of LYCAT expression in lung epithelium regulates development of pulmonary fibrosis. Objectives: To define a role for LYCAT in human and murine models of pulmonary fibrosis. Methods: We analyzed the correlation of LYCAT expression in peripheral blood mononuclear cells (PBMCs) with the outcomes of pulmonary functions and overall survival, and used the murine models to establish the role of LYCAT in fibrogenesis. We studied the LYCAT action on cardiolipin remodeling, mitochondrial reactive oxygen species generation, and apoptosis of alveolar epithelial cells under bleomycin challenge. Measurements and Main Results: LYCAT expression was significantly altered in PBMCs and lung tissues from patients with idiopathic pulmonary fibrosis (IPF), which was confirmed in two preclinical murine models of IPF, bleomycin- and radiation-induced pulmonary fibrosis. LYCAT mRNA expression in PBMCs directly and significantly correlated with carbon monoxide diffusion capacity, pulmonary function outcomes, and overall survival. In both bleomycin- and radiation-induced pulmonary fibrosis murine models, hLYCAT overexpression reduced several indices of lung fibrosis, whereas down-regulation of native LYCAT expression by siRNA accentuated fibrogenesis. In vitro studies demonstrated that LYCAT modulated bleomycin-induced cardiolipin remodeling, mitochondrial membrane potential, reactive oxygen species generation, and apoptosis of alveolar epithelial cells, potential mechanisms of LYCAT-mediated lung protection. Conclusions: This study is the first to identify modulation of LYCAT expression in fibrotic lungs and offers a novel therapeutic approach for ameliorating lung inflammation and pulmonary fibrosis. PMID:24779708

Balloon atrial septostomy in pulmonary arterial hypertension: effect on survival and associated outcomes.

PubMed

Chiu, Joanne S; Zuckerman, Warren A; Turner, Mariel E; Richmond, Marc E; Kerstein, Diane; Krishnan, Usha; Torres, Alejandro; Vincent, Julie A; Rosenzweig, Erika B

2015-03-01

Pulmonary arterial hypertension (PAH) is a progressive disease that, without early identification and treatment, may lead to right heart failure, multi-organ dysfunction and early death. In severe PAH, in addition to maximal medical therapy, balloon atrial septostomy (BAS) may be used for palliation and as a bridge to lung transplantation. We present our contemporary institutional experience utilizing BAS in adult and pediatric patients with severe PAH. We performed a retrospective analysis of 46 BASs performed in 32 patients with PAH from 2002 to 2013. Data obtained included vital status, functional class, medications, hemodynamic measurements from right heart catheterizations and biomarkers. Lung transplantation-free and repeat-BAS-free survival was analyzed. Median age at BAS was 23 (range 1 to 56) years. The most common indications were symptomatic right heart failure (21 of 46 patients) and pre-syncope/syncope (19 of 46 patients); 69% of patients were WHO Functional Class III or IV pre-BAS. There were no procedural complications or deaths. There were no significant differences in biomarkers or hemodynamic findings between pre-BAS and 1 year or latest follow-up. Seven patients were successfully bridged to lung transplantation. Lung transplantation-free and repeat-BAS-free survival at 30 days, 1 year and 5 years was 87%, 61% and 32%, respectively. In our experienced center, BAS was shown to be safe in patients with severe PAH on maximal medical management, with no procedural deaths or complications. BAS was safely used as a bridge to lung transplantation or to alleviate right heart failure symptoms and/or syncope. Other potential benefits for end-organ function and overall survival remain to be determined. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Elevated lung cancer risk is associated with deficiencies in cell cycle checkpoints: Genotype and phenotype analyses from a case-control study

PubMed Central

Zheng, Yun-Ling; Kosti, Ourania; Loffredo, Christopher; Bowman, Elise; Mechanic, Leah; Perlmutter, Donna; Jones, Raymond; Shields, Peter G.; Harris, Curtis

2010-01-01

Cell cycle checkpoints play critical roles in the maintenance of genomic integrity and inactivation of checkpoint genes, and are frequently perturbed in most cancers. In a case-control study of 299 non-small cell lung cancer cases and 550 controls in Maryland, we investigated the association between γ-radiation-induced G2/M arrest in cultured blood lymphocytes and lung cancer risk, and examined genotype-phenotype correlations between genetic polymorphisms of 20 genes involving in DNA repair and cell cycle control and γ-radiation-induced G2/M arrest. The study was specifically designed to examine race and gender differences in risk factors. Our data indicated that a less efficient DNA damage-induced G2/M checkpoint was associated with an increased risk of lung cancer in African American women with an adjusted odds ratio (OR) of 2.63 (95% CI = 1.01 – 7.26); there were no statistically significant associations for Caucasians, or African American men. When the African American women were categorized into quartiles, a significant reverse trend of decreased G2/M checkpoint function and increased lung cancer risk was present, with lowest-vs-highest quartile OR of 13.72 (95% CI = 2.30 – 81.92, Ptrend < 0.01). Genotype-phenotype correlation analysis indicated that polymorphisms in ATM, CDC25C, CDKN1A, BRCA2, ERCC6, TP53, and TP53BP1 genes were significantly associated with the γ-radiation-induced G2/M arrest phenotype. This study provides evidence that a less efficient G2/M checkpoint is significantly associated with lung cancer risk in African American women. The data also suggested that the function of G2/M checkpoint is modulated by genetic polymorphisms in genes involved in DNA repair and cell cycle control. PMID:19626602

MicroRNA-1285-5p influences the proliferation and metastasis of non-small-cell lung carcinoma cells via downregulating CDH1 and Smad4.

PubMed

Zhou, Shixia; Zhang, Zhongmian; Zheng, Pengyuan; Zhao, Wenchao; Han, Na

2017-06-01

Abnormal expression of microRNAs has been reported to regulate gene expression and cancer cell growth, invasion, and migration. Recently, upregulation of hsa-miR-1285 was demonstrated in bronchoalveolar lavage fluid samples from patients with lung cancer and downregulation in plasma level of stage-I lung cancer patients. However, the function and the underlying mechanism of miR-1285 in non-small-cell lung carcinoma have not been elucidated. In this study, we found that miR-1285-5p, the mature form of miR-1285, was significantly upregulated in human non-small-cell lung carcinoma cell lines A549 and SK-MES-1. Additionally, cells transfected with the miR-1285-5p inhibitor LV-anti-miR-1285-5p demonstrated significantly inhibited proliferation and invasion and depressed migration. Further analysis demonstrated that the miR-1285-5p precursor LV-miR-1285-5p attenuated the expression of Smad4 and cadherin-1 (CDH1) but that LV-anti-miR-1285-5p showed opposite results. A luciferase reporter assay confirmed that miR-1285-5p targeted Smad4 and CDH1. Mechanism analyses revealed that silence of Smad4 and CDH1 significantly attenuated the inhibitory effects of LV-anti-miR-1285-5p on non-small-cell lung carcinoma growth and invasion. Taken together, our data suggest that miR-1285-5p functions as a tumor promoter in the development of non-small-cell lung carcinoma by targeting Smad4 and CDH1, indicating a novel therapeutic strategy for non-small-cell lung carcinoma patients.

The regulation of inflammation and oxidative status against lung injury of residue polysaccharides by Lentinula edodes.

PubMed

Ren, Zhenzhen; Li, Juan; Song, Xinling; Zhang, Jianjun; Wang, Wenshuai; Wang, Xiuxiu; Gao, Zheng; Jing, Huijuan; Li, Shangshang; Jia, Le

2018-01-01

In present study, two hydrolyzed residue polysaccharides (RPS) of enzymatic-RPS (ERPS) and acidic-RPS (ARPS) were successfully obtained from the residue of Lentinula edodes, and the anti-inflammatory as well as antioxidative effects on lipopolysaccharide-induced (LPS-induced) lung injured mice were investigated. The results demonstrated that ERPS showed superior lung protective effects by ameliorating the lung wet-to-dry weight (W/D) ratio, reducing the TNF-α, IL-6, and IL-1β levels in BALF, lowing the pulmonary MPO activity, decreasing the serum C3 and hs-CPR contents, as well as improving the antioxidant status by enhancing pulmonary enzyme activities (SOD, GSH-Px, CAT, and T-AOC) and eliminating the lipid peroxidation (MDA and LPO), respectively. These conclusions indicated that both RPS and its hydrolysates (ARPS and ERPS) might be suitable for functional foods and a potentially effective candidate medicine for the treatment of lung injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Ex Vivo Lung Perfusion: Establishment and Operationalization in Iran.

PubMed

Shafaghi, Shadi; Abbasi Dezfuli, Azizollah; Ansari Aval, Zahra; Sheikhy, Kambiz; Farzanegan, Behrooz; Mortaz, Esmaeil; Emami, Habib; Aigner, Clemens; Hosseini-Baharanchi, Fatemeh Sadat; Najafizadeh, Katayoun

2017-02-01

Although the number of lung transplants is limited because of general shortage of organ donors, ex vivo lung perfusion is a novel method with 2 main benefits, including better evaluation of lung potential and recovery of injured lungs. The main aim of this study was to establish and operationalize ex vivo lung perfusion as the first experience in Iran. This was a prospective operational research study on 5 cases, including 1 pig from Vienna Medical University and 4 patients from Masih Daneshvari Hospital. All organ donations from brain dead donors were evaluated according to lung transplant or ex vivo lung perfusion criteria from May 2013 to July 2015 in Tehran, Iran. If a donor did not have any sign of severe chest trauma or pneumonia but had poor oxygenation due to possible atelectasis or neurogenic pulmonary edema, their lungs were included for ex vivo lung perfusion. A successful trend in the difference between the pulmonary arterial Po2 and the left atrial Po2 was observed, as well as an increasing pattern in other functional parameters, including dynamic lung compliance and a decreasing trend in pulmonary vascular resistance. These initial trials indicate that ex vivo lung perfusion can lead to remarkable progress in lung transplant in Iran. They also provide several important pieces of guidance for successful ex vivo lung perfusion, including the necessity of following standard lung retrieval procedures and monitoring temperature and pressure precisely. The development of novel methods can provide opportunities for further research studies on lungs of deceased donors and lead to undiscovered findings. By keeping this science up to date in Iran and developing such new and creative methods, we can reveal effective strategies to promote the quality of donor lungs to support patients on transplant wait lists.

Creation of Lung-Targeted Dexamethasone Immunoliposome and Its Therapeutic Effect on Bleomycin-Induced Lung Injury in Rats

PubMed Central

Li, Nan; Hu, Yang; Zhang, Yuan; Xu, Jin-Fu; Li, Xia; Ren, Jie; Su, Bo; Yuan, Wei-Zhong; Teng, Xin-Rong; Zhang, Rong-Xuan; Jiang, Dian-hua; Mulet, Xavier; Li, Hui-Ping

2013-01-01

Objective Acute lung injury (ALI), is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM)-loaded immunoliposome (NLP) functionalized with pulmonary surfactant protein A (SP-A) antibody (SPA-DXM-NLP) in an animal model. Methods DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. Results The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. Conclusions The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice. PMID:23516459

Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease

PubMed Central

Hunt, James M.; Bethea, Brian; Liu, Xiang; Gandjeva, Aneta; Mammen, Pradeep P. A.; Stacher, Elvira; Gandjeva, Marina R.; Parish, Elisabeth; Perez, Mario; Smith, Lynelle; Graham, Brian B.; Kuebler, Wolfgang M.

2013-01-01

Despite the importance of pulmonary veins in normal lung physiology and the pathobiology of pulmonary hypertension with left heart disease (PH-LHD), pulmonary veins remain largely understudied. Difficult to identify histologically, lung venous endothelium or smooth muscle cells display no unique characteristic functional and structural markers that distinguish them from pulmonary arteries. To address these challenges, we undertook a search for unique molecular markers in pulmonary veins. In addition, we addressed the expression pattern of a candidate molecular marker and analyzed the structural pattern of vascular remodeling of pulmonary veins in a rodent model of PH-LHD and in lung tissue of patients with PH-LHD obtained at time of placement on a left ventricular assist device. We detected urokinase plasminogen activator receptor (uPAR) expression preferentially in normal pulmonary veins of mice, rats, and human lungs. Expression of uPAR remained elevated in pulmonary veins of rats with PH-LHD; however, we also detected induction of uPAR expression in remodeled pulmonary arteries. These findings were validated in lungs of patients with PH-LHD. In selected patients with sequential lung biopsy at the time of removal of the left ventricular assist device, we present early data suggesting improvement in pulmonary hemodynamics and venous remodeling, indicating potential regression of venous remodeling in response to assist device treatment. Our data indicate that remodeling of pulmonary veins is an integral part of PH-LHD and that pulmonary veins share some key features present in remodeled yet not normotensive pulmonary arteries. PMID:24039255

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.

Dosimetric feasibility of 4DCT-ventilation imaging guided proton therapy for locally advanced non-small-cell lung cancer.

PubMed

Huang, Qijie; Jabbour, Salma K; Xiao, Zhiyan; Yue, Ning; Wang, Xiao; Cao, Hongbin; Kuang, Yu; Zhang, Yin; Nie, Ke

2018-04-25

The principle aim of this study is to incorporate 4DCT ventilation imaging into functional treatment planning that preserves high-functioning lung with both double scattering and scanning beam techniques in proton therapy. Eight patients with locally advanced non-small-cell lung cancer were included in this study. Deformable image registration was performed for each patient on their planning 4DCTs and the resultant displacement vector field with Jacobian analysis was used to identify the high-, medium- and low-functional lung regions. Five plans were designed for each patient: a regular photon IMRT vs. anatomic proton plans without consideration of functional ventilation information using double scattering proton therapy (DSPT) and intensity modulated proton therapy (IMPT) vs. functional proton plans with avoidance of high-functional lung using both DSPT and IMPT. Dosimetric parameters were compared in terms of tumor coverage, plan heterogeneity, and avoidance of normal tissues. Our results showed that both DSPT and IMPT plans gave superior dose advantage to photon IMRTs in sparing low dose regions of the total lung in terms of V5 (volume receiving 5Gy). The functional DSPT only showed marginal benefit in sparing high-functioning lung in terms of V5 or V20 (volume receiving 20Gy) compared to anatomical plans. Yet, the functional planning in IMPT delivery, can further reduce the low dose in high-functioning lung without degrading the PTV dosimetric coverages, compared to anatomical proton planning. Although the doses to some critical organs might increase during functional planning, the necessary constraints were all met. Incorporating 4DCT ventilation imaging into functional proton therapy is feasible. The functional proton plans, in intensity modulated proton delivery, are effective to further preserve high-functioning lung regions without degrading the PTV coverage.

Inhaled uranium ore dust and lung cancer risk in rats.

PubMed

Mitchel, R E; Jackson, J S; Heinmiller, B

1999-02-01

Using a nose-only inhalation system, male Sprague-Dawley rats were exposed 4.2 h d(-1), 5 days per week for 65 weeks to one of two concentrations of natural uranium ore dust aerosol (44% U, 50 mg m(-3) and 19 mg m(-3)) without significant radon content. After inhalation exposure ceased, the rats were allowed to live for their natural lifetime. Lung uranium burdens, measured at the time of death of each animal, declined exponentially after dust inhalation ceased, and the rate of decline was independent of the initial lung burden. Lymph node specific burdens ranged from 1 to 60 fold greater than the specific lung burden in the same animal. No lymph node tumors were observed. The frequency of primary malignant lung tumors was 0.016, 0.175 and 0.328 and primary non-malignant lung tumors 0.016, 0.135 and 0.131 in the control, low and high aerosol exposed groups, respectively. There was no difference in tumor latency between the groups. Absorbed dose to the lung was calculated for each animal in the study. The average doses for all the animals exposed to the low and high dust aerosol concentrations were 0.87 Gy and 1.64 Gy respectively, resulting in an average risk of malignant lung tumors of about 0.20 tumors per animal per Gy in both groups. The frequency of primary lung tumors was also calculated as a function of dose increment for both exposed groups individually and combined. The data indicate that, in spite of the above result, lung tumor frequency was not directly proportional to dose. However, when malignant lung tumor frequency was calculated as a function of dose rate (as measured by the lung burden at the end of dust inhalation) a direct linear relationship was seen (p < 0.01) suggesting dose rate may be a more important determinant of lung cancer risk than dose. Conversely, non-malignant lung tumors were significantly correlated with low lung burdens (p = 0.01). We conclude that chronic inhalation of natural uranium ore dust alone in rats creates a risk of primary malignant and non-malignant lung tumor formation and that malignant tumor risk was not directly proportional to dose, but was directly proportional to dose rate.

Exogenous surfactant preserves lung function and reduces alveolar Evans blue dye influx in a rat model of ventilation-induced lung injury.

PubMed

Verbrugge, S J; Vazquez de Anda, G; Gommers, D; Neggers, S J; Sorm, V; Böhm, S H; Lachmann, B

1998-08-01

Changes in pulmonary edema infiltration and surfactant after intermittent positive pressure ventilation with high peak inspiratory lung volumes have been well described. To further elucidate the role of surfactant changes, the authors tested the effect of different doses of exogenous surfactant preceding high peak inspiratory lung volumes on lung function and lung permeability. Five groups of Sprague-Dawley rats (n = 6 per group) were subjected to 20 min of high peak inspiratory lung volumes. Before high peak inspiratory lung volumes, four of these groups received intratracheal administration of saline or 50, 100, or 200 mg/kg body weight surfactant; one group received no intratracheal administration. Gas exchange was measured during mechanical ventilation. A sixth group served as nontreated, nonventilated controls. After death, all lungs were excised, and static pressure-volume curves and total lung volume at a transpulmonary pressure of 5 cm H2O were recorded. The Gruenwald index and the steepest part of the compliance curve (Cmax) were calculated. A bronchoalveolar lavage was performed; surfactant small and large aggregate total phosphorus and minimal surface tension were measured. In a second experiment in five groups of rats (n = 6 per group), lung permeability for Evans blue dye was measured. Before 20 min of high peak inspiratory lung volumes, three groups received intratracheal administration of 100, 200, or 400 mg/ kg body weight surfactant; one group received no intratracheal administration. A fifth group served as nontreated, nonventilated controls. Exogenous surfactant at a dose of 200 mg/kg preserved total lung volume at a pressure of 5 cm H2O, maximum compliance, the Gruenwald Index, and oxygenation after 20 min of mechanical ventilation. The most active surfactant was recovered in the group that received 200 mg/kg surfactant, and this dose reduced minimal surface tension of bronchoalveolar lavage to control values. Alveolar influx of Evans blue dye was reduced in the groups that received 200 and 400 mg/kg exogenous surfactant. Exogenous surfactant preceding high peak inspiratory lung volumes prevents impairment of oxygenation, lung mechanics, and minimal surface tension of bronchoalveolar lavage fluid and reduces alveolar influx of Evans blue dye. These data indicate that surfactant has a beneficial effect on ventilation-induced lung injury.

Veterinary practice and occupational health. An epidemiological study of several professional groups of Dutch veterinarians. I. General physical examination and prevalence of allergy, lung function disorders, and bronchial hyperreactivity.

PubMed

Elbers, A R; Blaauw, P J; de Vries, M; van Gulick, P J; Smithuis, O L; Gerrits, R P; Tielen, M J

1996-12-01

The prevalence of allergy, lung function disorders, and bronchial hyperreactivity was studied in 102 Dutch veterinarians, subdivided into five professional groups (predominantly working with either swine, cattle, poultry, companion animals, or as a non-practitioner). The mean age of the participants was 43 years; 6 participants were females. Twenty-two per cent of the participants were overweight, and relatively more non-practitioners than practitioners were overweight. Approximately 23% of the vets reported complaints of prolonged fatigue. The data suggest a relationship between complaints of prolonged fatigue and a more than average number of daily working hours. Only a small proportion of vets were sensitized against several allergens. There were no significant differences in prevalence of distinct lung function disorders or bronchial hyperreactivity between professional groups. It is hypothesized that the respiratory complaints (chronic coughing, chronic phlegm production, stuffed nose, sneezing) reported by the vets predominantly working in swine and/or poultry practice could be caused by irritation and/or inflammation of the first part of the trachea-bronchial tree that has no measurable and permanent consequences for changes in lung function or increased bronchial hyperreactivity. The results of a skin test against allergens and determination of allergen-specific IgE in blood indicated that the respiratory complaints were probably not related to allergy against the panel of allergens tested.

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.

The role of traffic noise on the association between air pollution and children's lung function.

PubMed

Franklin, Meredith; Fruin, Scott

2017-08-01

Although it has been shown that traffic-related air pollution adversely affects children's lung function, few studies have examined the influence of traffic noise on this association, despite both sharing a common source. Estimates of noise exposure (L dn, dB), and freeway and non-freeway emission concentrations of oxides of nitrogen (NO x , ppb) were spatially assigned to children in Southern California who were tested for forced vital capacity (FVC, n=1345), forced expiratory volume in 1s, (FEV 1, n=1332), and asthma. The associations between traffic-related NO x and these outcomes, with and without adjustment for noise, were examined using mixed effects models. Adjustment for noise strengthened the association between NO x and reduced lung function. A 14.5mL (95% CI -40.0, 11.0mL) decrease in FVC per interquartile range (13.6 ppb) in freeway NO x was strengthened to a 34.6mL decrease after including a non-linear function of noise (95% CI -66.3, -2.78mL). Similarly, a 6.54mL decrease in FEV 1 (95% CI -28.3, 15.3mL) was strengthened to a 21.1mL decrease (95% CI -47.6, 5.51) per interquartile range in freeway NO x . Our results indicate that where possible, noise should be included in epidemiological studies of the association between traffic-related air pollution on lung function. Without taking noise into account, the detrimental effects of traffic-related pollution may be underestimated. Copyright © 2017 Elsevier Inc. All rights reserved.

Leptin Promotes Fetal Lung Maturity and Upregulates SP-A Expression in Pulmonary Alveoli Type-II Epithelial Cells Involving TTF-1 Activation

PubMed Central

Huang, Hui; Wang, Zhen-Hua; Cheng, Rui; Cai, Wei-Bin

2013-01-01

The placental hormone leptin has important functions in fetal and neonatal growth, and prevents depressed respiration in leptin-deficient mice. The effect of leptin on respiratory distress suffered by low birth weight and premature infants has been studied. However, it is unclear how leptin enhances lung maturity in the fetus and ameliorates neonatal respiratory distress. In the present study, we found that antenatal treatment with leptin for 2 d significantly enhanced the relative alveolus area and improved the maturity of fetal lungs in a rat model of fetal growth restriction (FGR). Mean birth weight and lung wet weight were higher in the leptin-treated group than in the PBS-treated group, indicating promotion of fetal growth. Leptin upregulated the intracellular expression and extracellular secretion of surfactant protein (SP) A in type-II alveolar epithelial cells (AECs) in vivo and in vitro. Dual positive effects of leptin were found on protein expression and transcriptional activity of thyroid transcription factor-1 (TTF-1), a nuclear transcription essential for branching morphogenesis of the lung and expression of SP-A in type-II AECs. Knockdown of TTF-1 by RNA interference indicated that TTF-1 may play a vital role in leptin-induced SP-A expression. These results suggest that leptin may have great therapeutic potential for the treatment of FGR, and leptin-mediated SP-A induction and lung maturity of the fetus are TTF-1 dependent. PMID:23894445

Dose to mass for evaluation and optimization of lung cancer radiation therapy.

PubMed

Tyler Watkins, William; Moore, Joseph A; Hugo, Geoffrey D; Siebers, Jeffrey V

2017-11-01

To evaluate potential organ at risk dose-sparing by using dose-mass-histogram (DMH) objective functions compared with dose-volume-histogram (DVH) objective functions. Treatment plans were retrospectively optimized for 10 locally advanced non-small cell lung cancer patients based on DVH and DMH objectives. DMH-objectives were the same as DVH objectives, but with mass replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV-D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were intercompared to ascertain dose-to-volume vs. dose-to-mass differences. Additionally, the optimized doses were intercompared using DVH and DMH metrics to ascertain differences in optimized plans. Mean dose to volume, D v ‾, mean dose to mass, D M ‾, and fluence maps were intercompared. For a given dose distribution, DVH and DMH differ by >5% in heterogeneous structures. In homogeneous structures including heart and spinal cord, DVH and DMH are nearly equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose to OARs but reduced PTV-D v ‾ by 0.20±0.2Gy (p=0.02) and PTV-D M ‾ by 0.23±0.3Gy (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions and esophageal dose sparing (D v ‾ reduced 0.45±0.5Gy, p=0.02 and D M ‾ reduced 0.44±0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map comparisons indicate that DMH optimization reduces dose in the periphery of lung PTVs. DVH- and DMH-dose indices differ by >5% in lung and lung target volumes for fixed dose distributions, but optimizing DMH did not reduce dose to OARs. The primary difference observed in DVH- and DMH-optimized plans were variations in fluence to the periphery of lung target PTVs, where low density lung surrounds tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of acetylcholinesterase in lung cancer

PubMed Central

Xi, Hui-Jun; Wu, Ren-Pei; Liu, Jing-Jing; Zhang, Ling-Juan; Li, Zhao-Shen

2015-01-01

Acetylcholinesterase (AChE) plays a key role in catalytic hydrolysis of cholinergic neurotransmitters. Intensive research has proven the involvement of this protein in novel functions, such as cell adhesion, differentiation, and proliferation. In addition, several recent studies have indicated that acetylcholinesterase is potentially a marker and regulator of apoptosis. Importantly, AChE is also a promising tumor suppressor. In this review, we briefly summarize the involvement of AChE in apoptosis and cancer, focusing on the role of AChE in lung cancer, as well as the therapeutic consideration of AChE for cancer therapy. PMID:26273392

Scintigraphy at 3 months after single lung transplantation and observations of primary graft dysfunction and lung function.

PubMed

Belmaati, Esther Okeke; Iversen, Martin; Kofoed, Klaus F; Nielsen, Michael B; Mortensen, Jann

2012-06-01

Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation-perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation, and to investigate whether scintigraphic findings at 3 months were predictive for the outcome at 12 months in relation to primary graft dysfunction (PGD) and lung function. A retrospective study was carried out on all patients who prospectively and consecutively were referred for a routine lung scintigraphy procedure 3 months after single lung transplantation (SLTX). A total of 41 patients were included in the study: 20 women and 21 men with the age span of patients at transplantation being 38-66 years (mean ± SD: 54.2 ± 6.0). Patient records also included lung function tests and chest X-ray images. We found no significant correlation between lung function distribution at 3 months and PGD at 72 h. There was also no significant correlation between PGD scores at 72 h and lung function at 6 and 12 months. The same applied to scintigraphic scores for heterogeneity at 3 months compared with lung function at 6 and 12 months. Fifty-five percent of all patients had decreased ventilation function measured in the period from 6 to 12 months. Forty-nine percent of the patients had normal perfusion evaluations, and 51% had abnormal perfusion evaluations at 3 months. For ventilation evaluations, 72% were normal and 28% were abnormal. There was a significant difference in the normal versus abnormal perfusion and ventilation scintigraphic images evaluated from the same patients. Ventilation was distributed more homogenously in the transplanted lung than perfusion in the same lung. The relative distribution of perfusion and ventilation to the transplanted lung of patients with and without a primary diagnosis of fibrosis did not differ significantly from each other. We conclude that PGD defined at 72 h does not lead to recognizable changes in ventilation-perfusion scintigrapy at 3 months, and scintigraphic findings do not correlate with development in lung function in the first 12 months.

Stunting and the Prediction of Lung Volumes Among Tibetan Children and Adolescents at High Altitude.

PubMed

Weitz, Charles A; Garruto, Ralph M

2015-12-01

This study examines the extent to which stunting (height-for-age Z-scores ≤ -2) compromises the use of low altitude prediction equations to gauge the general increase in lung volumes during growth among high altitude populations. The forced vital capacity (FVC) and forced expiratory volume (FEV1) of 208 stunted and 365 non-stunted high-altitude Tibetan children and adolescents between the ages of 6 and 20 years are predicted using the Third National Health and Nutrition Examination Survey (NHANESIII) and the Global Lung Function Initiative (GLF) equations, and compared to observed lung volumes. Stunted Tibetan children show smaller positive deviations from both NHANESIII and GLF prediction equations at most ages than non-stunted children. Deviations from predictions do not correspond to differences in body proportions (sitting heights and chest circumferences relative to stature) between stunted and non-stunted children; but appear compatible with the effects of retarded growth and lung maturation that are likely to exist among stunted children. These results indicate that, before low altitude standards can be used to evaluate the effects of hypoxia, or before high altitude populations can be compared to any other group, it is necessary to assess the relative proportion of stunted children in the samples. If the proportion of stunted children in a high altitude population differs significantly from the proportion in the comparison group, lung function comparisons are unlikely to yield an accurate assessment of the hypoxia effect. The best solution to this problem is to (1) use stature and lung function standards based on the same low altitude population; and (2) assess the hypoxic effect by comparing observed and predicted values among high altitude children whose statures are most like those of children on whom the low altitude spirometric standard is based-preferably high altitude children with HAZ-scores ≥ -1.

[Lung scintigraphy].

PubMed

Schümichen, Carl; Schmidt, Matthias; Krause, Thomas

2018-06-01

The S1 guideline for lung scintigraphy has been updated and extended in order to emphasize the advantages oft the method in detecting acute pulmonary embolism (PE) in the periphery oft the lung (subsegmental PE), in underlying subacute and chronic pulmonary disorders, as well as in detecting chronic LE (CTEPH). Method of choice is ventilation / perfusion (V/P) SPECT or V/P SPECT/CT with even higher specificity. Because of its high sensitivity, a threshold (V/P mismatch in at least one segment or two subsegments) is introduced to avoid overtreatment. In case of a change in the therapeutic approach (observation only instead of anticoaculation) the threshold can be omitted. New data concerning the clinical and therapeutical impact of subsegmental PE are included, the chapters open questions have been extented. Other indications for V/P SPECT (secondary diagnoses, abnormalities in pulmonary perfusion, prediction of postoperative lung function) are presented with new data. Schattauer GmbH.

[The technique of sleeve resection on the bronchial and pulmonary vascular tree].

PubMed

Branscheid, D; Beshay, M

2013-06-01

Sleeve resections of the lungs have affected the oncologic radicality, parenchyma and lung function-saving resections and extended the indications for operations in thoracic surgery. Whenever lung amputations can be avoided by bronchoplastic and/or angioplastic procedures with the same radicality, sleeve resection should be performed. In centrally located distinct malignomas, intraluminal tumor growth (T3) infiltrations of peribronchial or extrabronchial areas, the lobular ostia and the pulmonary artery (T2/T3) as well as lymph node involvement (N1/N2), these procedures give a better qualitative survival and lower morbidity and mortality rates. Broncoscope-guided localization of a double lumen tube and routine anesthesia monitoring are mandatory. Before performing sleeve resections a complete lymph node dissection should be done without denuding the area of the anastomosis and sparing the bronchial arteries. Preoperative endoscopic biopsies, knowledge of the topography and mobilization of the vascular and bronchial tree, subtile operation techniques, perioperative and postoperative videobronchoscopic guidance as well as intraoperative frozen sections and a tension-free and smooth anastomosis, avoid postoperative complications. Depending on the blood supply of the bronchial tree a vascularized flap is indicated. Operability can therefore be achieved in elderly patients with limited pulmonary function, particularly those under adjuvant or neoadjuvant therapy who are no longer suitable for pneumonectomy.

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.

Practical Guidelines: Lung Transplantation in Patients with Cystic Fibrosis

PubMed Central

Hirche, T. O.; Knoop, C.; Hebestreit, H.; Shimmin, D.; Solé, A.; Elborn, J. S.; Ellemunter, H.; Aurora, P.; Hogardt, M.; Wagner, T. O. F.; ECORN-CF Study Group

2014-01-01

There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation. PMID:24800072

Respiratory mechanics in mechanically ventilated patients.

PubMed

Hess, Dean R

2014-11-01

Respiratory mechanics refers to the expression of lung function through measures of pressure and flow. From these measurements, a variety of derived indices can be determined, such as volume, compliance, resistance, and work of breathing. Plateau pressure is a measure of end-inspiratory distending pressure. It has become increasingly appreciated that end-inspiratory transpulmonary pressure (stress) might be a better indicator of the potential for lung injury than plateau pressure alone. This has resulted in a resurgence of interest in the use of esophageal manometry in mechanically ventilated patients. End-expiratory transpulmonary pressure might also be useful to guide the setting of PEEP to counterbalance the collapsing effects of the chest wall. The shape of the pressure-time curve might also be useful to guide the setting of PEEP (stress index). This has focused interest in the roles of stress and strain to assess the potential for lung injury during mechanical ventilation. This paper covers both basic and advanced respiratory mechanics during mechanical ventilation. Copyright © 2014 by Daedalus Enterprises.

Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy

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

Vinogradskiy, Yevgeniy, E-mail: yevgeniy.vinogradskiy@ucdenver.edu; Schubert, Leah; Diot, Quentin

2016-07-15

Purpose: The development of clinical trials is underway to use 4-dimensional computed tomography (4DCT) ventilation imaging to preferentially spare functional lung in patients undergoing radiation therapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer. Methods and Materials: A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging, deformable image registration, and a density-change–based algorithm. To assessmore » each patient's spatial ventilation profile both quantitative and qualitative metrics were developed, including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate functionally weighted mean lung doses and metrics that assessed the interplay between the spatial location of the dose and high-functioning lung. Results: Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups (P<.01). We determined that 65% of stage III and 28% of stage I patients had ventilation defects. Average functionally weighted mean lung dose was 19.6 Gy and 5.4 Gy for stage III and I patients, respectively, with both groups containing patients with large spatial overlap between dose and high-function regions. Conclusion: Our 118-patient retrospective study found that 65% of stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung, highlighting the importance of evaluating the function of each patient and developing a personalized functional avoidance treatment approach.« less

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

Sundar, Isaac K.; Hwang, Jae-Woong; Wu, Shaoping

Research highlights: {yields} Vitamin D deficiency is linked to accelerated decline in lung function. {yields} Levels of vitamin D receptor (VDR) are decreased in lungs of patients with COPD. {yields} VDR knock-out mouse showed increased lung inflammation and emphysema. {yields} This was associated with decline in lung function and increased MMPs. {yields} VDR knock-out mouse model is useful for studying the mechanisms of lung diseases. -- Abstract: Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. Themore » level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR{sup -/-}) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-{kappa}B) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction.« less

A herpes simplex virus type 2-encoded microRNA promotes tumor cell metastasis by targeting suppressor of cytokine signaling 2 in lung cancer.

PubMed

Wang, Xudong; Liu, Shupeng; Zhou, Zhenhua; Yan, Hongli; Xiao, Jianru

2017-05-01

Certain viruses use microRNAs to regulate the expression of their own genes, host genes, or both. A number of microRNAs expressed by herpes simplex virus type 2 have been confirmed by previous studies. However, whether these microRNAs play a role in the metastasis of lung cancers and how these viral microRNAs precisely regulated the tumor biological process in lung cancer bone metastasis remain obscure. We recently identified the high expression of an acutely and latently expressed viral microRNA, Hsv2-miR-H9-5p, encoded by herpes simplex virus type 2 latency-associated transcript through microarray and quantitative polymerase chain reaction analyses which compared the expression of microRNAs in bone metastasis from lung cancer with primary lung cancers. We now reported that Hsv2-miR-H9-5p was highly expressed in bone metastasis and closely associated with pathological and metastatic processes of lung cancers. The functions of Hsv2-miR-H9-5p were determined by overexpression which results in an increase in survival, migration, and invasion of lung cancer cells in vitro. We determined that Hsv2-miR-H9-5p directly targeted SOCS2 mechanistically by dual-luciferase reporter assay. Then, we investigated the functions of SOCS2 in the progress of lung cancers. Reduction of SOCS2 dosage by hsv2-miR-H9-5p induced increased migration and invasion of lung cancer cells. Overexpression of SOCS2 inverted these phenotypes generated by hsv2-miR-H9-5p, indicating the potential roles of SOCS2 in Hsv2-miR-H9-5p-driven metastasis in lung cancers. The results highlighted that Hsv2-miR-H9-5p regulated and contributed to bone metastasis of lung cancers. We proposed that Hsv2-miR-H9-5p could be used as a potential target in lung cancer therapy.

Functional Image-Guided Radiotherapy Planning in Respiratory-Gated Intensity-Modulated Radiotherapy for Lung Cancer Patients With Chronic Obstructive Pulmonary Disease

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

Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp; Nishibuchi, Ikuno; Murakami, Yuji

2012-03-15

Purpose: To investigate the incorporation of functional lung image-derived low attenuation area (LAA) based on four-dimensional computed tomography (4D-CT) into respiratory-gated intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) in treatment planning for lung cancer patients with chronic obstructive pulmonary disease (COPD). Methods and Materials: Eight lung cancer patients with COPD were the subjects of this study. LAA was generated from 4D-CT data sets according to CT values of less than than -860 Hounsfield units (HU) as a threshold. The functional lung image was defined as the area where LAA was excluded from the image of the total lung.more » Two respiratory-gated radiotherapy plans (70 Gy/35 fractions) were designed and compared in each patient as follows: Plan A was an anatomical IMRT or VMAT plan based on the total lung; Plan F was a functional IMRT or VMAT plan based on the functional lung. Dosimetric parameters (percentage of total lung volume irradiated with {>=}20 Gy [V20], and mean dose of total lung [MLD]) of the two plans were compared. Results: V20 was lower in Plan F than in Plan A (mean 1.5%, p = 0.025 in IMRT, mean 1.6%, p = 0.044 in VMAT) achieved by a reduction in MLD (mean 0.23 Gy, p = 0.083 in IMRT, mean 0.5 Gy, p = 0.042 in VMAT). No differences were noted in target volume coverage and organ-at-risk doses. Conclusions: Functional IGRT planning based on LAA in respiratory-guided IMRT or VMAT appears to be effective in preserving a functional lung in lung cancer patients with COPD.« less

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

Distribution and function of the peptide transporter PEPT2 in normal and cystic fibrosis human lung.

PubMed

Groneberg, D A; Eynott, P R; Döring, F; Dinh, Q Thai; Oates, T; Barnes, P J; Chung, K F; Daniel, H; Fischer, A

2002-01-01

Aerosol administration of peptide based drugs has an important role in the treatment of various pulmonary and systemic diseases. The characterisation of pulmonary peptide transport pathways can lead to new strategies in aerosol drug treatment. Immunohistochemistry and ex vivo uptake studies were established to assess the distribution and activity of the beta-lactam transporting high affinity proton coupled peptide transporter PEPT2 in normal and cystic fibrosis human airway tissue. PEPT2 immunoreactivity in normal human airways was localised to cells of the tracheal and bronchial epithelium and the endothelium of small vessels. In peripheral lung immunoreactivity was restricted to type II pneumocytes. In sections of cystic fibrosis lung a similar pattern of distribution was obtained with signals localised to endothelial cells, airway epithelium, and type II pneumocytes. Functional ex vivo uptake studies with fresh lung specimens led to an uptake of the fluorophore conjugated dipeptide derivative D-Ala-L-Lys-AMCA into bronchial epithelial cells and type II pneumocytes. This uptake was competitively inhibited by dipeptides and cephalosporins but not ACE inhibitors, indicating a substrate specificity as described for PEPT2. These findings provide evidence for the expression and function of the peptide transporter PEPT2 in the normal and cystic fibrosis human respiratory tract and suggest that PEPT2 is likely to play a role in the transport of pulmonary peptides and peptidomimetics.

Distribution and function of the peptide transporter PEPT2 in normal and cystic fibrosis human lung

PubMed Central

Groneberg, D; Eynott, P; Doring, F; Thai, D; Oates, T; Barnes, P; Chung, K; Daniel, H; Fischer, A

2002-01-01

Background: Aerosol administration of peptide based drugs has an important role in the treatment of various pulmonary and systemic diseases. The characterisation of pulmonary peptide transport pathways can lead to new strategies in aerosol drug treatment. Methods: Immunohistochemistry and ex vivo uptake studies were established to assess the distribution and activity of the ß-lactam transporting high affinity proton coupled peptide transporter PEPT2 in normal and cystic fibrosis human airway tissue. Results: PEPT2 immunoreactivity in normal human airways was localised to cells of the tracheal and bronchial epithelium and the endothelium of small vessels. In peripheral lung immunoreactivity was restricted to type II pneumocytes. In sections of cystic fibrosis lung a similar pattern of distribution was obtained with signals localised to endothelial cells, airway epithelium, and type II pneumocytes. Functional ex vivo uptake studies with fresh lung specimens led to an uptake of the fluorophore conjugated dipeptide derivative D-Ala-L-Lys-AMCA into bronchial epithelial cells and type II pneumocytes. This uptake was competitively inhibited by dipeptides and cephalosporins but not ACE inhibitors, indicating a substrate specificity as described for PEPT2. Conclusions: These findings provide evidence for the expression and function of the peptide transporter PEPT2 in the normal and cystic fibrosis human respiratory tract and suggest that PEPT2 is likely to play a role in the transport of pulmonary peptides and peptidomimetics. PMID:11809991

Experimental determination of the respiratory tract deposition of diesel combustion particles in patients with chronic obstructive pulmonary disease

PubMed Central

2012-01-01

Background Air pollution, mainly from combustion, is one of the leading global health risk factors. A susceptible group is the more than 200 million people worldwide suffering from chronic obstructive pulmonary disease (COPD). There are few data on lung deposition of airborne particles in patients with COPD and none for combustion particles. Objectives To determine respiratory tract deposition of diesel combustion particles in patients with COPD during spontaneous breathing. Methods Ten COPD patients and seven healthy subjects inhaled diesel exhaust particles generated during idling and transient driving in an exposure chamber. The respiratory tract deposition of the particles was measured in the size range 10–500 nm during spontaneous breathing. Results The deposited dose rate increased with increasing severity of the disease. However, the deposition probability of the ultrafine combustion particles (< 100 nm) was decreased in COPD patients. The deposition probability was associated with both breathing parameters and lung function, but could be predicted only based on lung function. Conclusions The higher deposited dose rate of inhaled air pollution particles in COPD patients may be one of the factors contributing to their increased vulnerability. The strong correlations between lung function and particle deposition, especially in the size range of 20–30 nm, suggest that altered particle deposition could be used as an indicator respiratory disease. PMID:22839109

Abnormal lung function in adults with congenital heart disease: prevalence, relation to cardiac anatomy, and association with survival.

PubMed

Alonso-Gonzalez, Rafael; Borgia, Francesco; Diller, Gerhard-Paul; Inuzuka, Ryo; Kempny, Aleksander; Martinez-Naharro, Ana; Tutarel, Oktay; Marino, Philip; Wustmann, Kerstin; Charalambides, Menelaos; Silva, Margarida; Swan, Lorna; Dimopoulos, Konstantinos; Gatzoulis, Michael A

2013-02-26

Restrictive lung defects are associated with higher mortality in patients with acquired chronic heart failure. We investigated the prevalence of abnormal lung function, its relation to severity of underlying cardiac defect, its surgical history, and its impact on outcome across the spectrum of adult congenital heart disease. A total of 1188 patients with adult congenital heart disease (age, 33.1±13.1 years) undergoing lung function testing between 2000 and 2009 were included. Patients were classified according to the severity of lung dysfunction based on predicted values of forced vital capacity. Lung function was normal in 53% of patients with adult congenital heart disease, mildly impaired in 17%, and moderately to severely impaired in the remainder (30%). Moderate to severe impairment of lung function related to complexity of underlying cardiac defect, enlarged cardiothoracic ratio, previous thoracotomy/ies, body mass index, scoliosis, and diaphragm palsy. Over a median follow-up period of 6.7 years, 106 patients died. Moderate to severe impairment of lung function was an independent predictor of survival in this cohort. Patients with reduced force vital capacity of at least moderate severity had a 1.6-fold increased risk of death compared with patients with normal lung function (P=0.04). A reduced forced vital capacity is prevalent in patients with adult congenital heart disease; its severity relates to the complexity of the underlying heart defect, surgical history, and scoliosis. Moderate to severe impairment of lung function is an independent predictor of mortality in contemporary patients with adult congenital heart disease.

Effect of preoperative and postoperative incentive spirometry on lung functions after laparoscopic cholecystectomy.

PubMed

Kundra, Pankaj; Vitheeswaran, Madhurima; Nagappa, Mahesh; Sistla, Sarath

2010-06-01

This study was designed to compare the effects of preoperative and postoperative incentive spirometry on lung functions after laparoscopic cholecystectomy in 50 otherwise normal healthy adults. Patients were randomized into a control group (group PO, n=25) and a study group (group PR, n=25). Patients in group PR were instructed to carry out incentive spirometry before the surgery 15 times, every fourth hourly, for 1 week whereas in group PO, incentive spirometry was carried out during the postoperative period. Lung functions were recorded at the time of preanesthetic evaluation, on the day before the surgery, postoperatively at 6, 24, and 48 hours, and at discharge. Significant improvement in the lung functions was seen after preoperative incentive spirometry (group PR), P<0.05. The lung functions were significantly reduced till the time of discharge in both the groups. However, lung functions were better preserved in group PR at all times when compared with group PO; P<0.05. To conclude, lung functions are better preserved with preoperative than postoperative incentive spirometry.

Comparison of gravimetric and a double-indicator dilution technique for assessment of extra-vascular lung water in endotoxaemia.

PubMed

Rossi, P; Oldner, A; Wanecek, M; Leksell, L G; Rudehill, A; Konrad, D; Weitzberg, E

2003-03-01

To compare a molecular double-indicator dilution technique with the gravimetrical reference method for measurement of extra-vascular lung water in porcine endotoxin shock. Open comparative experimental study. Animal research laboratory. In fourteen anaesthetised, mechanically ventilated landrace pigs, central and pulmonary haemodynamics as well as pulmonary gas exchange were measured. Extra-vascular lung water was quantitated gravimetrically as well as with a molecular double indicator dilution technique. Eight of these animals were subjected to endotoxaemia, the rest serving as sham controls. No difference in extra-vascular lung water was observed between the two methods in sham animals. Furthermore, extra-vascular lung water assessed with the molecular double-indicator dilution technique at the initiation of endotoxin infusion did not differ significantly from the corresponding values for sham animals. Endotoxaemia induced a hypodynamic shock with concurrent pulmonary hypertension and a pronounced deterioration in gas exchange. No increase in extra-vascular lung water was detected with the molecular double-indicator dilution technique in response to endotoxin, whereas this parameter was significantly higher when assessed with the gravimetric method. The molecular double-indicator dilution technique showed similar results as the gravimetrical method for assessment of extra-vascular lung water in non-endotoxaemic conditions. However, during endotoxin-induced lung injury the molecular double indicator dilution technique failed to detect the significant increase in extra-vascular lung water as measured by the gravimetric method. These data suggest that the molecular double indicator dilution technique may be of limited value during sepsis-induced lung injury.

LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION

PubMed Central

Chen, Kun; Hoffman, Eric A.; Seetharaman, Indu; Jiao, Feiran; Lin, Ching-Long; Chan, Kung-Sik

2017-01-01

The human lung airway is a complex inverted tree-like structure. Detailed airway measurements can be extracted from MDCT-scanned lung images, such as segmental wall thickness, airway diameter, parent-child branch angles, etc. The wealth of lung airway data provides a unique opportunity for advancing our understanding of the fundamental structure-function relationships within the lung. An important problem is to construct and identify important lung airway features in normal subjects and connect these to standardized pulmonary function test results such as FEV1%. Among other things, the problem is complicated by the fact that a particular airway feature may be an important (relevant) predictor only when it pertains to segments of certain generations. Thus, the key is an efficient, consistent method for simultaneously conducting group selection (lung airway feature types) and within-group variable selection (airway generations), i.e., bi-level selection. Here we streamline a comprehensive procedure to process the lung airway data via imputation, normalization, transformation and groupwise principal component analysis, and then adopt a new composite penalized regression approach for conducting bi-level feature selection. As a prototype of composite penalization, the proposed composite bridge regression method is shown to admit an efficient algorithm, enjoy bi-level oracle properties, and outperform several existing methods. We analyze the MDCT lung image data from a cohort of 132 subjects with normal lung function. Our results show that, lung function in terms of FEV1% is promoted by having a less dense and more homogeneous lung comprising an airway whose segments enjoy more heterogeneity in wall thicknesses, larger mean diameters, lumen areas and branch angles. These data hold the potential of defining more accurately the “normal” subject population with borderline atypical lung functions that are clearly influenced by many genetic and environmental factors. PMID:28280520

Cyclist route choice, traffic-related air pollution, and lung function: a scripted exposure study

PubMed Central

2013-01-01

Background A travel mode shift to active transportation such as bicycling would help reduce traffic volume and related air pollution emissions as well as promote increased physical activity level. Cyclists, however, are at risk for exposure to vehicle-related air pollutants due to their proximity to vehicle traffic and elevated respiratory rates. To promote safe bicycle commuting, the City of Berkeley, California, has designated a network of residential streets as “Bicycle Boulevards.” We hypothesized that cyclist exposure to air pollution would be lower on these Bicycle Boulevards when compared to busier roads and this elevated exposure may result in reduced lung function. Methods We recruited 15 healthy adults to cycle on two routes – a low-traffic Bicycle Boulevard route and a high-traffic route. Each participant cycled on the low-traffic route once and the high-traffic route once. We mounted pollutant monitors and a global positioning system (GPS) on the bicycles. The monitors were all synced to GPS time so pollutant measurements could be spatially plotted. We measured lung function using spirometry before and after each bike ride. Results We found that fine and ultrafine particulate matter, carbon monoxide, and black carbon were all elevated on the high-traffic route compared to the low-traffic route. There were no corresponding changes in the lung function of healthy non-asthmatic study subjects. We also found that wind-speed affected pollution concentrations. Conclusions These results suggest that by selecting low-traffic Bicycle Boulevards instead of heavily trafficked roads, cyclists can reduce their exposure to vehicle-related air pollution. The lung function results indicate that elevated pollutant exposure may not have acute negative effects on healthy cyclists, but further research is necessary to determine long-term effects on a more diverse population. This study and broader field of research have the potential to encourage policy-makers and city planners to expand infrastructure to promote safe and healthy bicycle commuting. PMID:23391029

SU-E-J-178: A Normalization Method Can Remove Discrepancy in Ventilation Function Due to Different Breathing Patterns

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

Qu, H; Yu, N; Stephans, K

2014-06-01

Purpose: To develop a normalization method to remove discrepancy in ventilation function due to different breathing patterns. Methods: Twenty five early stage non-small cell lung cancer patients were included in this study. For each patient, a ten phase 4D-CT and the voluntarily maximum inhale and exhale CTs were acquired clinically and retrospectively used for this study. For each patient, two ventilation maps were calculated from voxel-to-voxel CT density variations from two phases of the quiet breathing and two phases of the extreme breathing. For the quiet breathing, 0% (inhale) and 50% (exhale) phases from 4D-CT were used. An in-house toolmore » was developed to calculate and display the ventilation maps. To enable normalization, the whole lung of each patient was evenly divided into three parts in the longitude direction at a coronal image with a maximum lung cross section. The ratio of cumulated ventilation from the top one-third region to the middle one-third region of the lung was calculated for each breathing pattern. Pearson's correlation coefficient was calculated on the ratios of the two breathing patterns for the group. Results: For each patient, the ventilation map from the quiet breathing was different from that of the extreme breathing. When the cumulative ventilation was normalized to the middle one-third of the lung region for each patient, the normalized ventilation functions from the two breathing patterns were consistent. For this group of patients, the correlation coefficient of the normalized ventilations for the two breathing patterns was 0.76 (p < 0.01), indicating a strong correlation in the ventilation function measured from the two breathing patterns. Conclusion: For each patient, the ventilation map is dependent of the breathing pattern. Using a regional normalization method, the discrepancy in ventilation function induced by the different breathing patterns thus different tidal volumes can be removed.« less

Cyclist route choice, traffic-related air pollution, and lung function: a scripted exposure study.

PubMed

Jarjour, Sarah; Jerrett, Michael; Westerdahl, Dane; de Nazelle, Audrey; Hanning, Cooper; Daly, Laura; Lipsitt, Jonah; Balmes, John

2013-02-07

A travel mode shift to active transportation such as bicycling would help reduce traffic volume and related air pollution emissions as well as promote increased physical activity level. Cyclists, however, are at risk for exposure to vehicle-related air pollutants due to their proximity to vehicle traffic and elevated respiratory rates. To promote safe bicycle commuting, the City of Berkeley, California, has designated a network of residential streets as "Bicycle Boulevards." We hypothesized that cyclist exposure to air pollution would be lower on these Bicycle Boulevards when compared to busier roads and this elevated exposure may result in reduced lung function. We recruited 15 healthy adults to cycle on two routes - a low-traffic Bicycle Boulevard route and a high-traffic route. Each participant cycled on the low-traffic route once and the high-traffic route once. We mounted pollutant monitors and a global positioning system (GPS) on the bicycles. The monitors were all synced to GPS time so pollutant measurements could be spatially plotted. We measured lung function using spirometry before and after each bike ride. We found that fine and ultrafine particulate matter, carbon monoxide, and black carbon were all elevated on the high-traffic route compared to the low-traffic route. There were no corresponding changes in the lung function of healthy non-asthmatic study subjects. We also found that wind-speed affected pollution concentrations. These results suggest that by selecting low-traffic Bicycle Boulevards instead of heavily trafficked roads, cyclists can reduce their exposure to vehicle-related air pollution. The lung function results indicate that elevated pollutant exposure may not have acute negative effects on healthy cyclists, but further research is necessary to determine long-term effects on a more diverse population. This study and broader field of research have the potential to encourage policy-makers and city planners to expand infrastructure to promote safe and healthy bicycle commuting.

Impact of childhood anthropometry trends on adult lung function.

PubMed

Suresh, Sadasivam; O'Callaghan, Michael; Sly, Peter D; Mamun, Abdullah A

2015-04-01

Poor fetal growth rate is associated with lower respiratory function; however, there is limited understanding of the impact of growth trends and BMI during childhood on adult respiratory function. The current study data are from the Mater-University of Queensland Study of Pregnancy birth cohort. Prospective data were available from 1,740 young adults who performed standard spirometry at 21 years of age and whose birth weight and weight, height, and BMI at 5, 14, and 21 years of age were available. Catch-up growth was defined as an increase of 0.67 Z score in weight between measurements. The impact of catch-up growth on adult lung function and the relationship between childhood BMI trends and adult lung function were assessed using regression analyses. Lung function was higher at 21 years in those demonstrating catch-up growth from birth to 5 years (FVC, men: 5.33 L vs 5.54 L; women: 3.78 L vs 4.03 L; and FEV1, men: 4.52 L/s vs 4.64 L/s; women: 3.31 L/s vs 3.45 L/s). Subjects in the lowest quintile of birth (intrauterine growth retardation) also showed improved lung function if they had catch-up growth in the first 5 years of life. There was a positive correlation between increasing BMI and lung function at 5 years of age. However, in the later measurements when BMI increased into the obese category, a drop in lung function was observed. These data show evidence for a positive contribution of catch-up growth in early life to adult lung function. However, if weight gain or onset of obesity occurs after 5 years of age, an adverse impact on adult lung function is noted.

HOXB2, an adverse prognostic indicator for stage I lung adenocarcinomas, promotes invasion by transcriptional regulation of metastasis-related genes in HOP-62 non-small cell lung cancer cells.

PubMed

Inamura, Kentaro; Togashi, Yuki; Ninomiya, Hironori; Shimoji, Takashi; Noda, Tetsuo; Ishikawa, Yuichi

2008-01-01

Previously, using microarray and real-time RT-PCR analysis, we established that HOXB2 is an adverse prognostic indicator for Stage I lung adenocarcinomas. HOXB2 is one of the homeobox master development-controlling genes regulating morphogenesis and cell differentiation. The molecular functions of HOXB2 were analyzed with a small interfering RNA (siRNA) approach in HOP-62 human non-small cell lung cancer (NSCLC) cells featuring high HOXB2 expression. Matrigel invasion assays and microarray gene expression analysis were compared between the HOXB2-siRNA cells and the control cells. The Matrigel invasion assays showed attenuation of HOXB2 expression by siRNA to result in a significant decrease of invasiveness compared to the control cells (p = 0.0013, paired t-test). On microarray gene expression analysis, up-regulation of many metastasis-related genes and others correlating with HOXB2 expression was observed in the control case. With attenuation of HOXB2 expression, downregulation was noted for laminins alpha 4 and 5, involved in enriched signaling, and for Mac-2BP (Mac-2 binding protein) and integrin beta 4 amongst the genes having an enriched glycoprotein ontology. HOXB2 promotes invasion of lung cancer cells through the regulation of metastasis-related genes.

Role of novel type I interferon epsilon in viral infection and mucosal immunity

PubMed Central

Xi, Yang; Day, Stephanie L; Jackson, Ronald J; Ranasinghe, Charani

2012-01-01

Intranasal infection with vaccinia virus co-expressing interferon epsilon (VV-HIV-IFN-ɛ) was used to evaluate the role of IFN-ɛ in mucosal immunity. VV-HIV- IFN-ɛ infection induced a rapid VV clearance in lung that correlated with (i) an elevated lung VV-specific CD8+CD107a+IFN-γ+ population expressing activation markers CD69/CD103, (ii) enhanced lymphocyte recruitment to lung alveoli with reduced inflammation, and (iii) an heightened functional/cytotoxic CD8+CD4+ T-cell subset (CD3hiCCR7hiCD62Llo) in lung lymph nodes. These responses were different to that observed with intranasal VV-HA-IFN-α4 or VV-HA-IFN-β infections. When IFN-ɛ was used in an intranasal/intramuscular heterologous HIV prime-boost immunization, elevated HIV-specific effector, but not memory CD8+T cells responses, were observed in spleen, genito-rectal nodes, and Peyer's patch. Homing marker α4β7 and CCR9 analysis indicated that unlike other type I IFNs, IFN-ɛ could promote migration of antigen-specific CD8+T cells to the gut. Our results indicate that IFN-ɛ has a unique role in the mucosae and most likely can be used to control local lung and/or gut infections (i.e., microbicide) such as tuberculosis, HIV-1, or sexually transmitted diseases. PMID:22617838

Changes in Functional Lung Regions During the Course of Radiation Therapy and Their Potential Impact on Lung Dosimetry for Non-Small Cell Lung Cancer

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

Meng, Xue; Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan; Frey, Kirk

2014-05-01

Purpose: To study changes in functional activity on ventilation (V)/perfusion (Q) single-photon emission computed tomography (SPECT) during radiation therapy (RT) and explore the impact of such changes on lung dosimetry in patients with non-small cell lung cancer (NSCLC). Methods and Materials: Fifteen NSCLC patients with centrally located tumors were enrolled. All patients were treated with definitive RT dose of ≥60 Gy. V/Q SPECT-CT scans were performed prior to and after delivery of 45 Gy of fractionated RT. SPECT images were used to define temporarily dysfunctional regions of lung caused by tumor or other potentially reversible conditions as B3. The functional lung (FL)more » was defined on SPECT by 2 separate approaches: FL1, a threshold of 30% of the maximum uptake of the patient's lung; and FL2, FL1 plus B3 region. The impact of changes in FL between initiation of RT and delivery of 45 Gy on lung dosimetry were analyzed. Results: Fourteen patients (93%) had larger FL2 volumes than FL1 pre-RT (P<.001). Dysfunctional lung became functional in 11 patients (73%) on V SPECT and in 10 patients (67%) on Q SPECT. The dosimetric parameters generated from CT-based anatomical lung had significantly lower values in FL1 than FL2, with a median reduction in the volume of lung receiving a dose of at least 20 Gy (V{sub 20}) of 3%, 5.6%, and mean lung dose of 0.95 and 1.55 on V and Q SPECT respectively. Conclusions: Regional ventilation and perfusion function improve significantly during RT in centrally located NSCLC. Lung dosimetry values vary notably between different definitions of functional lung.« less

TLR9 expression is required for the development of cigarette smoke-induced emphysema in mice

PubMed Central

Foronjy, Robert F.; Salathe, Matthias A.; Dabo, Abdoulaye J.; Baumlin, Nathalie; Cummins, Neville; Eden, Edward

2016-01-01

The expression of Toll-like receptor (TLR)-9, a pathogen recognition receptor that recognizes unmethylated CpG sequences in microbial DNA molecules, is linked to the pathogenesis of several lung diseases. TLR9 expression and signaling was investigated in animal and cell models of chronic obstructive pulmonary disease (COPD). We observed enhanced TLR9 expression in mouse lungs following exposure to cigarette smoke. Tlr9−/− mice were resistant to cigarette smoke-induced loss of lung function as determined by mean linear intercept, total lung capacity, lung compliance, and tissue elastance analysis. Tlr9 expression also regulated smoke-mediated immune cell recruitment to the lung; apoptosis; expression of granulocyte-colony stimulating factor (G-CSF), the CXCL5 protein, and matrix metalloproteinase-2 (MMP-2); and protein tyrosine phosphatase 1B (PTP1B) activity in the lung. PTP1B, a phosphatase with anti-inflammatory abilities, was identified as binding to TLR9. In vivo delivery of a TLR9 agonist enhanced TLR9 binding to PTP1B, which inactivated PTP1B. Ptp1b−/− mice had elevated lung concentrations of G-CSF, CXCL5, and MMP-2, and tissue expression of type-1 interferon following TLR9 agonist administration, compared with wild-type mice. TLR9 responses were further determined in fully differentiated normal human bronchial epithelial (NHBE) cells isolated from nonsmoker, smoker, and COPD donors, and then cultured at air liquid interface. NHBE cells from smokers and patients with COPD expressed more TLR9 and secreted greater levels of G-CSF, IL-6, CXCL5, IL-1β, and MMP-2 upon TLR9 ligand stimulation compared with cells from nonsmoker donors. Although TLR9 combats infection, our results indicate that TLR9 induction can affect lung function by inactivating PTP1B and upregulating expression of proinflammatory cytokines. PMID:27288485

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

PubMed Central

Kawamura, Tomohiro; Wakabayashi, Nobunao; Shigemura, Norihisa; Huang, Chien-Sheng; Masutani, Kosuke; Tanaka, Yugo; Noda, Kentaro; Peng, Ximei; Takahashi, Toru; Billiar, Timothy R.; Okumura, Meinoshin; Toyoda, Yoshiya; Kensler, Thomas W.

2013-01-01

Hyperoxic lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine. Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to four experimental groups and administered the following gas mixtures for 60 h: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice. Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen. PMID:23475767

Stunting and the Prediction of Lung Volumes Among Tibetan Children and Adolescents at High Altitude

PubMed Central

Garruto, Ralph M.

2015-01-01

Abstract Weitz, Charles A., and Ralph M. Garruto. Stunting and the prediction of lung volumes among Tibetan children and adolescents at high altitude. High Alt Biol Med 16:306–317, 2015.—This study examines the extent to which stunting (height-for-age Z-scores ≤ −2) compromises the use of low altitude prediction equations to gauge the general increase in lung volumes during growth among high altitude populations. The forced vital capacity (FVC) and forced expiratory volume (FEV1) of 208 stunted and 365 non-stunted high-altitude Tibetan children and adolescents between the ages of 6 and 20 years are predicted using the Third National Health and Nutrition Examination Survey (NHANESIII) and the Global Lung Function Initiative (GLF) equations, and compared to observed lung volumes. Stunted Tibetan children show smaller positive deviations from both NHANESIII and GLF prediction equations at most ages than non-stunted children. Deviations from predictions do not correspond to differences in body proportions (sitting heights and chest circumferences relative to stature) between stunted and non-stunted children; but appear compatible with the effects of retarded growth and lung maturation that are likely to exist among stunted children. These results indicate that, before low altitude standards can be used to evaluate the effects of hypoxia, or before high altitude populations can be compared to any other group, it is necessary to assess the relative proportion of stunted children in the samples. If the proportion of stunted children in a high altitude population differs significantly from the proportion in the comparison group, lung function comparisons are unlikely to yield an accurate assessment of the hypoxia effect. The best solution to this problem is to (1) use stature and lung function standards based on the same low altitude population; and (2) assess the hypoxic effect by comparing observed and predicted values among high altitude children whose statures are most like those of children on whom the low altitude spirometric standard is based—preferably high altitude children with HAZ-scores ≥ −1. PMID:26397381

SU-C-BRA-06: Developing Clinical and Quantitative Guidelines for a 4DCT-Ventilation Functional Avoidance Clinical Trial

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

Vinogradskiy, Y; Waxweiler, T; Diot, Q

Purpose: 4DCT-ventilation is an exciting new imaging modality that uses 4DCTs to calculate lung ventilation. Because 4DCTs are acquired as part of routine care, calculating 4DCT-ventilation allows for lung function evaluation without additional cost or inconvenience to the patient. Development of a clinical trial is underway at our institution to use 4DCT-ventilation for thoracic functional avoidance with the idea that preferential sparing of functional lung regions can decrease pulmonary toxicity. The purpose of our work was to develop the practical aspects of a 4DCT-ventilation functional avoidance clinical trial including: 1.assessing patient eligibility 2.developing trial inclusion criteria and 3.developing treatment planningmore » and dose-function evaluation strategies. Methods: 96 stage III lung cancer patients from 2 institutions were retrospectively reviewed. 4DCT-ventilation maps were calculated using the patient’s 4DCTs, deformable image registrations, and a density-change-based algorithm. To assess patient eligibility and develop trial inclusion criteria we used an observer-based binary end point noting the presence or absence of a ventilation defect and developed an algorithm based on the percent ventilation in each lung third. Functional avoidance planning integrating 4DCT-ventilation was performed using rapid-arc and compared to the patient’s clinically used plan. Results: Investigator-determined clinical ventilation defects were present in 69% of patients. Our regional/lung-thirds ventilation algorithm identified that 59% of patients have lung functional profiles suitable for functional avoidance. Compared to the clinical plan, functional avoidance planning was able to reduce the mean dose to functional lung by 2 Gy while delivering comparable target coverage and cord/heart doses. Conclusions: 4DCT-ventilation functional avoidance clinical trials have great potential to reduce toxicity, and our data suggest that 59% of lung cancer patients have lung function profiles suitable for functional avoidance. Our study used a retrospective evaluation of a large lung cancer patient database to develop the practical aspects of a 4DCT-ventilation functional avoidance clinical trial. (R.C., E.C., T.G.), NIH Research Scientist Development Award K01-CA181292 (R.C.), and State of Colorado Advanced Industries Accelerator Grant (Y.V.)« less

Intravenous and intratracheal mesenchymal stromal cell injection in a mouse model of pulmonary emphysema.

PubMed

Tibboel, Jeroen; Keijzer, Richard; Reiss, Irwin; de Jongste, Johan C; Post, Martin

2014-06-01

The aim of this study was to characterize the evolution of lung function and -structure in elastase-induced emphysema in adult mice and the effect of mesenchymal stromal cell (MSC) administration on these parameters. Adult mice were treated with intratracheal (4.8 units/100 g bodyweight) elastase to induce emphysema. MSCs were administered intratracheally or intravenously, before or after elastase injection. Lung function measurements, histological and morphometric analysis of lung tissue were performed at 3 weeks, 5 and 10 months after elastase and at 19, 20 and 21 days following MSC administration. Elastase-treated mice showed increased dynamic compliance and total lung capacity, and reduced tissue-specific elastance and forced expiratory flows at 3 weeks after elastase, which persisted during 10 months follow-up. Histology showed heterogeneous alveolar destruction which also persisted during long-term follow-up. Jugular vein injection of MSCs before elastase inhibited deterioration of lung function but had no effects on histology. Intratracheal MSC treatment did not modify lung function or histology. In conclusion, elastase-treated mice displayed persistent characteristics of pulmonary emphysema. Jugular vein injection of MSCs prior to elastase reduced deterioration of lung function. Intratracheal MSC treatment had no effect on lung function or histology.

Evaluation of pulmonary function using breathing chest radiography with a dynamic flat panel detector: primary results in pulmonary diseases.

PubMed

Tanaka, Rie; Sanada, Shigeru; Okazaki, Nobuo; Kobayashi, Takeshi; Fujimura, Masaki; Yasui, Masahide; Matsui, Takeshi; Nakayama, Kazuya; Nanbu, Yuko; Matsui, Osamu

2006-10-01

Dynamic flat panel detectors (FPD) permit acquisition of distortion-free radiographs with a large field of view and high image quality. The present study was performed to evaluate pulmonary function using breathing chest radiography with a dynamic FPD. We report primary results of a clinical study and computer algorithm for quantifying and visualizing relative local pulmonary airflow. Dynamic chest radiographs of 18 subjects (1 emphysema, 2 asthma, 4 interstitial pneumonia, 1 pulmonary nodule, and 10 normal controls) were obtained during respiration using an FPD system. We measured respiratory changes in distance from the lung apex to the diaphragm (DLD) and pixel values in each lung area. Subsequently, the interframe differences (D-frame) and difference values between maximum inspiratory and expiratory phases (D-max) were calculated. D-max in each lung represents relative vital capacity (VC) and regional D-frames represent pulmonary airflow in each local area. D-frames were superimposed on dynamic chest radiographs in the form of color display (fusion images). The results obtained using our methods were compared with findings on computed tomography (CT) images and pulmonary functional test (PFT), which were examined before inclusion in the study. In normal subjects, the D-frames were distributed symmetrically in both lungs throughout all respiratory phases. However, subjects with pulmonary diseases showed D-frame distribution patterns that differed from the normal pattern. In subjects with air trapping, there were some areas with D-frames near zero indicated as colorless areas on fusion images. These areas also corresponded to the areas showing air trapping on computed tomography images. In asthma, obstructive abnormality was indicated by areas continuously showing D-frame near zero in the upper lung. Patients with interstitial pneumonia commonly showed fusion images with an uneven color distribution accompanied by increased D-frames in the area identified as normal on computed tomography images. Furthermore, measurement of DLD was very effective for evaluating diaphragmatic kinetics. This is a rapid and simple method for evaluation of respiratory kinetics for pulmonary diseases, which can reveal abnormalities in diaphragmatic kinetics and regional lung ventilation. Furthermore, quantification and visualization of respiratory kinetics is useful as an aid in interpreting dynamic chest radiographs.

EPIDEMIOLOGY OF AGE-DEPENDENCE IN SLEEP DISORDERED BREATHING (SDB) IN OLD AGE: THE BAY AREA SLEEP COHORT (BASC).

PubMed

Bliwise, Donald L

2009-03-01

Sleep Disordered Breathing (SDB) is highly prevalent in elderly populations and is thought to reflect, at least in part, age-dependence. Several studies suggest that SDB in elderly populations may hold different functional outcomes relative to SDB in middle-aged populations. Risk factors for SDB specific for the elderly remain uncertain. In this report, we examined changes in SDB, body weight and pulmonary function in 103 individuals over an average interval of 7 years to determine whether changes in these measures covaried. In-lab polysomnography was performed on members of an elderly cohort (Bay Area Sleep Cohort) on two separate occasions (Time 1, Time 2) with multiple nights of measurement typically made on each occasion. Results indicated that: a) SDB progressed over time in both men and women; b) changes in body weight were unrelated to the progression in SDB; c) relative declines in lung volumes (Forced Vital Capacity, Forced Expiratory Volume in 1.0 second) were associated with relative increases in SDB, with the effects slightly stronger in men. These data suggest that age-dependence in one commonly ascribed aging biomarker (lung function) were coupled to increments in SDB. Maintenance of healthy lung function into old age may confer some protective benefits in the development of age-dependent SDB.

Molecular mechanisms underlying variations in lung function: a systems genetics analysis

PubMed Central

Obeidat, Ma’en; Hao, Ke; Bossé, Yohan; Nickle, David C; Nie, Yunlong; Postma, Dirkje S; Laviolette, Michel; Sandford, Andrew J; Daley, Denise D; Hogg, James C; Elliott, W Mark; Fishbane, Nick; Timens, Wim; Hysi, Pirro G; Kaprio, Jaakko; Wilson, James F; Hui, Jennie; Rawal, Rajesh; Schulz, Holger; Stubbe, Beate; Hayward, Caroline; Polasek, Ozren; Järvelin, Marjo-Riitta; Zhao, Jing Hua; Jarvis, Deborah; Kähönen, Mika; Franceschini, Nora; North, Kari E; Loth, Daan W; Brusselle, Guy G; Smith, Albert Vernon; Gudnason, Vilmundur; Bartz, Traci M; Wilk, Jemma B; O’Connor, George T; Cassano, Patricia A; Tang, Wenbo; Wain, Louise V; Artigas, María Soler; Gharib, Sina A; Strachan, David P; Sin, Don D; Tobin, Martin D; London, Stephanie J; Hall, Ian P; Paré, Peter D

2016-01-01

Summary Background Lung function measures reflect the physiological state of the lung, and are essential to the diagnosis of chronic obstructive pulmonary disease (COPD). The SpiroMeta-CHARGE consortium undertook the largest genome-wide association study (GWAS) so far (n=48 201) for forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FEV1/FVC) in the general population. The lung expression quantitative trait loci (eQTLs) study mapped the genetic architecture of gene expression in lung tissue from 1111 individuals. We used a systems genetics approach to identify single nucleotide polymorphisms (SNPs) associated with lung function that act as eQTLs and change the level of expression of their target genes in lung tissue; termed eSNPs. Methods The SpiroMeta-CHARGE GWAS results were integrated with lung eQTLs to map eSNPs and the genes and pathways underlying the associations in lung tissue. For comparison, a similar analysis was done in peripheral blood. The lung mRNA expression levels of the eSNP-regulated genes were tested for associations with lung function measures in 727 individuals. Additional analyses identified the pleiotropic effects of eSNPs from the published GWAS catalogue, and mapped enrichment in regulatory regions from the ENCODE project. Finally, the Connectivity Map database was used to identify potential therapeutics in silico that could reverse the COPD lung tissue gene signature. Findings SNPs associated with lung function measures were more likely to be eQTLs and vice versa. The integration mapped the specific genes underlying the GWAS signals in lung tissue. The eSNP-regulated genes were enriched for developmental and inflammatory pathways; by comparison, SNPs associated with lung function that were eQTLs in blood, but not in lung, were only involved in inflammatory pathways. Lung function eSNPs were enriched for regulatory elements and were over-represented among genes showing differential expression during fetal lung development. An mRNA gene expression signature for COPD was identified in lung tissue and compared with the Connectivity Map. This in-silico drug repurposing approach suggested several compounds that reverse the COPD gene expression signature, including a nicotine receptor antagonist. These findings represent novel therapeutic pathways for COPD. Interpretation The system genetics approach identified lung tissue genes driving the variation in lung function and susceptibility to COPD. The identification of these genes and the pathways in which they are enriched is essential to understand the pathophysiology of airway obstruction and to identify novel therapeutic targets and biomarkers for COPD, including drugs that reverse the COPD gene signature in silico. Funding The research reported in this article was not specifically funded by any agency. See Acknowledgments for a full list of funders of the lung eQTL study and the Spiro-Meta CHARGE GWAS. PMID:26404118

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

Aerosol-administered alpha-tocopherol attenuates lung inflammation in rats given lipopolysaccharide intratracheally.

PubMed

Hybertson, Brooks M; Chung, Jin H; Fini, Mehdi A; Lee, Young M; Allard, Jenny D; Hansen, Brian N; Cho, Okyong J; Shibao, Gayle N; Repine, John E

2005-04-01

Intrapulmonary administration of bacterial lipopolysaccharide (LPS) induces a well-characterized lung inflammatory response involving alveolar macrophage activation, proinflammatory cytokine elaboration, and neutrophil influx. Vitamin E, a lipophilic antioxidant consisting of a family that includes tocopherols and tocotrienols, has previously been shown to have a variety of anti-inflammatory effects, raising interest in its possible uses in disease prevention or therapy. Because aerosol delivery is a specific and rapid way to administer agents to the lungs, the authors undertook to determine whether inhaled vitamin E aerosols would have an anti-inflammatory effect in the lungs. Using a rat model of acute lung inflammation caused by intratracheally administered LPS (10 microg Pseudomonas aeruginosa LPS), the authors examined the effect of aerosol-administered vitamin E, in this case alpha-tocopherol, on several indices of lung inflammation which are increased by LPS treatment. It was found that inhaled alpha-tocopherol aerosol, but not inhaled alpha-tocopherol acetate aerosol, decreased tumor necrosis factor alpha (TNFalpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA levels in lung tissue, TNFalpha and CINC-1 immunoreactive protein levels in lung lavage, and the number of neutrophils recoverable by lung lavage from rats given LPS intratracheally. These results contribute to the increasing body of work describing immunomodulatory functions of alpha-tocopherol, and support the idea that direct aerosol administration of alpha-tocopherol may play a beneficial role in strategies to control inflammatory lung illnesses.

Maresin 1 Ameliorates Lung Ischemia/Reperfusion Injury by Suppressing Oxidative Stress via Activation of the Nrf-2-Mediated HO-1 Signaling Pathway

PubMed Central

Wu, You; Zhao, Feng

2017-01-01

Lung ischemia/reperfusion (I/R) injury occurs in various clinical conditions and heavily damaged lung function. Oxidative stress reaction and antioxidant enzymes play a pivotal role in the etiopathogenesis of lung I/R injury. In the current study, we investigated the impact of Maresin 1 on lung I/R injury and explored the possible mechanism involved in this process. MaR 1 ameliorated I/R-induced lung injury score, wet/dry weight ratio, myeloperoxidase, tumor necrosis factor, bronchoalveolar lavage fluid (BALF) leukocyte count, BALF neutrophil ratio, and pulmonary permeability index levels in lung tissue. MaR 1 significantly reduced ROS, methane dicarboxylic aldehyde, and 15-F2t-isoprostane generation and restored antioxidative enzyme (superoxide dismutase, glutathione peroxidase, and catalase) activities. Administration of MaR 1 improved the expression of nuclear Nrf-2 and cytosolic HO-1 in I/R-treated lung tissue. Furthermore, we also found that the protective effects of MaR 1 on lung tissue injury and oxidative stress were reversed by HO-1 activity inhibitor, Znpp-IX. Nrf-2 transcription factor inhibitor, brusatol, significantly decreased MaR 1-induced nuclear Nrf-2 and cytosolic HO-1 expression. In conclusion, these results indicate that MaR 1 protects against lung I/R injury through suppressing oxidative stress. The mechanism is partially explained by activation of the Nrf-2-mediated HO-1 signaling pathway. PMID:28751936

Localized compliance of small airways in excised rat lungs using microfocal X-ray computed tomography.

PubMed

Sera, Toshihiro; Fujioka, Hideki; Yokota, Hideo; Makinouchi, Akitake; Himeno, Ryutaro; Schroter, Robert C; Tanishita, Kazuo

2004-05-01

Airway compliance is a key factor in understanding lung mechanics and is used as a clinical diagnostic index. Understanding such mechanics in small airways physiologically and clinically is critical. We have determined the "morphometric change" and "localized compliance" of small airways under "near"-physiological conditions; namely, the airways were embedded in parenchyma without dehydration and fixation. Previously, we developed a two-step method to visualize small airways in detail by staining the lung tissue with a radiopaque solution and then visualizing the tissue with a cone-beam microfocal X-ray computed tomography system (Sera et al. J Biomech 36: 1587-1594, 2003). In this study, we used this technique to analyze changes in diameter and length of the same small airways ( approximately 150 microm ID) and then evaluated the localized compliance as a function of airway generation (Z). For smaller (<300-microm-diameter) airways, diameter was 36% larger at end-tidal inspiration and 89% larger at total lung capacity; length was 18% larger at end-tidal inspiration and 43% larger at total lung capacity than at functional residual capacity. Diameter, especially at smaller airways, did not behave linearly with V(1/3) (where V is volume). With increasing lung pressure, diameter changed dramatically at a particular pressure and length changed approximately linearly during inflation and deflation. Percentage of airway volume for smaller airways did not behave linearly with that of lung volume. Smaller airways were generally more compliant than larger airways with increasing Z and exhibited hysteresis in their diameter behavior. Airways at higher Z deformed at a lower pressure than those at lower Z. These results indicated that smaller airways did not behave homogeneously.

3D segmentation of lung CT data with graph-cuts: analysis of parameter sensitivities

NASA Astrophysics Data System (ADS)

Cha, Jung won; Dunlap, Neal; Wang, Brian; Amini, Amir

2016-03-01

Lung boundary image segmentation is important for many tasks including for example in development of radiation treatment plans for subjects with thoracic malignancies. In this paper, we describe a method and parameter settings for accurate 3D lung boundary segmentation based on graph-cuts from X-ray CT data1. Even though previously several researchers have used graph-cuts for image segmentation, to date, no systematic studies have been performed regarding the range of parameter that give accurate results. The energy function in the graph-cuts algorithm requires 3 suitable parameter settings: K, a large constant for assigning seed points, c, the similarity coefficient for n-links, and λ, the terminal coefficient for t-links. We analyzed the parameter sensitivity with four lung data sets from subjects with lung cancer using error metrics. Large values of K created artifacts on segmented images, and relatively much larger value of c than the value of λ influenced the balance between the boundary term and the data term in the energy function, leading to unacceptable segmentation results. For a range of parameter settings, we performed 3D image segmentation, and in each case compared the results with the expert-delineated lung boundaries. We used simple 6-neighborhood systems for n-link in 3D. The 3D image segmentation took 10 minutes for a 512x512x118 ~ 512x512x190 lung CT image volume. Our results indicate that the graph-cuts algorithm was more sensitive to the K and λ parameter settings than to the C parameter and furthermore that amongst the range of parameters tested, K=5 and λ=0.5 yielded good results.

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.

Cancer-specific production of N-acetylaspartate via NAT8L overexpression in non-small cell lung cancer and its potential as a circulating biomarker

PubMed Central

Lou, Tzu-Fang; Sethuraman, Deepa; Dospoy, Patrick; Srivastva, Pallevi; Kim, Hyun Seok; Kim, Joongsoo; Ma, Xiaotu; Chen, Pei-Hsuan; Huffman, Kenneth E.; Frink, Robin E.; Larsen, Jill E.; Lewis, Cheryl; Um, Sang-Won; Kim, Duk-Hwan; Ahn, Jung-Mo; DeBerardinis, Ralph J.; White, Michael A.; Minna, John D.; Yoo, Hyuntae

2015-01-01

In order to identify new cancer-associated metabolites that may be useful for early detection of lung cancer, we performed a global metabolite profiling of a non-small cell lung cancer (NSCLC) line and immortalized normal lung epithelial cells from the same patient. Among several metabolites with significant cancer/normal differences, we identified a unique metabolic compound, N-acetylaspartate (NAA) in cancer cells — undetectable in normal lung epithelium. NAA’s cancer-specific detection was validated in additional cancer and control lung cells as well as selected NSCLC patient tumors and control tissues. NAA’s cancer-specificity was further supported in our analysis of NAA synthetase (gene symbol: NAT8L) gene expression levels in The Cancer Genome Atlas: elevated NAT8L expression in approximately 40% of adenocarcinoma and squamous cell carcinoma cases (N=577), with minimal expression in all non-malignant lung tissues (N=74). We then showed that NAT8L is functionally involved in NAA production of NSCLC cells through siRNA-mediated suppression of NAT8L, which caused selective reduction of intracellular and secreted NAA. Our cell culture experiments also indicated that NAA biosynthesis in NSCLC cells depends on glutamine availability. For preliminary evaluation of NAA’s clinical potential as a circulating biomarker, we developed a sensitive NAA blood assay and found that NAA blood levels were elevated in 46% of NSCLC patients (N=13) in comparison with age-matched healthy controls (N=21) among individuals aged 55 years or younger. Taken together, these results indicate that NAA is produced specifically in NSCLC tumors through NAT8L overexpression and its extracellular secretion can be detected in blood. PMID:26511490

COMPARATIVE SPIROMETRIC STUDIES BEFORE AND AFTER Co$sup 60$ IRRADIATION OF PATIENTS WITH BRONCHIAL CARCINOMA

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

Lichterfeld, A.; Widow, W.; Zahnert, R.

1961-08-01

Changes in respiratory function were evaluated after radiotherapy in 46 patients with lung cancer. Spirometric tests were conducted shortly before irradiation and 4 to 6 weeks after local gamma -radiation doses of 3500 r delivered over 2 to 3 weeks. A few patients received 6000 r over 4 to 5 weeks, and 40 unirradiated controls were also examined. In general, respiratory function was diminished following irradiation. The disturbances were most marked in the group receiving the higher dose, in which vital capacity fell by an average of 728 cm/sup 3/ (25%) postirradiation. With lower doses the decrease was 7%. Themore » decrease was greater after irradiation of supraclavicular fields. In over half the cases, radiotherapy resulted in regression of the tumor and an improvement of radioinduced atelectasis, which sometimes resulted in an improvement in the Tiffeneau test values. Radiation injury in the lung could be detected radiographically in only 8 cases, indicating that spirometry and histologic examination are more sensitive means of detecting the injury. It was concluded that preoperative radiotherapy of lung cancer may impair the patient's chances for recovery because of the resulting disorders in pulmonary function. (TCO)« less

Perceived health in lung cancer patients: the role of positive and negative affect.

PubMed

Hirsch, Jameson K; Floyd, Andrea R; Duberstein, Paul R

2012-03-01

To examine the association of affective experience and health-related quality of life in lung cancer patients, we hypothesized that negative affect would be positively, and positive affect would be negatively, associated with perceived health. A sample of 133 English-speaking lung cancer patients (33% female; mean age = 63.68 years old, SD = 9.37) completed a battery of self-report surveys. Results of our secondary analysis indicate that trait negative affect was significantly associated with poor physical and social functioning, greater role limitations due to emotional problems, greater bodily pain, and poor general health. Positive affect was significantly associated with adaptive social functioning, fewer emotion-based role limitations, and less severe bodily pain. In a full model, positive affect was significantly associated with greater levels of social functioning and general health, over and above the effects of negative affect. Reduction of negative affect is an important therapeutic goal, but the ability to maintain positive affect may result in greater perceived health. Indeed, engagement in behaviors that result in greater state positive affect may, over time, result in dispositional changes and enhancement of quality of life.

Respiratory adaptations in different types of sport.

PubMed

Lazovic, B; Mazic, S; Suzic-Lazic, J; Djelic, M; Djordjevic-Saranovic, S; Durmic, T; Zikic, D; Zugic, V

2015-06-01

Recent studies demonstrated that current European Respiratory Society/American Thoracic Society spirometric reference equations, used in general population, may not be applicable in population of elite athletes. Althought it is well known that physical activity may affect lung volumes, the effect of sporting activity on pulmonary function testing indices was never examined. The aim of this study was to examine the differences in functional respiratory parameters in various types of sports by measuring lung volumes and to extend the existing factors as well as sport disciplines which affect respiratory function the most. A total of 1639 elite male athletes, aged 18-35 years were divided in 4 groups according to the predominant characteristics of training: skill, power, mixed and endurance athletes. They performed basic anthropometric measurements and spirometry. Groups were compared, and Pearson's simple correlation was performed to test the relation between anthropometric and spirometric characteristics of athletes. All anthropometric characteristics significantly differed among groups and correlate with respiratory parameters. The highest correlation was found for body height and weight. Sports participation is associated with respiratory adaptation, and the extent of adaptation depends on type of activity. Endurance sports athletes have higher lung volumes in comparison with skill, mixed and power group of sport.

Lung function indices of children exposed to wood smoke in a fishing port in South-South Nigeria.

PubMed

Oloyede, Iso P; Ekrikpo, Udeme E; Ekanem, Emmanuel E

2013-10-01

Children in the warm rain forest are at risk of having their lung function compromised by a variety of factors, including smoke from wood fires. A total of 358 children from a fishing port and 400 children living in a farm settlement were tested to determine their peak expiratory flow rate (PEFR), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory volume in 1 s per cent and forced expiratory flow between 25 and 75%. The values for the PEFR, FVC, FEV1, forced expiratory volume in 1 s per cent and forced expiratory flow between 25 and 75% of the subjects were significantly lower than those of the controls (P value for males = <0.001, 0.01, 0.002, 0.01 and <0.001, respectively, whereas for their female counterparts = <0.001, 0.003, 0.001, 0.04 and <0.001, respectively). These deficits were observed to be more with increasing duration of exposure to wood smoke for PEFR, FVC and FEV1. Chronic exposure to fish drying using firewood can impair lung function in children. There is a need for alternative methods of fish preservation for those engaged in fish drying.

Designing To Learn about Complex Systems.

ERIC Educational Resources Information Center

Hmelo, Cindy E.; Holton, Douglas L.; Kolodner, Janet L.

2000-01-01

Indicates the presence of complex structural, behavioral, and functional relations to understanding. Reports on a design experiment in which 6th grade children learned about the human respiratory system by designing artificial lungs and building partial working models. Makes suggestions for successful learning from design activities. (Contains 44…

HEALTH EFFECTS OF REAL-WORLD EXPOSURE TO DIESEL EXHAUST IN PERSONS WITH ASTHMA

EPA Science Inventory

Investigators anticipate that this proposed research will indicate that lung function is slightly decreased and some markers of airway inflammation are increased in people with asthma who are exposed to ambient urban air in a roadside environment dominated by diesel vehicle...

SMALL AIRWAYS FUNCTION RESPONSE IN SMOKERS AND PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASE FOLLOWING EXPOSURE TO CONCENTRATED AMBIENT AIR PARTICLES

EPA Science Inventory

Numerous field and epidemiological studies have shown significant associations between particulate matter (PM) exposure and various morbidity outcomes including hospital admissions for bronchitis and asthma. These population based studies indicate that persons with chronic obstru...

Advanced Techniques in Pulmonary Function Test Analysis Interpretation and Diagnosis

PubMed Central

Gildea, T.J.; Bell, C. William

1980-01-01

The Pulmonary Functions Analysis and Diagnostic System is an advanced clinical processing system developed for use at the Pulmonary Division, Department of Medicine at the University of Nebraska Medical Center. The system generates comparative results and diagnostic impressions for a variety of routine and specialized pulmonary functions test data. Routine evaluation deals with static lung volumes, breathing mechanics, diffusing capacity, and blood gases while specialized tests include lung compliance studies, small airways dysfunction studies and dead space to tidal volume ratios. Output includes tabular results of normal vs. observed values, clinical impressions and commentary and, where indicated, a diagnostic impression. A number of pulmonary physiological and state variables are entered or sampled (A to D) with periodic status reports generated for the test supervisor. Among the various physiological variables sampled are respiratory frequency, minute ventilation, oxygen consumption, carbon dioxide production, and arterial oxygen saturation.

Lung Cancer Risk Prediction Model Incorporating Lung Function: Development and Validation in the UK Biobank Prospective Cohort Study.

PubMed

Muller, David C; Johansson, Mattias; Brennan, Paul

2017-03-10

Purpose Several lung cancer risk prediction models have been developed, but none to date have assessed the predictive ability of lung function in a population-based cohort. We sought to develop and internally validate a model incorporating lung function using data from the UK Biobank prospective cohort study. Methods This analysis included 502,321 participants without a previous diagnosis of lung cancer, predominantly between 40 and 70 years of age. We used flexible parametric survival models to estimate the 2-year probability of lung cancer, accounting for the competing risk of death. Models included predictors previously shown to be associated with lung cancer risk, including sex, variables related to smoking history and nicotine addiction, medical history, family history of lung cancer, and lung function (forced expiratory volume in 1 second [FEV1]). Results During accumulated follow-up of 1,469,518 person-years, there were 738 lung cancer diagnoses. A model incorporating all predictors had excellent discrimination (concordance (c)-statistic [95% CI] = 0.85 [0.82 to 0.87]). Internal validation suggested that the model will discriminate well when applied to new data (optimism-corrected c-statistic = 0.84). The full model, including FEV1, also had modestly superior discriminatory power than one that was designed solely on the basis of questionnaire variables (c-statistic = 0.84 [0.82 to 0.86]; optimism-corrected c-statistic = 0.83; p FEV1 = 3.4 × 10 -13 ). The full model had better discrimination than standard lung cancer screening eligibility criteria (c-statistic = 0.66 [0.64 to 0.69]). Conclusion A risk prediction model that includes lung function has strong predictive ability, which could improve eligibility criteria for lung cancer screening programs.

On the contribution of height to predict lung volumes, capacities and diffusion in healthy school children of 10-17 years.

PubMed

Gupta, C K; Mishra, G; Mehta, S C; Prasad, J

1993-01-01

Lung volumes, capacities, diffusion and alveolar volumes with physical characteristics (age, height and weight) were recorded for 186 healthy school children (96 boys and 90 girls) of 10-17 years age group. The objective was to study the relative importance of physical characteristics as regressor variables in regression models to estimate lung functions. We observed that height is best correlated with all the lung functions. Inclusion of all physical characteristics in the models have little gain compared to the ones having just height as regressor variable. We also find that exponential models were not only statistically valid but fared better compared to the linear ones. We conclude that lung functions covary with height and other physical characteristics but do not depend upon them. The rate of increase in the functions depend upon initial lung functions. Further, we propose models and provide ready reckoners to give estimates of lung functions with 95 per cent confidence limits based on heights from 125 to 170 cm for the age group of 10 to 17 years.

Estimation of Lung Ventilation

NASA Astrophysics Data System (ADS)

Ding, Kai; Cao, Kunlin; Du, Kaifang; Amelon, Ryan; Christensen, Gary E.; Raghavan, Madhavan; Reinhardt, Joseph M.

Since the primary function of the lung is gas exchange, ventilation can be interpreted as an index of lung function in addition to perfusion. Injury and disease processes can alter lung function on a global and/or a local level. MDCT can be used to acquire multiple static breath-hold CT images of the lung taken at different lung volumes, or with proper respiratory control, 4DCT images of the lung reconstructed at different respiratory phases. Image registration can be applied to this data to estimate a deformation field that transforms the lung from one volume configuration to the other. This deformation field can be analyzed to estimate local lung tissue expansion, calculate voxel-by-voxel intensity change, and make biomechanical measurements. The physiologic significance of the registration-based measures of respiratory function can be established by comparing to more conventional measurements, such as nuclear medicine or contrast wash-in/wash-out studies with CT or MR. An important emerging application of these methods is the detection of pulmonary function change in subjects undergoing radiation therapy (RT) for lung cancer. During RT, treatment is commonly limited to sub-therapeutic doses due to unintended toxicity to normal lung tissue. Measurement of pulmonary function may be useful as a planning tool during RT planning, may be useful for tracking the progression of toxicity to nearby normal tissue during RT, and can be used to evaluate the effectiveness of a treatment post-therapy. This chapter reviews the basic measures to estimate regional ventilation from image registration of CT images, the comparison of them to the existing golden standard and the application in radiation therapy.

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

The effect of gender on health-related quality of life and related factors in post-lobectomy lung-cancer patients.

PubMed

Chang, Nai-Wen; Lin, Kuan-Chia; Hsu, Wen-Hu; Lee, Shih-Chun; Chan, James Yi-Hsin; Wang, Kwua-Yun

2015-06-01

While studies have documented gender differences by histologic type among lung cancer patients, the effect of these differences on the health-related quality of life (HRQoL) of post-lobectomy lungcancer patients and related factors remain uncertain. This study examines gender-specific HRQoL and related factors in post-lobectomy lung-cancer patients. A cross-sectional study design was applied. A convenience sample of 231 post-lobectomy lungcancer patients was recruited from the thoracic surgery outpatient departments of two teaching hospitals in Taipei, Taiwan from March to December 2012. Patients performed a spirometry test and completed instruments that included a Beck Depression Inventory-II, an Interpersonal Support Evaluation List, and the symptom and function scales of the Quality of Life Questionnaire. Data analysis used descriptive statistics, including mean and standard deviations, frequency, and percentage values. Independent-sample Student's t-tests and multivariate analyses were used for comparative purposes. This study confirmed a significant gender effect on HRQoL and HRQoL-related factors such as marital status, religious affiliation, smoking status, histologic type, symptoms, pulmonary function, depression, and family support. Moreover, multivariate analysis found gender to be a significant determinant of the HRQoL aspects of physical functioning, emotional functioning, and cognitive functioning. Finally, results indicated that factors other than gender were also significant determinants of HRQoL. Gender impacts the HRQoL and related factors of postoperative lung-cancer patients. Therefore, gender should be considered in assessing and addressing the individual care needs of these patients in order to attain optimal treatment outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Surfactant protein-A nanobody-conjugated liposomes loaded with methylprednisolone increase lung-targeting specificity and therapeutic effect for acute lung injury.

PubMed

Li, Nan; Weng, Dong; Wang, Shan-Mei; Zhang, Yuan; Chen, Shan-Shan; Yin, Zhao-Fang; Zhai, Jiali; Scoble, Judy; Williams, Charlotte C; Chen, Tao; Qiu, Hui; Wu, Qin; Zhao, Meng-Meng; Lu, Li-Qin; Mulet, Xavier; Li, Hui-Ping

2017-11-01

The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS-NSSLs-SPANb. MPS-NSSLs-SPANb exhibited good size distribution, morphology, and encapsulation efficiency. Animal experiments demonstrated the high specificity of MPS-NSSLs-SPANb to the lung. Treatment with MPS-NSSLs-SPANb reduced the levels of TNF-α, IL-8, and TGF-β1 in rat bronchoalveolar lavage fluid and the expression of NK-κB in the lung tissues, thereby alleviating lung injuries and increasing rat survival. The nanobody functionalized nanoparticles demonstrate superior performance to treat lung injury when compared to that of antibody functionalized systems.

Joint Effects of Smoking and Sedentary Lifestyle on Lung Function in African Americans: The Jackson Heart Study Cohort

PubMed Central

Campbell Jenkins, Brenda W.; Sarpong, Daniel F.; Addison, Clifton; White, Monique S.; Hickson, DeMarc A.; White, Wendy; Burchfiel, Cecil

2014-01-01

This study examined: (a) differences in lung function between current and non current smokers who had sedentary lifestyles and non sedentary lifestyles and (b) the mediating effect of sedentary lifestyle on the association between smoking and lung function in African Americans. Sedentary lifestyle was defined as the lowest quartile of the total physical activity score. The results of linear and logistic regression analyses revealed that non smokers with non sedentary lifestyles had the highest level of lung function, and smokers with sedentary lifestyles had the lowest level. The female non-smokers with sedentary lifestyles had a significantly higher FEV1% predicted and FVC% predicted than smokers with non sedentary lifestyles (93.3% vs. 88.6%; p = 0.0102 and 92.1% vs. 86.9%; p = 0.0055 respectively). FEV1/FVC ratio for men was higher in non smokers with sedentary lifestyles than in smokers with non sedentary lifestyles (80.9 vs. 78.1; p = 0.0048). Though smoking is inversely associated with lung function, it seems to have a more deleterious effect than sedentary lifestyle on lung function. Physically active smokers had higher lung function than their non physically active counterparts. PMID:24477212

Joint effects of smoking and sedentary lifestyle on lung function in African Americans: the Jackson Heart Study cohort.

PubMed

Campbell Jenkins, Brenda W; Sarpong, Daniel F; Addison, Clifton; White, Monique S; Hickson, Demarc A; White, Wendy; Burchfiel, Cecil

2014-01-28

This study examined: (a) differences in lung function between current and non current smokers who had sedentary lifestyles and non sedentary lifestyles and (b) the mediating effect of sedentary lifestyle on the association between smoking and lung function in African Americans. Sedentary lifestyle was defined as the lowest quartile of the total physical activity score. The results of linear and logistic regression analyses revealed that non smokers with non sedentary lifestyles had the highest level of lung function, and smokers with sedentary lifestyles had the lowest level. The female non-smokers with sedentary lifestyles had a significantly higher FEV1% predicted and FVC% predicted than smokers with non sedentary lifestyles (93.3% vs. 88.6%; p = 0.0102 and 92.1% vs. 86.9%; p = 0.0055 respectively). FEV1/FVC ratio for men was higher in non smokers with sedentary lifestyles than in smokers with non sedentary lifestyles (80.9 vs. 78.1; p = 0.0048). Though smoking is inversely associated with lung function, it seems to have a more deleterious effect than sedentary lifestyle on lung function. Physically active smokers had higher lung function than their non physically active counterparts.

Chest circumference and birth weight are good predictors of lung function in preschool children from an e-waste recycling area.

PubMed

Zeng, Xiang; Xu, Xijin; Zhang, Yuling; Li, Weiqiu; Huo, Xia

2017-10-01

The purpose of this study was to investigate the associations between birth weight, chest circumference, and lung function in preschool children from e-waste exposure area. A total of 206 preschool children from Guiyu (an e-waste recycling area) and Haojiang and Xiashan (the reference areas) in China were recruited and required to undergo physical examination, blood tests, and lung function tests during the study period. Birth outcome such as birth weight and birth height were obtained by questionnaire. Children living in the e-waste-exposed area have a lower birth weight, chest circumference, height, and lung function when compare to their peers from the reference areas (all p value <0.05). Both Spearman and partial correlation analyses showed that birth weight and chest circumference were positively correlated with lung function levels including forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ). After adjustment for the potential confounders in further linear regression analyses, birth weight, and chest circumference were positively associated with lung function levels, respectively. Taken together, birth weight and chest circumference may be good predictors for lung function levels in preschool children.

Diagnostic accuracy of a pocket screening spirometer in diagnosing chronic obstructive pulmonary disease in general practice: a cross sectional validation study using tertiary care as a reference.

PubMed

Labor, Marina; Vrbica, Žarko; Gudelj, Ivan; Labor, Slavica; Plavec, Davor

2016-08-19

COPD-6™ is a lung function testing device for a rapid pre-spirometry testing to screen-out at-risk individuals not having COPD and indicating those at risk. The aim of this study was to validate COPD-6™ lung function testing (index test) in general practice in discriminating patients with COPD out of the population at risk - smokers/ex-smokers with no previous diagnosis of COPD, using measurements at tertiary care as reference standard. Consecutive 227 subjects (115 women, 185 smokers/42 ex-smokers, ≥20 pack-years) with no previous diagnosis of COPD, aged 52.5 (SD 6.8) years from 26 general practitioners (GPs) were recruited, lung function tested with COPD-6™, referred to the tertiary institution for repeated COPD-6™ testing followed by spirometry with a bronchodilator (salbutamol), examination, and pulmonologist consultation for the diagnosis and severity of COPD. COPD was diagnosed in 43 subjects (18.9 %), with an AUC of 0.827 (95 % CI 0.769-0.875, P < 0.001) for the diagnosis of COPD when lung function was measured using COPD-6™ in GP's office with a specificity of 100 % (95 % CI, 97.95-100 %) but a very low sensitivity of 32.56 % (95 % CI, 20.49-47.48 %). Significant agreement for forced expiratory volume in 1 s measured at GP's office and at lung function lab was found (mean difference 0.01 L, p = 0.667) but not for other measured parameters (p < 0.001 for all). Our study results point out that active case finding in a population at risk for COPD should be instituted (almost 20 % of undiagnosed COPD). Based on our results lung function testing with COPD-6™ can substitute spirometry testing in cases where it is not readily available to the patient/physician taken into account that the traditional FEV1/FEV6 cutoff value of <0.7 is not the only criterion for diagnosis and/or further referral. ClinicalTrials.gov Identifier NCT01550679 Registered 28 September 2014, retrospectively registered.

Evaluation of vulnerable PM2.5-exposure individuals: a repeated-measure study in an elderly population.

PubMed

Chu, Haiyan; Xin, Junyi; Yuan, Qi; Zhang, Xu; Pan, Wang; Zeng, Xinying; Chen, Yaoyao; Ma, Gaoxiang; Ge, Yuqiu; Du, Mulong; Tong, Na; Li, Xiaobo; Zhang, Zhengdong; Wang, Meilin

2018-04-01

Numerous studies have shown that elderly people are susceptible to high-level particles with aerodynamic diameter ≤ 2.5 μm (PM 2.5 ) exposure. However, not all elderly people exposed to PM 2.5 suffer from diseases. In this study, we aim to establish a method to predict the vulnerable PM 2.5 -exposure individuals among elderly population. Fourteen elderly people were recruited from May 8 to July 4, 2016, in Nanjing, China. Ten physiological indicators were repeatedly measured for 15 times. Liner mixed-effects model, principal component analysis (PCA), and PM 2.5 lag score were used to estimate the effects of PM 2.5 on blood pressure, pulse, and lung function. As a result, each quartile increase of ambient PM 2.5 was significantly associated with increased pulse (P < 0.05 for lag0, 1, 4, 0-1, 0-2, 0-3, and 0-5 days), decreased blood pressure (P < 0.05 for lag4 and 0-3 days), and decreased lung function (P < 0.05 for lag0, 1, 0-1, and 0-2 days) among the 14 elderly people. In terms of pulse or lung function, three elderly people were considered as vulnerable PM 2.5 -exposure individuals. No vulnerable individual was found for blood pressure. Blood pressure, pulse, and lung function could be affected by high-level PM 2.5 exposure in elderly people. This method for screening three elderly people may provide a new insight on identifying the vulnerable PM 2.5 -exposure individuals.

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.

Quantitative Pulmonary Imaging Using Computed Tomography and Magnetic Resonance Imaging

PubMed Central

Washko, George R.; Parraga, Grace; Coxson, Harvey O.

2011-01-01

Measurements of lung function, including spirometry and body plethesmography, are easy to perform and are the current clinical standard for assessing disease severity. However, these lung functional techniques do not adequately explain the observed variability in clinical manifestations of disease and offer little insight into the relationship of lung structure and function. Lung imaging and the image based assessment of lung disease has matured to the extent that it is common for clinical, epidemiologic, and genetic investigation to have a component dedicated to image analysis. There are several exciting imaging modalities currently being used for the non-invasive study of lung anatomy and function. In this review we will focus on two of them, x-ray computed tomography and magnetic resonance imaging. Following a brief introduction of each method we detail some of the most recent work being done to characterize smoking-related lung disease and the clinical applications of such knowledge. PMID:22142490

Step climbing capacity in patients with pulmonary hypertension.

PubMed

Fox, Benjamin Daniel; Langleben, David; Hirsch, Andrew; Boutet, Kim; Shimony, Avi

2013-01-01

Patients with pulmonary hypertension (PH) typically have exercise intolerance and limitation in climbing steps. To explore the exercise physiology of step climbing in PH patients, on a laboratory-based step test. We built a step oximetry system from an 'aerobics' step equipped with pressure sensors and pulse oximeter linked to a computer. Subjects mounted and dismounted from the step until their maximal exercise capacity or 200 steps was achieved. Step-count, SpO(2) and heart rate were monitored throughout exercise and recovery. We derived indices of exercise performance, desaturation and heart rate. A 6-min walk test and serum NT-proBrain Natriuretic Peptide (BNP) level were measured. Lung function tests and hemodynamic parameters were extracted from the medical record. Eighty-six subjects [52 pulmonary arterial hypertension (PAH), 14 chronic thromboembolic PH (CTEPH), 20 controls] were recruited. Exercise performance (climbing time, height gained, velocity, energy expenditure, work-rate and climbing index) on the step test was significantly worse with PH and/or worsening WHO functional class (ANOVA, p < 0.001). There was a good correlation between exercise performance on the step and 6-min walking distance-climb index (r = -0.77, p < 0.0001). The saturation deviation (mean of SpO(2) values <95 %) on the step test correlated with diffusion capacity of the lung (ρ = -0.49, p = 0.001). No correlations were found between the step test indices and other lung function tests, hemodynamic parameters or NT-proBNP levels. Patients with PAH/CTEPH have significant limitation in step climbing ability that correlates with functional class and 6-min walking distance. This is a significant impediment to their daily activities.

The association between anthropometric measures and lung function in a population-based study of Canadian adults.

PubMed

Rowe, A; Hernandez, P; Kuhle, S; Kirkland, S

2017-10-01

Decreased lung function has health impacts beyond diagnosable lung disease. It is therefore important to understand the factors that may influence even small changes in lung function including obesity, physical fitness and physical activity. The aim of this study was to determine the anthropometric measure most useful in examining the association with lung function and to determine how physical activity and physical fitness influence this association. The current study used cross-sectional data on 4662 adults aged 40-79 years from the Canadian Health Measures Survey Cycles 1 and 2. Linear regression models were used to examine the association between the anthropometric and lung function measures (forced expiratory volume in 1 s [FEV 1 ] and forced vital capacity [FVC]); R 2 values were compared among models. Physical fitness and physical activity terms were added to the models and potential confounding was assessed. Models using sum of 5 skinfolds and waist circumference consistently had the highest R 2 values for FEV 1 and FVC, while models using body mass index consistently had among the lowest R 2 values for FEV 1 and FVC and for men and women. Physical activity and physical fitness were confounders of the relationships between waist circumference and the lung function measures. Waist circumference remained a significant predictor of FVC but not FEV 1 after adjustment for physical activity or physical fitness. Waist circumference is an important predictor of lung function. Physical activity and physical fitness should be considered as potential confounders of the relationship between anthropometric measures and lung function. Copyright © 2017. Published by Elsevier Ltd.

[Testing and analyzing the lung functions in the normal population in Hebei province].

PubMed

Chen, Li; Zhao, Ming; Han, Shao-mei; Li, Zhong-ming; Zhu, Guang-jin

2004-08-01

To investigate the lung function of the normal subjects living in Hebei province and its correlative factors such as living circumstance, age, height, and body weight. The lung volumes and breath capacities of 1,587 normal subjects were tested by portable spirometers (Scope Rotry) from August to October in 2002. The influences of living circumstance, age, gender, height, and body weight on lung functions were observed and analyzed. No significant difference was found between urban and rural areas in all indexes (P > 0.05); however, significant difference existed between male and female subjects (P = 0.000). The change trends of lung function in male and female subjects were similar. Growth spurt appeared at the age of 12-16 years in male subjects and 12-14 years in female subjects. Vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) reached their peaks at the age of 26-34 years and then decreased with age. Peak expiratory flow (PEF), 25% forced expiratory flow (FEF50%), and 75% forced expiratory flow (FEF75%) appeared at the age of 18 and then went down with age. Both height and weight had a correlation with all the indexes of lung functions, although the influence of height is stronger than weight. All the indexes of lung function have correlations with age, height, and weight. Lung function changes with aging, therefore different expected values shall be available for the adolescence, young adults, and middle-aged and old people. This study provides reference values of lung function for normal population.

Risk factors for radiation pneumonitis after stereotactic radiation therapy for lung tumours: clinical usefulness of the planning target volume to total lung volume ratio.

PubMed

Ueyama, Tomoko; Arimura, Takeshi; Takumi, Koji; Nakamura, Fumihiko; Higashi, Ryutaro; Ito, Soichiro; Fukukura, Yoshihiko; Umanodan, Tomokazu; Nakajo, Masanori; Koriyama, Chihaya; Yoshiura, Takashi

2018-06-01

To identify risk factors for symptomatic radiation pneumonitis (RP) after stereotactic radiation therapy (SRT) for lung tumours. We retrospectively evaluated 68 lung tumours in 63 patients treated with SRT between 2011 and 2015. RP was graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0. SRT was delivered at 7.0-12.0 Gy per each fraction, once daily, to a total of 48-64 Gy (median, 50 Gy). Univariate analysis was performed to assess patient- and treatment-related factors, including age, sex, smoking index (SI), pulmonary function, tumour location, serum Krebs von den Lungen-6 value (KL-6), dose-volume metrics (V5, V10, V20, V30, V40 and VS5), homogeneity index of the planning target volume (PTV), PTV dose, mean lung dose (MLD), contralateral MLD and V2, PTV volume, lung volume and the PTV/lung volume ratio (PTV/Lung). Performance of PTV/Lung in predicting symptomatic RP was also analysed using receiver operating characteristic (ROC) analysis. The median follow-up period was 21 months. 10 of 63 patients (15.9%) developed symptomatic RP after SRT. On univariate analysis, V10, V20, PTV volume and PTV/Lung were significantly associated with occurrence of RP  ≥Grade 2. ROC curves indicated that symptomatic RP could be predicted using PTV/Lung [area under curve (AUC): 0.88, confidence interval (CI: 0.78-0.95), cut-off value: 1.09, sensitivity: 90.0% and specificity: 72.4%]. PTV/Lung is a good predictor of symptomatic RP after SRT. Advances in knowledge: The cases with high PTV/Lung should be carefully monitored with caution for the occurrence of RP after SRT.

Poster - Thurs Eve-23: Effect of lung density and geometry variation on inhomogeneity correction algorithms: A Monte Carlo dosimetry evaluation.

PubMed

Chow, J; Leung, M; Van Dyk, J

2008-07-01

This study provides new information on the evaluation of the lung dose calculation algorithms as a function of the relative electron density of lung, ρ e,lung . Doses calculated using the collapsed cone convolution (CCC) and adaptive convolution (AC) algorithm in lung with the Pinnacle 3 system were compared to those calculated using the Monte Carlo (MC) simulation (EGSnrc-based code). Three groups of lung phantoms, namely, "Slab", "Column" and "Cube" with different ρ e,lung (0.05-0.7), positions, volumes and shapes of lung in water were used. 6 and 18MV photon beams with 4×4 and 10×10cm 2 field sizes produced by a Varian 21EX Linac were used in the MC dose calculations. Results show that the CCC algorithm agrees well with AC to within ±1% for doses calculated in the lung phantoms, indicating that the AC, with 3-4 times less computing time required than CCC, is a good substitute for the CCC method. Comparing the CCC and AC with MC, dose deviations are found when ρ e,lung are ⩽0.1-0.3. The degree of deviation depends on the photon beam energy and field size, and is relatively large when high-energy photon beams with small field are used. For the penumbra widths (20%-80%), the CCC and AC agree well with MC for the "Slab" and "Cube" phantoms with the lung volumes at the central beam axis (CAX). However, deviations >2mm occur in the "Column" phantoms, with two lung volumes separated by a water column along the CAX, using the 18MV (4×4cm 2 ) photon beams with ρ e,lung ⩽0.1. © 2008 American Association of Physicists in Medicine.

Regulatory interactions between long noncoding RNA LINC00968 and miR-9-3p in non-small cell lung cancer: A bioinformatic analysis based on miRNA microarray, GEO and TCGA.

PubMed

Li, Dong-Yao; Chen, Wen-Jie; Shang, Jun; Chen, Gang; Li, Shi-Kang

2018-06-01

Long non-coding RNAs (lncRNAs) have been demonstrated to mediate carcinogenesis in various types of cancer. However, the regulatory role of lncRNA LINC00968 in lung adenocarcinoma remains unclear. The microRNA (miRNA) expression in LINC00968-overexpressing human lung adenocarcinoma A549 cells was detected using miRNA microarray analysis. miR-9-3p was selected for further analysis, and its expression was verified in the Gene Expression Omnibus (GEO) database. In addition, the regulatory axis of LINC00968 was validated using The Cancer Genome Atlas (TCGA) database. Results of the GEO database indicated miR-9-3p expression in lung adenocarcinoma was significantly higher compared with normal tissues. Functional enrichment analyses of the target genes of miR-9-3p indicated protein binding and the AMP-activated protein kinase pathway were the most enriched Gene Ontology and KEGG terms, respectively. Combining target genes with the correlated genes of LINC00968 and miR-9-3p, 120 objective genes were obtained, which were used to construct a protein-protein interaction (PPI) network. Cyclin A2 (CCNA2) was identified to have a vital role in the PPI network. Significant correlations were detected between LINC00968, miR-9-3p and CCNA2 in lung adenocarcinoma. The LINC00968/miR-9-3p/CCNA2 regulatory axis provides a new foundation for further evaluating the regulatory mechanisms of LINC00968 in lung adenocarcinoma.

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

Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter.

PubMed

Lovinsky-Desir, Stephanie; Jung, Kyung Hwa; Jezioro, Jacqueline R; Torrone, David Z; de Planell-Saguer, Mariangels; Yan, Beizhan; Perera, Frederica P; Rundle, Andrew G; Perzanowski, Matthew S; Chillrud, Steven N; Miller, Rachel L

2017-01-01

Physical activity is associated with improvement in lung function; however, pollution exposure during physical activity can lead to a transient reduction in lung function. This paradoxical relationship may be linked to altered T regulatory (Treg) cell activity, which increases with exercise and suppresses airway inflammation, but decreases in association with exposure to air pollution. To clarify these relationships, we investigated buccal cell DNA methylation of the forkhead box p3 ( FOXP3 ) gene promoter, a proposed biomarker of Treg activity. We hypothesized that active urban children would have lower FOXP3 promoter methylation, associated with better lung function compared to non-active children. We also hypothesized that this relationship would be attenuated by high exposure to the air pollutant black carbon (BC). We performed a cross-sectional study of 135 children ages 9-14 who live in New York City. Activity was measured across 6 days. BC exposure was assessed by personal monitors worn for two 24-h periods, followed by lung function assessment. Buccal swabs were collected for DNA methylation analysis of three regions (six CpG sites) in the FOXP3 promoter. In multivariable regression models, overall, there was no significant relationship between physical activity and FOXP3 promoter methylation ( p  > 0.05). However, in stratified analyses, among children with higher BC exposure (≥1200 ng/m 3 ), physical activity was associated with 2.37% lower methylation in promoter 2 (CpGs -77, -65, and -58) ( β estimate  = -2.37%, p  < 0.01) but not among those with lower BC exposure ( β estimate  = 0.54%, p  > 0.05). Differences across strata were statistically significant ( p interaction  = 0.04). Among all children, after controlling for BC concentration, promoter 2 methylation was associated with reduced FEV 1 /FVC ( β estimate  = -0.40%, p  < 0.01) and reduced FEF 25-75% ( β estimate  = -1.46%, p  < 0.01). Physical activity in urban children appeared associated with lower FOXP3 promoter methylation, a possible indicator of greater Treg function, under conditions of high BC exposure. Reduced FOXP3 promoter methylation was associated with higher lung function. These findings suggest that physical activity may induce immunologic benefits, particularly for urban children with greater risk of impaired lung function due to exposure to higher air pollution. FOXP3 promoter buccal cell methylation may function as a useful biomarker of that benefit.

Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target

PubMed Central

Watanabe, Hideo; Francis, Joshua M.; Woo, Michele S.; Etemad, Banafsheh; Lin, Wenchu; Fries, Daniel F.; Peng, Shouyong; Snyder, Eric L.; Tata, Purushothama Rao; Izzo, Francesca; Schinzel, Anna C.; Cho, Jeonghee; Hammerman, Peter S.; Verhaak, Roel G.; Hahn, William C.; Rajagopal, Jayaraj; Jacks, Tyler; Meyerson, Matthew

2013-01-01

The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To study the transcriptional impact of NKX2-1 amplification, we generated an expression signature associated with NKX2-1 amplification in human lung adenocarcinoma and analyzed DNA-binding sites of NKX2-1 by genome-wide chromatin immunoprecipitation. Integration of these expression and cistromic analyses identified LMO3, itself encoding a transcription regulator, as a candidate direct transcriptional target of NKX2-1. Further cistromic and overexpression analyses indicated that NKX2-1 can cooperate with the forkhead box transcription factor FOXA1 to regulate LMO3 gene expression. RNAi analysis of NKX2-1-amplified cells compared with nonamplified cells demonstrated that LMO3 mediates cell survival downstream from NKX2-1. Our findings provide new insight into the transcriptional regulatory network of NKX2-1 and suggest that LMO3 is a transcriptional signal transducer in NKX2-1-amplified lung adenocarcinomas. PMID:23322301

Detection of early changes in lung-cell cytology by flow-systems analysis techniques. Progress report, January 1--June 30, 1976

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

Steinkamp, J. A.; Hansen, K. M.; Wilson, J. S.

1976-08-01

This report summarizes results of preliminary experiments to develop cytological and biochemical indicators for estimating damage to respiratory epithelium exposed to toxic agents associated with the by-products of nonnuclear energy production using advanced flow-systems cell-analysis technologies. Since initiation of the program one year ago, progress has been made in obtaining adequate numbers of exfoliated lung cells from the Syrian hamster for flow analysis; cytological techniques developed on human exfoliated gynecological samples have been adapted to hamster lung epithelium for obtaining single-cell suspensions; and lung-cell samples have been initially characterized based on DNA content, total protein, nuclear and cytoplasmic size, andmore » multiangle light-scatter measurements. Preliminary results from measurements of the above parameters which recently became available are described in this report. As the flow-systems technology is adapted further to analysis of exfoliated lung cells, measurements of changes in physical and biochemical cellular properties as a function of exposure to toxic agents will be performed.« less

Antioxidative, anti-inflammation and lung-protective effects of mycelia selenium polysaccharides from Oudemansiella radicata.

PubMed

Gao, Zheng; Li, Juan; Song, Xinling; Zhang, Jianjun; Wang, Xiuxiu; Jing, Huijuan; Ren, Zhenzhen; Li, Shangshang; Zhang, Chen; Jia, Le

2017-11-01

The present work was designed to investigated the antioxidant, anti-inflammation, and pulmonary protective effects of SMPS and MPS from Oudemansiella radicata on LPS-induced lung injured mice. The results demonstrated that SMPS showed potential effects on relieving lung injury and preventing oxidative stress, reflecting by decreasing the serum levels of C3, CRP and GGT, increasing the pulmonary activities of SOD, GSH-Px, CAT and T-AOC, as well as down-regulating the MDA and LPO contents, respectively. Furthermore, the levels of TNF-α (224.211±3.12ng/mL), IL-1β (254.557±2.18ng/L), and IL-6 (18.214±0.15ng/L) in BALF of mice treated with SMPS at the dosage of 400mg/kg/d significantly lower than that in the lung injured mice. These conclusions indicated that both SMPS and MPS possessed potent antioxidants and anti-inflammation activities, and could be used as functional foods and natural drugs in preventing lung injury. Copyright © 2017 Elsevier B.V. All rights reserved.

[Primitive lung abscess: an unusual situation in children].

PubMed

Bouyahia, O; Jlidi, S; Sammoud, A

2014-12-01

Lung abscess is a localized area of non tuberculosis suppurative necrosis of the parenchyma lung, resulting in formation of a cavity containing purulent material. This pathology is uncommon in childhood. A 3-year-6 month-old boy was admitted with prolonged fever and dyspnea. Chest X-ray showed a non systemized, well limited, thick walled, hydric, and excavated opacity containing an air-fluid level. Chest ultrasound examination showed a collection of 6. 8 cm of diameter in the right pulmonary field with an air-fluid level. Hemoculture showed Staphylococcus aureus. The patient received large spectrum antibiotherapy. Three days after, he presented a septic shock and surgical drainage was indicated. Histological examination confirmed the diagnosis of lung abscess. Any underlying condition such as inoculation site, local cause or immune deficiency, was noted and diagnosis of primary abscess was made. The patient demonstrated complete recovery. He is asymptomatic with normal chest X-ray and pulmonary function after 3 years of evolution. Lung abscess represent a rare cause of prolonged fever in childhood. An underlying condition must be excluded to eliminate secondary abscess. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Comparative studies on toxicity of various dielectrics, petroleum derivatives, used in electroerosion technology. IV. Morphological and cytoenzymatic changes in the lungs and acid-base imbalance in rats chronically exposed to petroleum hydrocarbons].

PubMed

Starek, A; Kamiński, M

1981-01-01

In rats exposed to odourless kerosene of 75 and 300 mg/m3 concentration, for 14 weeks, morphologic and cytoenzymatic examinations of lungs have been carried out and acid-base equilibrium indices in blood have been determined. Passive congestion of lung parenchyma, subpleural blood extravasation, atelectasis foci, thickened interalveolar septa with infiltrates from neutrophils, lymphocytes, eosinophils and macrophages have been found. In addition a decrease in succinic dehydrogenase activity, NADPH -- tetrazolium reductase, and Mg++-ATP-ase and increase in acid phosphatase activity have been revealed. Those have been focal changes, involving, apart from bronchial tree (low exposure -- 75 mg/m3), the remaining lung parenchyma segments (high exposure -- 300 mg/m3). In addition, disturbances in acid-base equilibrium in form of compensated metabolic alkalosis (75 mg/m3) and compensated metabolic acidosis (300 mg/m3) have occurred. The obtained results demonstrate toxic effects of kerosene hydrocarbons on the function and structure of lungs.

Time to First Cigarette, Physical Activity, and Pulmonary Function in Middle-aged to Older Adult Smokers.

PubMed

Nye, Russell T; Mercincavage, Melissa; Branstetter, Steven A

2017-08-01

How addiction severity relates to physical activity (PA), and if PA moderates the relation between PA and lung function among smokers, is unknown. This study explored the independent and interactive associations of nicotine addiction severity and PA with lung function. The study used cross-sectional data from 343 adult smokers aged 40 to 79 participating in the 2009-10 and 2011-12 National Health and Nutrition Examination Survey. Assessed were the independent relations of nicotine addiction severity, as measured by the time to first cigarette (TTFC), and average daily minutes of moderate and vigorous PA with lung function ratio (FEV1/FVC). Additional analysis examined whether PA moderated the relationship between addiction severity and lung function. Greater lung function was independently associated with moderate PA and later TTFC, but not vigorous PA, when controlling for cigarettes per day (CPD), past month smoking, ethnicity, years smoked, and gender (P-values < .05). PA did not moderate the association between addiction severity (TTFC) and lung function (P = .441). Among middle-aged to older smokers, increased PA and lower addiction severity were associated with greater lung function, independent of CPD. This may inform research into the protective role of PA and identification of risk factors for interventions.

Postoperative complications do not influence the pattern of early lung function recovery after lung resection for lung cancer in patients at risk

PubMed Central

2014-01-01

Background The pattern and factors influencing the lung function recovery in the first postoperative days are still not fully elucidated, especially in patients at increased risk. Methods Prospective study on 60 patients at increased risk, who underwent a lung resection for primary lung cancer. Inclusion criteria: complete resection and one or more known risk factors in form of COPD, cardiovascular disorders, advanced age or other comorbidities. Previous myocardial infarction, myocardial revascularization or stenting, cardiac rhythm disorders, arterial hypertension and myocardiopathy determined the increased cardiac risk. The severity of COPD was graded according to GOLD criteria. The trend of the postoperative lung function recovery was assessed by performing spirometry with a portable spirometer. Results Cardiac comorbidity existed in 55%, mild and moderate COPD in 20% and 35% of patients respectively. Measured values of FVC% and FEV1% on postoperative days one, three and seven, showed continuous improvement, with significant difference between the days of measurement, especially between days three and seven. There was no difference in the trend of the lung function recovery between patients with and without postoperative complications. Whilst pO2 was decreasing during the first three days in a roughly parallel fashion in patients with respiratory, surgical complications and in patients without complications, a slight hypercapnia registered on the first postoperative day was gradually abolished in all groups except in patients with cardiac complications. Conclusion Extent of the lung resection and postoperative complications do not significantly influence the trend of the lung function recovery after lung resection for lung cancer. PMID:24884793

Postoperative complications do not influence the pattern of early lung function recovery after lung resection for lung cancer in patients at risk.

PubMed

Ercegovac, Maja; Subotic, Dragan; Zugic, Vladimir; Jakovic, Radoslav; Moskovljevic, Dejan; Bascarevic, Slavisa; Mujovic, Natasa

2014-05-19

The pattern and factors influencing the lung function recovery in the first postoperative days are still not fully elucidated, especially in patients at increased risk. Prospective study on 60 patients at increased risk, who underwent a lung resection for primary lung cancer. complete resection and one or more known risk factors in form of COPD, cardiovascular disorders, advanced age or other comorbidities. Previous myocardial infarction, myocardial revascularization or stenting, cardiac rhythm disorders, arterial hypertension and myocardiopathy determined the increased cardiac risk. The severity of COPD was graded according to GOLD criteria. The trend of the postoperative lung function recovery was assessed by performing spirometry with a portable spirometer. Cardiac comorbidity existed in 55%, mild and moderate COPD in 20% and 35% of patients respectively. Measured values of FVC% and FEV1% on postoperative days one, three and seven, showed continuous improvement, with significant difference between the days of measurement, especially between days three and seven. There was no difference in the trend of the lung function recovery between patients with and without postoperative complications. Whilst pO2 was decreasing during the first three days in a roughly parallel fashion in patients with respiratory, surgical complications and in patients without complications, a slight hypercapnia registered on the first postoperative day was gradually abolished in all groups except in patients with cardiac complications. Extent of the lung resection and postoperative complications do not significantly influence the trend of the lung function recovery after lung resection for lung cancer.

Effects of cannabis on lung function: a population-based cohort study.

PubMed

Hancox, R J; Poulton, R; Ely, M; Welch, D; Taylor, D R; McLachlan, C R; Greene, J M; Moffitt, T E; Caspi, A; Sears, M R

2010-01-01

The effects of cannabis on lung function remain unclear and may be different from those of tobacco. We compared the associations between use of these substances and lung function in a population-based cohort (n = 1,037). Cannabis and tobacco use were reported at ages 18, 21, 26 and 32 yrs. Spirometry, plethysmography and carbon monoxide transfer factor were measured at 32 yrs. Associations between lung function and exposure to each substance were adjusted for exposure to the other substance. Cumulative cannabis use was associated with higher forced vital capacity, total lung capacity, functional residual capacity and residual volume. Cannabis was also associated with higher airway resistance but not with forced expiratory volume in 1 s, forced expiratory ratio or transfer factor. These findings were similar among those who did not smoke tobacco. In contrast, tobacco use was associated with lower forced expiratory volume in 1 s, lower forced expiratory ratio, lower transfer factor and higher static lung volumes, but not with airway resistance. Cannabis appears to have different effects on lung function from those of tobacco. Cannabis use was associated with higher lung volumes, suggesting hyperinflation and increased large-airways resistance, but there was little evidence for airflow obstruction or impairment of gas transfer.

Mechanobiology in Lung Epithelial Cells: Measurements, Perturbations, and Responses

PubMed Central

Waters, Christopher M.; Roan, Esra; Navajas, Daniel

2015-01-01

Epithelial cells of the lung are located at the interface between the environment and the organism and serve many important functions including barrier protection, fluid balance, clearance of particulate, initiation of immune responses, mucus and surfactant production, and repair following injury. Because of the complex structure of the lung and its cyclic deformation during the respiratory cycle, epithelial cells are exposed to continuously varying levels of mechanical stresses. While normal lung function is maintained under these conditions, changes in mechanical stresses can have profound effects on the function of epithelial cells and therefore the function of the organ. In this review, we will describe the types of stresses and strains in the lungs, how these are transmitted, and how these may vary in human disease or animal models. Many approaches have been developed to better understand how cells sense and respond to mechanical stresses, and we will discuss these approaches and how they have been used to study lung epithelial cells in culture. Understanding how cells sense and respond to changes in mechanical stresses will contribute to our understanding of the role of lung epithelial cells during normal function and development and how their function may change in diseases such as acute lung injury, asthma, emphysema, and fibrosis. PMID:23728969

Lung function not affected by asbestos exposure in workers with normal Computed Tomography scan.

PubMed

Schikowsky, Christian; Felten, Michael K; Eisenhawer, Christian; Das, Marco; Kraus, Thomas

2017-05-01

It has been suggested that asbestos exposure affects lung function, even in the absence of asbestos-related pulmonary interstitial or pleural changes or emphysema. We analyzed associations between well-known asbestos-related risk factors, such as individual cumulative asbestos exposure, and key lung function parameters in formerly asbestos-exposed power industry workers (N = 207) with normal CT scans. For this, we excluded participants with emphysema, fibrosis, pleural changes, or any combination of these. The lung function parameters of FVC, FEV1, DLCO/VA, and airway resistance were significantly associated with the burden of smoking, BMI and years since end of exposure (only DLCO/VA). However, they were not affected by factors directly related to amount (eg, cumulative exposure) or duration of asbestos exposure. Our results confirm the well-known correlation between lung function, smoking habits, and BMI. However, we found no significant association between lung function and asbestos exposure. © 2017 Wiley Periodicals, Inc.

Computational Modeling of Airway and Pulmonary Vascular Structure and Function: Development of a “Lung Physiome”

PubMed Central

Tawhai, M. H.; Clark, A. R.; Donovan, G. M.; Burrowes, K. S.

2011-01-01

Computational models of lung structure and function necessarily span multiple spatial and temporal scales, i.e., dynamic molecular interactions give rise to whole organ function, and the link between these scales cannot be fully understood if only molecular or organ-level function is considered. Here, we review progress in constructing multiscale finite element models of lung structure and function that are aimed at providing a computational framework for bridging the spatial scales from molecular to whole organ. These include structural models of the intact lung, embedded models of the pulmonary airways that couple to model lung tissue, and models of the pulmonary vasculature that account for distinct structural differences at the extra- and intra-acinar levels. Biophysically based functional models for tissue deformation, pulmonary blood flow, and airway bronchoconstriction are also described. The development of these advanced multiscale models has led to a better understanding of complex physiological mechanisms that govern regional lung perfusion and emergent heterogeneity during bronchoconstriction. PMID:22011236

Impact of gas emboli and hyperbaric treatment on respiratory function of loggerhead sea turtles (Caretta caretta).

PubMed

Portugues, Cyril; Crespo-Picazo, Jose Luis; García-Párraga, Daniel; Altimiras, Jordi; Lorenzo, Teresa; Borque-Espinosa, Alicia; Fahlman, Andreas

2018-01-01

Fisheries interactions are the most serious threats for sea turtle populations. Despite the existence of some rescue centres providing post-traumatic care and rehabilitation, adequate treatment is hampered by the lack of understanding of the problems incurred while turtles remain entrapped in fishing gears. Recently it was shown that bycaught loggerhead sea turtles ( Caretta caretta ) could experience formation of gas emboli (GE) and develop decompression sickness (DCS) after trawl and gillnet interaction. This condition could be reversed by hyperbaric O 2 treatment (HBOT). The goal of this study was to assess how GE alters respiratory function in bycaught turtles before recompression therapy and measure the improvement after this treatment. Specifically, we assessed the effect of DCS on breath duration, expiratory and inspiratory flow and tidal volume ( V T ), and the effectiveness of HBOT to improve these parameters. HBOT significantly increased respiratory flows by 32-45% while V T increased by 33-35% immediately after HBOT. Repeated lung function testing indicated a temporal increase in both respiratory flow and V T for all bycaught turtles, but the changes were smaller than those seen immediately following HBOT. The current study suggests that respiratory function is significantly compromised in bycaught turtles with GE and that HBOT effectively restores lung function. Lung function testing may provide a novel means to help diagnose the presence of GE, be used to assess treatment efficacy, and contribute to sea turtle conservation efforts.

Impact of gas emboli and hyperbaric treatment on respiratory function of loggerhead sea turtles (Caretta caretta)

PubMed Central

Portugues, Cyril; Crespo-Picazo, Jose Luis; García-Párraga, Daniel; Altimiras, Jordi; Lorenzo, Teresa; Borque-Espinosa, Alicia

2018-01-01

Abstract Fisheries interactions are the most serious threats for sea turtle populations. Despite the existence of some rescue centres providing post-traumatic care and rehabilitation, adequate treatment is hampered by the lack of understanding of the problems incurred while turtles remain entrapped in fishing gears. Recently it was shown that bycaught loggerhead sea turtles (Caretta caretta) could experience formation of gas emboli (GE) and develop decompression sickness (DCS) after trawl and gillnet interaction. This condition could be reversed by hyperbaric O2 treatment (HBOT). The goal of this study was to assess how GE alters respiratory function in bycaught turtles before recompression therapy and measure the improvement after this treatment. Specifically, we assessed the effect of DCS on breath duration, expiratory and inspiratory flow and tidal volume (VT), and the effectiveness of HBOT to improve these parameters. HBOT significantly increased respiratory flows by 32–45% while VT increased by 33–35% immediately after HBOT. Repeated lung function testing indicated a temporal increase in both respiratory flow and VT for all bycaught turtles, but the changes were smaller than those seen immediately following HBOT. The current study suggests that respiratory function is significantly compromised in bycaught turtles with GE and that HBOT effectively restores lung function. Lung function testing may provide a novel means to help diagnose the presence of GE, be used to assess treatment efficacy, and contribute to sea turtle conservation efforts. PMID:29340152

Infection, inflammation, and lung function decline in infants with cystic fibrosis.

PubMed

Pillarisetti, Naveen; Williamson, Elizabeth; Linnane, Barry; Skoric, Billy; Robertson, Colin F; Robinson, Phil; Massie, John; Hall, Graham L; Sly, Peter; Stick, Stephen; Ranganathan, Sarath

2011-07-01

Better understanding of evolution of lung function in infants with cystic fibrosis (CF) and its association with pulmonary inflammation and infection is crucial in informing both early intervention studies aimed at limiting lung damage and the role of lung function as outcomes in such studies. To describe longitudinal change in lung function in infants with CF and its association with pulmonary infection and inflammation. Infants diagnosed after newborn screening or clinical presentation were recruited prospectively. FVC, forced expiratory volume in 0.5 seconds (FEV(0.5)), and forced expiratory flows at 75% of exhaled vital capacity (FEF(75)) were measured using the raised-volume technique, and z-scores were calculated from published reference equations. Pulmonary infection and inflammation were measured in bronchoalveolar lavage within 48 hours of lung function testing. Thirty-seven infants had at least two successful repeat lung function measurements. Mean (SD) z-scores for FVC were -0.8 (1.0), -0.9 (1.1), and -1.7 (1.2) when measured at the first visit, 1-year visit, or 2-year visit, respectively. Mean (SD) z-scores for FEV(0.5) were -1.4 (1.2), -2.4 (1.1), and -4.3 (1.6), respectively. In those infants in whom free neutrophil elastase was detected, FVC z-scores were 0.81 lower (P=0.003), and FEV(0.5) z-scores 0.96 lower (P=0.001), respectively. Significantly greater decline in FEV(0.5) z-scores occurred in those infected with Staphylococcus aureus (P=0.018) or Pseudomonas aeruginosa (P=0.021). In infants with CF, pulmonary inflammation is associated with lower lung function, whereas pulmonary infection is associated with a greater rate of decline in lung function. Strategies targeting pulmonary inflammation and infection are required to prevent early decline in lung function in infants with CF.

Relationship between ultrasound bone parameters, lung function, and body mass index in healthy student population.

PubMed

Cvijetić, Selma; Pipinić, Ivana Sabolić; Varnai, Veda Maria; Macan, Jelena

2017-03-01

Low bone mineral density has been reported in paediatric and adult patients with different lung diseases, but limited data are available on the association between lung function and bone density in a healthy young population. We explored the predictors of association between bone mass and pulmonary function in healthy first-year university students, focusing on body mass index (BMI). In this cross-sectional study we measured bone density with ultrasound and lung function with spirometry in 370 university students (271 girls and 99 boys). Information on lifestyle habits, such as physical activity, smoking, and alcohol consumption were obtained with a questionnaire. All lung function and bone parameters were significantly higher in boys than in girls (P<0.001). Underweight students had a significantly lower forced vital capacity (FVC%) (P=0.001 girls; P=0.012 boys), while overweight students had a significantly higher FVC% than normal weight students (P=0.024 girls; P=0.001 boys). BMI significantly correlated with FVC% (P=0.001) and forced expiratory volume in 1 second (FEV1 %) in both genders (P=0.001 girls; P=0.018 boys) and with broadband ultrasound attenuation (BUA) in boys. There were no significant associations between any of the bone and lung function parameters either in boys or girls. The most important determinant of lung function and ultrasound bone parameters in our study population was body mass index, with no direct association between bone density and lung function.

Lower lung function associates with cessation of menstruation: UK Biobank data.

PubMed

Amaral, André F S; Strachan, David P; Gómez Real, Francisco; Burney, Peter G J; Jarvis, Deborah L

2016-11-01

Little is known about the effect of cessation of menstruation on lung function. The aims of the study were to examine the association of lung function with natural and surgical cessation of menstruation, and assess whether lower lung function is associated with earlier age at cessation of menstruation.The study was performed in 141 076 women from the UK Biobank, who had provided acceptable and reproducible spirometry measurements and information on menstrual status. The associations of lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), spirometric restriction (FVC < lower limit of normal (LLN)), airflow obstruction (FEV 1 /FVC

Comprehensive evaluation of lung allograft function in infants after lung and heart-lung transplantation.

PubMed

Hayes, Don; Naguib, Aymen; Kirkby, Stephen; Galantowicz, Mark; McConnell, Patrick I; Baker, Peter B; Kopp, Benjamin T; Lloyd, Eric A; Astor, Todd L

2014-05-01

Limited data exist on methods to evaluate allograft function in infant recipients of lung and heart-lung transplants. At our institution, we developed a procedural protocol in coordination with pediatric anesthesia where infants were sedated to perform infant pulmonary function testing, computed tomography imaging of the chest, and flexible fiberoptic bronchoscopy with transbronchial biopsies. A retrospective review was performed of children aged younger than 1 year who underwent lung or heart-lung transplantation at our institution to assess the effect of this procedural protocol in the evaluation of infant lung allografts. Since 2005, 5 infants have undergone thoracic transplantation (3 heart-lung, 2 lung). At time of transplant, the mean ± standard deviation age was 7.2 ± 2.8 months (range, 3-11 months). Of 24 procedural sessions performed to evaluate lung allografts, 83% (20 of 24) were considered surveillance where the patients were completely asymptomatic. Of the surveillance procedures, 80% were performed as an outpatient, whereas 20% were done as inpatients during the lung or heart-lung transplant post-operative period before discharge home. Sedation was performed with propofol alone (23 of 24) or in addition to ketamine (1 of 24) infusion; mean sedation time was 141 ± 39 minutes (range, 70-214) minutes. Of the 16 outpatient procedures, patients were discharged after 14 (88%) on the same day, and after 2 (12%) were admitted for observation, with 1 being due to transportation issues and the other due to fever during the observation period. A comprehensive procedural protocol to evaluate allograft function in infant lung and heart-lung transplant recipients was performed safely as an outpatient. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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.

Quantification of Age-Related Lung Tissue Mechanics under Mechanical Ventilation.

PubMed

Kim, JongWon; Heise, Rebecca L; Reynolds, Angela M; Pidaparti, Ramana M

2017-09-29

Elderly patients with obstructive lung diseases often receive mechanical ventilation to support their breathing and restore respiratory function. However, mechanical ventilation is known to increase the severity of ventilator-induced lung injury (VILI) in the elderly. Therefore, it is important to investigate the effects of aging to better understand the lung tissue mechanics to estimate the severity of ventilator-induced lung injuries. Two age-related geometric models involving human bronchioles from generation G10 to G23 and alveolar sacs were developed. The first is for a 50-year-old (normal) and second is for an 80-year old (aged) model. Lung tissue mechanics of normal and aged models were investigated under mechanical ventilation through computational simulations. Results obtained indicated that lung tissue strains during inhalation (t = 0.2 s) decreased by about 40% in the alveolar sac (G23) and 27% in the bronchiole (G20), respectively, for the 80-year-old as compared to the 50-year-old. The respiratory mechanics parameters (work of breathing per unit volume and maximum tissue strain) over G20 and G23 for the 80-year-old decreased by about 64% (three-fold) and 80% (four-fold), respectively, during the mechanical ventilation breathing cycle. However, there was a significant increase (by about threefold) in lung compliance for the 80-year-old in comparison to the 50-year-old. These findings from the computational simulations demonstrated that lung mechanical characteristics are significantly compromised in aging tissues, and these effects were quantified in this study.

Air Pollution and Epigenetics: Effects on SP-A and Innate Host Defense in the Lung

PubMed Central

Silveyra, Patricia; Floros, Joanna

2013-01-01

Summary An appropriate immune and inflammatory response is key to defend against harmful agents present in the environment such as pathogens, allergens, and inhaled pollutants, including ozone and particulate matter. Air pollution is a serious public health concern worldwide, and cumulative evidence revealed that air pollutants contribute to epigenetic variation in several genes, and this in turn can contribute to disease susceptibility. Several groups of experts have recently reviewed findings on epigenetics and air pollution [1–6]. Surfactant proteins play a central role in pulmonary host defense by mediating pathogen clearance, modulating allergic responses and facilitating the resolution of lung inflammation. Recent evidence indicates that surfactant proteins are subject to epigenetic regulation under hypoxia and other conditions. Oxidative stress caused by ozone, and exposure to particulate matter have been shown to affect the expression of surfactant protein A (SP-A), an important lung host defense molecule, as well as alter its functions. In this review, we discuss recent findings in the fields of epigenetics and air pollution effects on innate immunity, with focus on SP-A, and the human SP-A variants in particular. Their function may be differentially affected by pollutants and specifically by ozone-induced oxidative stress, and this in turn may differentially affect susceptibility to lung disease. PMID:22553125

Development of a Zealand White Rabbit Deposition Model to Study Inhalation Anthrax

PubMed Central

Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, A.P.; Corley, Richard A.

2016-01-01

Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits. PMID:26895308

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology.

PubMed

Bodas, Manish; Vij, Neeraj

2017-05-04

Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease. The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown. To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described. Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity. In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models. Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention. While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.

IN VIVO COMPARISON OF EPITHELIAL RESPONSES FOR S-8 VERSUS JP-8 JET FUELS BELOW PERMISSIBLE EXPOSURE LIMIT

PubMed Central

Wong, Simon S.; Vargas, Jason; Thomas, Alana; Fastje, Cindy; McLaughlin, Michael; Camponovo, Ryan; Lantz, R. Clark; Heys, Jeffrey; Witten, Mark L.

2010-01-01

This study was designed to characterize and compare the pulmonary effects in distal lung from a low-level exposure to jet propellant-8 fuel (JP-8) and a new synthetic-8 fuel (S-8). It is hypothesized that both fuels have different airway epithelial deposition and responses. Consequently, male C57BL/6 mice were nose-only exposed to S-8 and JP-8 at average concentrations of 53 mg/m3 for 1 hour/day for 7 days. A pulmonary function test performed 24 hr after the final exposure indicated that there was a significant increase in expiratory lung resistance in the S-8 mice, whereas JP-8 mice had significant increases in both inspiratory and expiratory lung resistance compared to control values. Neither significant S-8 nor JP-8 respiratory permeability changes were observed compared to controls, suggesting no loss of epithelial barrier integrity. Morphological examination and morphometric analysis of airway tissue demonstrated that both fuels showed different patterns of targeted epithelial cells: bronchioles in S-8 and alveoli/terminal bronchioles in JP-8. Collectively, our data suggest that both fuels may have partially different deposition patterns, which may possibly contribute to specific different adverse effects in lung ventilatory function. PMID:18930109

National Comparison of Hospital Performances in Lung Cancer Surgery: The Role Of Casemix Adjustment.

PubMed

Beck, Naomi; Hoeijmakers, Fieke; van der Willik, Esmee M; Heineman, David J; Braun, Jerry; Tollenaar, Rob A E M; Schreurs, Wilhelmina H; Wouters, Michel W J M

2018-04-03

When comparing hospitals on outcome indicators, proper adjustment for casemix (a combination of patient- and disease characteristics) is indispensable. This study examines the need for casemix adjustment in evaluating hospital outcomes for Non-Small Cell Lung Cancer (NSCLC) surgery. Data from the Dutch Lung Cancer Audit for Surgery was used to validate factors associated with postoperative 30-day mortality and complicated course with multivariable logistic regression models. Between-hospital variation in casemix was studied by calculating medians and interquartile ranges for separate factors on hospital level and the 'expected' outcomes per hospital as a composite measure. 8040 patients, distributed over 51 Dutch hospitals were included for analysis. Mean observed postoperative mortality and complicated course were 2.2% and 13.6% respectively. Age, ASA-classification, ECOG performance score, lung function, extent of resection, tumor stage and postoperative histopathology were individual significant predictors for both outcomes of postoperative mortality and complicated course. A considerable variation of these casemix factors between hospital-populations was observed, with the expected mortality and complicated course per hospital ranging from 1.4 to 3.2% and 11.5 to 17.1%. The between-hospital variation in casemix of patients undergoing surgery for NSCLC emphasizes the importance of proper adjustment when comparing hospitals on outcome indicators. Copyright © 2018. Published by Elsevier Inc.

Anti-fibrotic effects of chronic treatment with the selective FXR agonist obeticholic acid in the bleomycin-induced rat model of pulmonary fibrosis.

PubMed

Comeglio, Paolo; Filippi, Sandra; Sarchielli, Erica; Morelli, Annamaria; Cellai, Ilaria; Corcetto, Francesca; Corno, Chiara; Maneschi, Elena; Pini, Alessandro; Adorini, Luciano; Vannelli, Gabriella Barbara; Maggi, Mario; Vignozzi, Linda

2017-04-01

Farnesoid X receptor (FXR) activation by obeticholic acid (OCA) has been demonstrated to inhibit inflammation and fibrosis development in liver, kidney and intestine in multiple disease models. FXR activation has also been demonstrated to suppress the inflammatory response and to promote lung repair after lung injury. This study investigated the protective effects of OCA treatment (3 or 10mg/kg/day) on inflammation, tissue remodeling and fibrosis in the bleomycin-induced pulmonary fibrosis rat model. Effects of OCA treatment on morphological and molecular alterations of the lung, as well as remodeling of the alveoli and the right ventricle were also evaluated. Lung function was assessed by measuring airway resistance to inflation. In the acute phase (7days), bleomycin promoted an initial thickening and fibrosis of the lung interstitium, with upregulation of genes related to epithelial proliferation, tissue remodeling and hypoxia. At 28days, an evident increase in the deposition of collagen in the lungs was observed. This excessive deposition was accompanied by an upregulation of transcripts related to the extracellular matrix (TGFβ1, SNAI1 and SNAI2), indicating lung fibrosis. Administration of OCA protected against bleomycin-induced lung damage by suppressing molecular mechanisms related to epithelial-to-mesenchymal transition (EMT), inflammation and collagen deposition, with a dose-dependent reduction of proinflammatory cytokines such as IL-1β and IL-6, as well as TGF-β1 and SNAI1 expression. Pirfenidone, a recently approved treatment for idiopathic pulmonary fibrosis (IPF), significantly counteracted bleomycin-induced pro-fibrotic genes expression, but did not exert significant effects on IL-1β and IL-6. OCA treatment in bleomycin-challenged rats also improved pulmonary function, by effectively normalizing airway resistance to inflation and lung stiffness in vivo. Results with OCA were similar, or even superior, to those obtained with pirfenidone. In conclusion, our results suggest an important protective effect of OCA against bleomycin-induced lung fibrosis by blunting critical mediators in the pathogenesis of IPF. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Autophagy in lung disease pathogenesis and therapeutics

PubMed Central

Ryter, Stefan W.; Choi, Augustine M.K.

2015-01-01

Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy) may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics. PMID:25617802

Terpene exposure and respiratory effects among workers in Swedish joinery shops.

PubMed

Eriksson, K A; Levin, J O; Sandström, T; Lindström-Espeling, K; Lindén, G; Stjernberg, N L

1997-04-01

Exposure to monoterpenes (alpha-pinene, beta-pinene and delta 3-carene) in joinery shops was studied in Sweden during the processing of Scot's pine, and the acute respiratory effects among the employees were evaluated. A cross-sectional study of 38 workers was carried out in 4 joinery shops. The investigation included personal air sampling of monoterpenes, biological monitoring of metabolites of alpha-pinene in the workers' urine, interviews following a standardized questionnaire, and dynamic spirometry. The personal exposure to monoterpenes in the joinery shops was 10-214 mg/m3. The correlation (correlation coefficient = 0.69) between exposure to alpha-pinene and verbenols (metabolites from alpha-pinene) in urine was relatively good. No acute effects on forced vital capacity or forced expiratory volume during 1 s were detected. The workers had significantly reduced preshift lung function values when compared with the values of a local reference group, even when smokers and ex-smokers were excluded. Personal exposure to the monoterpenes alpha-pinene, and delta 3-carene in joinery shops may exceed the present Swedish occupational exposure limit of 150 mg/m3 during the winter season when workroom air is commonly recirculated. The determination of metabolites of alpha-pinene (verbenols) in urine can be used as an index of exposure to fumes released during wood-treating processes. The results from the lung function tests indicate chronic rather than acute reactions in the airways. The fact that there were no major changes in lung function over a workshift indicates chronic reaction in the airways.

Apigenin inhibits cell proliferation, migration, and invasion by targeting Akt in the A549 human lung cancer cell line.

PubMed

Zhou, Zhongping; Tang, Miaomiao; Liu, Yi; Zhang, Zhuyi; Lu, Rongzhu; Lu, Jian

2017-04-01

Apigenin (APG), a widely distributed flavonoid in vegetables and fruits, with low toxicity, and a nonmutagenic characteristic, has been reported to have many targets. Evidence indicates that APG can inhibit the proliferation, migration, invasion, and metastasis of some tumor cells, but the mechanism, specifically in lung cancer, is unclear. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway regulates a diverse set of cellular functions relevant to the growth and progression of lung cancer, including proliferation, survival, migration, and invasion. Our results showed that APG exerted anti-proliferation, anti-migration, and anti-invasion effects in A549 human lung cancer cells by targeting the PI3K/Akt signaling pathway. 3-(4, 5-dimethylthiszol-2-yl)-2, 5-diphenytetrazolium bromide assay and colony formation assay showed that APG suppressed cell proliferation in a dose-dependent and time-dependent manner. Cell motility and invasiveness were assayed using a wound healing and Transwell assay, suggesting that APG inhibited the migration and invasion of A549 cells. Western blot analyses were carried out to examine the Akt signaling pathways. The results confirmed that APG decreased Akt expression and its activation. Then, cells were transfected with Akt-active and Akt-DN plasmids separately. The migration and invasion of A549 cells were significantly changed, constitutively activating Akt or knocking down Akt, indicating that APG can suppress the migration and invasion of lung cancer cells by modulating the PI3K/Akt signaling pathway. Furthermore, the results indicated that APG not only suppressed phosphorylation of Akt, thereby preventing its activation, but also inhibited its downstream gene expression of matrix metalloproteinases-9, glycogen synthase kinase-3β, and HEF1. Together, APG is a new inhibitor of Akt in lung cancer and a potential natural compound for cancer chemoprevention.

Microbial colonization and lung function in adolescents with cystic fibrosis.

PubMed

Hector, Andreas; Kirn, Tobias; Ralhan, Anjali; Graepler-Mainka, Ute; Berenbrinker, Sina; Riethmueller, Joachim; Hogardt, Michael; Wagner, Marlies; Pfleger, Andreas; Autenrieth, Ingo; Kappler, Matthias; Griese, Matthias; Eber, Ernst; Martus, Peter; Hartl, Dominik

2016-05-01

With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern of bacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preserved lung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa. Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. Collectively, this study identified potentially protective and harmful microbial colonization patterns in adolescent CF patients. Further studies in different patient cohorts are required to evaluate these microbial patterns and to assess their clinical relevance. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

PubMed

McGeachie, M J; Yates, K P; Zhou, X; Guo, F; Sternberg, A L; Van Natta, M L; Wise, R A; Szefler, S J; Sharma, S; Kho, A T; Cho, M H; Croteau-Chonka, D C; Castaldi, P J; Jain, G; Sanyal, A; Zhan, Y; Lajoie, B R; Dekker, J; Stamatoyannopoulos, J; Covar, R A; Zeiger, R S; Adkinson, N F; Williams, P V; Kelly, H W; Grasemann, H; Vonk, J M; Koppelman, G H; Postma, D S; Raby, B A; Houston, I; Lu, Q; Fuhlbrigge, A L; Tantisira, K G; Silverman, E K; Tonascia, J; Weiss, S T; Strunk, R C

2016-05-12

Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Aspergillus fumigatus colonization in cystic fibrosis: implications for lung function?

PubMed

de Vrankrijker, A M M; van der Ent, C K; van Berkhout, F T; Stellato, R K; Willems, R J L; Bonten, M J M; Wolfs, T F W

2011-09-01

Aspergillus fumigatus is commonly found in the respiratory secretions of patients with cystic fibrosis (CF). Although allergic bronchopulmonary aspergillosis (ABPA) is associated with deterioration of lung function, the effects of A. fumigatus colonization on lung function in the absence of ABPA are not clear. This study was performed in 259 adults and children with CF, without ABPA. A. fumigatus colonization was defined as positivity of >50% of respiratory cultures in a given year. A cross-sectional analysis was performed to study clinical characteristics associated with A. fumigatus colonization. A retrospective cohort analysis was performed to study the effect of A. fumigatus colonization on lung function observed between 2002 and 2007. Longitudinal data were analysed with a linear mixed model. Sixty-one of 259 patients were at least intermittently colonized with A. fumigatus. An association was found between A. fumigatus colonization and increased age and use of inhaled antibiotics. In the longitudinal analysis, 163 patients were grouped according to duration of colonization. After adjustment for confounders, there was no significant difference in lung function between patients colonized for 0 or 1 year and patients with 2-3 or more than 3 years of colonization (p 0.40 and p 0.64) throughout the study. There was no significant difference in lung function decline between groups. Although colonization with A. fumigatus is more commonly found in patients with more severe lung disease and increased treatment burden, it is not independently associated with lower lung function or more severe lung function decline over a 5-year period. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

Lung function in North American Indian children: reference standards for spirometry, maximal expiratory flow volume curves, and peak expiratory flow.

PubMed

Wall, M A; Olson, D; Bonn, B A; Creelman, T; Buist, A S

1982-02-01

Reference standards of lung function was determined in 176 healthy North American Indian children (94 girls, 82 boys) 7 to 18 yr of age. Spirometry, maximal expiratory flow volume curves, and peak expiratory flow rate were measured using techniques and equipment recommended by the American Thoracic Society. Standing height was found to be an accurate predictor of lung function, and prediction equations for each lung function variable are presented using standing height as the independent variable. Lung volumes and expiratory flow rates in North American Indian children were similar to those previously reported for white and Mexican-American children but were greater than those in black children. In both boys and girls, lung function increased in a curvilinear fashion. Volume-adjusted maximal expiratory flow rates after expiring 50 or 75% of FVC tended to decrease in both sexes as age and height increased. Our maximal expiratory flow volume curve data suggest that as North American Indian children grow, lung volume increases at a slightly faster rate than airway size does.

Physiologic Basis for Improved Pulmonary Function after Lung Volume Reduction

PubMed Central

Fessler, Henry E.; Scharf, Steven M.; Ingenito, Edward P.; McKenna, Robert J.; Sharafkhaneh, Amir

2008-01-01

It is not readily apparent how pulmonary function could be improved by resecting portions of the lung in patients with emphysema. In emphysema, elevation in residual volume relative to total lung capacity reduces forced expiratory volumes, increases inspiratory effort, and impairs inspiratory muscle mechanics. Lung volume reduction surgery (LVRS) better matches the size of the lungs to the size of the thorax containing them. This restores forced expiratory volumes and the mechanical advantage of the inspiratory muscles. In patients with heterogeneous emphysema, LVRS may also allow space occupied by cysts to be reclaimed by more normal lung. Newer, bronchoscopic methods for lung volume reduction seek to achieve similar ends by causing localized atelectasis, but may be hindered by the low collateral resistance of emphysematous lung. Understanding of the mechanisms of improved function after LVRS can help select patients more likely to benefit from this approach. PMID:18453348

Effects of Body Mass Index on Lung Function Index of Chinese Population

NASA Astrophysics Data System (ADS)

Guo, Qiao; Ye, Jun; Yang, Jian; Zhu, Changan; Sheng, Lei; Zhang, Yongliang

2018-01-01

To study the effect of body mass index (BMI) on lung function indexes in Chinese population. A cross-sectional study was performed on 10, 592 participants. The linear relationship between lung function and BMI was evaluated by multivariate linear regression analysis, and the correlation between BMI and lung function was assessed by Pearson correlation analysis. Correlation analysis showed that BMI was positively related with the decreasing of forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and FEV1/FVC (P <0.05), the increasing of FVC% predicted value (FVC%pre) and FEV1% predicted value (FEV1%pre). These suggested that Chinese people can restrain the decline of lung function to prevent the occurrence and development of COPD by the control of BMI.

Lung function in type 2 diabetes: the Normative Aging Study.

PubMed

Litonjua, Augusto A; Lazarus, Ross; Sparrow, David; Demolles, Debbie; Weiss, Scott T

2005-12-01

Cross-sectional studies have noted that subjects with diabetes have lower lung function than non-diabetic subjects. We conducted this analysis to determine whether diabetic subjects have different rates of lung function change compared with non-diabetic subjects. We conducted a nested case-control analysis in 352 men who developed diabetes and 352 non-diabetic subjects in a longitudinal observational study of aging in men. We assessed lung function among cases and controls at three time points: Time0, prior to meeting the definition of diabetes; Time1, the point when the definition of diabetes was met; and Time2, the most recent follow-up exam. Cases had lower forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) at all time points, even with adjustment for age, height, weight, and smoking. In multiple linear regression models adjusting for relevant covariates, there were no differences in rates of FEV1 or FVC change over time between cases and controls. Men who are predisposed to develop diabetes have decreased lung function many years prior to the diagnosis, compared with men who do not develop diabetes. This decrement in lung function remains after the development of diabetes. We postulate that mechanisms involved in the insulin resistant state contribute to the diminished lung function observed in our subjects.

Ultrasonographic assessment of the diaphragm in chronic obstructive pulmonary disease patients: relationships with pulmonary function and the influence of body composition - a pilot study.

PubMed

Smargiassi, Andrea; Inchingolo, Riccardo; Tagliaboschi, Linda; Di Marco Berardino, Alessandro; Valente, Salvatore; Corbo, Giuseppe Maria

2014-01-01

Skeletal muscle weakness with loss of fat-free mass (FFM) is one of the main systemic effects of chronic obstructive pulmonary disease (COPD). The diaphragm is also involved, leading to disadvantageous conditions and poor contractile capacities. We measured the thickness of the diaphragm (TD) by ultrasonography to evaluate the relationships between echographic measurements, parameters of respiratory function and body composition data. Thirty-two patients (23 males) underwent (1) pulmonary function tests, (2) echographic assessment of TD in the zone of apposition at various lung volumes, i.e. TD at residual volume (TDRV), TD at functional residual capacity (TDFRC) and TD at total lung capacity (TDTLC), and (3) bioelectrical body impedance analysis. The BMI and the BODE (BMI-Obstruction-Dyspnea-Exercise) index values were reported. TDRV, TDFRC and TDTLC measured 3.3, 3.6 and 6 mm, respectively, with good intraobserver reproducibility (0.97, 0.97 and 0.96, respectively). All the TDs were found to be related to FFM, with the relationship being greater for TDFRC (r(2) = 0.39 and p = 0.0002). With regard to lung volumes, inspiratory capacity (IC) was found to be closely related to TDTLC (r(2) = 0.42 and p = 0.0001). The difference between TDTLC and TDRV, as a thickening value (TDTLCRV), was closely related to FVC (r(2) = 0.34 and p = 0.0004) and to air-trapping indices (RV/TLC, FRC/TLC and IC/TLC): the degree of lung hyperinflation was greater and the TDTLCRV was less. Finally, we found a progressive reduction of both thicknesses and thickenings as the severity of IC/TLC increased, with a significant p value for the trend in both analyses (p = 0.02). Ultrasonographic assessment of the diaphragm could be a useful tool for studying disease progression in COPD patients, in terms of lung hyperinflation and the loss of FFM. © 2014 S. Karger AG, Basel.

MRI and CT lung biomarkers: Towards an in vivo understanding of lung biomechanics.

PubMed

Young, Heather M; Eddy, Rachel L; Parraga, Grace

2017-09-29

The biomechanical properties of the lung are necessarily dependent on its structure and function, both of which are complex and change over time and space. This makes in vivo evaluation of lung biomechanics and a deep understanding of lung biomarkers, very challenging. In patients and animal models of lung disease, in vivo evaluations of lung structure and function are typically made at the mouth and include spirometry, multiple-breath gas washout tests and the forced oscillation technique. These techniques, and the biomarkers they provide, incorporate the properties of the whole organ system including the parenchyma, large and small airways, mouth, diaphragm and intercostal muscles. Unfortunately, these well-established measurements mask regional differences, limiting their ability to probe the lung's gross and micro-biomechanical properties which vary widely throughout the organ and its subcompartments. Pulmonary imaging has the advantage in providing regional, non-invasive measurements of healthy and diseased lung, in vivo. Here we summarize well-established and emerging lung imaging tools and biomarkers and how they may be used to generate lung biomechanical measurements. We review well-established and emerging lung anatomical, microstructural and functional imaging biomarkers generated using synchrotron x-ray tomographic-microscopy (SRXTM), micro-x-ray computed-tomography (micro-CT), clinical CT as well as magnetic resonance imaging (MRI). Pulmonary imaging provides measurements of lung structure, function and biomechanics with high spatial and temporal resolution. Imaging biomarkers that reflect the biomechanical properties of the lung are now being validated to provide a deeper understanding of the lung that cannot be achieved using measurements made at the mouth. Copyright © 2017 Elsevier Ltd. All rights reserved.

Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants

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

Dairou, Julien; Petit, Emile; Ragunathan, Nilusha

2009-05-01

Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and {beta}-naphthylamine ({beta}-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating thatmore » inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H{sub 2}O{sub 2} or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.« less

Detection of early changes in lung cell cytology by flow-systems analysis techniques. Progress report, July 1--December 31, 1977

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

Steinkamp, J.A.; Hansen, K.M.; Wilson, J.S.

1978-04-01

This report summarizes ongoing experiments to develop cytological and biochemical indicators for measuring damage to respiratory tract cells exposed by inhalation of environmental toxic agents. The specific goal of this project is to apply flow cytometric methods to analyze and detect changes in lung epithelium as a function of exposure to toxic agents such as those associated with the production of synthetic fuels from oil shale and coal. The objectives during the past 6 months were to complete modifications to the multiparameter cell separator by adding a krypton laser with an output capability of specific wavelengths ranging from the uvmore » to the ir; analyze and separate lung cells based on their DNA content; evaluate some new fluorescent DNA and protein stains; and treat hamster lung cells with proteolytic enzymes for increasing cell yield. Future experiments will involve the continued analysis and characterization of exfoliated lung cells based primarily on cellular DNA content, protein, morphological features, and specific enzyme activities; quantitation of macrophage activity; exposure of hamsters to toxic agents such as oil shale particulates and ozone; and continued analysis of cells based on DNA content. As this new technology becomes adapted to analyzing respiratory tract cells, the measurement of physical and biochemical cell properties as a function of exposure to toxic agents will be increased. This analytical approach is designed to assist in the establishment of guidelines for estimating risks to exposed humans.« less

Gene Profiles in a Smoke-Induced COPD Mouse Lung Model Following Treatment with Mesenchymal Stem Cells.

PubMed

Kim, You-Sun; Kokturk, Nurdan; Kim, Ji-Young; Lee, Sei Won; Lim, Jaeyun; Choi, Soo Jin; Oh, Wonil; Oh, Yeon-Mok

2016-10-01

Mesenchymal stem cells (MSCs) effectively reduce airway inflammation and regenerate the alveolus in cigarette- and elastase-induced chronic obstructive pulmonary disease (COPD) animal models. The effects of stem cells are thought to be paracrine and immune-modulatory because very few stem cells remain in the lung one day after their systemic injection, which has been demonstrated previously. In this report, we analyzed the gene expression profiles to compare mouse lungs with chronic exposure to cigarette smoke with non-exposed lungs. Gene expression profiling was also conducted in a mouse lung tissue with chronic exposure to cigarette smoke following the systemic injection of human cord blood-derived mesenchymal stem cells (hCB-MSCs). Globally, 834 genes were differentially expressed after systemic injection of hCB-MSCs. Seven and 21 genes, respectively, were up-and downregulated on days 1, 4, and 14 after HCB-MSC injection. The Hbb and Hba, genes with oxygen transport and antioxidant functions, were increased on days 1 and 14. A serine protease inhibitor was also increased at a similar time point after injection of hCB-MSCs. Gene Ontology analysis indicated that the levels of genes related to immune responses, metabolic processes, and blood vessel development were altered, indicating host responses after hCB-MSC injection. These gene expression changes suggest that MSCs induce a regeneration mechanism against COPD induced by cigarette smoke. These analyses provide basic data for understanding the regeneration mechanisms promoted by hCB-MSCs in cigarette smoke-induced COPD.

Chronic effects on JP-8 jet fuel exposure on the lungs. Final technical report, 1 April 1991-31 March 1994

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

Witten, M.L.

1994-06-02

There are four major findings from the three years of work devoted to the effects of chronic JP-8 jet fuel exposure on the lungs and secondary organs. These findings are the following chronic exposure to JP-8 jet fuel alters pulmonary function and lung structures with an acute response with as little as seven days of low dose, approximately 500 mg/m3, exposure to JP-8 jet fuel; chronic exposure to JP-8 jet fuel increased liver, spleen, and kidney weights compared to controls. Microscopic evaluation of liver sections were normal; however, kidney and spleen had histological changes consistent with organic solvent exposure. Theremore » is a correlation between JP-8 jet fuel exposure-induced decreases in lung Substance P levels and lung neutral endopeptidase levels. Chronic exposure to JP-8 jet fuel caused a decrease in lung Substance P levels with a corresponding increase in lung neutral endopeptidase levels; and, there is a recovery process in the 56 day low dose JP-8 jet fuel-exposed lungs as marked by a return to baseline and longitudinal control 99mTcDTPA values. The 99mTcDTPA data was very consistent with our pathologic findings of very little lung injury in the 56 day low dose JP-8 jet fuel-exposed rats. We speculate that this finding indicates that there is a 'threshold' level of JP-8 jet fuel exposure that the lungs' defense mechanism(s) can tolerate.« less

Changes in Regional Ventilation During Treatment and Dosimetric Advantages of CT Ventilation Image Guided Radiation Therapy for Locally Advanced Lung Cancer.

PubMed

Yamamoto, Tokihiro; Kabus, Sven; Bal, Matthieu; Bzdusek, Karl; Keall, Paul J; Wright, Cari; Benedict, Stanley H; Daly, Megan E

2018-05-04

Lung functional image guided radiation therapy (RT) that avoids irradiating highly functional regions has potential to reduce pulmonary toxicity following RT. Tumor regression during RT is common, leading to recovery of lung function. We hypothesized that computed tomography (CT) ventilation image-guided treatment planning reduces the functional lung dose compared to standard anatomic image-guided planning in 2 different scenarios with or without plan adaptation. CT scans were acquired before RT and during RT at 2 time points (16-20 Gy and 30-34 Gy) for 14 patients with locally advanced lung cancer. Ventilation images were calculated by deformable image registration of four-dimensional CT image data sets and image analysis. We created 4 treatment plans at each time point for each patient: functional adapted, anatomic adapted, functional unadapted, and anatomic unadapted plans. Adaptation was performed at 2 time points. Deformable image registration was used for accumulating dose and calculating a composite of dose-weighted ventilation used to quantify the lung accumulated dose-function metrics. The functional plans were compared with the anatomic plans for each scenario separately to investigate the hypothesis at a significance level of 0.05. Tumor volume was significantly reduced by 20% after 16 to 20 Gy (P = .02) and by 32% after 30 to 34 Gy (P < .01) on average. In both scenarios, the lung accumulated dose-function metrics were significantly lower in the functional plans than in the anatomic plans without compromising target volume coverage and adherence to constraints to critical structures. For example, functional planning significantly reduced the functional mean lung dose by 5.0% (P < .01) compared to anatomic planning in the adapted scenario and by 3.6% (P = .03) in the unadapted scenario. This study demonstrated significant reductions in the accumulated dose to the functional lung with CT ventilation image-guided planning compared to anatomic image-guided planning for patients showing tumor regression and changes in regional ventilation during RT. Copyright © 2018 Elsevier Inc. All rights reserved.

Obstructive lung disease as a complication in post pulmonary TB

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

Estimation of gas and tissue lung volumes by MRI: functional approach of lung imaging.

PubMed

Qanadli, S D; Orvoen-Frija, E; Lacombe, P; Di Paola, R; Bittoun, J; Frija, G

1999-01-01

The purpose of this work was to assess the accuracy of MRI for the determination of lung gas and tissue volumes. Fifteen healthy subjects underwent MRI of the thorax and pulmonary function tests [vital capacity (VC) and total lung capacity (TLC)] in the supine position. MR examinations were performed at inspiration and expiration. Lung volumes were measured by a previously validated technique on phantoms. Both individual and total lung volumes and capacities were calculated. MRI total vital capacity (VC(MRI)) was compared with spirometric vital capacity (VC(SP)). Capacities were correlated to lung volumes. Tissue volume (V(T)) was estimated as the difference between the total lung volume at full inspiration and the TLC. No significant difference was seen between VC(MRI) and VC(SP). Individual capacities were well correlated (r = 0.9) to static volume at full inspiration. The V(T) was estimated to be 836+/-393 ml. This preliminary study demonstrates that MRI can accurately estimate lung gas and tissue volumes. The proposed approach appears well suited for functional imaging of the lung.

Combined effect of urinary monohydroxylated polycyclic aromatic hydrocarbons and impaired lung function on diabetes.

PubMed

Hou, Jian; Sun, Huizhen; Xiao, Lili; Zhou, Yun; Yin, Wenjun; Xu, Tian; Cheng, Juan; Chen, Weihong; Yuan, Jing

2016-07-01

Associations of type 2 diabetes with exposure to polycyclic aromatic hydrocarbons and reduced lung function have been reported. The aim of the present study was to investigate effect of reduced lung function and exposure to background PAHs on diabetes. A total of 2730 individuals were drawn from the Wuhan-Zhuhai (WHZH) Cohort Study (n=3053). Participants completed physical examination, measurement of lung function and urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs). Risk factors for type 2 diabetes were identified by multiple logistic regression analysis, and the presence of additive interaction between levels of urinary OH-PAHs and lower lung function was evaluated by calculation of the relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP). Urinary OH-PAHs levels was positively associated with type 2 diabetes among individuals with impaired lung function (p<0.05). Forced expiratory volume in one second (FEV1, odd ratio (OR): 0.664, 95% confidence interval (CI): 0.491-0.900) and forced vital capacity (FVC, OR: 0.693, 95% CI: 0.537-0.893) were negatively associated with diabetes among individuals. Additive interaction of higher urinary levels of OH-PAHs and lower FVC (RERI: 0.679, 95% CI: 0.120-1.238); AP: 0.427, 95% CI: 0.072-0.782) was associated with diabetes. Exposure to background PAHs was related to diabetes among individuals with lower lung function. Urinary levels of OH-PAHs and reduced lung function had an additive effect on diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Can Stem Cells be Used to Generate New Lungs? Ex Vivo Lung Bioengineering with Decellularized Whole Lung Scaffolds

PubMed Central

Wagner, Darcy E.; Bonvillain, Ryan W.; Jensen, Todd J.; Girard, Eric D.; Bunnell, Bruce A.; Finck, Christine M.; Hoffman, Andrew M.; Weiss, Daniel J.

2013-01-01

For patients with end-stage lung diseases, lung transplantation is the only available therapeutic option. However, the number of suitable donor lungs is insufficient and lung transplants are complicated by significant graft failure and complications of immunosuppressive regimens. An alternative to classic organ replacement is desperately needed. Engineering of bioartificial organs using either natural or synthetic scaffolds is an exciting new potential option for generation of functional pulmonary tissue for human clinical application. Natural organ scaffolds can be generated by decellularization of native tissues; these acellular scaffolds retain the native organ ultrastructure and can be seeded with autologous cells toward the goal of regenerating functional tissues. Several decellularization strategies have been employed for lung, however, there is no consensus on the optimal approach. A variety of cell types have been investigated as potential candidates for effective recellularization of acellular lung scaffolds. Candidate cells that might be best utilized are those which can be easily and reproducibly isolated, expanded in vitro, seeded onto decellularized matrices, induced to differentiate into pulmonary lineage cells, and which survive to functional maturity. Whole lung cell suspensions, endogenous progenitor cells, embryonic and adult stem cells, and induced pluripotent stem (iPS) cells have been investigated for their applicability to repopulate acellular lung matrices. Ideally, patient-derived autologous cells would be used for lung recellularization as they have the potential to reduce the need for post-transplant immunosuppression. Several studies have performed transplantation of rudimentary bioengineered lung scaffolds in animal models with limited, short-term functionality but much further study is needed. PMID:23614471

Dielectric properties of lung tissue as a function of air content.

PubMed

Nopp, P; Rapp, E; Pfützner, H; Nakesch, H; Ruhsam, C

1993-06-01

Dielectric measurements were made on lung samples with different electrode systems in the frequency range 5 kHz-100 kHz. In the case of plate electrodes and spot electrodes, the effects of electrode polarization were partly corrected. An air filling factor F is defined, which is determined from the mass and volume of the sample. The results indicate that the electrical properties of lung tissue are highly dependent on the condition of the tissue. Furthermore they show that the conductivity sigma as well as the relative permittivity epsilon r decreases with increasing F. This is discussed using histological material. Using a simple theoretical model, the decrease of sigma and epsilon r is explained by the thinning of the alveolar walls as well as by the deformation of the epithelial cells and blood vessels through the expansion of the alveoli.

Effects of cognate, non-cognate and synthetic CXCR4 and ACKR3 ligands on human lung endothelial cell barrier function.

PubMed

Cheng, You-Hong; Eby, Jonathan M; LaPorte, Heather M; Volkman, Brian F; Majetschak, Matthias

2017-01-01

Recent evidence suggests that chemokine CXCL12, the cognate agonist of chemokine receptors CXCR4 and ACKR3, reduces thrombin-mediated impairment of endothelial barrier function. A detailed characterization of the effects of CXCL12 on thrombin-mediated human lung endothelial hyperpermeability is lacking and structure-function correlations are not available. Furthermore, effects of other CXCR4/ACKR3 ligands on lung endothelial barrier function are unknown. Thus, we tested the effects of a panel of CXCR4/ACKR3 ligands (CXCL12, CXCL11, ubiquitin, AMD3100, TC14012) and compared the CXCR4/ACKR3 activities of CXCL12 variants (CXCL12α/β, CXCL12(3-68), CXCL121, CXCL122, CXCL12-S-S4V, CXCL12-R47E, CXCL12-K27A/R41A/R47A) with their effects on human lung endothelial barrier function in permeability assays. CXCL12α enhanced human primary pulmonary artery endothelial cell (hPPAEC) barrier function, whereas CXCL11, ubiquitin, AMD3100 and TC14012 were ineffective. Pre-treatment of hPPAEC with CXCL12α and ubiquitin reduced thrombin-mediated hyperpermeability. CXCL12α-treatment of hPPAEC after thrombin exposure reduced barrier function impairment by 70% (EC50 0.05-0.5nM), which could be antagonized with AMD3100; ubiquitin (0.03-3μM) was ineffective. In a human lung microvascular endothelial cell line (HULEC5a), CXCL12α and ubiquitin post-treatment attenuated thrombin-induced hyperpermeability to a similar degree. CXCL12(3-68) was inefficient to activate CXCR4 in Presto-Tango β-arrestin2 recruitment assays; CXCL12-S-S4V, CXCL12-R47E and CXCL12-K27A/R41A/R47A showed significantly reduced potencies to activate CXCR4. While the potencies of all proteins in ACKR3 Presto-Tango assays were comparable, the efficacy of CXCL12(3-68) to activate ACKR3 was significantly reduced. The potencies to attenuate thrombin-mediated hPPAEC barrier function impairment were: CXCL12α/β, CXCL121, CXCL12-K27A/R41A/R47A > CXCL12-S-S4V, CXCL12-R47E > CXCL122 > CXCL12(3-68). Our findings indicate that CXCR4 activation attenuates thrombin-induced lung endothelial barrier function impairment and suggest that protective effects of CXCL12 are dictated by its CXCR4 agonist activity and interactions of distinct protein moieties with heparan sulfate on the endothelial surface. These data may facilitate development of compounds with improved pharmacological properties to attenuate thrombin-induced vascular leakage in the pulmonary circulation.

WE-AB-202-01: Evaluating the Toxicity Reduction with CT-Ventilation Functional Avoidance Radiation Therapy

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

Vinogradskiy, Y; Miyasaka, Y; Kadoya, N

Purpose: CT-ventilation is an exciting new imaging modality that uses 4DCTs to calculate lung ventilation. Studies have proposed to use 4DCT-ventilation imaging for functional avoidance radiotherapy which implies designing treatment plans to spare functional portions of the lung. Although retrospective studies have been performed to evaluate the dosimetric gains to functional lung; no work has been done to translate the dosimetric gains to an improvement in pulmonary toxicity. The purpose of our work was to evaluate the potential reduction in toxicity for 4DCT-ventilation based functional avoidance. Methods: 70 lung cancer patients with 4DCT imaging were used for the study. CT-ventilationmore » maps were calculated using the patient’s 4DCT, deformable image registrations, and a density-change-based algorithm. Radiation pneumonitis was graded using imaging and clinical information. Log-likelihood methods were used to fit a normal-tissue-complication-probability (NTCP) model predicting grade 2+ radiation pneumonitis as a function of doses (mean and V20) to functional lung (>15% ventilation). For 20 patients a functional plan was generated that reduced dose to functional lung while meeting RTOG 0617-based constraints. The NTCP model was applied to the functional plan to determine the reduction in toxicity with functional planning Results: The mean dose to functional lung was 16.8 and 17.7 Gy with the functional and clinical plans respectively. The corresponding grade 2+ pneumonitis probability was 26.9% with the clinically-used plan and 24.6% with the functional plan (8.5% reduction). The V20-based grade 2+ pneumonitis probability was 23.7% with the clinically-used plan and reduced to 19.6% with the functional plan (20.9% reduction). Conclusion: Our results revealed a reduction of 9–20% in complication probability with functional planning. To our knowledge this is the first study to apply complication probability to convert dosimetric results to toxicity improvement. The results presented in the current work provide seminal data for prospective clinical trials in functional avoidance. YV discloses funding from State of Colorado. TY discloses National Lung Cancer Partnership; Young Investigator Research grant.« less

Respiratory pathogens mediate the association between lung function and temperature in cystic fibrosis.

PubMed

Collaco, Joseph M; Raraigh, Karen S; Appel, Lawrence J; Cutting, Garry R

2016-11-01

Mean annual ambient temperature is a replicated environmental modifier of cystic fibrosis (CF) lung disease with warmer temperatures being associated with lower lung function. The mechanism of this relationship is not completely understood. However, Pseudomonas aeruginosa, a pathogen that infects the lungs of CF individuals and decreases lung function, also has a higher prevalence in individuals living in warmer climates. We therefore investigated the extent to which respiratory pathogens mediated the association between temperature and lung function. Thirteen respiratory pathogens observed on CF respiratory cultures were assessed in multistep fashion using clustered linear and logistic regression to determine if any mediated the association between temperature and lung function. Analysis was performed in the CF Twin-Sibling Study (n=1730; primary population); key findings were then evaluated in the U.S. CF Foundation Data Registry (n=15,174; replication population). In the primary population, three respiratory pathogens (P. aeruginosa, mucoid P. aeruginosa, and methicillin-resistant Staphylococcus aureus) mediated the association between temperature and lung function. P. aeruginosa accounted for 19% of the association (p=0.003), mucoid P. aeruginosa for 31% (p=0.001), and MRSA for 13% (p=0.023). The same three pathogens mediated association in the replication population (7%, p<0.001; 7%, p=0.002; and 4%, (p=0.002), respectively). Three important respiratory pathogens in CF mediate the association between lower lung function and warmer temperatures. These findings have implications for understanding regional variations in clinical outcomes, and interpreting results of epidemiologic studies and clinical trials that encompass regions with different ambient temperatures. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage migration inhibitory factor (MIF) family members in non-small cell lung carcinomas.

PubMed

Brock, Stephanie E; Rendon, Beatriz E; Yaddanapudi, Kavitha; Mitchell, Robert A

2012-11-02

AMP-activated protein kinase (AMPK) is a nutrient- and metabolic stress-sensing enzyme activated by the tumor suppressor kinase, LKB1. Because macrophage migration inhibitory factor (MIF) and its functional homolog, d-dopachrome tautomerase (d-DT), have protumorigenic functions in non-small cell lung carcinomas (NSCLCs) but have AMPK-activating properties in nonmalignant cell types, we set out to investigate this apparent paradox. Our data now suggest that, in contrast to MIF and d-DTs AMPK-activating properties in nontransformed cells, MIF and d-DT act cooperatively to inhibit steady-state phosphorylation and activation of AMPK in LKB1 wild type and LKB1 mutant human NSCLC cell lines. Our data further indicate that MIF and d-DT, acting through their shared cell surface receptor, CD74, antagonize NSCLC AMPK activation by maintaining glucose uptake, ATP production, and redox balance, resulting in reduced Ca(2+)/calmodulin-dependent kinase kinase β-dependent AMPK activation. Combined, these studies indicate that MIF and d-DT cooperate to inhibit AMPK activation in an LKB1-independent manner.

Lung function gain in preterm infants with and without bronchopulmonary dysplasia.

PubMed

Sanchez-Solis, Manuel; Perez-Fernandez, Virginia; Bosch-Gimenez, Vicente; Quesada, Juan J; Garcia-Marcos, Luis

2016-09-01

The aim of our study was to determine whether the development of lung function, during the first 2 years of life, is different in preterm infants who suffered or did not suffer from Bronchopulmonary dysplasia (BPD). We also assessed the role of nutritional status and growth in that development. Lung function tests were performed in 71 preterm infants at two time points: 6 months of corrected age and 1 year after. FVC, FEV0.5, FEF75 , and FEF25-75 were obtained from maximal expiratory volume curves by means of the raised volume rapid thoraco-abdominal compression technique. When comparing lung function measurements, we found that FVC (P = 0.033) FEV0.5 (P = 0.044), FEF75 (P = 0.014), and FEF25-75 (P = 0.036) were significantly lower in BPD infants. We did not find any catch-up of lung function during the study time, in neither the whole group of children nor within the BPD or non-BPD groups. The increase in lung function was directly proportional to the increase in weight and length. The multivariate analysis showed that the increase in z-score of FVC (P = 0.043), FEV0.5 (P = 0.015), and FEF75 (P = 0.042), was related with the height velocity during the study period. Infants who suffered from BPD have lower lung function (FVC, FEV0.5 , FEF75 , and FEF25-75 ), than those non-BPD, at two different time points 1 year apart. During the study period, there was no lung function catch-up in either BPD or non-BPD infants. The increase in length is closely associated to the increase in lung function. Pediatr Pulmonol. 2016; 51:936-942. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Gene-by-environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma.

PubMed

Bunyavanich, S; Boyce, J A; Raby, B A; Weiss, S T

2012-02-01

Distinct receptors likely exist for leukotriene (LT)E(4), a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE(4)-induced airways inflammation, and P2Y12 antagonism attenuates house dust mite-induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied. To test for association between variants in the P2Y12 gene (P2RY12) and lung function in human subjects with asthma, and to examine for gene-by-environment interaction with house dust mite exposure. Nineteen single nucleotide polymorphisms (SNPs) in P2RY12 were genotyped in 422 children with asthma and their parents (n = 1266). Using family based methods, we tested for associations between these SNPs and five lung function measures. We performed haplotype association analyses and tested for gene-by-environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons. Five SNPs in P2RY12 were associated with multiple lung function measures (P-values 0.006–0.025). Haplotypes in P2RY12 were also associated with lung function (P-values 0.0055–0.046). House dust mite exposure modulated associations between P2RY12 and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction P-values 0.0028–0.040). The P2RY12 variants were associated with lung function in a large family-based asthma cohort. House dust mite exposure caused significant gene-by-environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment.

The lung in paracoccidioidomycosis: new insights into old problems

PubMed Central

Costa, Andre Nathan; Benard, Gil; Albuquerque, Andre Luis Pereira; Fujita, Carmem Lucia; Magri, Adriana Satie Kono; Salge, João Marcos; Shikanai-Yasuda, Maria Aparecida; Carvalho, Carlos Roberto Ribeiro

2013-01-01

OBJECTIVES: Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, patients may present with residual respiratory abnormalities due to fungus-induced lung fibrosis. METHODS: A cross-sectional analysis of 50 consecutive inactive, chronic paracoccidioidomycosis patients was performed using high resolution computed tomography, pulmonary function tests, ergospirometry, the six-minute walk test and health-related quality of life questionnaires. RESULTS: Radiological abnormalities were present in 98% of cases, the most frequent of which were architectural distortion (90%), reticulate and septal thickening (88%), centrilobular and paraseptal emphysema (84%) and parenchymal bands (74%). Patients typically presented with a mild obstructive disorder and a mild reduction in diffusion capacity with preserved exercise capacity, including VO2max and six-minute walking distance. Patient evaluation with the Saint-George Respiratory Questionnaire showed low impairment in the health-related quality of life, and the Medical Research Council questionnaire indicated a low dyspnea index. There were, however, patients with significant oxygen desaturation upon exercise that was associated with respiratory distress compared with the non-desaturated patients. The initial counterimmunoelectrophoresis of these patients was higher and lung emphysema was more prominent; however, there were no differences in the interstitial fibrotic tomographic abnormalities, tobacco exposure, functional responses, exercise capacity or quality of life. CONCLUSIONS: Inactive, chronic paracoccidioidomycosis patients show persistent and disseminated radiological abnormalities by high resolution computed tomography, short impairments in pulmonary function and low impacts on aerobic capacity and quality of life. However, there was a subset of individuals whose functional impairment was more severe. These patients present with higher initial serology and more severe emphysema, stressing the importance of adequate treatment associated with tobacco exposure cessation. PMID:23778339

Short and long term response to pulmonary exacerbation treatment in cystic fibrosis

PubMed Central

Heltshe, Sonya L.; Goss, Christopher H.; Thompson, Valeria; Sagel, Scott D.; Sanders, Don B.; Marshall, Bruce C.; Flume, Patrick A.

2016-01-01

Background Treatment of pulmonary exacerbations (PEx) in cystic fibrosis (CF) varies widely with no consensus on management practices or best indicators of therapeutic success. To design trials evaluating PEx treatment factors, we characterize the heterogeneity of PEx care in adults and pediatrics, and correlate it with measures of clinical response including short and long term lung function changes, change in symptom severity score, and time to next intravenous (IV) antibiotic therapy. Methods Data were used from a prospective observational study of CF patients ≥10 years of age enrolled at six sites between 2007 and 2010. All were started on IV antibiotics for a clinically diagnosed PEx. ANOVA, logistic and Cox regression were used to examine the association of treatment factors with short and long term clinical response. Results Of 123 CF patients (60% female, aged 23.1±10.2 years), 33% experienced <10% relative improvement in FEV1 during treatment which was associated with failing to recover baseline lung function three months after treatment (OR=7.8, 95% CI=(1.9, 31.6), p=0.004) and a longer time to next IV antibiotic (HR=0.48, 95% CI=(0.27, 0.85), p=0.011). Symptom improvement was observed but was not associated with subsequent lung function or time to next antibiotic therapy which had a median recurrence time of 143 days. Conclusions Immediate symptomatic or respiratory response to PEx treatment did not have a clear relationship with subsequent outcomes such as lung function or IV antibiotic-free interval. These results can inform future research of treatment regimens for PEx in terms of interventions and outcome measures. PMID:25911223

Right ventricular function during one-lung ventilation: effects of pressure-controlled and volume-controlled ventilation.

PubMed

Al Shehri, Abdullah M; El-Tahan, Mohamed R; Al Metwally, Roshdi; Qutub, Hatem; El Ghoneimy, Yasser F; Regal, Mohamed A; Zien, Haytham

2014-08-01

To test the effects of pressure-controlled (PCV) and volume-controlled (VCV) ventilation during one-lung ventilation (OLV) for thoracic surgery on right ventricular (RV) function. A prospective, randomized, double-blind, controlled, crossover study. A single university hospital. Fourteen pairs of consecutive patients scheduled for elective thoracotomy. Patients were assigned randomly to ventilate the dependent lung with PCV or VCV mode, each in a randomized crossover order using tidal volume of 6 mL/kg, I: E ratio 1: 2.5, positive end-expiratory pressure (PEEP) of 5 cm H2O and respiratory rate adjusted to maintain normocapnia. Intraoperative changes in RV function (systolic and early diastolic tricuspid annular velocity (TAV), end-systolic volume (ESV), end-diastolic volume (EDV) and fractional area changes (FAC)), airway pressures, compliance and oxygenation index were recorded. The use of PCV during OLV resulted in faster systolic (10.1±2.39 vs. 5.8±1.67 cm/s, respectively), diastolic TAV (9.2±1.99 vs. 4.6±1.42 cm/s, respectively) (p<0.001) and compliance and lower ESV, EDV and airway pressures (p<0.05) than during the use of VCV. Oxygenation indices were similar during the use of VCV and PCV. The use of PCV offers more improved RV function than the use of VCV during OLV for open thoracotomy. These results apply specifically to younger patients with good ventricular and pulmonary functions. © 2014 Elsevier Inc. All rights reserved.

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.

Magnetic resonance elastography of the lung parenchyma in an in situ porcine model with a noninvasive mechanical driver: correlation of shear stiffness with trans-respiratory system pressures.

PubMed

Mariappan, Yogesh K; Kolipaka, Arunark; Manduca, Armando; Hubmayr, Rolf D; Ehman, Richard L; Araoz, Philip; McGee, Kiaran P

2012-01-01

Quantification of the mechanical properties of lung parenchyma is an active field of research due to the association of this metric with normal function, disease initiation and progression. A phase contrast MRI-based elasticity imaging technique known as magnetic resonance elastography is being investigated as a method for measuring the shear stiffness of lung parenchyma. Previous experiments performed with small animals using invasive drivers in direct contact with the lungs have indicated that the quantification of lung shear modulus with (1) H based magnetic resonance elastography is feasible. This technique has been extended to an in situ porcine model with a noninvasive mechanical driver placed on the chest wall. This approach was tested to measure the change in parenchymal stiffness as a function of airway opening pressure (P(ao) ) in 10 adult pigs. In all animals, shear stiffness was successfully quantified at four different P(ao) values. Mean (±STD error of mean) pulmonary parenchyma density corrected stiffness values were calculated to be 1.48 (±0.09), 1.68 (±0.10), 2.05 (±0.13), and 2.23 (±0.17) kPa for P(ao) values of 5, 10, 15, and 20 cm H2O, respectively. Shear stiffness increased with increasing P(ao) , in agreement with the literature. It is concluded that in an in situ porcine lung shear stiffness can be quantitated with (1) H magnetic resonance elastography using a noninvasive mechanical driver and that it is feasible to measure the change in shear stiffness due to change in P(ao) . Copyright © 2011 Wiley-Liss, Inc.

Murine lung eosinophil activation and chemokine production in allergic airway inflammation

PubMed Central

Rose, C Edward; Lannigan, Joanne A; Kim, Paul; Lee, James J; Fu, Shu Man; Sung, Sun-sang J

2010-01-01

Eosinophils play important roles in asthma and lung infections. Murine models are widely used for assessing the functional significance and mechanistic basis for eosinophil involvements in these diseases. However, little is known about tissue eosinophils in homeostasis. In addition, little data on eosinophil chemokine production during allergic airway inflammation are available. In this study, the properties and functions of homeostatic and activated eosinophils were compared. Eosinophils from normal tissues expressed costimulation and adhesion molecules B7-1, B7-2 and ICAM-1 for Ag presentation but little major histocompatibility complex (MHC) class II, and were found to be poor stimulators of T-cell proliferation. However, these eosinophils expressed high levels of chemokine mRNA including C10, macrophage inflammatory protein (MIP)-1α, MIP-1γ, MIP-2, eotaxin and monocyte chemoattractant protein-5 (MCP-5), and produced chemokine proteins. Eosinophil intracellular chemokines decreased rapidly with concomitant surface marker downregulation upon in vitro culturing consistent with piecemeal degranulation. Lung eosinophils from mice with induced allergic airway inflammation exhibited increased chemokines mRNA expression and chemokines protein production and upregulated MHC class II and CD11c expression. They were also found to be the predominant producers of the CCR1 ligands CCL6/C10 and CCL9/MIP-1γ in inflamed lungs. Eosinophil production of C10 and MIP-1γ correlated with the marked influx of CD11bhigh lung dendritic cells during allergic airway inflammation and the high expression of CCR1 on these dendritic cells (DCs). The study provided baseline information on tissue eosinophils, documented the upregulation of activation markers and chemokine production in activated eosinophils, and indicated that eosinophils were a key chemokine-producing cell type in allergic lung inflammation. PMID:20622891

[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.

[Impact of the legislation for smoke-free workplaces on respiratory health in hospitality workers--review of epidemiological studies].

PubMed

Polańska, Kinga; Hanke, Wojciech; Konieczko, Katarzyna

2011-01-01

Environmental tobacco smoke exposure (ETS) is a significant risk factor for the development of many diseases, including lung cancer, lower respiratory tract infections, asthma and eye, throat and nasal irritations. Hospitality workers form an occupational group with high exposure to ETS in their workplace. Taking into account the health consequences of ETS exposure and high prevalence of exposure in public places, including workplaces, many countries have implemented the smoking ban that prohibits or restricts smoking in workplaces, including restaurants and bars. The epidemiological studies have indicated a significant reduction in the exposure level after implementation of the smoking ban. Most studies have also indicated a significant reduction in respiratory and sensory symptoms. The impact of the smoking ban on the lung function measurements is still not clear.

Effect of acute ozone exposure on the lung metabolomes of obese and lean mice.

PubMed

Mathews, Joel Andrew; Kasahara, David Itiro; Cho, Youngji; Bell, Lauren Nicole; Gunst, Philip Ross; Karoly, Edward D; Shore, Stephanie Ann

2017-01-01

Pulmonary responses to the air pollutant, ozone, are increased in obesity. Both obesity and ozone cause changes in systemic metabolism. Consequently, we examined the impact of ozone on the lung metabolomes of obese and lean mice. Lean wildtype and obese db/db mice were exposed to acute ozone (2 ppm for 3 h) or air. 24 hours later, the lungs were excised, flushed with PBS to remove blood and analyzed via liquid-chromatography or gas-chromatography coupled to mass spectrometry for metabolites. Both obesity and ozone caused changes in the lung metabolome. Of 321 compounds identified, 101 were significantly impacted by obesity in air-exposed mice. These included biochemicals related to carbohydrate and lipid metabolism, which were each increased in lungs of obese versus lean mice. These metabolite changes may be of functional importance given the signaling capacity of these moieties. Ozone differentially affected the lung metabolome in obese versus lean mice. For example, almost all phosphocholine-containing lysolipids were significantly reduced in lean mice, but this effect was attenuated in obese mice. Glutathione metabolism was also differentially affected by ozone in obese and lean mice. Finally, the lung metabolome indicated a role for the microbiome in the effects of both obesity and ozone: all measured bacterial/mammalian co-metabolites were significantly affected by obesity and/or ozone. Thus, metabolic derangements in obesity appear to impact the response to ozone.

Supine posture changes lung volumes and increases ventilation heterogeneity in cystic fibrosis.

PubMed

Smith, Laurie J; Macleod, Kenneth A; Collier, Guilhem J; Horn, Felix C; Sheridan, Helen; Aldag, Ina; Taylor, Chris J; Cunningham, Steve; Wild, Jim M; Horsley, Alex

2017-01-01

Lung Clearance Index (LCI) is recognised as an early marker of cystic fibrosis (CF) lung disease. The effect of posture on LCI however is important when considering longitudinal measurements from infancy and when comparing LCI to imaging studies. 35 children with CF and 28 healthy controls (HC) were assessed. Multiple breath washout (MBW) was performed both sitting and supine in triplicate and analysed for LCI, Scond, Sacin, and lung volumes. These values were also corrected for the Fowler dead-space to create 'alveolar' indices. From sitting to supine there was a significant increase in LCI and a significant decrease in FRC for both CF and HC (p<0.01). LCI, when adjusted to estimate 'alveolar' LCI (LCIalv), increased the magnitude of change with posture for both LCIalv and FRCalv in both groups, with a greater effect of change in lung volume in HC compared with children with CF. The % change in LCIalv for all subjects correlated significantly with lung volume % changes, most notably tidal volume/functional residual capacity (Vtalv/FRCalv (r = 0.54,p<0.001)). There is a significant increase in LCI from sitting to supine, which we believe to be in part due to changes in lung volume and also increasing ventilation heterogeneity related to posture. This may have implications in longitudinal measurements from infancy to older childhood and for studies comparing supine imaging methods to LCI.

A biomechanical approach for in vivo diaphragm muscle motion prediction during normal respiration

NASA Astrophysics Data System (ADS)

Coelho, Brett; Karami, Elham; Haddad, Seyyed M. H.; Seify, Behzad; Samani, Abbas

2017-03-01

Lung cancer is one of the leading causes of cancer death in men and women. External Beam Radiation Therapy (EBRT) is a commonly used primary treatment for the condition. A major challenge with such treatments is the delivery of sufficient radiation dose to the lung tumor while ensuring that surrounding healthy lung parenchyma receives only minimal dose. This can be achieved by coupling EBRT with respiratory computer models which can predict the tumour location as a function of phase during the breathing cycle1. The diaphragm muscle contraction is mainly responsible for a large portion of the lung tumor motion during normal breathing, especially when tumours are in the lower lobes, therefore the importance of accurately modelling the diaphragm is paramount in lung tumour motion prediction. The goal of this research is to develop a biomechanical model of the diaphragm, including its active and passive response, using detailed geometric, biomechanical and anatomical information that mimics the diaphragmatic behaviour in a patient specific manner. For this purpose, a Finite Element Model (FEM) of the diaphragm was developed in order to predict the in vivo motion of the diaphragm, paving the way for computer assisted lung cancer tumor tracking in EBRT. Preliminary results obtained from the proposed model are promising and they indicate that it can be used as a plausible tool for effective lung cancer EBRT to improve patient care.

Lung functions among patients with pulmonary tuberculosis in Dar es Salaam - a cross-sectional study.

PubMed

Manji, Mohamed; Shayo, Grace; Mamuya, Simon; Mpembeni, Rose; Jusabani, Ahmed; Mugusi, Ferdinand

2016-04-23

Approximately 40-60 % of patients remain sufferers of sequela of obstructive, restrictive or mixed patterns of lung disease despite treatment for pulmonary tuberculosis (PTB). The prevalence of these abnormalities in Tanzania remains unknown. A descriptive cross-sectional study was carried out among 501 patients with PTB who had completed at least 20 weeks of treatment. These underwent spirometry and their lung functions were classified as normal or abnormal (obstructive, restrictive or mixed). Logistic regression models were used to explore factors associated with abnormal lung functions. Abnormal lung functions were present in 371 (74 %) patients. There were 210 (42 %) patients with obstructive, 65 (13 %) patients with restrictive and 96 (19 %) patients with mixed patterns respectively. Significant factors associated with abnormal lung functions included recurrent PTB (Adj OR 2.8, CI 1.274 - 6.106), Human Immunodeficiency Virus (HIV) negative status (Adj OR 1.7, CI 1.055 - 2.583), age more than 40 years (Adj OR 1.7, CI 1.080 - 2.804) and male sex (Adj OR 1.7, CI 1.123 - 2.614). The prevalence of abnormal lung functions is high and it is associated with male sex, age older than 40 years, recurrent PTB and HIV negative status.

Lung vital capacity and oxygen saturation in adults with cerebral palsy

PubMed Central

Lampe, Renée; Blumenstein, Tobias; Turova, Varvara; Alves-Pinto, Ana

2014-01-01

Background Individuals with infantile cerebral palsy have multiple disabilities. The most conspicuous syndrome being investigated from many aspects is motor movement disorder with a spastic gait pattern. The lung function of adults with spasticity attracts less attention in the literature. This is surprising because decreased thoracic mobility and longstanding scoliosis should have an impact on lung function. With increasing age and the level of disability, individuals become susceptible to lung infections and reflux illness, and these are accompanied by increased aspiration risk. This study examined, with different methods, to what extent adults with congenital cerebral palsy and acquired spastic paresis – following traumatic brain injury – showed restriction of lung function. It also assessed the contribution of disability level on this restriction. Methods The oxygen saturation of 46 adults with a diagnosis of cerebral palsy was measured with an oximeter. Lung vital capacity was measured with a mobile spirometer and excursion of the thorax was clinically registered. The gross motor function levels and the presence or absence of scoliosis were determined. Results A significantly positive correlation between lung vital capacity and chest expansion was established. Both the lung vital capacity and the thorax excursion decreased with increases in gross motor function level. Oxygen saturation remained within the normal range in all persons, in spite of reduced values of the measured lung parameters. No statistically significant dependency between lung vital capacity and oxygen saturation, and between chest expansion and oxygen saturation was found. The scoliotic deformities of the spine were associated with an additional decrease in the vital capacity, but this did not affect blood oxygen supply. Conclusion Despite the decreased chest expansion and the significantly reduced lung volume in adults with cerebral palsy, sufficient oxygen supply was registered. PMID:25525345

Abnormal lung function at preschool age asthma in adolescence?

PubMed

Lajunen, Katariina; Kalliola, Satu; Kotaniemi-Syrjänen, Anne; Sarna, Seppo; Malmberg, L Pekka; Pelkonen, Anna S; Mäkelä, Mika J

2018-05-01

Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate. This longitudinal study relates lung function assessed with impulse oscillometry (IOS) in preschool children to asthma in adolescence. Lung function was measured with IOS in 255 children with asthma-like symptoms aged 4-7 years. Baseline measurements were followed by exercise challenge and bronchodilation tests. At age 12-16 years, 121 children participated in the follow-up visit, when lung function was assessed with spirometry, followed by a bronchodilation test. Asthma symptoms and medication were recorded by a questionnaire and atopy defined by skin prick tests. Abnormal baseline values in preschool IOS were significantly associated with low lung function, the need for asthma medication, and asthma symptoms in adolescence. Preschool abnormal R5 at baseline (z-score ≥1.645 SD) showed 9.2 odds ratio (95%CI 2.7;31.7) for abnormal FEV1/FVC, use of asthma medication in adolescence, and 9.9 odds ratio (95%CI 2.9;34.4) for asthma symptoms. Positive exercise challenge and modified asthma-predictive index at preschool age predicted asthma symptoms and the need for asthma medication, but not abnormal lung function at teenage. Abnormal preschool IOS is associated with asthma and poor lung function in adolescence and might be utilised for identification of asthma persistence. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Tramadol regulates proliferation, migration and invasion via PTEN/PI3K/AKT signaling in lung adenocarcinoma cells.

PubMed

Xia, M; Tong, J-H; Ji, N-N; Duan, M-L; Tan, Y-H; Xu, J-G

2016-06-01

Tramadol is used mainly for the treatment of moderate to severe chronic cancer pain. However, the effect of tramadol on lung cancer remains unclear. Therefore, it is important to explore the mechanism accounting for the function of tramadol on lung cancer. We investigated the effects of tramadol on the proliferation, migration and invasion in human lung adenocarcinoma cells in vitro by CCK-8 assay, wound healing assay and Transwell assay, respectively. We also explored the potential mechanism of tramadol on lung cancer cells by Western blotting. A549 and PC-9 cells were incubated with 2 µM tramadol for different time (0, 7, 14 and 28 d). The in vitro experiments showed that tramadol treatment significantly inhibited cell proliferation, migration and invasion in a time-dependent manner. Moreover, administration of tramadol suppressed tumor growth in vivo. The data also revealed that tramadol could up-regulate the protein expression level of PTEN and consistently inhibit the phosphorylation level of PI3K and Akt, whereas the total level of PI3K and Akt remain unchanged. These findings indicated that tramadol inhibited proliferation, migration and invasion of human lung adenocarcinoma cells through elevation of PTEN and inactivation of PI3K/Akt signaling.

Development of A Novel Murine Model of Combined Radiation and Peripheral Tissue Trauma Injuries

PubMed Central

Antonic, Vlado; Jackson, Isabel L.; Ganga, Gurung; Shea-Donohue, Terez; Vujaskovic, Zeljko

2017-01-01

Detonation of a 10-kiloton nuclear bomb in an urban setting would result in >1 million casualties, the majority of which would present with combined injuries. Combined injuries, such as peripheral tissue trauma and radiation exposure, trigger inflammatory events that lead to multiple organ dysfunction (MOD) and death, with gastrointestinal (GI) and pulmonary involvement playing crucial roles. The objective of this study was to develop an animal model of combined injuries, peripheral tissue trauma (TBX animal model) combined with total body irradiation with 5% bone marrow shielding (TBI/BM5) to investigate if peripheral tissue trauma contributes to reduced survival. Male C57BL/6J mice were exposed to TBX10%, irradiation (TBI/BM5), or combined injuries (TBX10% + TBI/BM5). Experiments were conducted to evaluate mortality at day 7 after TBI/BM5. Serial euthanasia was performed at day 1, 3 and 6 or 7 after TBI/BM5 to evaluate the time course of pathophysiologic processes in combined injuries. Functional tests were performed to assess pulmonary function and GI motility. Postmortem samples of lungs and jejunum were collected to assess tissue damage. Results indicated higher lethality and shorter survival in the TBX10% +T BI/BM5 group than in the TBX10% or TBI/BM5 groups (day 1 vs. day 7 and 6, respectively). TBI/BM5 alone had no effects on the lungs but significantly impaired GI function at day 6. As expected, in the animals that received severe trauma (TBX10%), we observed impairment in lung function and delay in GI transit in the first 3 days, effects that decreased at later time points. Trauma combined with radiation (TBX10% + TBI/BM5) significantly augmented impairment of the lung and GI function in comparison to TBX10% and TBI/BM5 groups at 24 h. Histologic evaluation indicated that combined injuries caused greater tissue damage in the intestines in TBX10% + TBI/BM5 group when compared to other groups. We describe here the first combined tissue trauma/radiation injury model that will allow conduction of mechanistic studies to identify new therapeutic targets and serve as a platform for testing novel therapeutic interventions. PMID:28118112

Ozone personal exposures and health effects for selected groups residing in the Fraser Valley

NASA Astrophysics Data System (ADS)

Brauer, Michael; Brook, Jeffrey R.

Due to concern regarding poor ambient air quality in the Fraser Valley, a series of exposure and health effects assessments were performed to evaluate the impact of summer photochemical air pollution. In 1992 and 1993, three groups of individuals were selected for personal monitoring of ozone exposure, based on prior expectations of their activity patterns. The first group spent a majority of the work day indoors or commuting, the second group spent more time outdoors and the third group spent the entire personal monitoring period outdoors. Time-activity data were collected for the first two groups and differences in personal ozone exposures were found to be associated with the fraction of time a person spent outdoors. Similarly, differences among groups in the mean ozone exposure were associated with time spent outdoors. These results and other exposure information were used to design a study of the health impacts of summer ambient air pollution that was conducted during the time period of the Pacific'93 field campaign. Aerosol acidity levels in the Fraser Valley were observed to be very low in 1992 so the health study focused on the effects of ozone exposure. The subjects were adult farm workers (26 male, 32 female; mean age 44.4, range 10-69) who spent the entire working day outdoors (a subset of group 3 above). Lung function measurements were made twice daily on each subject, once before and once after their work shift, from 23 June-26 August 1993. Ambient O 3 concentrations were measured continuously at several nearby locations. In a regression model including individual lung function level, date, temperature and daily maximum O 3, a statistically significant ( p < 0.001) negative association was observed between ozone and lung function. This association between ozone and reduced lung function was still apparent the following day, suggesting a persistent ozone effect. These results indicate that exposure to ambient O 3 concentrations below either the U.S. NAAQS (120 ppb) or the Canadian Air Quality Objective (82 ppb) may have an adverse effect on the lung function of people engaged in outdoor work for several hours a day.

The association between substantiated childhood maltreatment, asthma and lung function: A prospective investigation.

PubMed

Abajobir, Amanuel Alemu; Kisely, Steve; Williams, Gail; Strathearn, Lane; Suresh, Sadasivam; Najman, Jake Moses

2017-10-01

Asthma reflects multiple and likely complex causal pathways. We investigate the possibility that childhood maltreatment is one such causal pathway. Childhood maltreatment can be interpreted as a form of early life adversity and like other life adversities may predict a range of negative health outcomes, including asthma. A total of 3762 young adults (52.63% female) from the Mater Hospital-University of Queensland Study of Pregnancy (MUSP) participated in this study. MUSP is a prospective Australian birth cohort study of mothers consecutively recruited during their first antenatal clinic visit at Brisbane's Mater Hospital from 1981 to 1983. The study followed both mother-child dyads to the age of 21years after birth. Participants reported whether they had been diagnosed by a physician with asthma by the 21-year follow-up. Trained research assistants also performed gender- and height-standardized lung function tests using a Spirobank G spirometer system attached to a laptop computer. We linked this dataset with data obtained from the child protection services and which comprised all substantiated cases of childhood maltreatment in the MUSP cohort. Substantiations of childhood maltreatment included children in an age range of 0-14years. The experience of any childhood maltreatment, particularly emotional abuse, was independently associated with self-reported physician-diagnosed asthma by the 21-year follow-up. The association was no longer significant after adjustment for a range of confounders and covariates in neglected children. Childhood maltreatment, including multiple events, was not associated with lung function in adjusted models. Childhood maltreatment, including emotional abuse, was associated with lifetime ever asthma. This was in contrast to the absence of an association with objective measures of lung function. More research is indicated on the effect of childhood maltreatment on lung function using objective measures. In the meantime, there should be a greater awareness of the potential impact of childhood maltreatment on the potential to develop asthma, as well as of the possibility that asthma in adulthood may precede childhood maltreatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Intermedin Stabilized Endothelial Barrier Function and Attenuated Ventilator-induced Lung Injury in Mice

PubMed Central

Müller-Redetzky, Holger Christian; Kummer, Wolfgang; Pfeil, Uwe; Hellwig, Katharina; Will, Daniel; Paddenberg, Renate; Tabeling, Christoph; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

2012-01-01

Background Even protective ventilation may aggravate or induce lung failure, particularly in preinjured lungs. Thus, new adjuvant pharmacologic strategies are needed to minimize ventilator-induced lung injury (VILI). Intermedin/Adrenomedullin-2 (IMD) stabilized pulmonary endothelial barrier function in vitro. We hypothesized that IMD may attenuate VILI-associated lung permeability in vivo. Methodology/Principal Findings Human pulmonary microvascular endothelial cell (HPMVEC) monolayers were incubated with IMD, and transcellular electrical resistance was measured to quantify endothelial barrier function. Expression and localization of endogenous pulmonary IMD, and its receptor complexes composed of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs) 1–3 were analyzed by qRT-PCR and immunofluorescence in non ventilated mouse lungs and in lungs ventilated for 6 h. In untreated and IMD treated mice, lung permeability, pulmonary leukocyte recruitment and cytokine levels were assessed after mechanical ventilation. Further, the impact of IMD on pulmonary vasoconstriction was investigated in precision cut lung slices (PCLS) and in isolated perfused and ventilated mouse lungs. IMD stabilized endothelial barrier function in HPMVECs. Mechanical ventilation reduced the expression of RAMP3, but not of IMD, CRLR, and RAMP1 and 2. Mechanical ventilation induced lung hyperpermeability, which was ameliorated by IMD treatment. Oxygenation was not improved by IMD, which may be attributed to impaired hypoxic vasoconstriction due to IMD treatment. IMD had minor impact on pulmonary leukocyte recruitment and did not reduce cytokine levels in VILI. Conclusions/Significance IMD may possibly provide a new approach to attenuate VILI. PMID:22563471

ATP promotes cell survival via regulation of cytosolic [Ca2+] and Bcl-2/Bax ratio in lung cancer cells

PubMed Central

Song, Shanshan; Jacobson, Krista N.; McDermott, Kimberly M.; Reddy, Sekhar P.; Cress, Anne E.; Tang, Haiyang; Dudek, Steven M.; Black, Stephen M.; Garcia, Joe G. N.; Makino, Ayako

2015-01-01

Adenosine triphosphate (ATP) is a ubiquitous extracellular messenger elevated in the tumor microenvironment. ATP regulates cell functions by acting on purinergic receptors (P2X and P2Y) and activating a series of intracellular signaling pathways. We examined ATP-induced Ca2+ signaling and its effects on antiapoptotic (Bcl-2) and proapoptotic (Bax) proteins in normal human airway epithelial cells and lung cancer cells. Lung cancer cells exhibited two phases (transient and plateau phases) of increase in cytosolic [Ca2+] ([Ca2+]cyt) caused by ATP, while only the transient phase was observed in normal cells. Removal of extracellular Ca2+ eliminated the plateau phase increase of [Ca2+]cyt in lung cancer cells, indicating that the plateau phase of [Ca2+]cyt increase is due to Ca2+ influx. The distribution of P2X (P2X1-7) and P2Y (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11) receptors was different between lung cancer cells and normal cells. Proapoptotic P2X7 was nearly undetectable in lung cancer cells, which may explain why lung cancer cells showed decreased cytotoxicity when treated with high concentration of ATP. The Bcl-2/Bax ratio was increased in lung cancer cells following treatment with ATP; however, the antiapoptotic protein Bcl-2 demonstrated more sensitivity to ATP than proapoptotic protein Bax. Decreasing extracellular Ca2+ or chelating intracellular Ca2+ with BAPTA-AM significantly inhibited ATP-induced increase in Bcl-2/Bax ratio, indicating that a rise in [Ca2+]cyt through Ca2+ influx is the critical mediator for ATP-mediated increase in Bcl-2/Bax ratio. Therefore, despite high ATP levels in the tumor microenvironment, which would induce cell apoptosis in normal cells, the decreased P2X7 and elevated Bcl-2/Bax ratio in lung cancer cells may enable tumor cells to survive. Increasing the Bcl-2/Bax ratio by exposure to high extracellular ATP may, therefore, be an important selective pressure promoting transformation and cancer progression. PMID:26491047

Sustained Effects of Sirolimus on Lung Function and Cystic Lung Lesions in Lymphangioleiomyomatosis

PubMed Central

Yao, Jianhua; Jones, Amanda M.; Julien-Williams, Patricia; Stylianou, Mario; Moss, Joel

2014-01-01

Rationale: Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis. Objectives: To determine whether sirolimus has beneficial effects on lung function, cystic areas, and adjacent lung parenchyma; whether these effects are sustained; and whether sirolimus is well tolerated by patients. Methods: Lung function decline over time, lung volume occupied by cysts (cyst score), and lung tissue texture in the vicinity of the cysts were quantified with a computer-aided diagnosis system in 38 patients. Then we compared cyst scores from the last study on sirolimus with studies done on sirolimus therapy. In 12 patients, we evaluated rates of change in lung function and cyst scores off and on sirolimus. Measurements and Main Results: Sirolimus reduced yearly declines in FEV1 (−2.3 ± 0.1 vs. 1.0 ± 0.3% predicted; P < 0.001) and diffusing capacity of carbon monoxide (−2.6 ± 0.1 vs. 0.9 ± 0.2% predicted; P < 0.001). Cyst scores 1.2 ± 0.8 years (30.5 ± 11.9%) and 2.5 ± 2 years (29.7 ± 12.1%) after initiating sirolimus were not significantly different from pretreatment values (28.4 ± 12.5%). In 12 patients followed for 5 years, a significant reduction in rates of yearly decline in FEV1 (−1.4 ± 0.2 vs. 0.3 ± 0.4% predicted; P = 0.025) was observed. Analyses of 104 computed tomography scans showed a nonsignificant (P = 0.23) reduction in yearly rates of change of cyst scores (1.8 ± 0.2 vs. 0.3 ± 0.3%; P = 0.23) and lung texture features. Despite adverse events, most patients were able to continue sirolimus therapy. Conclusions: Sirolimus therapy slowed down lung function decline and increase in cystic lesions. Most patients were able to tolerate sirolimus therapy. PMID:25329516

Lung Ultrasound in the Critically Ill Neonate

PubMed Central

Lichtenstein, Daniel A; Mauriat, Philippe

2012-01-01

Critical ultrasound is a new tool for first-line physicians, including neonate intensivists. The consideration of the lung as one major target allows to redefine the priorities. Simple machines work better than up-to-date ones. We use a microconvex probe. Ten standardized signs allow a majority of uses: the bat sign (pleural line), lung sliding and the A-line (normal lung surface), the quad sign and sinusoid sign indicating pleural effusion regardless its echogenicity, the tissue-like sign and fractal sign indicating lung consolidation, the B-line artifact and lung rockets (indicating interstitial syndrome), abolished lung sliding with the stratosphere sign, suggesting pneumothorax, and the lung point, indicating pneumothorax. Other signs are used for more sophisticated applications (distinguishing atelectasis from pneumonia for instance...). All these disorders were assessed in the adult using CT as gold standard with sensitivity and specificity ranging from 90 to 100%, allowing to consider ultrasound as a reasonable bedside gold standard in the critically ill. The same signs are found, with no difference in the critically ill neonate. Fast protocols such as the BLUE-protocol are available, allowing immediate diagnosis of acute respiratory failure using seven standardized profiles. Pulmonary edema e.g. yields anterior lung rockets associated with lung sliding, making the B-profile. The FALLS-protocol, inserted in a Limited Investigation including a simple model of heart and vessels, assesses acute circulatory failure using lung artifacts. Interventional ultrasound (mainly, thoracocenthesis) provides maximal safety. Referrals to CT can be postponed. CEURF proposes personnalized bedside trainings since 1990. Lung ultrasound opens physicians to a visual medicine. PMID:23255876

Lung Ultrasound in the Critically Ill Neonate.

PubMed

Lichtenstein, Daniel A; Mauriat, Philippe

2012-08-01

Critical ultrasound is a new tool for first-line physicians, including neonate intensivists. The consideration of the lung as one major target allows to redefine the priorities. Simple machines work better than up-to-date ones. We use a microconvex probe. Ten standardized signs allow a majority of uses: the bat sign (pleural line), lung sliding and the A-line (normal lung surface), the quad sign and sinusoid sign indicating pleural effusion regardless its echogenicity, the tissue-like sign and fractal sign indicating lung consolidation, the B-line artifact and lung rockets (indicating interstitial syndrome), abolished lung sliding with the stratosphere sign, suggesting pneumothorax, and the lung point, indicating pneumothorax. Other signs are used for more sophisticated applications (distinguishing atelectasis from pneumonia for instance...). All these disorders were assessed in the adult using CT as gold standard with sensitivity and specificity ranging from 90 to 100%, allowing to consider ultrasound as a reasonable bedside gold standard in the critically ill. The same signs are found, with no difference in the critically ill neonate. Fast protocols such as the BLUE-protocol are available, allowing immediate diagnosis of acute respiratory failure using seven standardized profiles. Pulmonary edema e.g. yields anterior lung rockets associated with lung sliding, making the B-profile. The FALLS-protocol, inserted in a Limited Investigation including a simple model of heart and vessels, assesses acute circulatory failure using lung artifacts. Interventional ultrasound (mainly, thoracocenthesis) provides maximal safety. Referrals to CT can be postponed. CEURF proposes personnalized bedside trainings since 1990. Lung ultrasound opens physicians to a visual medicine.

Pulmonary function test findings in patients with acute inhalation injury caused by smoke bombs

PubMed Central

Cao, Lu; Zhang, Xin-Gang; Wang, Jian-Guo; Wang, Han-Bin; Chen, Yi-Bing; Zhao, Da-Hui; Shi, Wen-Fang

2016-01-01

Background This study aimed to determine the effects of smoke bomb-induced acute inhalation injury on pulmonary function at different stages of lung injury. Methods We performed pulmonary function tests (PFTs) in 15 patients with acute inhalation injury from days 3 to 180 after smoke inhalation. We measured the trace element zinc in whole blood on days 4 and 17, and correlations of zinc levels with PFTs were performed. Results In the acute stage of lung injury (day 3), 3 of 11 patients with mild symptoms had normal pulmonary function and 8 patients with restrictive ventilatory dysfunction and reduced diffusing capacity. Some patients also had mild obstructive ventilatory dysfunction (5 patients) and a decline in small airway function (6 patients). For patients with severe symptoms, PFT results showed moderate to severe restrictive ventilatory dysfunction and reduced diffusing capacity. PaCO2 was significantly higher (P=0.047) in patients with reduced small airway function compared with those with normal small airway function. Whole blood zinc levels in the convalescence stage (day 17) were significantly lower than those in the acute stage (day 4). Zinc in the acute stage was negatively correlated with DLCO/VA on days 3, 10, and 46 (r=−0.633, −0.676, and −0.675 respectively, P<0.05). Conclusions Smoke inhalation injury mainly causes restrictive ventilatory dysfunction and reduced diffusing capacity, and causes mild obstructive ventilatory dysfunction and small airway function decline in some patients. Zinc is negatively correlated with DLCO/VA. Zinc levels may be able to predict prognosis and indicate the degree of lung injury. PMID:28066595

Serum Methylarginines and Spirometry-Measured Lung Function in Older Adults

PubMed Central

McEvoy, Mark A.; Schofield, Peter W.; Smith, Wayne T.; Agho, Kingsley; Mangoni, Arduino A.; Soiza, Roy L.; Peel, Roseanne; Hancock, Stephen J.; Carru, Ciriaco; Zinellu, Angelo; Attia, John R.

2013-01-01

Rationale Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function. PMID:23690915

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

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

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

2010-06-04

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

Secreted Phosphoprotein 1 Is a Determinant of Lung Function Development in Mice

PubMed Central

Martin, Timothy M.; Concel, Vincent J.; Upadhyay, Swapna; Bein, Kiflai; Brant, Kelly A.; George, Leema; Mitra, Ankita; Thimraj, Tania A.; Fabisiak, James P.; Vuga, Louis J.; Fattman, Cheryl; Kaminski, Naftali; Schulz, Holger; Leikauf, George D.

2014-01-01

Secreted phosphoprotein 1 (Spp1) is located within quantitative trait loci associated with lung function that was previously identified by contrasting C3H/HeJ and JF1/Msf mouse strains that have extremely divergent lung function. JF1/Msf mice with diminished lung function had reduced lung SPP1 transcript and protein during the peak stage of alveologenesis (postnatal day [P]14–P28) as compared with C3H/HeJ mice. In addition to a previously identified genetic variant that altered runt-related transcription factor 2 (RUNX2) binding in the Spp1 promoter, we identified another promoter variant in a putative RUNX2 binding site that increased the DNA protein binding. SPP1 induced dose-dependent mouse lung epithelial-15 cell proliferation. Spp1(−/−) mice have decreased specific total lung capacity/body weight, higher specific compliance, and increased mean airspace chord length (Lm) compared with Spp1(+/+) mice. Microarray analysis revealed enriched gene ontogeny categories, with numerous genes associated with lung development and/or respiratory disease. Insulin-like growth factor 1, Hedgehog-interacting protein, wingless-related mouse mammary tumor virus integration site 5A, and NOTCH1 transcripts decreased in the lung of P14 Spp1(−/−) mice as determined by quantitative RT-PCR analysis. SPP1 promotes pneumocyte growth, and mice lacking SPP1 have smaller, more compliant lungs with enlarged airspace (i.e., increased Lm). Microarray analysis suggests a dysregulation of key lung developmental transcripts in gene-targeted Spp1(−/−) mice, particularly during the peak phase of alveologenesis. In addition to its known roles in lung disease, this study supports SPP1 as a determinant of lung development in mice. PMID:24816281

Assessment of regional ventilation and deformation using 4D-CT imaging for healthy human lungs during tidal breathing

PubMed Central

Jahani, Nariman; Choi, Jiwoong; Iyer, Krishna; Hoffman, Eric A.

2015-01-01

This study aims to assess regional ventilation, nonlinearity, and hysteresis of human lungs during dynamic breathing via image registration of four-dimensional computed tomography (4D-CT) scans. Six healthy adult humans were studied by spiral multidetector-row CT during controlled tidal breathing as well as during total lung capacity and functional residual capacity breath holds. Static images were utilized to contrast static vs. dynamic (deep vs. tidal) breathing. A rolling-seal piston system was employed to maintain consistent tidal breathing during 4D-CT spiral image acquisition, providing required between-breath consistency for physiologically meaningful reconstructed respiratory motion. Registration-derived variables including local air volume and anisotropic deformation index (ADI, an indicator of preferential deformation in response to local force) were employed to assess regional ventilation and lung deformation. Lobar distributions of air volume change during tidal breathing were correlated with those of deep breathing (R2 ≈ 0.84). Small discrepancies between tidal and deep breathing were shown to be likely due to different distributions of air volume change in the left and the right lungs. We also demonstrated an asymmetric characteristic of flow rate between inhalation and exhalation. With ADI, we were able to quantify nonlinearity and hysteresis of lung deformation that can only be captured in dynamic images. Nonlinearity quantified by ADI is greater during inhalation, and it is stronger in the lower lobes (P < 0.05). Lung hysteresis estimated by the difference of ADI between inhalation and exhalation is more significant in the right lungs than that in the left lungs. PMID:26316512

Six minute walking test and carbon monoxide diffusing capacity for non-small cell lung cancer: easy performed tests in every day practice.

PubMed

Zarogoulidis, Paul; Kerenidi, Theodora; Huang, Haidong; Kontakiotis, Theodoros; Tremma, Ourania; Porpodis, Konstantinos; Kalianos, Anastasios; Rapti, Ageliki; Foroulis, Christoforos; Zissimopoulos, Athanasios; Courcoutsakis, Nikolaos; Zarogoulidis, Konstantinos

2012-12-01

Several studies have demonstrated that reduced lung function is a significant risk factor for lung cancer and increased surgical risk in patients with operable stages of lung cancer. The aim of the study was to perform pulmonary function tests and investigate which is a favorable respiratory function test for overall survival between lung cancer stages. Lung function tests were performed to lung cancer patients with non-small cell lung cancer of stage I, II, III and IV (241 patients in total). They had the last follow-up consecutively between December 2006 and July 2008. The staging was decided according to the sixth edition of TNM classification of NSCLC. The Forced Expiratory Volume in 1sec (FEV1), Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) were measured according to American Thoracic Society/European Respiratory Society guidelines. The 6 Minute Walking Test (6MWT) was measured according to the American Thoracic Society. There was a significant association of the DLCO upon diagnosis and overall survival for stage II (P<0.007) and IV (P<0.003). Furthermore, there was a significant association between 6MWT and overall survival for stage III (P<0.001) and stage IV (P<0.010). The significance for each lung function test is different among the stages of NSCLC. DLCO and 6MWT upon admission are the most valuable prognostic factors for overall survival of NSCLC.

Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis.

PubMed

Singh, Brijendra; Kasam, Rajesh K; Sontake, Vishwaraj; Wynn, Thomas A; Madala, Satish K

2017-11-01

IL-4 and IL-13 are major T-helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared with saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Histological staining and lung function measurements demonstrated that collagen deposition and lung function decline were attenuated in mice deficient in either IL-13 or IL-4Rα-driven signaling compared with wild-type mice treated with bleomycin. Furthermore, our results demonstrated that IL-13 and IL-4Rα-driven signaling are involved in excessive migration of macrophages and fibroblasts. Notably, our findings demonstrated that IL-13-driven migration involves increased phospho-focal adhesion kinase signaling and F-actin polymerization. Importantly, in vivo findings demonstrated that IL-13 augments matrix metalloproteinase (MMP)-2 and MMP9 activity that has also been shown to increase migration and invasiveness of fibroblasts in the lungs during bleomycin-induced pulmonary fibrosis. Together, our findings demonstrate a pathogenic role for Th2-cytokine signaling that includes excessive migration and protease activity involved in severe fibrotic lung disease.

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.

Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

ClinicalTrials.gov

2017-04-12

Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Assessment of respiratory symptoms and lung function values among the brick field workers of West Bengal, India.

PubMed

Das, Banibrata

2016-07-03

Brick manufacturing process releases large amounts of silica dust into the work environment due to the use of silica-containing materials. The main aim of the study was to investigate the impairment of lung function and prevalence of respiratory symptoms among the different groups of brick field workers in comparison with control subjects. A total of 250 brick field workers and 130 unexposed control subjects were randomly selected in which demographic characteristics, respiratory symptoms, and lung function values were recorded. The result showed significantly lower p value (<.001) in lung function and respiratory symptoms among brick field workers when compared with control group. The prevalence of respiratory symptoms was dyspnea (46.8%), phlegm (39.2%), and chest tightness (27.6%). Dust exposure in working environment affected the lung function values and increased the respiratory symptoms among the brick field workers.

Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury.

PubMed

Spieth, Peter M; Carvalho, Alysson R; Pelosi, Paolo; Hoehn, Catharina; Meissner, Christoph; Kasper, Michael; Hübler, Matthias; von Neindorff, Matthias; Dassow, Constanze; Barrenschee, Martina; Uhlig, Stefan; Koch, Thea; de Abreu, Marcelo Gama

2009-04-15

Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies.

Predictive role of arterial carboxyhemoglobin concentrations in ovine burn and smoke inhalation-induced lung injury.

PubMed

Lange, Matthias; Cox, Robert A; Enkhbaatar, Perenlei; Whorton, Elbert B; Nakano, Yoshimitsu; Hamahata, Atsumori; Jonkam, Collette; Esechie, Aimalohi; von Borzyskowski, Sanna; Traber, Lillian D; Traber, Daniel L

2011-05-01

Inhalation injury frequently occurs in burn patients and contributes to the morbidity and mortality of these injuries. Arterial carboxyhemoglobin has been proposed as an indicator of the severity of inhalation injury; however, the interrelation between arterial carboxyhemoglobin and histological alterations has not yet been investigated. Chronically instrumented sheep were subjected to a third degree burn of 40% of the total body surface area and inhalation of 48 breaths of cotton smoke. Carboxyhemoglobin was measured immediately after injury and correlated to clinical parameters of pulmonary function as well as histopathology scores from lung tissue harvested 24 hours after the injury. The injury was associated with a significant decline in pulmonary oxygenation and increases in pulmonary shunting, lung lymph flow, wet/dry weight ratio, congestion score, edema score, inflammation score, and airway obstruction scores. Carboxyhemoglobin was negatively correlated to pulmonary oxygenation and positively correlated to pulmonary shunting, lung lymph flow, and lung wet/dry weight ratio. No significant correlations could be detected between carboxyhemoglobin and histopathology scores and airway obstruction scores. Arterial carboxyhemoglobin in sheep with combined burn and inhalation injury are correlated with the degree of pulmonary failure and edema formation, but not with certain histological alterations including airway obstruction scores.

Combined Ventilation and Perfusion Imaging Correlates With the Dosimetric Parameters of Radiation Pneumonitis in Radiation Therapy Planning for Lung Cancer

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

Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp; Doi, Yoshiko; Nakashima, Takeo

2015-11-15

Purpose: The purpose of this study was to prospectively investigate clinical correlations between dosimetric parameters associated with radiation pneumonitis (RP) and functional lung imaging. Methods and Materials: Functional lung imaging was performed using four-dimensional computed tomography (4D-CT) for ventilation imaging, single-photon emission computed tomography (SPECT) for perfusion imaging, or both (V/Q-matched region). Using 4D-CT, ventilation imaging was derived from a low attenuation area according to CT numbers below different thresholds (vent-860 and -910). Perfusion imaging at the 10th, 30th, 50th, and 70th percentile perfusion levels (F10-F70) were defined as the top 10%, 30%, 50%, and 70% hyperperfused normal lung, respectively.more » All imaging data were incorporated into a 3D planning system to evaluate correlations between RP dosimetric parameters (where fV20 is the percentage of functional lung volume irradiated with >20 Gy, or fMLD, the mean dose administered to functional lung) and the percentage of functional lung volume. Radiation pneumonitis was evaluated using Common Terminology Criteria for Adverse Events version 4.0. Statistical significance was defined as a P value of <.05. Results: Sixty patients who underwent curative radiation therapy were enrolled (48 patients for non-small cell lung cancer, and 12 patients for small cell lung cancer). Grades 1, 2, and ≥3 RP were observed in 16, 44, and 6 patients, respectively. Significant correlations were observed between the percentage of functional lung volume and fV20 (r=0.4475 in vent-860 and 0.3508 in F30) or fMLD (r=0.4701 in vent-860 and 0.3128 in F30) in patients with grade ≥2 RP. F30∩vent-860 results exhibited stronger correlations with fV20 and fMLD in patients with grade ≥2 (r=0.5509 in fV20 and 0.5320 in fMLD) and grade ≥3 RP (r=0.8770 in fV20 and 0.8518 in fMLD). Conclusions: RP dosimetric parameters correlated significantly with functional lung imaging.« less

Lung transplantation in patients who have undergone prior cardiothoracic procedures.

PubMed

Omara, Mohamed; Okamoto, Toshihiro; Arafat, Amr; Thuita, Lucy; Blackstone, Eugene H; McCurry, Kenneth R

2016-12-01

Patients who have undergone prior cardiothoracic procedures offer technical challenges that may affect post-transplant outcomes and be a reason to decline listing. Data are currently limited regarding the indication for lung transplantation among recipients who have had prior cardiothoracic procedures. Of 453 lung transplants performed at Cleveland Clinic from January 2005 to July 2010, 206 recipients (45%) had undergone prior cardiothoracic procedures: 157 lung only, 15 cardiac only, 10 cardiac + lung, 10 pleurodesis + lung, and 14 other. Chest tube placement was performed in 202 patients. Survival, post-transplant length of intensive care unit and hospital stays, primary graft dysfunction, and pulmonary function outcomes were compared with outcomes of patients not having prior procedures using propensity score adjustment. Short-term and long-term survival was similar between the 2 groups. Survival at 30 days, 1 year, and 5 years was 94%, 83%, and 55% for the prior cardiothoracic procedure group and 96%, 84%, and 53% for the no prior cardiothoracic procedure group (log-rank p = 0.9). Intensive care unit stay was longer (6 days vs 5 days, p = 0.02) in the prior cardiothoracic procedure group; this was particularly true for pleurodesis + lung (10 days, p = 0.05), although post-transplant hospital stay was similar (16 days, 16 days, and 22 days; p = 0.13). Primary graft dysfunction was not increased in the prior cardiothoracic procedure group. Forced expiratory volume in 1 second was similar for both groups but lower for thoracotomy and lung procedures using a bilateral chest tube (p < 0.05 each). A prior cardiothoracic procedure is not a contraindication for lung transplantation. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Spirometry and volumetric capnography in lung function assessment of obese and normal-weight individuals without asthma.

PubMed

Ferreira, Mariana S; Mendes, Roberto T; Marson, Fernando A L; Zambon, Mariana P; Antonio, Maria A R G M; Paschoal, Ilma A; Toro, Adyléia A D C; Severino, Silvana D; Ribeiro, Maria A G O; Ribeiro, José D

To analyze and compare lung function of obese and healthy, normal-weight children and adolescents, without asthma, through spirometry and volumetric capnography. Cross-sectional study including 77 subjects (38 obese) aged 5-17 years. All subjects underwent spirometry and volumetric capnography. The evaluations were repeated in obese subjects after the use of a bronchodilator. At the spirometry assessment, obese individuals, when compared with the control group, showed lower values of forced expiratory volume in the first second by forced vital capacity (FEV 1 /FVC) and expiratory flows at 75% and between 25 and 75% of the FVC (p<0.05). Volumetric capnography showed that obese individuals had a higher volume of produced carbon dioxide and alveolar tidal volume (p<0.05). Additionally, the associations between dead space volume and tidal volume, as well as phase-3 slope normalized by tidal volume, were lower in healthy subjects (p<0.05). These data suggest that obesity does not alter ventilation homogeneity, but flow homogeneity. After subdividing the groups by age, a greater difference in lung function was observed in obese and healthy individuals aged >11 years (p<0.05). Even without the diagnosis of asthma by clinical criteria and without response to bronchodilator use, obese individuals showed lower FEV 1 /FVC values and forced expiratory flow, indicating the presence of an obstructive process. Volumetric capnography showed that obese individuals had higher alveolar tidal volume, with no alterations in ventilation homogeneity, suggesting flow alterations, without affecting lung volumes. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

LHX6, An Independent Prognostic Factor, Inhibits Lung Adenocarcinoma Progression through Transcriptional Silencing of β-catenin.

PubMed

Yang, Juntang; Han, Fei; Liu, Wenbin; Zhang, Mingqian; Huang, Yongsheng; Hao, Xianglin; Jiang, Xiao; Yin, Li; Chen, Hongqiang; Cao, Jia; Zhang, Huidong; Liu, Jinyi

2017-01-01

Introduction: Our previous study identified LIM homeobox domain 6 (LHX6) as a frequently epigenetically silenced tumor-suppressor gene in lung cancer. However, its clinical value has never been evaluated, and the in-depth anti-tumor mechanism remains unclear. Methods: Public database was used for lung cancer, lung adenocarcinoma and lung squamous carcinoma patients and tissue microarray data was used for lung adenocarcinoma patients to study prognostic outcome of LHX6 expression by Kaplan-Meier and Cox-regression analysis. In vitro proliferation, metastasis and in vivo nude mice model were used to evaluate the anti-tumor effect of LHX6 on lung adenocarcinoma cell lines. The mechanisms were explored using western blot, TOP/FOP flash assays and luciferase reporter assays. LHX6 expression and clinical stages data were collected from The Cancer Genome Atlas database (TCGA). Results: Expression of LHX6 was found to be a favorable independent prognostic factor for overall survival (OS) of total lung adenocarcinoma patients (P=0.014) and patients with negative lymph nodes status (P=0.014) but not related the prognostic outcome of lung squamous cell carcinoma patients. The expression status of LHX6 significantly correlated to histological grade (P<0.01), tumor size (P=0.026), lymph node status (P=0.039) and clinical stages (P<0.01) of lung adenocarcinoma patients. Functionally, LHX6 inhibited the proliferation and metastasis of lung adenocarcinoma cells in vitro and in vivo . Furthermore, LHX6 suppressed the Wnt/β-catenin pathway through transcriptionally silencing the expression of β-catenin, and the promoter region (-1161 bp to +27 bp) was crucial for its inhibitory activity. Conclusions: Our data indicate that the expression of LHX6 may serve as a favorable prognostic biomarker for lung adenocarcinoma patients and provide a novel mechanism of LHX6 involving in the tumorigenesis of lung adenocarcinoma.

LHX6, An Independent Prognostic Factor, Inhibits Lung Adenocarcinoma Progression through Transcriptional Silencing of β-catenin

PubMed Central

Yang, Juntang; Han, Fei; Liu, Wenbin; Zhang, Mingqian; Huang, Yongsheng; Hao, Xianglin; Jiang, Xiao; Yin, Li; Chen, Hongqiang; Cao, Jia; Zhang, Huidong; Liu, Jinyi

2017-01-01

Introduction: Our previous study identified LIM homeobox domain 6 (LHX6) as a frequently epigenetically silenced tumor-suppressor gene in lung cancer. However, its clinical value has never been evaluated, and the in-depth anti-tumor mechanism remains unclear. Methods: Public database was used for lung cancer, lung adenocarcinoma and lung squamous carcinoma patients and tissue microarray data was used for lung adenocarcinoma patients to study prognostic outcome of LHX6 expression by Kaplan-Meier and Cox-regression analysis. In vitro proliferation, metastasis and in vivo nude mice model were used to evaluate the anti-tumor effect of LHX6 on lung adenocarcinoma cell lines. The mechanisms were explored using western blot, TOP/FOP flash assays and luciferase reporter assays. LHX6 expression and clinical stages data were collected from The Cancer Genome Atlas database (TCGA). Results: Expression of LHX6 was found to be a favorable independent prognostic factor for overall survival (OS) of total lung adenocarcinoma patients (P=0.014) and patients with negative lymph nodes status (P=0.014) but not related the prognostic outcome of lung squamous cell carcinoma patients. The expression status of LHX6 significantly correlated to histological grade (P<0.01), tumor size (P=0.026), lymph node status (P=0.039) and clinical stages (P<0.01) of lung adenocarcinoma patients. Functionally, LHX6 inhibited the proliferation and metastasis of lung adenocarcinoma cells in vitro and in vivo. Furthermore, LHX6 suppressed the Wnt/β-catenin pathway through transcriptionally silencing the expression of β-catenin, and the promoter region (-1161 bp to +27 bp) was crucial for its inhibitory activity. Conclusions: Our data indicate that the expression of LHX6 may serve as a favorable prognostic biomarker for lung adenocarcinoma patients and provide a novel mechanism of LHX6 involving in the tumorigenesis of lung adenocarcinoma. PMID:28900494

Identification of the tumor‑suppressive function of circular RNA FOXO3 in non‑small cell lung cancer through sponging miR‑155.

PubMed

Zhang, Yanni; Zhao, Hui; Zhang, Lichuan

2018-06-01

Circular RNAs (circRNAs) are a class of endo-genous noncoding RNAs that have been demonstrated to be potential regulators in the development and progression of various types of human cancer. However, little is known about their roles in cancer initiation and progression, particular in non‑small cell lung cancer (NSCLC). In the present study, the expression level of circRNA‑forkhead box O3 class (FOXO3) in NSCLC specimens was determined and its functional role was investigated in NSCLC cells. By performing Taq‑man based RT‑qPCR, it was identified that circRNA‑FOXO3 was downregulated in NSCLC tissues and cell lines. Receiver operating curve analysis indicated that circRNA‑FOXO3 had a relatively higher diagnostic accuracy. The functional relevance was further examined by biological assays. circRNA‑FOXO3 significantly promoted the ability of cell proliferation, migration and invasion of NSCLC cells. The linear isomer of circRNA‑FOXO3, FOXO3 gene, was identified as a downstream target. RNA immunoprecipitation indicated that circRNA‑FOXO3 sequestering miR‑155, which further promoted linear FOXO3 expression. In addition, gain and loss functional assays indicated that circRNA‑FOXO3 served an anti‑oncogenic role through sequestering miR‑155 and enhancing FOXO3 expression. These results suggest that circRNA‑FOXO3 is a tumor‑suppressor in NSCLC and may serve as a promising therapeutic target. Therefore, restoration of circRNA‑FOXO3 expression could be a future approach to develop a novel treatment strategy.

Guards at the gate: physiological and pathological roles of tissue-resident innate lymphoid cells in the lung.

PubMed

Cheng, Hang; Jin, Chengyan; Wu, Jing; Zhu, Shan; Liu, Yong-Jun; Chen, Jingtao

2017-12-01

The lung is an important open organ and the primary site of respiration. Many life-threatening diseases develop in the lung, e.g., pneumonia, asthma, chronic obstructive pulmonary diseases (COPDs), pulmonary fibrosis, and lung cancer. In the lung, innate immunity serves as the frontline in both anti-irritant response and anti-tumor defense and is also critical for mucosal homeostasis; thus, it plays an important role in containing these pulmonary diseases. Innate lymphoid cells (ILCs), characterized by their strict tissue residence and distinct function in the mucosa, are attracting increased attention in innate immunity. Upon sensing the danger signals from damaged epithelium, ILCs activate, proliferate, and release numerous cytokines with specific local functions; they also participate in mucosal immune-surveillance, immune-regulation, and homeostasis. However, when their functions become uncontrolled, ILCs can enhance pathological states and induce diseases. In this review, we discuss the physiological and pathological functions of ILC subsets 1 to 3 in the lung, and how the pathogenic environment affects the function and plasticity of ILCs.

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

Frank, Evan A.; Birch, M. Eileen; Yadav, Jagjit S., E-mail: Jagjit.Yadav@uc.edu

Carbon nanotubes (CNTs) are rapidly emerging as high-priority occupational toxicants. CNT powders contain fibrous particles that aerosolize readily in places of manufacture and handling, posing an inhalation risk for workers. Studies using animal models indicate that lung exposure to CNTs causes prolonged inflammatory responses and diffuse alveolar injury. The mechanisms governing CNT-induced lung inflammation are not fully understood but have been suggested to involve alveolar macrophages (AMs). In the current study, we sought to systematically assess the effector role of AMs in vivo in the induction of lung inflammatory responses to CNT exposures and investigate their cell type-specific mechanisms. Multi-wallmore » CNTs characterized for various physicochemical attributes were used as the CNT type. Using an AM-specific depletion and repopulation approach in a mouse model, we unambiguously demonstrated that AMs are major effector cells necessary for the in vivo elaboration of CNT-induced lung inflammation. We further investigated in vitro AM responses and identified molecular targets which proved critical to pro-inflammatory responses in this model, namely MyD88 as well as MAPKs and Ca{sup 2} {sup +}/CamKII. We further demonstrated that MyD88 inhibition in donor AMs abrogated their capacity to reconstitute CNT-induced inflammation when adoptively transferred into AM-depleted mice. Taken together, this is the first in vivo demonstration that AMs act as critical effector cell types in CNT-induced lung inflammation and that MyD88 is required for this in vivo effector function. AMs and their cell type-specific mechanisms may therefore represent potential targets for future therapeutic intervention of CNT-related lung injury. - Highlights: • Demonstrated in vivo effector role of alveolar macrophages (AMs) in CNT toxicity • MyD88, MAPKs, and Ca{sup 2} {sup +}/CamKII are required for AM inflammatory responses in vitro. • MyD88 signaling is required for in vivo effector function of AMs. • MyD88 may be a potential target for intervention in CNT lung exposures.« less

Involvement of MicroRNAs in Lung Cancer Biology and Therapy

PubMed Central

Liu, Xi; Sempere, Lorenzo F.; Guo, Yongli; Korc, Murray; Kauppinen, Sakari; Freemantle, Sarah J.; Dmitrovsky, Ethan

2011-01-01

MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression. Expression profiles of specific miRNAs have improved cancer diagnosis and classification and even provided prognostic information in many human cancers, including lung cancer. Tumor suppressive and oncogenic miRNAs were uncovered in lung carcinogenesis. The biological functions of these miRNAs in lung cancer were recently validated in well characterized cellular, murine transgenic as well as transplantable lung cancer models and in human paired normal-malignant lung tissue banks and tissue arrays. Tumor suppressive and oncogenic miRNAs that were identified in lung cancer will be reviewed here. Emphasis is placed on highlighting those functionally validated miRNAs that are not only biomarkers of lung carcinogenesis, but also candidate pharmacologic targets. How these miRNA findings advance an understanding of lung cancer biology and could improve lung cancer therapy are discussed in this article. PMID:21420030

A prospective study of decline in lung function in relation to welding emissions.

PubMed

Christensen, Sigve W; Bonde, Jens Peter; Omland, Oyvind

2008-02-26

Numerous cross-sectional studies have reported reduced lung function among welders but limitations of exposure assessment and design preclude causal inference. The aim of this study was to investigate if long-term exposure to welding fume particulates accelerates the age-related decline in lung function. Lung function was measured by spirometry in 1987 and 2004 among 68 steel welders and 32 non-welding production workers. The decline in forced expiratory volume (FEV1) was analysed in relation to cumulated exposure to fume particulates among welders during the follow-up period. Among smokers the decline in FEV1 through follow-up period was in average 150 ml larger among welders than non-welders while the difference was negligible among non-smokers. The results did not reach statistical significance and within welders the decline in lung function was not related to the cumulated welding particulate exposure during follow-up period Long-term exposure to welding emissions may accelerate the age-related decline of lung function but at exposure levels in the range of 1.5 to 6.5 mg/m3 the average annual excess loss of FEV1 is unlikely to exceed 25 ml in smokers and 10 ml in non-smokers.

Lung function and exhaled nitric oxide in healthy unsedated African infants

PubMed Central

Gray, Diane; Willemse, Lauren; Visagie, Ane; Smith, Emilee; Czövek, Dorottya; Sly, Peter D; Hantos, Zoltán; Hall, Graham L; Zar, Heather J

2015-01-01

Background and objective Population-appropriate lung function reference data are essential to accurately identify respiratory disease and measure response to interventions. There are currently no reference data in African infants. The aim was to describe normal lung function in healthy African infants. Methods Lung function was performed on healthy South African infants enrolled in a birth cohort study, the Drakenstein child health study. Infants were excluded if they were born preterm or had a history of neonatal respiratory distress or prior respiratory tract infection. Measurements, made during natural sleep, included the forced oscillation technique, tidal breathing, exhaled nitric oxide and multiple breath washout measures. Results Three hundred sixty-three infants were tested. Acceptable and repeatable measurements were obtained in 356 (98%) and 352 (97%) infants for tidal breathing analysis and exhaled nitric oxide outcomes, 345 (95%) infants for multiple breath washout and 293 of the 333 (88%) infants for the forced oscillation technique. Age, sex and weight-for-age z score were significantly associated with lung function measures. Conclusions This study provides reference data for unsedated infant lung function in African infants and highlights the importance of using population-specific data. PMID:26134556

[The specificity between "fei and dachang" in the lung injury of rats with ulcerative colitis].

PubMed

Zhu, Li; Wang, Xin-yue; Yang, Xue; Jing, Shan; Zhou, Bo; Huang, Xiu-xia; Jia, Xu

2013-03-01

To observe the features of bronchopulmonary lesions in ulcerative colitis (UC) rats and the specificity with Fei and Dachang, thus providing reliance for the theory of "intestinal diseases involved Fei". The UC rat model was duplicated by using rabbit intestine mucosa tissue allergenic model and TNBS-ethanol model. A normal rat group was set up as the control. The pulmonary functions [including inspiratory resistance (Ri), expiratory resistance (Re), forced vital capacity (FVC); FEV. 2/FVC, maximal voluntary ventilation (MVV), forced expiratory flow rate (FEF25% - 75%)], and indicators of liver and kidney functions [serum alanine aminotransferase (ALT), aspartate amino transferase (AST), blood urea nitrogen (BUN), and creatinine (Cr)] were detected in the two groups. The pathological changes of colon, lung, liver, and kidney were observed in the two groups. Rats in the model group in both acute and chronic stages had weight loss, mucus and loose stool. Partial rats had such symptoms as dyspnea, shortness of breath, and wheezing. Compared with the normal group, the MW, FVC, FEV0.2 and FEF25% -75% in the acute stage; Ri, Re, MVV, FVC, and FEF25% - 75% in the chronic stage all significantly decreased (P <0.05, P <0.01), and FEV0.2/FVC significantly increased in the model group (P <0.05). The pathological results showed interstitial pneumonia and pulmonary interstitial fibrosis in the model group. But the indicators of liver and kidney functions were all in the normal range. No obvious pathological change was seen in the renal and liver tissues in the two groups. UC could specifically induce bronchopulmonary lesions. Lung injury was one of UC's intestinal manifestations. The theory of "Fei and Dachang being interior-exteriorly correlated" was demonstrated from the theory of "intestinal diseases involved Fei".

Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease

PubMed Central

Collaco, J. Michael; Vanscoy, Lori; Bremer, Lindsay; McDougal, Kathryn; Blackman, Scott M.; Bowers, Amanda; Naughton, Kathleen; Jennings, Jacky; Ellen, Jonathan; Cutting, Garry R.

2011-01-01

Context Disease variation can be substantial even in conditions with a single gene etiology such as cystic fibrosis (CF). Simultaneously studying the effects of genes and environment may provide insight into the causes of variation. Objective To determine whether secondhand smoke exposure is associated with lung function and other outcomes in individuals with CF, whether socioeconomic status affects the relationship between secondhand smoke exposure and lung disease severity, and whether specific gene-environment interactions influence the effect of secondhand smoke exposure on lung function. Design, Setting, and Participants Retrospective assessment of lung function, stratified by environmental and genetic factors. Data were collected by the US Cystic Fibrosis Twin and Sibling Study with missing data supplemented by the Cystic Fibrosis Foundation Data Registry. All participants were diagnosed with CF, were recruited between October 2000 and October 2006, and were primarily from the United States. Main Outcome Measures Disease-specific cross-sectional and longitudinal measures of lung function. Results Of 812 participants with data on secondhand smoke in the home, 188 (23.2%) were exposed. Of 780 participants with data on active maternal smoking during gestation, 129 (16.5%) were exposed. Secondhand smoke exposure in the home was associated with significantly lower cross-sectional (9.8 percentile point decrease; P<.001) and longitudinal lung function (6.1 percentile point decrease; P=.007) compared with those not exposed. Regression analysis demonstrated that socioeconomic status did not confound the adverse effect of secondhand smoke exposure on lung function. Interaction between gene variants and secondhand smoke exposure resulted in significant percentile point decreases in lung function, namely in CFTR non-ΔF508 homozygotes (12.8 percentile point decrease; P=.001), TGFβ1-509 TT homozygotes (22.7 percentile point decrease; P=.006), and TGFβ1 codon 10 CC homozygotes (20.3 percentile point decrease; P=.005). Conclusions Any exposure to secondhand smoke adversely affects both cross-sectional and longitudinal measures of lung function in individuals with CF. Variations in the gene that causes CF (CFTR) and a CF-modifier gene (TGFβ1) amplify the negative effects of secondhand smoke exposure. PMID:18230779

Comparison of particulate matter dose and acute heart rate variability response in cyclists, pedestrians, bus and train passengers.

PubMed

Nyhan, Marguerite; McNabola, Aonghus; Misstear, Bruce

2014-01-15

Exposure to airborne particulate matter (PM) has been linked to cardiovascular morbidity and mortality. Heart rate variability (HRV) is a measure of the change in cardiac autonomic function, and consistent links between PM exposure and decreased HRV have been documented in studies. This study quantitatively assesses the acute relative variation of HRV with predicted PM dose in the lungs of commuters. Personal PM exposure, HR and HRV were monitored in 32 young healthy cyclists, pedestrians, bus and train passengers. Inhaled and lung deposited PM doses were determined using a numerical model of the human respiratory tract which accounted for varying ventilation rates between subjects and during commutes. Linear mixed models were used to examine air pollution dose and HRV response relationships in 122 commutes sampled. Elevated PM2.5 and PM10 inhaled and lung deposited doses were significantly (p<0.05) associated with decreased HRV indices. Percent declines in SDNN (standard deviation of normal RR intervals) relative to resting, due to an inter-quartile range increase in PM10 lung deposited dose were stronger in cyclists (-6.4%, 95% CI: -11.7, -1.3) and pedestrians (-5.8%, 95% CI: -11.3, -0.5), in comparison to bus (-3.2%, 95% CI: -6.4, -0.1) and train (-1.8%, -7.5, 3.8) passengers. A similar trend was observed in the case of PM2.5 lung deposited dose and results for rMSSD (the square root of the squared differences of successive normal RR intervals) followed similar trends to SDNN. Inhaled and lung deposited doses accounting for varying ventilation rates between modes, individuals and during commutes have been neglected in other studies relating PM to HRV. The findings here indicate that exercise whilst commuting has an influence on inhaled PM and PM lung deposited dose, and these were significantly associated with acute declines in HRV, especially in pedestrians and cyclists. © 2013.

Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis.

PubMed

Ramsey, Kathryn A; Ranganathan, Sarath; Park, Judy; Skoric, Billy; Adams, Anne-Marie; Simpson, Shannon J; Robins-Browne, Roy M; Franklin, Peter J; de Klerk, Nick H; Sly, Peter D; Stick, Steve M; Hall, Graham L

2014-11-15

Pulmonary inflammation, infection, and structural lung disease occur early in life in children with cystic fibrosis. We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung function in childhood. Lung function (forced expiratory volume in the first three-quarters of a second [FEV0.75], FVC) was assessed in individuals with cystic fibrosis diagnosed after newborn screening and healthy subjects during infancy (0-2 yr) and again at early school age (4-8 yr). Individuals with cystic fibrosis underwent annual bronchoalveolar lavage fluid examination, and chest computed tomography. We examined which clinical outcomes (pulmonary inflammation, infection, structural lung disease, respiratory hospitalizations, antibiotic prophylaxis) measured in the first 2 years of life were associated with reduced lung function in infants and young children with cystic fibrosis, using a mixed effects model. Children with cystic fibrosis (n = 56) had 8.3% (95% confidence interval [CI], -15.9 to -6.6; P = 0.04) lower FEV0.75 compared with healthy subjects (n = 18). Detection of proinflammatory bacterial pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus species, Streptococcus pneumoniae) in bronchoalveolar lavage fluid was associated with clinically significant reductions in FEV0.75 (ranging between 11.3 and 15.6%). The onset of lung disease in infancy, specifically the occurrence of lower respiratory tract infection, is associated with low lung function in young children with cystic fibrosis. Deficits in lung function measured in infancy persist into childhood, emphasizing the need for targeted therapeutic interventions in infancy to maximize functional outcomes later in life.

Heart-lung transplantation: pediatric indications and outcomes

PubMed Central

2014-01-01

As indications for heart-lung transplant (HLT) have changed to some degree in the past 30 years, this treatment is being used less frequently in children due to more advanced care of severe heart and lung disease. This is fortunate as the outcomes for HLT are poor compared to other solid organ transplants and this is mainly due to the poorer outcome of the lung graft. PMID:25132980

Development of a Zealand white rabbit deposition model to study inhalation anthrax

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

Asgharian, Bahman; Price, Owen; Kabilan, Senthil

Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits asmore » a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.« less

Lung function parameters improve prediction of VO2peak in an elderly population: The Generation 100 study.

PubMed

Hassel, Erlend; Stensvold, Dorthe; Halvorsen, Thomas; Wisløff, Ulrik; Langhammer, Arnulf; Steinshamn, Sigurd

2017-01-01

Peak oxygen uptake (VO2peak) is an indicator of cardiovascular health and a useful tool for risk stratification. Direct measurement of VO2peak is resource-demanding and may be contraindicated. There exist several non-exercise models to estimate VO2peak that utilize easily obtainable health parameters, but none of them includes lung function measures or hemoglobin concentrations. We aimed to test whether addition of these parameters could improve prediction of VO2peak compared to an established model that includes age, waist circumference, self-reported physical activity and resting heart rate. We included 1431 subjects aged 69-77 years that completed a laboratory test of VO2peak, spirometry, and a gas diffusion test. Prediction models for VO2peak were developed with multiple linear regression, and goodness of fit was evaluated. Forced expiratory volume in one second (FEV1), diffusing capacity of the lung for carbon monoxide and blood hemoglobin concentration significantly improved the ability of the established model to predict VO2peak. The explained variance of the model increased from 31% to 48% for men and from 32% to 38% for women (p<0.001). FEV1, diffusing capacity of the lungs for carbon monoxide and hemoglobin concentration substantially improved the accuracy of VO2peak prediction when added to an established model in an elderly population.

Effects of budesonide on the lung functions, inflammation and apoptosis in a saline-lavage model of acute lung injury.

PubMed

Mokra, D; Kosutova, P; Balentova, S; Adamkov, M; Mikolka, P; Mokry, J; Antosova, M; Calkovska, A

2016-12-01

Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26.7 kPa in FiO 2 1.0. Then, one group of animals was treated with corticosteroid budesonide (Pulmicort susp inh, AstraZeneca; 0.25 mg/kg) given intratracheally by means of inpulsion regime of high-frequency jet ventilation, while another group was non-treated, and both groups were oxygen-ventilated for following 5 hours. Another group of animals served as healthy controls. After sacrifice of animals, left lung was saline-lavaged and protein content was measured and cells in the lavage fluid were determined microscopically. Right lung tissue was used for estimation of edema formation (expressed as wet/dry weight ratio), for histomorphological investigation, immunohistochemical determination of apoptosis of lung cells, and for determination of markers of inflammation and lung injury (IL-1β, IL-6, IL-8, TNF-α, IFNγ, esRAGE, caspase-3) by ELISA methods. Levels of several cytokines were estimated also in plasma. Repetitive lung lavage worsened gas exchange, induced lung injury, inflammation and lung edema and increased apoptosis of lung epithelial cells. Budesonide reduced lung edema, cell infiltration into the lung and apoptosis of epithelial cells and decreased concentrations of proinflammatory markers in the lung and blood. These changes resulted in improved ventilation. Concluding, curative intratracheal treatment with budesonide alleviated lung injury, inflammation, apoptosis of lung epithelial cells and lung edema and improved lung functions in a lavage model of ALI. These findings suggest a potential of therapy with inhaled budesonide also for patients with ARDS.

Unravelling a Clinical Paradox - Why Does Bronchial Thermoplasty Work in Asthma?

PubMed

Donovan, Graham M; Elliot, John G; Green, Francis H Y; James, Alan L; Noble, Peter B

2018-04-18

Rationale Bronchial thermoplasty is a relatively new but effective treatment in asthmatic subjects who do not respond to conventional therapy. While the favoured mechanism is ablation of the airway smooth muscle layer, because bronchial thermoplasty treats only a small number of central airways, there is ongoing debate regarding its precise method of action. Objectives Elucidate the underlying method of action behind bronchial thermoplasty. Methods We employ a combination of extensive human lung specimens and novel computational methods. Whole left lungs were acquired from the Prairie Provinces Fatal Asthma Study. Subjects were classified as control (N=31), non-fatal asthma (N=32), or fatal asthma (N=25). Simulated lungs for each group were constructed stochastically, and flow distributions and functional indicators were quantified both before and after a 70% reduction in airway smooth muscle in the thermoplasty-treated airways. Main Results Bronchial thermoplasty triggers global redistribution of clustered flow patterns, wherein structural changes to the treated central airways lead to a re-opening cascade in the small airways and significant improvement in lung function via reduced spatial heterogeneity of flow patterns. This mechanism accounts for progressively greater efficacy of thermoplasty with both severity of asthma and degree of muscle activation, consistent with existing empirical results. Conclusions We report a probable mechanism of action for bronchial thermoplasty: alteration of lung-wide flow patterns in response to structural alteration of the treated central airways. This insight could lead to improved therapy via patient-specific, tailored versions of the treatment -- as well as implications for more conventional asthma therapies.

Estimating local scaling properties for the classification of interstitial lung disease patterns

NASA Astrophysics Data System (ADS)

Huber, Markus B.; Nagarajan, Mahesh B.; Leinsinger, Gerda; Ray, Lawrence A.; Wismueller, Axel

2011-03-01

Local scaling properties of texture regions were compared in their ability to classify morphological patterns known as 'honeycombing' that are considered indicative for the presence of fibrotic interstitial lung diseases in high-resolution computed tomography (HRCT) images. For 14 patients with known occurrence of honeycombing, a stack of 70 axial, lung kernel reconstructed images were acquired from HRCT chest exams. 241 regions of interest of both healthy and pathological (89) lung tissue were identified by an experienced radiologist. Texture features were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM), Minkowski Dimensions (MDs), and the estimation of local scaling properties with Scaling Index Method (SIM). A k-nearest-neighbor (k-NN) classifier and a Multilayer Radial Basis Functions Network (RBFN) were optimized in a 10-fold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions including the Bonferroni correction. The best classification results were obtained by the set of SIM features, which performed significantly better than all the standard GLCM and MD features (p < 0.005) for both classifiers with the highest accuracy (94.1%, 93.7%; for the k-NN and RBFN classifier, respectively). The best standard texture features were the GLCM features 'homogeneity' (91.8%, 87.2%) and 'absolute value' (90.2%, 88.5%). The results indicate that advanced texture features using local scaling properties can provide superior classification performance in computer-assisted diagnosis of interstitial lung diseases when compared to standard texture analysis methods.

Decreased lung function with mediation of blood parameters linked to e-waste lead and cadmium exposure in preschool children.

PubMed

Zeng, Xiang; Xu, Xijin; Boezen, H Marike; Vonk, Judith M; Wu, Weidong; Huo, Xia

2017-11-01

Blood lead (Pb) and cadmium (Cd) levels have been associated with lower lung function in adults and smokers, but whether this also holds for children from electronic waste (e-waste) recycling areas is still unknown. To investigate the contribution of blood heavy metals and lung function levels, and the relationship among living area, the blood parameter levels, and the lung function levels, a total of 206 preschool children from Guiyu (exposed area), and Haojiang and Xiashan (reference areas) were recruited and required to undergo blood tests and lung function tests during the study period. Preschool children living in e-waste exposed areas were found to have a 1.37 μg/dL increase in blood Pb, 1.18 μg/L increase in blood Cd, and a 41.00 × 10 9 /L increase in platelet counts, while having a 2.82 g/L decrease in hemoglobin, 92 mL decrease in FVC and 86 mL decrease in FEV 1 . Each unit of hemoglobin (1 g/L) decline was associated with 5 mL decrease in FVC and 4 mL decrease in FEV 1 . We conclude that children living in e-waste exposed area have higher levels of blood Pb, Cd and platelets, and lower levels of hemoglobin and lung function. Hemoglobin can be a good predictor for lung function levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic effects of air pollution on lung function after lung transplantation in the Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) study.

PubMed

Benmerad, Meriem; Slama, Rémy; Botturi, Karine; Claustre, Johanna; Roux, Antoine; Sage, Edouard; Reynaud-Gaubert, Martine; Gomez, Carine; Kessler, Romain; Brugière, Olivier; Mornex, Jean-François; Mussot, Sacha; Dahan, Marcel; Boussaud, Véronique; Danner-Boucher, Isabelle; Dromer, Claire; Knoop, Christiane; Auffray, Annick; Lepeule, Johanna; Malherbe, Laure; Meleux, Frederik; Nicod, Laurent; Magnan, Antoine; Pison, Christophe; Siroux, Valérie

2017-01-01

An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs).The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6 months. The levels of air pollutants (nitrogen dioxide (NO 2 ), particulate matter with an aerodynamic cut-off diameter of x µm (PM x ) and ozone (O 3 )) at the patients' home address were averaged in the 12 months before each spirometry test. The effects of air pollutants on forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) in % predicted were estimated using mixed linear regressions. We assessed the effect modification of macrolide antibiotics in this relationship.Increased 12-month levels of pollutants were associated with lower levels of FVC % pred (-2.56%, 95% CI -3.86--1.25 for 5 µg·m -3 of PM 10 ; -0.75%, 95% CI -1.38--0.12 for 2 µg·m -3 of PM 2.5 and -2.58%, 95% CI -4.63--0.53 for 10 µg·m -3 of NO 2 ). In patients not taking macrolides, the deleterious association between PM and FVC tended to be stronger and PM 10 was associated with lower FEV 1 Our study suggests a deleterious effect of chronic exposure to air pollutants on lung function levels in LTRs, which might be modified with macrolides. Copyright ©ERS 2017.

Perinatal stress and early life programming of lung structure and function

PubMed Central

Wright, Rosalind J.

2010-01-01

Exposure to environmental toxins during critical periods of prenatal and/or postnatal development may alter the normal course of lung morphogenesis and maturation, potentially resulting in changes that affect both structure and function of the respiratory system. Moreover, these early effects may persist into adult life magnifying the potential public health impact. Aberrant or excessive pro-inflammatory immune responses, occurring both locally and systemically, that result in inflammatory damage to the airway are a central determinant of lung structure-function changes throughout life. Disruption of neuroendocrine function in early development, specifically the hypothalamic-pituitary-adrenal (HPA) axis, may alter functional status of the immune system. Autonomic nervous system (ANS) function (sympathovagal imbalance) is another integral component of airway function and immunity in childhood. This overview discusses the evidence linking psychological factors to alterations in these interrelated physiological processes that may, in turn, influence childhood lung function and identifies gaps in our understanding. PMID:20080145

Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy.

PubMed

Dane, D Merrill; Yan, Xiao; Tamhane, Rahul M; Johnson, Robert L; Estrera, Aaron S; Hogg, Deborah C; Hogg, Richard T; Hsia, Connie C W

2004-03-01

To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-CT)) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-CT) were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.

Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway

PubMed Central

Hwang, Jae-Woong; Sundar, Isaac K.; Yao, Hongwei; Sellix, Michael T.; Rahman, Irfan

2014-01-01

Patients with obstructive lung diseases display abnormal circadian rhythms in lung function. We determined the mechanism whereby environmental tobacco/cigarette smoke (CS) modulates expression of the core clock gene BMAL1, through Sirtuin1 (SIRT1) deacetylase during lung inflammatory and injurious responses. Adult C57BL6/J and various mice mutant for SIRT1 and BMAL1 were exposed to both chronic (6 mo) and acute (3 and 10 d) CS, and we measured the rhythmic expression of clock genes, circadian rhythms of locomotor activity, lung function, and inflammatory and emphysematous responses in the lungs. CS exposure (100–300 mg/m3 particulates) altered clock gene expression and reduced locomotor activity by disrupting the central and peripheral clocks and increased lung inflammation, causing emphysema in mice. BMAL1 was acetylated and degraded in the lungs of mice exposed to CS and in patients with chronic obstructive pulmonary disease (COPD), compared with lungs of the nonsmoking controls, linking it mechanistically to CS-induced reduction of SIRT1. Targeted deletion of Bmal1 in lung epithelium augmented inflammation in response to CS, which was not attenuated by the selective SIRT1 activator SRT1720 (EC50=0.16 μM) in these mice. Thus, the circadian clock, specifically the enhancer BMAL1 in epithelium, plays a pivotal role, mediated by SIRT1-dependent BMAL1, in the regulation of CS-induced lung inflammatory and injurious responses.— Hwang, J.-W., Sundar, I. K., Yao, H., Sellix, M. T., Rahman, I. Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway. PMID:24025728

Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer.

PubMed Central

Isidoro, Antonio; Martínez, Marta; Fernández, Pedro L; Ortega, Alvaro D; Santamaría, Gema; Chamorro, Margarita; Reed, John C; Cuezva, José M

2004-01-01

Recent findings indicate that the expression of the beta-catalytic subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) is depressed in liver, kidney and colon carcinomas, providing further a bioenergetic signature of cancer that is associated with patient survival. In the present study, we performed an analysis of mitochondrial and glycolytic protein markers in breast, gastric and prostate adenocarcinomas, and in squamous oesophageal and lung carcinomas. The expression of mitochondrial and glycolytic markers varied significantly in these carcinomas, when compared with paired normal tissues, with the exception of prostate cancer. Overall, the relative expression of beta-F1-ATPase was significantly reduced in breast and gastric adenocarcinomas, as well as in squamous oesophageal and lung carcinomas, strongly suggesting that alteration of the bioenergetic function of mitochondria is a hallmark of these types of cancer. PMID:14683524

Health hazard evaluation report HETA 88-391-2156, Morton Salt Company, Weeks Island, Louisiana. (Revised April 1993)

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

Ferguson, R.P.; Knutti, E.B.

1993-04-01

In response to a request from the International Chemical Workers Union, an investigation was made of exposures to asbestos and diesel emissions at the Morton Salt Company, Weeks Island, Louisiana. The most significant source of particulates was diesel exhaust. None of the 20 personal breathing zone or area air samples collected in the mill exceeded limits for asbestos. An increased prevalence of chronic cough and phlegm was reported by workers. More complaints of eye irritation and tearing of the eyes were noted in underground workers, consistent with diesel byproduct exposure. Pulmonary function studies indicated that four workers had mild obstructivemore » lung disease and one had moderate obstructive lung disease. Three workers with mild restriction of lung volume were also noted. None of the 61 chest films taken was positive for pneumoconiosis. The authors conclude that a potential hazard existed from exposure to diesel exhaust.« less

Peroxidasin contributes to lung host defense by direct binding and killing of gram-negative bacteria.

PubMed

Shi, Ruizheng; Cao, Zehong; Li, Hong; Graw, Jochen; Zhang, Guogang; Thannickal, Victor J; Cheng, Guangjie

2018-05-01

Innate immune recognition is classically mediated by the interaction of host pattern-recognition receptors and pathogen-associated molecular patterns; this triggers a series of downstream signaling events that facilitate killing and elimination of invading pathogens. In this report, we provide the first evidence that peroxidasin (PXDN; also known as vascular peroxidase-1) directly binds to gram-negative bacteria and mediates bactericidal activity, thus, contributing to lung host defense. PXDN contains five leucine-rich repeats and four immunoglobulin domains, which allows for its interaction with lipopolysaccharide, a membrane component of gram-negative bacteria. Bactericidal activity of PXDN is mediated via its capacity to generate hypohalous acids. Deficiency of PXDN results in a failure to eradicate Pseudomonas aeruginosa and increased mortality in a murine model of Pseudomonas lung infection. These observations indicate that PXDN mediates previously unrecognized host defense functions against gram-negative bacterial pathogens.

miR-448 is a novel prognostic factor of lung squamous cell carcinoma and regulates cells growth and metastasis by targeting DCLK1.

PubMed

Shan, Changting; Fei, Fan; Li, Fengzhu; Zhuang, Bo; Zheng, Yulong; Wan, Yufeng; Chen, Jianhui

2017-05-01

MicroRNA-448 (miR-448) has been showed to be low-expressed and function as tumor suppressor in most human cancers. However, there are limited reports on the clinical significance and biological function of miR-448 in lung squamous cell carcinoma. In this study, we observed that miR-448 expression was decreased in lung squamous cell carcinoma tissues and cell lines. Meanwhile, miR-448 expression associated with differentiated degree, T classification (tumor size), N classification (lymph node metastasis), M classification (distant metastasis), clinical stage and prognosis of lung squamous cell carcinoma patients. In survival analysis, low expression of miR-448 was a poor independent prognostic factor for lung squamous cell carcinoma patients. Moreover, gain-of-function and loss-of-function studies showed miR-448 acted as a tumor suppressor regulating lung squamous cell carcinoma cells growth and metastasis. Furthermore, DCLK1 has been identified as a potential target for miR-448 to regulate lung squamous cell carcinoma cells growth and metastasis. In conclusion, miR-448 low-expression was a poor prognostic factor for lung squamous cell carcinoma patients, and miR-448 served as a tumor suppressor in lung squamous cell carcinoma cells via targeting DCLK1. Copyright © 2017. Published by Elsevier Masson SAS.

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

Relation between lung function, exercise capacity, and exposure to asbestos cement.

PubMed Central

Wollmer, P; Eriksson, L; Jonson, B; Jakobsson, K; Albin, M; Skerfving, S; Welinder, H

1987-01-01

A group of 137 male workers with known exposure (mean 20 fibre years per millilitre) to asbestos cement who had symptoms or signs of pulmonary disease was studied together with a reference group of 49 healthy industrial workers with no exposure to asbestos. Lung function measurements were made at rest and during exercise. Evidence of lung fibrosis was found as well as of obstructive airways disease in the exposed group compared with the reference group. Asbestos cement exposure was related to variables reflecting lung fibrosis but not to variables reflecting airflow obstruction. Smoking was related to variables reflecting obstructive lung disease. Exercise capacity was reduced in the exposed workers and was related to smoking and to lung function variables, reflecting obstructive airways disease. There was no significant correlation between exercise capacity and exposure to asbestos cement. PMID:3651353

[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.

Common cold decreases lung function in infants with recurrent wheezing.

PubMed

Mallol, J; Aguirre, V; Wandalsen, G

2010-01-01

Common acute viral respiratory infections (colds) are the most frequent cause of exacerbations in infants with recurrent wheezing (RW). However, there is no quantitative information about the effect of colds on the lung function of infants with RW. This study was undertaken to determine the effect of common cold on forced expiratory parameters measured from raised lung volume in infants with RW. Spirometric lung function (expiratory flows from raised lung volume) was randomly assessed in 28 infants with RW while they had a common cold and when asymptomatic. It was found that during colds there was a significant decrease in all forced expiratory parameters and this was much more evident for flows (FEF(50%), FEF(75%) and FEF(25-75%)) which were definitively abnormal (less than -1.65 z-score) in the majority of infants. There was not association between family asthma, tobacco exposure, and other factors, with the extent of lung function decrease during colds. Tobacco during pregnancy but not a history of family asthma was significantly associated to lower expiratory flows; however, the association was significant only when infants were asymptomatic. This study shows that common colds cause a marked reduction of lung function in infants with RW. 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Video-assisted thoracoscopic bullectomy and talc poudrage for spontaneous pneumothoraces: effect on short-term lung function.

PubMed

Dubois, Luc; Malthaner, Richard A

2010-12-01

We measured lung function before and after video-assisted thoracoscopic apical bullectomy and talc poudrage in patients with spontaneous pneumothoraces. Seventy-two patients were prospectively followed up for 12 months. The indications for surgery were recurrent pneumothoraces (n = 58), bilateral pneumothoraces (n = 8), and persistent air leak (n = 6). There were 46 males and 26 females with mean age of 29 years (range 15-61 years). The results were analyzed using paired t tests. There were no recurrences. There were 4 complications (5.6%): 1 wound infection, 1 case of pneumonia, and 2 persistent air leaks each lasting 1 week. There were no conversions to open surgery. Preoperative and 6-month pulmonary function test results were available on 41 patients, and 35 patients completed 12-month pulmonary function tests. Twelve-month values (mean percent ± SD) were as follows: Forced expiratory volume in 1 second fell from 95 ± 19 to 89 ± 16 (P = .02); forced expiratory volume in 1 second/forced vital capacity ratio was unchanged, 95 ± 12 versus 94 ± 13 (P = .9); total lung capacity fell from 106 ± 19 to 98 ± 12 (P = 0.002); vital capacity fell from 100 ± 22 to 96 ± 16 (P = .05); residual volume fell from 126 ± 32 to 107 ± 29 (P = .002); and diffusion capacity for carbon monoxide corrected for alveolar volume was unchanged, 88 ± 15 versus 91 ± 17 (P = .07). Flow rates and diffusion capacities were preserved, but lung volumes were slightly reduced at 1 year. Video-assisted thoracoscopic apical bullectomy and talc poudrage is an effective treatment for spontaneous pneumothoraces with a low complication rate and recurrence rate and only minor changes in pulmonary function at 1 year. Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Post-tuberculous lung function impairment in a tuberculosis reference clinic in Cameroon.

PubMed

Mbatchou Ngahane, Bertrand Hugo; Nouyep, Junior; Nganda Motto, Malea; Mapoure Njankouo, Yacouba; Wandji, Adeline; Endale, Mireille; Afane Ze, Emmanuel

2016-05-01

After completion of treatment, a proportion of pulmonary TB (pTB) patients experience lung function impairment which can influence their quality of life. This study aimed to determine the prevalence of lung function impairment in patients treated for pTB and investigate its associated factors. A cross-sectional study was conducted in TB clinic of the Douala Laquintinie Hospital in Cameroon. Patients aged 15 and above who were treated for pTB between 2008 and 2012 were included in the study. Demographic data, respiratory symptoms prior TB diagnosis, comorbidities and chest radiography findings prior to TB treatment were collected. All participants underwent spirometric measurements. Airflow obstruction was defined as a post-bronchodilation FEV1/FVC <70% with FVC >80%, restrictive defects as an FEV1/FVC ratio of ≥70% with an FVC <80% predicted, and mixed defects as FVC of <80% predicted and an FEV1/FVC ratio of <70%. Lung function impairment was defined by the presence of at least one of these three abnormalities. Logistic regression analysis was employed to investigate risk factors of lung function impairment. Of a total of 269 participants included in the study, 146 (54.3%) were male. The median age of participants was 33 years. The median duration of symptoms before diagnosis of TB was 4 weeks [interquartile range (IQR) 3-8]. The prevalence of lung function impairment was 45.4% (95% CI 39-51). The multivariate analysis identified duration of symptoms [OR 1.08; 95% CI (1.01-1.15)] and fibrotic pattern [OR 3.54; 95% CI (1.40-8.95)] as independent risk factors for lung function impairment. Post-tuberculous pulmonary function impairment is frequent in Douala. Sensitization of patient with symptoms of pulmonary TB for an earlier visit to healthcare facilities could reduce the impact of pTB on lung function of patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Towards a virtual lung: multi-scale, multi-physics modelling of the pulmonary system.

PubMed

Burrowes, K S; Swan, A J; Warren, N J; Tawhai, M H

2008-09-28

The essential function of the lung, gas exchange, is dependent on adequate matching of ventilation and perfusion, where air and blood are delivered through complex branching systems exposed to regionally varying transpulmonary and transmural pressures. Structure and function in the lung are intimately related, yet computational models in pulmonary physiology usually simplify or neglect structure. The geometries of the airway and vascular systems and their interaction with parenchymal tissue have an important bearing on regional distributions of air and blood, and therefore on whole lung gas exchange, but this has not yet been addressed by modelling studies. Models for gas exchange have typically incorporated considerable detail at the level of chemical reactions, with little thought for the influence of structure. To date, relatively little attention has been paid to modelling at the cellular or subcellular level in the lung, or to linking information from the protein structure/interaction and cellular levels to the operation of the whole lung. We review previous work in developing anatomically based models of the lung, airways, parenchyma and pulmonary vasculature, and some functional studies in which these models have been used. Models for gas exchange at several spatial scales are briefly reviewed, and the challenges and benefits from modelling cellular function in the lung are discussed.

Antihistamine medication may alleviate negative effects of prenatal exposure to polycyclic aromatic hydrocarbons (PAH) on lung function in children. Birth cohort prospective study.

PubMed

Jedrychowski, Wieslaw A; Perera, Frederica P; Maugeri, Umberto; Majewska, Renata; Spengler, Jack; Mroz, Elzbieta; Flak, Elzbieta; Klimaszewska-Rembiasz, Maria; Camman, David

2015-05-01

The main purpose of the present study was to test the hypothesis that the depressed lung growth attributable to prenatal exposure to polycyclic aromatic hydrocarbons (PAH) may be modified by the intake of antihistamine medications. Individual prenatal PAH exposure was assessed by personal air monitoring in 176 children who were followed over nine years, in the course of which outdoor residential air monitoring, allergic skin tests for indoor allergens, lung function tests (FVC, FEV(1), FEV(05), and FEF(25-75)) were performed. The analysis with the General Estimated Equation (GEE) showed no association between prenatal PAH exposure and lung function in the group of children who were reported to be antihistamine users. However, in the group of antihistamine non-users all lung function tests except for FEF(25-75) were significantly and inversely associated with prenatal airborne PAH exposure. The results of the study suggest that the intake of antihistamine medications in early childhood may inhibit the negative effect of fetal PAH exposure on lung growth and provides additional indirect evidence for the hypothesis that lung alterations in young children resulting from PAH exposure may be caused by the allergic inflammation within lung. © 2014 Wiley Periodicals, Inc.

Housing conditions, respiratory illness, and lung function in children in South Wales.

PubMed Central

Yarnell, J W; St Leger, A S

1977-01-01

The hypothesis was tested that respiratory illness in children occurs more commonly in old housing than in housing built to modern standards. Three areas of housing were chosen in a South Wales valley: a recently constructed council estate with district central heating; a modern council estate heated with open coal fires; and an area of much older, traditional valley housing. Mothers reported the greatest proportion of children free of colds and sore throats during the previous 12 months in the area of traditional valley housing; mothers of children in the centrally heated estate reported the least proportion of children free of colds. Children's lung function was best in the area of traditional valley housing and worst in the centrally heated council estate. Data on demographic indices and respiratory morbidity suggest that the inhabitants of the two council estates have comparable characteristics. Another hypothesis which may explain the findings is proposed. PMID:588858

Biomarkers of carcinogen exposure and cancer risk in a coke plant.

PubMed Central

Assennato, G; Ferri, G M; Tockman, M S; Poirier, M C; Schoket, B; Porro, A; Corrado, V; Strickland, P T

1993-01-01

To evaluate the association between an indicator of carcinogen exposure (peripheral blood leukocyte DNA adducts of polycyclic aromatic hydrocarbons) and an early indicator of neoplastic transformation (sputum epithelial cell membrane antigens binding by monoclonal antibodies against small cell lung cancer and against nonsmall cell lung cancer), a survey of 350 coke-oven workers and 100 unexposed workers was planned. This paper reports a pilot investigation on a subgroup of 23 coke-oven workers and 8 unexposed controls. A "gas regulator" worker with positive tumor antigen binding was identified. Results show that smokers, subjects with decreased pulmonary function (forced expiratory volume in 1 sec/forced vital capacity% < 80), and those with morphological dysplasia of sputum cells have higher levels of DNA adducts. The gas regulators showed the highest values for adducts; however, no significant difference of adduct levels was found between the coke-oven group and unexposed controls. PMID:8319632

[Research advance on mechanism and application of HATs and HDACs in epithelial-mesenchymal transition of lung cancer].

PubMed

Chang, Rui; You, Jiacong; Zhou, Qinghua

2013-04-01

Lung cancer is one of the most common diseases that endanger health and life of people domestically. A number of recurrence and death of lung cancer originated from metastasis. As a key step in metastasis of lung cancer, epithelial to mesenchymal transition involved down-regulation of E-cadherin, as well as regulated by EMT transcription factors. HATs and HDACs is a protein family that catalyzes acetylation and deacetylation of histones. Not only they have vital functions in tumor pathogenesis, but also participate in the EMT of lung cancer. HATs and HDACs interact with certain EMT transcription factors. Moreover, the function of these EMT transcription factors may be regulated by acetylation, which has influence on EMT program in lung cancer. Therefore, this review introduces the event of HATs and HDACs function in EMT of lung cancer, and investigate the molecular mechanism of their interaction. Then, the potential of HDAC inhibitor utilization in the inhibition of EMT and lung cancer therapy were discussed, as to pave the way for the related basic research and clinical practice.

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

Characteristic patterns in the fibrotic lung. Comparing idiopathic pulmonary fibrosis with chronic lung allograft dysfunction.

PubMed

Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver

2015-03-01

Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.

Lung densitometry: why, how and when

PubMed Central

Camiciottoli, Gianna; Diciotti, Stefano

2017-01-01

Lung densitometry assesses with computed tomography (CT) the X-ray attenuation of the pulmonary tissue which reflects both the degree of inflation and the structural lung abnormalities implying decreased attenuation, as in emphysema and cystic diseases, or increased attenuation, as in fibrosis. Five reasons justify replacement with lung densitometry of semi-quantitative visual scales used to measure extent and severity of diffuse lung diseases: (I) improved reproducibility; (II) complete vs. discrete assessment of the lung tissue; (III) shorter computation times; (IV) better correlation with pathology quantification of pulmonary emphysema; (V) better or equal correlation with pulmonary function tests (PFT). Commercially and open platform software are available for lung densitometry. It requires attention to technical and methodological issues including CT scanner calibration, radiation dose, and selection of thickness and filter to be applied to sections reconstructed from whole-lung CT acquisition. Critical is also the lung volume reached by the subject at scanning that can be measured in post-processing and represent valuable information per se. The measurements of lung density include mean and standard deviation, relative area (RA) at −970, −960 or −950 Hounsfield units (HU) and 1st and 15th percentile for emphysema in inspiratory scans, and RA at −856 HU for air trapping in expiratory scans. Kurtosis and skewness are used for evaluating pulmonary fibrosis in inspiratory scans. The main indication for lung densitometry is assessment of emphysema component in the single patient with chronic obstructive pulmonary diseases (COPD). Additional emerging applications include the evaluation of air trapping in COPD patients and in subjects at risk of emphysema and the staging in patients with lymphangioleiomyomatosis (LAM) and with pulmonary fibrosis. It has also been applied to assess prevalence of smoking-related emphysema and to monitor progression of smoking-related emphysema, alpha1 antitrypsin deficiency emphysema, and pulmonary fibrosis. Finally, it is recommended as end-point in pharmacological trials of emphysema and lung fibrosis. PMID:29221318

WE-G-BRD-07: Investigation of Distal Lung Atelectasis Following Stereotactic Body Radiation Therapy Using Regional Lung Volume Changes Between Pre- and Post- Treatment CT Scans

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

Diot, Q; Kavanagh, B; Miften, M

2014-06-15

Purpose: To propose a quantitative method using lung deformations to differentiate between radiation-induced fibrosis and potential airway stenosis with distal atelectasis in patients treated with stereotactic body radiation therapy (SBRT) for lung tumors. Methods: Twenty-four lung patients with large radiation-induced density increases outside the high dose region had their pre- and post-treatment CT scans manually registered. They received SBRT treatments at our institution between 2002 and 2009 in 3 or 5 fractions, to a median total dose of 54Gy (range, 30–60). At least 50 anatomical landmarks inside the lung (airway branches) were paired for the pre- and post-treatment scans tomore » guide the deformable registration of the lung structure, which was then interpolated to the whole lung using splines. Local volume changes between the planning and follow-up scans were calculated using the deformation field Jacobian. Hyperdense regions were classified as atelectatic or fibrotic based on correlations between regional density increases and significant volume contractions compared to the surrounding tissues. Results: Out of 24 patients, only 7 demonstrated a volume contraction that was at least one σ larger than the remaining lung average. Because they did not receive high doses, these shrunk hyperdense regions were likely showing distal atelectasis resulting from radiation-induced airway stenosis rather than conventional fibrosis. On average, the hyperdense regions extended 9.2 cm farther than the GTV contours but not significantly more than 8.6 cm for the other patients (p>0.05), indicating that a large offset between the radiation and hyperdense region centers is not a good surrogate for atelectasis. Conclusion: A method based on the relative comparison of volume changes between different dates was developed to identify potential lung regions experiencing distal atelectasis. Such a tool is essential to study which lung structures need to be avoided to prevent atelectasis and limit lung function loss.« less

[Correlations between OCT4 expression and clinicopathological factors and prognosis of patients with lung adenocarcinoma].

PubMed

Zhang, Xueyan; Wang, Huimin; Jin, Bo; Dong, Qianggang; Huang, Jinsu; Han, Baohui

2013-04-01

In recent years, cases of lung adenocarcinoma morbidity have consistently grown. OCT4 is the key gene that controls the automatic renewal of stem cells, and regulates the proliferation and differentiation of cancer stem cells. The aim of this study is to detect OCT4 expression in lung adenocarcinoma tissues, and to evaluate its relevance in the metastasis, chemotherapeutic effect, and prognosis in lung adenocarcinoma patients. Immunofluorescence method was employed to detect OCT4 expression in lung adenocarcinoma tissues. The relationship between OCT4 expression and clinical pathological indicators is examined through chi-square test. Moreover, the survival rate is calculated through the Kaplan-Meier survivorship curve. Finally, the relevance between the indicators and patient survival is estimated using Cox analysis. Among the 126 tissue samples of lung adenocarcinoma, 91 showed OCT4 positive cells. OCT4 expression is closely related to metastasis and chemoresistance in lung adenocarcinoma patients, and negatively corresponds to the patients' disease-free survival and survival periods. OCT4 expression is related to metastasis and chemoresistance in lung adenocarcinoma patients, and thus indicates poor prognosis.

Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema.

PubMed

Mondoñedo, Jarred R; Suki, Béla

2017-02-01

Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction.

Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema

PubMed Central

Mondoñedo, Jarred R.

2017-01-01

Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction. PMID:28182686

MicroRNA-944 Affects Cell Growth by Targeting EPHA7 in Non-Small Cell Lung Cancer.

PubMed

Liu, Minxia; Zhou, Kecheng; Cao, Yi

2016-09-26

MicroRNAs (miRNAs) have critical roles in lung tumorigenesis and development. To determine aberrantly expressed miRNAs involved in non-small cell lung cancer (NSCLC) and investigate pathophysiological functions and mechanisms, we firstly carried out small RNA deep sequencing in NSCLC cell lines (EPLC-32M1, A549 and 801D) and a human immortalized cell line 16HBE, we then studied miRNA function by cell proliferation and apoptosis. cDNA microarray, luciferase reporter assay and miRNA transfection were used to investigate interaction between the miRNA and target gene. miR-944 was significantly down-regulated in NSCLC and had many putative targets. Moreover, the forced expression of miR-944 significantly inhibited the proliferation of NSCLC cells in vitro. By integrating mRNA expression data and miR-944-target prediction, we disclosed that EPHA7 was a potential target of miR-944, which was further verified by luciferase reporter assay and microRNA transfection. Our data indicated that miR-944 targets EPHA7 in NSCLC and regulates NSCLC cell proliferation, which may offer a new mechanism underlying the development and progression of NSCLC.

Low level CO2 effects on pulmonary function in humans

NASA Technical Reports Server (NTRS)

Sexton, J.; Mueller, K.; Elliott, A.; Gerzer, D.; Strohl, K. P.; West, J. B. (Principal Investigator)

1998-01-01

The purpose of the study was to determine whether chamber exposure to low levels of CO2 results in functional alterations in gas mixing and closing volume in humans. Four healthy volunteer subjects were exposed to 0.7% CO2 and to 1.2% CO2. Spirometry, lung volumes, single breath nitrogen washout, diffusing capacity for carbon monoxide (DLCO) by two methods, and cardiac output were measured in triplicate. Values were obtained over two non-consecutive days during the training period (control) and on days 2 or 3, 4, 6, 10, 13, and 23 of exposure to each CO2 level. Measurements were made during the same time of day. There was one day of testing after exposure, while still in the chamber but off carbon dioxide. The order of testing, up until measurements of DLCO and cardiac output, were randomized to avoid presentation effects. The consistent findings were a reduction in diffusing capacity for carbon monoxide and a fall in cardiac output, occurring to a similar degree with both exposures. For the group as a whole, there was no indication of major effects on spirometry, lung volumes, gas mixing or dead space. We conclude that small changes may occur in the function of distal gas exchanging units; however, these effects were not associated with any adverse health effects. The likelihood of pathophysiologic changes in lung function or structure with 0.7 or 1.2% CO2 exposure for this period of time, is therefore, low.

Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis

USDA-ARS?s Scientific Manuscript database

Pulmonary neuroendocrine cells (PNECs) are proposed to be the first specialized cell type to appear in the lung, but their ontogeny remains obscure. Although studies of PNECs have suggested their involvement in a number of lung functions, neither their in vivo significance nor the molecular mechanis...

Imaging Lung Function in Mice Using SPECT/CT and Per-Voxel Analysis

PubMed Central

Jobse, Brian N.; Rhem, Rod G.; McCurry, Cory A. J. R.; Wang, Iris Q.; Labiris, N. Renée

2012-01-01

Chronic lung disease is a major worldwide health concern but better tools are required to understand the underlying pathologies. Ventilation/perfusion (V/Q) single photon emission computed tomography (SPECT) with per-voxel analysis allows for non-invasive measurement of regional lung function. A clinically adapted V/Q methodology was used in healthy mice to investigate V/Q relationships. Twelve week-old mice were imaged to describe normal lung function while 36 week-old mice were imaged to determine how age affects V/Q. Mice were ventilated with Technegas™ and injected with 99mTc-macroaggregated albumin to trace ventilation and perfusion, respectively. For both processes, SPECT and CT images were acquired, co-registered, and quantitatively analyzed. On a per-voxel basis, ventilation and perfusion were moderately correlated (R = 0.58±0.03) in 12 week old animals and a mean log(V/Q) ratio of −0.07±0.01 and standard deviation of 0.36±0.02 were found, defining the extent of V/Q matching. In contrast, 36 week old animals had significantly increased levels of V/Q mismatching throughout the periphery of the lung. Measures of V/Q were consistent across healthy animals and differences were observed with age demonstrating the capability of this technique in quantifying lung function. Per-voxel analysis and the ability to non-invasively assess lung function will aid in the investigation of chronic lung disease models and drug efficacy studies. PMID:22870297

High resolution multidetector CT aided tissue analysis and quantification of lung fibrosis

NASA Astrophysics Data System (ADS)

Zavaletta, Vanessa A.; Karwoski, Ronald A.; Bartholmai, Brian; Robb, Richard A.

2006-03-01

Idiopathic pulmonary fibrosis (IPF, also known as Idiopathic Usual Interstitial Pneumontis, pathologically) is a progressive diffuse lung disease which has a median survival rate of less than four years with a prevalence of 15-20/100,000 in the United States. Global function changes are measured by pulmonary function tests and the diagnosis and extent of pulmonary structural changes are typically assessed by acquiring two-dimensional high resolution CT (HRCT) images. The acquisition and analysis of volumetric high resolution Multi-Detector CT (MDCT) images with nearly isotropic pixels offers the potential to measure both lung function and structure. This paper presents a new approach to three dimensional lung image analysis and classification of normal and abnormal structures in lungs with IPF.

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

A Catalog of Genes Homozygously Deleted in Human Lung Cancer and the Candidacy of PTPRD as a Tumor Suppressor Gene

PubMed Central

Kohno, Takashi; Otsuka, Ayaka; Girard, Luc; Sato, Masanori; Iwakawa, Reika; Ogiwara, Hideaki; Sanchez-Cespedes, Montse; Minna, John D.; Yokota, Jun

2010-01-01

A total of 176 genes homozygously deleted in human lung cancer were identified by DNA array-based whole genome scanning of 52 lung cancer cell lines and subsequent genomic PCR in 74 cell lines, including the 52 cell lines scanned. One or more exons of these genes were homozygously deleted in one (1%) to 20 (27%) cell lines. These genes included known tumor suppressor genes, e.g., CDKN2A/p16, RB1, and SMAD4, and candidate tumor suppressor genes whose hemizygous or homozygous deletions were reported in several types of human cancers, such as FHIT, KEAP1, and LRP1B/LRP-DIP. CDKN2A/p16 and p14ARF located in 9p21 were most frequently deleted (20/74, 27%). The PTPRD gene was most frequently deleted (8/74, 11%) among genes mapping to regions other than 9p21. Somatic mutations, including a nonsense mutation, of the PTPRD gene were detected in 8/74 (11%) of cell lines and 4/95 (4%) of surgical specimens of lung cancer. Reduced PTPRD expression was observed in the majority (>80%) of cell lines and surgical specimens of lung cancer. Therefore, PTPRD is a candidate tumor suppressor gene in lung cancer. Microarray-based expression profiling of 19 lung cancer cell lines also indicated that some of the 176 genes, such as KANK and ADAMTS1, are preferentially inactivated by epigenetic alterations. Genetic/epigenetic as well as functional studies of these 176 genes will increase our understanding of molecular mechanisms behind lung carcinogenesis. PMID:20073072

The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure.

PubMed

Jones, Christina V; Alikhan, Maliha A; O'Reilly, Megan; Sozo, Foula; Williams, Timothy M; Harding, Richard; Jenkin, Graham; Ricardo, Sharon D

2014-09-06

Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration. Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 μg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry. Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an exacerbation of lung injury. The trophic functions of macrophages in lung development requires further elucidation in order to explore macrophage modulation as a strategy for promoting lung maturation.

Lung perfusion measured using magnetic resonance imaging: New tools for physiological insights into the pulmonary circulation.

PubMed

Hopkins, Susan R; Prisk, G Kim

2010-12-01

Since the lung receives the entire cardiac output, sophisticated imaging techniques are not required in order to measure total organ perfusion. However, for many years studying lung function has required physiologists to consider the lung as a single entity: in imaging terms as a single voxel. Since imaging, and in particular functional imaging, allows the acquisition of spatial information important for studying lung function, these techniques provide considerable promise and are of great interest for pulmonary physiologists. In particular, despite the challenges of low proton density and short T2* in the lung, noncontrast MRI techniques to measure pulmonary perfusion have several advantages including high reliability and the ability to make repeated measurements under a number of physiologic conditions. This brief review focuses on the application of a particular arterial spin labeling (ASL) technique, ASL-FAIRER (flow sensitive inversion recovery with an extra radiofrequency pulse), to answer physiologic questions related to pulmonary function in health and disease. The associated measurement of regional proton density to correct for gravitational-based lung deformation (the "Slinky" effect (Slinky is a registered trademark of Pauf-Slinky incorporated)) and issues related to absolute quantification are also discussed. Copyright © 2010 Wiley-Liss, Inc.

Respiratory Symptoms, Sleep, and Quality of Life in Patients With Advanced Lung Cancer.

PubMed

Lou, Vivian W Q; Chen, Elaine J; Jian, Hong; Zhou, Zhen; Zhu, Jingfen; Li, Guohong; He, Yaping

2017-02-01

Maintenance of quality of life and symptom management are important in lung cancer therapy. To the author's knowledge, the interplay of respiratory symptoms and sleep disturbance in affecting quality of life in advanced lung cancer remains unexamined. The study was designed to examine the relationships among respiratory symptoms, sleep disturbance, and quality of life in patients with advanced lung cancer. A total of 128 patients with advanced lung cancer (from chest oncology inpatient-units in Shanghai, China) participated in the study. They completed two questionnaires: the Functional Assessment of Cancer Therapy-Lung and the Pittsburgh Sleep Quality Index. Symptomatic breathing difficulty, coughing, shortness of breath, and tightness in the chest were reported in 78.1%, 70.3%, 60.9%, and 60.2% of the patients, respectively. Sleep disturbance affected 62.5% of the patients. The patients with severe respiratory symptoms were more likely to be poor sleepers and to have a lower quality of life. After the covariates were controlled for, regression analysis showed that respiratory symptoms and sleep disturbance were significant indicators of quality of life. In addition, some of the effect of the respiratory symptoms on quality of life was mediated by sleep disturbance. Respiratory symptoms and sleep disturbance were common in the advanced lung cancer patients and had a negative impact on their quality of life; sleep disturbance may mediate the relationship between respiratory symptoms and quality of life. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Prolonged use of wind or brass instruments does not alter lung function in musicians.

PubMed

Fuhrmann, Anita G; Franklin, Peter J; Hall, Graham L

2011-05-01

Respiratory function impacts on musical expression for wind/brass (W/B) musicians. Investigation of musicians' respiratory health to date has rarely progressed further than assessments of flow limitation through spirometry. This study aimed to compare W/B musicians' respiratory function to a non-wind/brass (NW/B) group with a comprehensive respiratory function assessment. Non-smoking, non-asthmatic participants aged 18-60 years completed a respiratory health questionnaire followed by spirometry, static lung volumes, respiratory mechanics, using forced oscillations, gas transfer and airway responsiveness (AR). Measurements were compared between participant groups using T-tests and linear regression modelling. Data from 102 participants (55 W/B musicians and 47 NW/B subjects) were included in the analysis. There were no differences between the two groups for any spirometry or lung volume outcomes, with the exception of RV/TLC which was decreased among W/B musicians (p=0.03). Measures of gas transfer and AR were similar between participant groups. Resistance at 6 Hz, measured by forced oscillation, was increased among W/B musicians compared to NW/B musicians (p=0.02) but reactance at 6 Hz was similar between the groups (p=0.10). The results suggest that W/B musicians' do not have altered respiratory function when compared to a non-musical control group. However, increased R(rs6) may indicate inflammatory, remodelling or other pathophysiological processes associated with W/B playing. Although the difference between groups was small it warrants further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Invited commentary: on population subgroups, mathematics, and interventions.

PubMed

Jacobs, David R; Meyer, Katie A

2011-02-15

New sex-specific equations, each with race/ethnic-specific intercept, for predicted lung function illustrate a methodological point, that complex differences between groups may not imply interactions with other predictors, such as age and height. The new equations find that race/ethnic identity does not interact with either age or height in the prediction equations, although there are race/ethnic-specific offsets. Further study is warranted of the effect of possible small race/ethnic interactions on disease classification. Additional study of repeated measures of lung function is warranted, given that the new equations were developed in cross-sectional designs. Predicting lung function is more than a methodological exercise. Predicted values are important in disease diagnosis and monitoring. It is suggested that measurement and tracking of lung function throughout young adulthood could be used to provide an early warning of potential long-term lung function losses to encourage improvement of risky behaviors including smoking and failure to maintain normal body weight in the general population.

Novel role of NPY in neuroimmune interaction and lung growth after intrauterine growth restriction.

PubMed

Thangaratnarajah, Chansutha; Dinger, Katharina; Vohlen, Christina; Klaudt, Christian; Nawabi, Jawed; Lopez Garcia, Eva; Kwapiszewska, Grazyna; Dobner, Julia; Nüsken, Kai D; van Koningsbruggen-Rietschel, Silke; von Hörsten, Stephan; Dötsch, Jörg; Alejandre Alcázar, Miguel A

2017-09-01

Individuals with intrauterine growth restriction (IUGR) are at risk for chronic lung disease. Using a rat model, we showed in our previous studies that altered lung structure is related to IL-6/STAT3 signaling. As neuropeptide Y (NPY), a coneurotransmitter of the sympathetic nervous system, regulates proliferation and immune response, we hypothesized that dysregulated NPY after IUGR is linked to IL-6, impaired myofibroblast function, and alveolar growth. IUGR was induced in rats by isocaloric low-protein diet; lungs were analyzed on embryonic day (E) 21, postnatal day (P) 3, P12, and P23. Finally, primary neonatal lung myofibroblasts (pnF) and murine embryonic fibroblasts (MEF) were used to assess proliferation, apoptosis, migration, and IL-6 expression. At E21, NPY and IL-6 expression was decreased, and AKT/PKC and STAT3/AMPKα signaling was reduced. Early reduction of NPY/IL-6 was associated with increased chord length in lungs after IUGR at P3, indicating reduced alveolar formation. At P23, however, IUGR rats exhibited a catch-up of body weight and alveolar growth coupled with more proliferating myofibroblasts. These structural findings after IUGR were linked to activated NPY/PKC, IL-6/AMPKα signaling. Complementary, IUGR-pnF showed increased survival, impaired migration, and reduced IL-6 compared with control-pnF (Co-pnF). In contrast, NPY induced proliferation, migration, and increased IL-6 synthesis in fibroblasts. Additionally, NPY -/- mice showed reduced IL-6 signaling and less proliferation of lung fibroblasts. Our study presents a novel role of NPY during alveolarization: NPY regulates 1 ) IL-6 and lung STAT3/AMPKα signaling, and 2 ) proliferation and migration of myofibroblasts. These new insights in pulmonary neuroimmune interaction offer potential strategies to enable lung growth. Copyright © 2017 the American Physiological Society.

Computer-aided pulmonary image analysis in small animal models

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

Xu, Ziyue; Mansoor, Awais; Mollura, Daniel J.

Purpose: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models. Methods: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors’ system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next.more » The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters. Results: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT’09 data set. Conclusions: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.« less

Attenuating endogenous Fgfr2b ligands during bleomycin-induced lung fibrosis does not compromise murine lung repair

PubMed Central

MacKenzie, BreAnne; Henneke, Ingrid; Hezel, Stefanie; Al Alam, Denise; El Agha, Elie; Chao, Cho-Ming; Quantius, Jennifer; Wilhelm, Jochen; Jones, Matthew; Goth, Kerstin; Li, Xiaokun; Seeger, Werner; Königshoff, Melanie; Herold, Susanne; Rizvanov, Albert A.; Günther, Andreas

2015-01-01

Fibroblast growth factors (Fgfs) mediate organ repair. Lung epithelial cell overexpression of Fgf10 postbleomycin injury is both protective and therapeutic, characterized by increased survival and attenuated fibrosis. Exogenous administration of FGF7 (palifermin) also showed prophylactic survival benefits in mice. The role of endogenous Fgfr2b ligands on bleomycin-induced lung fibrosis is still elusive. This study reports the expression of endogenous Fgfr2b ligands, receptors, and signaling targets in wild-type mice following bleomycin lung injury. In addition, the impact of attenuating endogenous Fgfr2b-ligands following bleomycin-induced fibrosis was tested by using a doxycycline (dox)-based inducible, soluble, dominant-negative form of the Fgfr2b receptor. Double-transgenic (DTG) Rosa26rtTA/+;tet(O)solFgfr2b mice were validated for the expression and activity of soluble Fgfr2b (failure to regenerate maxillary incisors, attenuated recombinant FGF7 signal in the lung). As previously reported, no defects in lung morphometry were detected in DTG (+dox) mice exposed from postnatal days (PN) 1 through PN105. Female single-transgenic (STG) and DTG mice were subjected to various levels of bleomycin injury (1.0, 2.0, and 3.0 U/kg). Fgfr2b ligands were attenuated either throughout injury (days 0–11; days 0–28) or during later stages (days 6–28 and 14–28). No significant changes in survival, weight, lung function, confluent areas of fibrosis, or hydroxyproline deposition were detected in DTG mice. These results indicate that endogenous Fgfr2b ligands do not significantly protect against bleomycin injury, nor do they expedite the resolution of bleomycin-induced lung injury in mice. PMID:25820524

Nutritional state and lung disease in cystic fibrosis.

PubMed

Bakker, W

1992-10-01

The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the severity and progress of the pulmonary involvement associated with the disease. Many data support the view that malnutrition and deterioration of lung function are closely interrelated and interdependent, with each affecting the other, leading to a spiral decline in both. The occurrence of malnutrition appears to be associated with poor lung function and poor survival, and conversely prevention of malnutrition appears to be associated with better lung function and improved survival. Nutritional intervention may lead to an improvement in body weight, lung function and exercise tolerance, provided that the intervention is combined with exercise training in order to increase both respiratory and other muscle mass. These improvements can be preserved when patients have the stamina to continue with a high-energy, high-fat diet and daily exercise training at home.

The biology, function and clinical implications of exosomes in lung cancer.

PubMed

Zhou, Li; Lv, Tangfeng; Zhang, Qun; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Song, Yong

2017-10-28

Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. In addition, we also discuss current challenges that might impede the clinical use of exosomes. Further studies on the functional roles of exosomes in lung cancer requires thorough research. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice

PubMed Central

2009-01-01

To determine if nuclear factor-κB (NF-κB) activation may be a key factor in lung inflammation and respiratory dysfunction, we investigated whether NF-κB can be blocked by intratracheal administration of NF-κB decoy oligodeoxynucleotides (ODNs), and whether decoy ODN-mediated NF-κB inhibition can prevent smoke-induced lung inflammation, respiratory dysfunction, and improve pathological alteration in the small airways and lung parenchyma in the long-term smoke-induced mouse model system. We also detected changes in transcriptional factors. In vivo, the transfection efficiency of NF-κB decoy ODNs to alveolar macrophages in BALF was measured by fluorescein isothiocyanate (FITC)-labeled NF-κB decoy ODNs and flow cytometry post intratracheal ODN administration. Pulmonary function was measured by pressure sensors, and pathological changes were assessed using histology and the pathological Mias software. NF-κB and activator protein 1(AP-1) activity was detected by the electrophoretic motility shift assay (EMSA). Mouse cytokine and chemokine pulmonary expression profiles were investigated by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and lung tissue homogenates, respectively, after repeated exposure to cigarette smoke. After 24 h, the percentage of transfected alveolar macrophages was 30.00 ± 3.30%. Analysis of respiratory function indicated that transfection of NF-κB decoy ODNs significantly impacted peak expiratory flow (PEF), and bronchoalveolar lavage cytology displayed evidence of decreased macrophage infiltration in airways compared to normal saline-treated or scramble NF-κB decoy ODNs smoke exposed mice. NF-κB decoy ODNs inhibited significantly level of macrophage inflammatory protein (MIP) 1α and monocyte chemoattractant protein 1(MCP-1) in lung homogenates compared to normal saline-treated smoke exposed mice. In contrast, these NF-κB decoy ODNs-treated mice showed significant increase in the level of tumor necrosis factor-α(TNF-α) and pro-MMP-9(pro-matrix metalloproteinase-9) in mice BALF. Further measurement revealed administration of NF-κB decoy ODNs did not prevent pathological changes. These findings indicate that NF-κB activation play an important role on the recruitment of macrophages and pulmonary dysfunction in smoke-induced chronic lung inflammation, and with the exception of NF-κB pathway, there might be complex mechanism governing molecular dynamics of pro-inflammatory cytokines expression and structural changes in small airways and pulmonary parenchyma in vivo. PMID:19706153

[Lung diffusion capacity and quality of life 6 months after discharge from the ICU among survivors of acute respiratory distress syndrome due to influenza A H1N1].

PubMed

Quispe-Laime, A M; Fiore, C; González-Ros, M N; Bettini, J E; Rolfo, V E; Campagne, C G; Barberio, P A

2012-01-01

An evaluation is made of lung function and quality of life 6 months after discharge from the Intensive Care Unit (ICU) among survivors of acute respiratory distress syndrome (ARDS) due to pandemic 2009 influenza A H1N1, based on studies of lung function and the EQ-5D health questionnaire. Case series. The ICU of Dr. Leónidas Lucero Acute Cases Municipal Hospital, Bahía Blanca, Argentina. PATIENTS discharged from the ICU who had been admitted with ARDS in 2009 due to influenza A H1N1. Eleven patients were studied. Seven were positive for influenza H1N1 and four were negative. The mean age was 37±9.5 years, and 73% were males. Quality of life, as measured by the EQ-5D, showed changes in the 5 components in all patients, particularly in the pain/discomfort dimension 1.55±0.52; health status (EQ%health) was 70%±24. The indices adjusted for Argentina were Time Trade Off (TTO) 0.903±0.085 and Visual Analog Scale (VAS) 0.827±0.153. In all patients, spirometry and the study of pulmonary diffusion (DLCO) showed values of >80%. There was no correlation between lung diffusion and quality of life (%DLCO and EQ%health). A correlation was observed between quality of life and TTO (EQ%health and TTO), and between quality of life and the VAS score (EQ%health and VAS). Although the sample is small, our results suggest that patients with ARDS due to influenza A H1N1 evaluated 6 months after discharge from the ICU show no deterioration of lung function, and the impact on quality of life is moderate-in contrast to the situation found in patients with ARDS of other etiologies. Copyright © 2011 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Association between the Type of Workplace and Lung Function in Copper Miners

PubMed Central

Gruszczyński, Leszek; Wojakowska, Anna; Ścieszka, Marek; Turczyn, Barbara; Schmidt, Edward

2016-01-01

The aim of the analysis was to retrospectively assess changes in lung function in copper miners depending on the type of workplace. In the groups of 225 operators, 188 welders, and 475 representatives of other jobs, spirometry was performed at the start of employment and subsequently after 10, 20, and 25 years of work. Spirometry Longitudinal Data Analysis software was used to estimate changes in group means for FEV1 and FVC. Multiple linear regression analysis was used to assess an association between workplace and lung function. Lung function assessed on the basis of calculation of longitudinal FEV1 (FVC) decline was similar in all studied groups. However, multiple linear regression model used in cross-sectional analysis revealed an association between workplace and lung function. In the group of welders, FEF75 was lower in comparison to operators and other miners as early as after 10 years of work. Simultaneously, in smoking welders, the FEV1/FVC ratio was lower than in nonsmokers (p < 0,05). The interactions between type of workplace and smoking (p < 0,05) in their effect on FVC, FEV1, PEF, and FEF50 were shown. Among underground working copper miners, the group of smoking welders is especially threatened by impairment of lung ventilatory function. PMID:27274987

Association of area socioeconomic status with lung function in children.

PubMed

Wu, Yi-Fan; Wu, Cho-Kai; Chen, Duan-Rung; Chie, Wei-Chu; Lee, Yungling Leo

2012-12-01

The study investigates the association between area-level socioeconomic status (SES) and children's lung function. Participants were 3994 seventh grade students from the Taiwan Children Health Study living in 14 communities in Taiwan and were recruited in 2007. Area-level SES predictors were population size, occupation type, income and education level. Hierarchical linear models (HLM) were used to examine the effects of area-level SES on lung function, after accounting for area air pollution and individual SES (parental education and family income). Areas with high income were independently associated with lower child lung function. The coefficients for log transformation of area tax per person in HLM were -47.8 (95% confidence interval (CI): -80.9, -14.8) in FEV(1), -43.8 (95% CI: -75.2, -12.5) in FVC, -93.4 (95% CI: -179.3, -7.5) in FEF(25-75) and -203.2 (95% CI: -349.1, -57.2) in PEF. All SES predictors influenced in the same direction and affected males more. The interaction of area tax per person with parental educational level was significant on PEF, suggesting significant association of greater parental education with lower lung function in children. High area SES was inversely associated with lung function in Taiwanese children. Copyright © 2012 Elsevier Inc. All rights reserved.

Exposure to industrial air pollutant emissions and lung function in children: Canadian Health Measures Survey, 2007 to 2011.

PubMed

Wong, Suzy L; Coates, Allan L; To, Teresa

2016-02-01

Long-term exposure to ambient air pollution has been associated with adverse effects on children's lung function. Few studies have examined lung function in relation to industrial emissions of air pollutants. This cross-sectional study was based on 2,833 respondents aged 6 to 18 for whom spirometry data were collected by the Canadian Health Measures Survey, 2007 to 2011. The weighted sum of industrial air emissions of nitrogen oxides (NOₓ) and fine particulate matter (PM2.5) within 25 km of the respondent's residence was derived using National Pollutant Release Inventory data. Multivariate linear regression was used to examine the relationship between NOₓ and PM2.5 emissions and forced vital capacity (FVC), the forced expiratory volume in 1 sec (FEV₁), and the ratio of the two (FEV₁/FVC). Industrial air emissions of NOₓ were not significantly associated with lung function among males or females. Emissions of PM2.5 were negatively associated with FEV₁ and FEV₁/FVC, but not FVC, among males. PM2.5 was not significantly related to lung function among females. The associations that emerged between lung function and industrial emissions of PM2.5 among males were consistent with airway obstruction. Further research is warranted to investigate the gender differences observed in this study.

Lung function imaging methods in Cystic Fibrosis pulmonary disease.

PubMed

Kołodziej, Magdalena; de Veer, Michael J; Cholewa, Marian; Egan, Gary F; Thompson, Bruce R

2017-05-17

Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis. X-ray phase-contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis lung assessment which provides dynamic morphological and functional information, albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI) is a non-ionising radiation imaging method that is garnering growing interest among researchers and clinicians working with Cystic Fibrosis patients. Recent advances in MRI have opened up the possibilities to observe lung function in real time to potentially allow sensitive and accurate assessment of disease progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be tailored to clinical needs. While MRI offers significant promise it still suffers from poor spatial resolution and the development of an objective scoring system especially for ventilation assessment.

Lung transplantation in patients with cystic fibrosis.

PubMed

Morton, Judith; Glanville, Allan R

2009-10-01

Cystic fibrosis is one of the most common indications for lung transplantation worldwide and certainly the most common indication for all pediatric lung transplants and for bilateral lung transplantation irrespective of age. Outcomes are outstanding when compared with other indications for lung transplantation, and an increasing number of centers now report mean survival of greater than 10 years posttransplant. Hence it is important to concentrate on the broad panoply of potential systemic complications of cystic fibrosis and address proactively issues that may be associated with adverse outcomes. Optimum management of infectious, nutritional, diabetic, renal, bone, and gut complications is critical to long-term success so that recipients may realize their full potential. Timing of referral for consideration of active listing should allow sufficient time for the patient and lung transplant team to develop a productive working relationship based on best available evidence and mutual trust, which will culminate in a long-term successful outcome. Copyright Thieme Medical Publishers.

Hyperpolarized xenon magnetic resonance of the lung and the brain

NASA Astrophysics Data System (ADS)

Venkatesh, Arvind Krishnamachari

2001-04-01

Hyperpolarized noble gas Magnetic Resonance Imaging (MRI) is a new diagnostic modality that has been used successfully for lung imaging. Xenon is soluble in blood and inhaled xenon is transported to the brain via circulating blood. Xenon also accumulates in the lipid rich white matter of the brain. Hyperpolarized xenon can hence be used as a tissue- sensitive probe of brain function. The goals of this study were to identify the NMR resonances of xenon in the rat brain and evaluate the role of hyperpolarized xenon for brain MRI. We have developed systems to produce sufficient volumes of hyperpolarized xenon for in vivo brain experiments. The specialized instrumentation developed include an apparatus for optical pump-cell manufacture and high purity gas manifolds for filling cells. A hyperpolarized gas delivery system was designed to ventilate small animals with hyperpolarized xenon for transport to the brain. The T1 of xenon dissolved in blood indicates that the lifetime of xenon in the blood is sufficient for significant magnetization to be transferred to distal tissues. A variety of carrier agents for intravenous delivery of hyperpolarized xenon were tested for transport to distal tissues. Using our new gas delivery system, high SNR 129Xe images of rat lungs were obtained. Spectroscopy with hyperpolarized xenon indicated that xenon was transported from the lungs to the blood and tissues with intact magnetization. After preliminary studies that indicated the feasibility for in vivo rat brain studies, experiments were performed with adult rats and young rats with different stages of white matter development. Both in vivo and in vitro experiments showed the prominence of one peak from xenon in the rat brain, which was assigned to brain lipids. Cerebral brain perfusion was calculated from the wash-out of the hyperpolarized xenon signal in the brain. An increase in brain perfusion during maturation was observed. These experiments showed that hyperpolarized xenon MRI can be used to develop unique approaches to studying white matter and gray matter in the brain. Some of the possible applications of hyperpolarized xenon MRI in the brain are clinical diagnosis of white matter diseases, functional MRI (fMRI) and measurement of cerebral blood perfusion.

Foetal airway motor tone in prenatal lung development of the pig.

PubMed

Sparrow, M P; Warwick, S P; Mitchell, H W

1994-08-01

The terminal airways from embryonic lung in situ or as explants exhibit rhythmic spontaneous contractions. Our objective was to see whether narrowing responses of the airways occurred throughout the bronchial tree in the first trimester foetus and, if so, to characterize them. The bronchial tree was freed of vasculature and parenchyma from the lungs of 20-35 g pig foetuses (44-48 days gestation). The airway lumen was visualized directly with transmitted light, and narrowing was recorded in real time by video-imaging microscopy. From the main stem bronchi to the terminal regions of late generation branches (20-35 microns i.d.) strong bronchoconstrictor responses to micromolar concentrations of acetylcholine (ACh), histamine, substance P and K+ depolarizing solution were seen, whilst inhibition of narrowing with beta-adrenoceptor agonists was evidence of beta-receptors on the smooth muscle. Moreover, strong narrowing responses to electrical field stimulation, which were blocked by atropine, indicated that functional cholinergic nerves were present. A remarkable display of spontaneous narrowing in the airways of many of the bronchial tree preparations caused the movement of lung liquid to and fro. We speculate that the bronchomotor tone and associated spontaneous activity, which move the lung fluid along the airways, serve to maintain an even positive pressure in localized areas of the bronchial tree which is essential to provide the stimulus for continued growth of the lung.

Effect of gender specific anthropometric characteristics on lung function in young competitive triathletes from Malaysia.

PubMed

Johari, Hanapi M; Zainudin, Hakimi A; Knight, Victor F; Lumley, Steven A; Subramanium, Ananthan S; Caszo, Brinnell A; Gnanou, Justin V

2017-04-01

Anthropometric and lung function characteristics of triathletes are important for the implementation of individual specific training and recovery recommendations. However, limited data are available for these parameters in triathletes. Hence, the aim of this study was to characterize and examine the gender differences of lung function and anthropometry parameters in competitive triathletes from Malaysia. Body composition assessment and lung function tests were performed on sixteen competitive triathletes (nine male and seven female). The subject's body composition profile including muscle mass (kg), fat free mass (kg), and percent body fat was measured using a bio-impedance segmental body composition analyzer. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured by Quark PFT2 spirometer. The anthropometric measurements revealed that male triathletes were significantly taller than female triathletes and had significantly more protein and skeletal muscle mass. The female triathletes, however, had significantly higher percent body fat. Male triathletes had statistically significant higher FVC and FEV1 than female triathletes. Both the male and female triathletes showed a positive correlation between height, fat free mass and the lung function markers FVC and FEV1. This association was not seen with Body Mass Index (BMI) in female triathletes. The data from our study shows that anthropometric parameters are directly linked to lung function of a triathlete. We also found the relationship between BMI and lung function to be gender specific in triathletes and is dependent on the body protein and fat content. Hence, body composition characterization is essential and provides valuable information for developing individual specific training modules.

Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity.

PubMed

Botelho, Danielle J; Leo, Bey Fen; Massa, Christopher B; Sarkar, Srijata; Tetley, Terry D; Chung, Kian Fan; Chen, Shu; Ryan, Mary P; Porter, Alexandra E; Zhang, Junfeng; Schwander, Stephan K; Gow, Andrew J

2016-01-01

Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 μg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.

Menopause Is Associated with Accelerated Lung Function Decline.

PubMed

Triebner, Kai; Matulonga, Bobette; Johannessen, Ane; Suske, Sandra; Benediktsdóttir, Bryndís; Demoly, Pascal; Dharmage, Shyamali C; Franklin, Karl A; Garcia-Aymerich, Judith; Gullón Blanco, José Antonio; Heinrich, Joachim; Holm, Mathias; Jarvis, Debbie; Jõgi, Rain; Lindberg, Eva; Moratalla Rovira, Jesús Martínez; Muniozguren Agirre, Nerea; Pin, Isabelle; Probst-Hensch, Nicole; Puggini, Luca; Raherison, Chantal; Sánchez-Ramos, José Luis; Schlünssen, Vivi; Sunyer, Jordi; Svanes, Cecilie; Hustad, Steinar; Leynaert, Bénédicte; Gómez Real, Francisco

2017-04-15

Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. To study whether lung function decline, assessed by FVC and FEV 1 , is accelerated in women who undergo menopause. The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect. Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV 1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women. Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.

CAVEOLINS AND LUNG FUNCTION

PubMed Central

Maniatis, Nikolaos A.; Chernaya, Olga; Shinin, Vasily; Minshall, Richard D.

2012-01-01

The primary function of the mammalian lung is to facilitate diffusion of oxygen to venous blood and to ventilate carbon dioxide produced by catabolic reactions within cells. However, it is also responsible for a variety of other important functions, including host defense and production of vasoactive agents to regulate not only systemic blood pressure, but also water, electrolyte and acid-base balance. Caveolin-1 is highly expressed in the majority of cell types in the lung, including epithelial, endothelial, smooth muscle, connective tissue cells, and alveolar macrophages. Deletion of caveolin-1 in these cells results in major functional aberrations, suggesting that caveolin-1 may be crucial to lung homeostasis and development. Furthermore, generation of mutant mice that under-express caveolin-1 results in severe functional distortion with phenotypes covering practically the entire spectrum of known lung diseases, including pulmonary hypertension, fibrosis, increased endothelial permeability, and immune defects. In this Chapter, we outline the current state of knowledge regarding caveolin-1-dependent regulation of pulmonary cell functions and discuss recent research findings on the role of caveolin-1 in various pulmonary disease states, including obstructive and fibrotic pulmonary vascular and inflammatory diseases. PMID:22411320

Extracellular matrix in lung development, homeostasis and disease

DOE PAGES

Zhou, Yong; Horowitz, Jeffrey C.; Naba, Alexandra; ...

2018-03-08

Here, the lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECMmore » in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.« less

Extracellular matrix in lung development, homeostasis and disease

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

Zhou, Yong; Horowitz, Jeffrey C.; Naba, Alexandra

Here, the lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECMmore » in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.« less

Extracellular matrix in lung development, homeostasis and disease

DOE PAGES

Zhou, Yong; Horowitz, Jeffrey C.; Naba, Alexandra; ...

2018-03-08

The lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this paper, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECM inmore » normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. Finally, we identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.« less

Elevated airway liquid volumes at birth: a potential cause of transient tachypnea of the newborn.

PubMed

McGillick, Erin V; Lee, Katie; Yamaoka, Shigeo; Te Pas, Arjan B; Crossley, Kelly J; Wallace, Megan J; Kitchen, Marcus J; Lewis, Robert A; Kerr, Lauren T; DeKoninck, Philip; Dekker, Janneke; Thio, Marta; McDougall, Annie R A; Hooper, Stuart B

2017-11-01

Excessive liquid in airways and/or distal lung tissue may underpin the respiratory morbidity associated with transient tachypnea of the newborn (TTN). However, its effects on lung aeration and respiratory function following birth are unknown. We investigated the effect of elevated airway liquid volumes on newborn respiratory function. Near-term rabbit kittens (30 days gestation; term ~32 days) were delivered, had their lung liquid-drained, and either had no liquid replaced (control; n = 7) or 30 ml/kg of liquid re-added to the airways [liquid added (LA); n = 7]. Kittens were mechanically ventilated in a plethysmograph. Measures of chest and lung parameters, uniformity of lung aeration, and airway size were analyzed using phase contrast X-ray imaging. The maximum peak inflation pressure required to recruit a tidal volume of 8 ml/kg was significantly greater in LA compared with control kittens (35.0 ± 0.7 vs. 26.8 ± 0.4 cmH 2 O, P < 0.001). LA kittens required greater time to achieve lung aeration (106 ± 14 vs. 60 ± 6 inflations, P = 0.03) and had expanded chest walls, as evidenced by an increased total chest area (32 ± 9%, P < 0.0001), lung height (17 ± 6%, P = 0.02), and curvature of the diaphragm (19 ± 8%, P = 0.04). LA kittens had lower functional residual capacity during stepwise changes in positive end-expiratory pressures (5, 3, 0, and 5 cmH 2 0). Elevated lung liquid volumes had marked adverse effects on lung structure and function in the immediate neonatal period and reduced the ability of the lung to aerate efficiently. We speculate that elevated airway liquid volumes may underlie the initial morbidity in near-term babies with TTN after birth. NEW & NOTEWORTHY Transient tachypnea of the newborn reduces respiratory function in newborns and is thought to result due to elevated airway liquid volumes following birth. However, the effect of elevated airway liquid volumes on neonatal respiratory function is unknown. Using phase contrast X-ray imaging, we show that elevated airway liquid volumes have adverse effects on lung structure and function in the immediate newborn period, which may underlie the pathology of TTN in near-term babies after birth. Copyright © 2017 the American Physiological Society.

Cooccurrence of and remission from general anxiety, depression, and posttraumatic stress disorder symptoms after acute lung injury: a 2-year longitudinal study.

PubMed

Bienvenu, O Joseph; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A; Shanholtz, Carl; Dennison-Himmelfarb, Cheryl R; Pronovost, Peter J; Needham, Dale M

2015-03-01

To evaluate the cooccurrence, and predictors of remission, of general anxiety, depression, and posttraumatic stress disorder symptoms during 2-year follow-up in survivors of acute lung injury treated in an ICU. Prospective cohort study, with follow-up at 3, 6, 12, and 24 months post-acute lung injury. Thirteen medical and surgical ICUs in four hospitals. Survivors among 520 patients with acute lung injury. The outcomes of interest were measured using the Hospital Anxiety and Depression Scale anxiety and depression subscales (scores ≥ 8 indicating substantial symptoms) and the Impact of Event Scale-Revised (scores ≥ 1.6 indicating substantial posttraumatic stress disorder symptoms). Of the 520 enrolled patients, 274 died before 3-month follow-up; 186 of 196 consenting survivors (95%) completed at least one Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised assessment during 2-year follow-up, and most completed multiple assessments. Across follow-up time points, the prevalence of suprathreshold general anxiety, depression, and posttraumatic stress disorder symptoms ranged from 38% to 44%, 26% to 33%, and 22% to 24%, respectively; more than half of the patients had suprathreshold symptoms in at least one domain during 2-year follow-up. The majority of survivors (59%) with any suprathreshold symptoms were above threshold for two or more types of symptoms (i.e., general anxiety, depression, and/or posttraumatic stress disorder). In fact, the most common pattern involved simultaneous general anxiety, depression, and posttraumatic stress disorder symptoms. Most patients with general anxiety, depression, or posttraumatic stress disorder symptoms during 2-year follow-up had suprathreshold symptoms at 24-month (last) follow-up. Higher Short-Form-36 physical functioning domain scores at the prior visit were associated with a greater likelihood of remission from general anxiety and posttraumatic stress disorder symptoms during follow-up. The majority of acute lung injury survivors had clinically significant general anxiety, depression, or posttraumatic stress disorder symptoms, and these symptoms tended to co-occur across domains. Better physical functioning during recovery predicted subsequent remission of general anxiety and posttraumatic stress disorder symptoms.

Overweight, Obesity, and Lung Function in Children and Adults-A Meta-analysis.

PubMed

Forno, Erick; Han, Yueh-Ying; Mullen, James; Celedón, Juan C

There is conflicting evidence on the effect of obesity on lung function in adults and children with and without asthma. We aimed to evaluate the relation between overweight or obesity and lung function, and whether such relationship varies by age, sex, or asthma status. We searched PubMed, Scopus, CINAHL, Cochrane, and EMBASE for all studies (in English) reporting on obesity status (by body mass index) and lung function, from 2005 to 2017. Main outcomes were forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC, forced expiratory flow between 25th and 75th percentile of the forced vital capacity (FEF 25-75 ), total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC). Random-effects models were used to calculate the pooled risk estimates; each study was weighed by the inverse effect size variance. For each outcome, we compared overweight or obese ("obese") subjects with those of normal weight. All measures of lung function were decreased among obese subjects. Obese adults showed a pattern (lower FEV 1 , FVC, TLC, and RV) different from obese children (more pronounced FEV 1 /FVC deficit with unchanged FEV 1 or FVC). There were also seemingly different patterns by asthma status, in that subjects without asthma had more marked decreases in FEV 1 , TLC, RV, and FRC than subjects with asthma. Subjects who were obese (as compared with overweight) had even further decreased FEV 1 , FVC, TLC, RV, and FRC. Obesity is detrimental to lung function, but specific patterns differ between children and adults. Physicians should be aware of adverse effects of obesity on lung function, and weight control should be considered in the management of airway disease among the obese. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The associations between weight-related anthropometrics during childhood and lung function in late childhood: a retrospective cohort study.

PubMed

Byberg, Kristine Kjer; Mikalsen, Ingvild Bruun; Eide, Geir Egil; Forman, Michele R; Júlíusson, Pétur Benedikt; Øymar, Knut

2018-01-19

An association between body weight in childhood and subsequent lung function and asthma has been suggested, but few longitudinal studies exist. Our aim was to explore whether weight-related anthropometric measurements through childhood were associated with lung function in late childhood. From an original nested case-control study, a cohort study was conducted, where lung function was measured in 463 children aged 12.8 years, and anthropometry was measured at several ages from birth through 12.8 years of age. Associations between anthropometrics and lung function were analysed using multiple linear and fractional polynomial regression analysis. Birthweight and body mass index (BMI; kg/m 2 ) at different ages through childhood were positively associated with forced vital capacity in percent of predicted (FVC %) and forced expiratory volume in the first second in percent of predicted (FEV 1 %) at 12.8 years of age. BMI, waist circumference, waist-to-height ratio and skinfolds at 12.8 years of age and the change in BMI from early to late childhood were positively associated with FVC % and FEV 1 % and negatively associated with FEV 1 /FVC and forced expiratory flow at 25-75% of FVC/FVC. Interaction analyses showed that positive associations between anthropometrics other than BMI and lung function were mainly found in girls. Inverse U-shaped associations were found between BMI at the ages of 10.8/11.8 (girls/boys) and 12.8 years (both genders) and FVC % and FEV 1 % at 12.8 years of age. Weight-related anthropometrics through childhood may influence lung function in late childhood. These findings may be physiological or associated with air flow limitation. Inverse U-shaped associations suggest a differential impact on lung function in normal-weight and overweight children. This study was observational without any health care intervention for the participants. Therefore, no trial registration number is available.

The effect of oxidative stress polymorphisms on the association between long-term black carbon exposure and lung function among elderly men.

PubMed

Mordukhovich, Irina; Lepeule, Johanna; Coull, Brent A; Sparrow, David; Vokonas, Pantel; Schwartz, Joel

2015-02-01

Black carbon (BC) is a pro-oxidant, traffic-related pollutant linked with lung function decline. We evaluated the influence of genetic variation in the oxidative stress pathway on the association between long-term BC exposure and lung function decline. Lung function parameters (FVC and FEV1) were measured during one or more study visits between 1995 and 2011 (n=651 participants) among an elderly cohort: the Normative Aging Study. Residential BC exposure levels were estimated using a spatiotemporal land use regression model. We evaluated whether oxidative stress variants, combined into a genetic score, modify the association between 1-year and 5-year moving averages of BC exposure and lung function levels and rates of decline, using linear mixed models. We report stronger associations between long-term BC exposure and increased rate of lung function decline, but not baseline lung function level, among participants with higher oxidative stress allelic risk profiles compared with participants with lower risk profiles. Associations were strongest when evaluating 5-year moving averages of BC exposure. A 0.5 µg/m(3) increase in 5-year BC exposure was associated with a 0.1% yearly increase in FVC (95% CI -0.5 to 0.7) among participants with low genetic risk scores and a 1.3% yearly decrease (95% CI -1.8 to -0.8) among those with high scores (p-interaction=0.0003). Our results suggest that elderly men with high oxidative stress genetic scores may be more susceptible to the effects of BC on lung function decline. The results, if confirmed, should inform air-quality recommendations in light of a potentially susceptible subgroup. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

PubMed

Morales, Eva; Garcia-Esteban, Raquel; de la Cruz, Oscar Asensio; Basterrechea, Mikel; Lertxundi, Aitana; de Dicastillo, Maria D Martinez López; Zabaleta, Carlos; Sunyer, Jordi

2015-01-01

Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed. Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

PubMed Central

Sundar, Isaac K.; Ahmad, Tanveer; Yao, Hongwei; Hwang, Jae-woong; Gerloff, Janice; Lawrence, B. Paige; Sellix, Michael T.; Rahman, Irfan

2015-01-01

Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations. PMID:25923474

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

PubMed

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

2015-03-14

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

Effect of inhaled corticosteroid treatment on exhaled breath condensate leukotriene E(4) in children with mild asthma.

PubMed

Steiss, Jens-Oliver; Rudloff, Silvia; Landmann, Eva; Rückes-Nilges, Claudia; Zimmer, Klaus-Peter; Lindemann, Herrmann

2008-01-01

Chronic airway inflammation in children with asthma might be present even in the absence of pathological lung function tests and is known to increase the risk of permanent pulmonary damage. Thus, we aimed at investigating to what extent inflammatory markers such as leukotrienes (LTs) in exhaled breath condensate (EBC) or fractional exhaled nitric oxide (FE(NO)) reflect therapeutic effects in these patients. Fifty steroid-naive patients (aged 8.8 +/- 2.7 years) were included in the study. EBC was collected before and 6 months after therapy with inhaled corticosteroids. LTs were determined by using commercially available ELISA. In addition, FE(NO) was measured by means of a chemiluminescence analyzer. Conventional lung function testing was performed revealing vital capacity, forced expiratory volume, maximum expiratory flow, and specific resistance. In EBC, LTE(4) but not LTB(4) levels significantly decreased after steroid therapy from 45.3 +/- 36.0 pg/mL to 17.2 +/- 11.4 pg/mL (p < 0.0001) concomitant with a slight, but significant improvement of lung function parameters. Mean FE(NO) also indicated therapeutic success; however, in 20 of 50 patients, exhaled NO concentrations were higher after therapy. These findings suggest that LTE(4) in breath condensate may be helpful in latent inflammatory activity in the bronchial mucosa in children with asthma.

Structure–Function Analysis of the Non-Muscle Myosin Light Chain Kinase (nmMLCK) Isoform by NMR Spectroscopy and Molecular Modeling: Influence of MYLK Variants

PubMed Central

Shen, Kui; Ramirez, Benjamin; Mapes, Brandon; Shen, Grace R.; Gokhale, Vijay; Brown, Mary E.; Santarsiero, Bernard; Ishii, Yoshitaka; Dudek, Steven M.; Wang, Ting; Garcia, Joe G. N.

2015-01-01

The MYLK gene encodes the multifunctional enzyme, myosin light chain kinase (MLCK), involved in isoform-specific non-muscle and smooth muscle contraction and regulation of vascular permeability during inflammation. Three MYLK SNPs (P21H, S147P, V261A) alter the N-terminal amino acid sequence of the non-muscle isoform of MLCK (nmMLCK) and are highly associated with susceptibility to acute lung injury (ALI) and asthma, especially in individuals of African descent. To understand the functional effects of SNP associations, we examined the N-terminal segments of nmMLCK by 1H-15N heteronuclear single quantum correlation (HSQC) spectroscopy, a 2-D NMR technique, and by in silico molecular modeling. Both NMR analysis and molecular modeling indicated SNP localization to loops that connect the immunoglobulin-like domains of nmMLCK, consistent with minimal structural changes evoked by these SNPs. Molecular modeling analysis identified protein-protein interaction motifs adversely affected by these MYLK SNPs including binding by the scaffold protein 14-3-3, results confirmed by immunoprecipitation and western blot studies. These structure-function studies suggest novel mechanisms for nmMLCK regulation, which may confirm MYLK as a candidate gene in inflammatory lung disease and advance knowledge of the genetic underpinning of lung-related health disparities. PMID:26111161

Initiating transitional care for adolescents with cystic fibrosis at the age of 12 is both feasible and promising.

PubMed

Skov, M; Teilmann, G; Damgaard, I N; Nielsen, K G; Hertz, P G; Holgersen, M G; Presfeldt, M; Dalager, A M S; Brask, M; Boisen, K A

2018-05-05

Adolescence is a vulnerable period in cystic fibrosis, associated with declining lung function. This study described, implemented and evaluated a transition programme for adolescents. We conducted a single centre, non-randomised and non-controlled prospective programme at the cystic fibrosis centre at Copenhagen University Hospital Rigshospitalet from 2010-2011, assessing patients aged 12 to 18 at baseline and after 12 months. Changes implemented included staff training on communication, a more youth friendly feel to the outpatient clinic, the introduction of youth consultations partly alone with the adolescent, and a parents' evening focusing on cystic fibrosis in adolescence. Lung function and body mass index (BMI) were measured monthly and adolescents were assessed for their readiness for transition and quality of life at baseline and 12 months. We found that 40 (98%) of the eligible patients participated and youth consultations were successfully implemented with no dropouts. The readiness checklist score increased significantly over the one-year study period, indicating increased readiness for transfer and self-care. Overall quality of life, lung function and BMI remained stable during the study period. A well structured transition programme for cystic fibrosis patients as young as 12 years of age proved to be both feasible and sustainable. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Acute treatment with kerosene damages the dermal barrier and alters the distribution of topically applied benzo(a)pyrene in mice.

PubMed

LaDow, Kathy; Schumann, Brenda L; Luse, Nicole; Warshawsky, Dave; Pickens, William L; Hoath, Steven B; Talaska, Glenn

2011-12-01

The dermal route is important in many occupational exposures. Some materials may reduce the barrier function of the skin to enhance absorption and effect on internal organs. We have reported previously that kerosene cleaning following treatment with used engine oil increased DNA adduct levels in the lungs of mice compared with animals treated with used oil alone. To investigate what other physiological parameters might be affected by kerosene, we conducted in vitro and in vivo measurements of skin barrier function. We also topically applied (3)H-BAP(100 nM in 25 μL acetone) and washed half the mice with 25 μL kerosene 1 hr after carcinogen application. Groups of four mice were euthanized from 1 to 72 hr after treatment. Skin, lungs, and livers were harvested from each animal and stored separately. Kerosene application reduced the barrier function of the skin in vitro beyond the effect of the acetone vehicle and the vehicle plus BAP. In vivo studies indicated that kerosene treatment reduced the barrier function at 4 and 8 hr post application and that the barrier function recovered at 24 hr after a single treatment. The fraction of the radiolabel remaining in the skin of animals treated with (3)H-BAP and washed with kerosene was significantly less than those not washed, beginning at 24 hr (p< 0.05). Fractional distribution to the lungs and livers of these animals became significantly elevated at this time. Kerosene treatment compromises dermal barrier function and the ability of the skin to retain water, enhances carcinogen absorption, and alters organ distribution. This appears to contribute to the increase in BAP DNA adducts we reported earlier.

Lung physiology during ECS resuscitation of DCD donors followed by in situ assessment of lung function.

PubMed

Reoma, Junewai L; Rojas, Alvaro; Krause, Eric M; Obeid, Nabeel R; Lafayette, Nathan G; Pohlmann, Joshua R; Padiyar, Niru P; Punch, Jeffery D; Cook, Keith E; Bartlett, Robert H

2009-01-01

Extracorporeal cardiopulmonary support (ECS) of donors after cardiac death (DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in vivo method to assess if lungs are suitable for transplantation from DCD donors after ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10 min of warm ischemia. Cannulae were placed into the right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90 min with lungs inflated, group 1 (n = 5) or deflated, group 2 (n = 3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-ventricular (bi-VAD) system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1-hr assessment period. The oxygenator was turned off, and ventilation was restarted. Flows, blood gases, PA and left atrial pressures, and compliance were recorded. In both the groups, LA pressure was <15 mm Hg during ECS. During the lung assessment period, PA flows were 1.4-2.2 L/min. PO2 was >300 mm Hg, with normal PCO2. Extracorporeal cardiopulmonary support resuscitation of DCD donors is feasible and allows for assessment of function before procurement. Extracorporeal cardiopulmonary support does not cause pulmonary congestion, and the lungs retain adequate function for transplantation. Compliance correlated with lung function.

LUNG PHYSIOLOGY DURING ECS RESUSCITATION OF DCD DONORS FOLLOWED BY IN-SITU ASSESSMENT OF LUNG FUNCTION

PubMed Central

Reoma, Junewai L.; Rojas, Alvaro; Krause, Eric M.; Obeid, Nabeel R.; Lafayette, Nathan G.; Pohlmann, Joshua R.; Padiyar, Niru P.; Punch, Jeffery D; Cook, Keith E.; Bartlett, Robert H

2009-01-01

Extracorporeal cardiopulmonary support(ECS) of donors following cardiac death(DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in-vivo method to assess if lungs are suitable for transplantation from DCD donors following ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10min. of warm ischemia. Cannulas were placed into right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90min with lungs inflated, Group 1 (n=5) or deflated Group 2 (n=3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-VAD system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1hr assessment period. The oxygenator was turned off, and ventilation restarted. Flows, blood gases, pulmonary artery and left atrial pressures, and compliance were recorded. In both groups: LA pressure was <15mmHg during ECS. During the lung assessment period, PA flows were 1.4−2.2 liter/min. PO2 was >300mmHg, with normal PCO2. ECS resuscitation of DCD donors is feasible and allows for assessment of function prior to procurement. ECS does not cause pulmonary congestion, and lungs retain adequate function for transplantation. Compliance correlated with lung function. PMID:19506464

Lung function decline rates according to GOLD group in patients with chronic obstructive pulmonary disease

PubMed Central

Kim, Joohae; Yoon, Ho Il; Oh, Yeon-Mok; Lim, Seong Yong; Lee, Ji-Hyun; Kim, Tae-Hyung; Lee, Sang Yeub; Lee, Jin Hwa; Lee, Sang-Do; Lee, Chang-Hoon

2015-01-01

Background Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A–D were introduced, the lung function changes according to group have been evaluated rarely. Objective We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines. Methods Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included. The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression. Results A total 175 participants were included. No significant postbronchodilator FEV1 decline was observed between the groups (−34.4±7.9 [group A]; −26.2±9.4 [group B]; −22.7±16.0 [group C]; and −24.0±8.7 mL/year [group D]) (P=0.79). The group with less symptoms (−32.3±7.2 vs −25.0±6.5 mL/year) (P=0.44) and the low risk group (−31.0±6.1 vs −23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant. However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline. Conclusion There was no significant difference in lung function decline rates according to the GOLD groups. Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification. PMID:26379432

Structure and epitope distribution of heparan sulfate is disrupted in experimental lung hypoplasia: a glycobiological epigenetic cause for malformation?

PubMed

Thompson, Sophie M; Connell, Marilyn G; van Kuppevelt, Toin H; Xu, Ruoyan; Turnbull, Jeremy E; Losty, Paul D; Fernig, David G; Jesudason, Edwin C

2011-06-14

Heparan sulfate (HS) is present on the surface of virtually all mammalian cells and is a major component of the extracellular matrix (ECM), where it plays a pivotal role in cell-cell and cell-matrix cross-talk through its large interactome. Disruption of HS biosynthesis in mice results in neonatal death as a consequence of malformed lungs, indicating that HS is crucial for airway morphogenesis. Neonatal mortality (~50%) in newborns with congenital diaphragmatic hernia (CDH) is principally associated with lung hypoplasia and pulmonary hypertension. Given the importance of HS for lung morphogenesis, we investigated developmental changes in HS structure in normal and hypoplastic lungs using the nitrofen rat model of CDH and semi-synthetic bacteriophage ('phage) display antibodies, which identify distinct HS structures. The pulmonary pattern of elaborated HS structures is developmentally regulated. For example, the HS4E4V epitope is highly expressed in sub-epithelial mesenchyme of E15.5 - E17.5 lungs and at a lower level in more distal mesenchyme. However, by E19.5, this epitope is expressed similarly throughout the lung mesenchyme.We also reveal abnormalities in HS fine structure and spatiotemporal distribution of HS epitopes in hypoplastic CDH lungs. These changes involve structures recognised by key growth factors, FGF2 and FGF9. For example, the EV3C3V epitope, which was abnormally distributed in the mesenchyme of hypoplastic lungs, is recognised by FGF2. The observed spatiotemporal changes in HS structure during normal lung development will likely reflect altered activities of many HS-binding proteins regulating lung morphogenesis. Abnormalities in HS structure and distribution in hypoplastic lungs can be expected to perturb HS:protein interactions, ECM microenvironments and crucial epithelial-mesenchyme communication, which may contribute to lung dysmorphogenesis. Indeed, a number of epitopes correlate with structures recognised by FGFs, suggesting a functional consequence of the observed changes in HS in these lungs. These results identify a novel, significant molecular defect in hypoplastic lungs and reveals HS as a potential contributor to hypoplastic lung development in CDH. Finally, these results afford the prospect that HS-mimetic therapeutics could repair defective signalling in hypoplastic lungs, improve lung growth, and reduce CDH mortality.

Structure and epitope distribution of heparan sulfate is disrupted in experimental lung hypoplasia: a glycobiological epigenetic cause for malformation?

PubMed Central

2011-01-01

Background Heparan sulfate (HS) is present on the surface of virtually all mammalian cells and is a major component of the extracellular matrix (ECM), where it plays a pivotal role in cell-cell and cell-matrix cross-talk through its large interactome. Disruption of HS biosynthesis in mice results in neonatal death as a consequence of malformed lungs, indicating that HS is crucial for airway morphogenesis. Neonatal mortality (~50%) in newborns with congenital diaphragmatic hernia (CDH) is principally associated with lung hypoplasia and pulmonary hypertension. Given the importance of HS for lung morphogenesis, we investigated developmental changes in HS structure in normal and hypoplastic lungs using the nitrofen rat model of CDH and semi-synthetic bacteriophage ('phage) display antibodies, which identify distinct HS structures. Results The pulmonary pattern of elaborated HS structures is developmentally regulated. For example, the HS4E4V epitope is highly expressed in sub-epithelial mesenchyme of E15.5 - E17.5 lungs and at a lower level in more distal mesenchyme. However, by E19.5, this epitope is expressed similarly throughout the lung mesenchyme. We also reveal abnormalities in HS fine structure and spatiotemporal distribution of HS epitopes in hypoplastic CDH lungs. These changes involve structures recognised by key growth factors, FGF2 and FGF9. For example, the EV3C3V epitope, which was abnormally distributed in the mesenchyme of hypoplastic lungs, is recognised by FGF2. Conclusions The observed spatiotemporal changes in HS structure during normal lung development will likely reflect altered activities of many HS-binding proteins regulating lung morphogenesis. Abnormalities in HS structure and distribution in hypoplastic lungs can be expected to perturb HS:protein interactions, ECM microenvironments and crucial epithelial-mesenchyme communication, which may contribute to lung dysmorphogenesis. Indeed, a number of epitopes correlate with structures recognised by FGFs, suggesting a functional consequence of the observed changes in HS in these lungs. These results identify a novel, significant molecular defect in hypoplastic lungs and reveals HS as a potential contributor to hypoplastic lung development in CDH. Finally, these results afford the prospect that HS-mimetic therapeutics could repair defective signalling in hypoplastic lungs, improve lung growth, and reduce CDH mortality. PMID:21672206

Clonidine Reduces Norepinephrine and Improves Bone Marrow Function in a Rodent Model of Lung Contusion, Hemorrhagic Shock and Chronic Stress

PubMed Central

Alamo, Ines G.; Kannan, Kolenkode B.; Ramos, Harry; Loftus, Tyler J.; Efron, Philip A.; Mohr, Alicia M.

2016-01-01

Background Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Methods Male Sprague-Dawley rats underwent six days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75μg/kg) after the restraint stress. On post-injury day seven, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor (G-CSF), and peripheral blood mobilization of hematopoietic progenitor cells (HPC), as well as bone marrow cellularity and erythroid progenitor cell growth. Results The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress, significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1±0.6 vs. 10.8±0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased HPC mobilization and restored G-CSF levels. Conclusions After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. PMID:27742030

Variable versus conventional lung protective mechanical ventilation during open abdominal surgery: study protocol for a randomized controlled trial.

PubMed

Spieth, Peter M; Güldner, Andreas; Uhlig, Christopher; Bluth, Thomas; Kiss, Thomas; Schultz, Marcus J; Pelosi, Paolo; Koch, Thea; Gama de Abreu, Marcelo

2014-05-02

General anesthesia usually requires mechanical ventilation, which is traditionally accomplished with constant tidal volumes in volume- or pressure-controlled modes. Experimental studies suggest that the use of variable tidal volumes (variable ventilation) recruits lung tissue, improves pulmonary function and reduces systemic inflammatory response. However, it is currently not known whether patients undergoing open abdominal surgery might benefit from intraoperative variable ventilation. The PROtective VARiable ventilation trial ('PROVAR') is a single center, randomized controlled trial enrolling 50 patients who are planning for open abdominal surgery expected to last longer than 3 hours. PROVAR compares conventional (non-variable) lung protective ventilation (CV) with variable lung protective ventilation (VV) regarding pulmonary function and inflammatory response. The primary endpoint of the study is the forced vital capacity on the first postoperative day. Secondary endpoints include further lung function tests, plasma cytokine levels, spatial distribution of ventilation assessed by means of electrical impedance tomography and postoperative pulmonary complications. We hypothesize that VV improves lung function and reduces systemic inflammatory response compared to CV in patients receiving mechanical ventilation during general anesthesia for open abdominal surgery longer than 3 hours. PROVAR is the first randomized controlled trial aiming at intra- and postoperative effects of VV on lung function. This study may help to define the role of VV during general anesthesia requiring mechanical ventilation. Clinicaltrials.gov NCT01683578 (registered on September 3 3012).