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

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.

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.

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.

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.

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.

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

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.

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

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.

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

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

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.

Importance of the lung perfusion scintigraphy in single lung transplantation.

PubMed

Rodríguez Mesa, N V; Guerrero Cancio, M C; Cordero Jiménez, M D; Alvarez Velázquez, I K

2012-01-01

Lung perfusion scintigraphy (LPS) with (99m)Tc-MAA gives valuable information about patients who will undergo a single lung transplantation. This technique makes it possible to evaluate and quantify the relative function of both lungs to select the organ to be transplanted. Once the surgery has been performed, the LPS represents a diagnostic method to study the status of the transplanted organ. Two patients who underwent single lung transplantation were studied in our hospital. In both cases, a pre-operative LPS was performed before surgery for selection of the organ to be transplanted and the scintigraphy study was performed a few months after transplantation to establish the perfusion function of the transplanted lung. Copyright © 2011 Elsevier España, S.L. y SEMNIM. 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.

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.

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.

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).

[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.

Serum Tocopherol Levels and Vitamin E Intake are Associated with Lung Function in the Normative Aging Study

PubMed Central

Hanson, Corrine; Lyden, Elizabeth; Furtado, Jeremy; Campos, Hannia; Sparrow, David; Vokonas, Pantel; Litonjua, Augusto A.

2015-01-01

Background and Aims The results of studies assessing relationships between vitamin E intake and status and lung function are conflicting. This study aimed to evaluate the effect of vitamin E intake and serum levels of tocopherol isoforms on lung function in a cross-sectional sample of 580 men from the Normative Aging Study, a longitudinal aging study. Methods Regression models were used to look at associations of serum tocopherol isoform levels and vitamin E intake with lung function parameters after adjustment for confounders. Vitamin E intake was measured using a food frequency questionnaire and serum levels of γ, α, and δ-tocopherol levels were measured using high-performance liquid chromatography. Results After adjustment for potential confounders, serum γ-tocopherol had a significant inverse association with forced vital capacity (β=-0.10, p=0.05). Alpha and δ-tocopherol were not associated with any lung function parameter. After classifying COPD status according to Global Initiative for Obstructive Lung Disease (GOLD) stage criteria, serum levels of δ-tocopherol were lower in participants with more severe COPD (p=0.01). Serum levels of δ-tocopherol were also lower in participants with greater levels of smoking (p=0.02). Both vitamin E intake (β=0.03, p=0.02; β=0.03, p=0.01) and use of vitamin E supplements (β=0.05, p=0.03; β=0.06. p=0.02) were positively associated with FEV1 and FVC, after adjusting for confounders. Subjects who took vitamin E supplements had significantly higher α-tocopherol levels (p<0.0001) and lower γ-tocopherol levels (p<0.0001) than non-users. Conclusion In this study, there is a positive association between dietary vitamin E intake and lung function, and evidence of an inverse relationship between serum levels of γ-tocopherol and lung function. PMID:25715694

"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.

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.

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.

Air Pollution and Lung Function in Minority Youth with Asthma in the GALA II (Genes-Environments and Admixture in Latino Americans) and SAGE II (Study of African Americans, Asthma, Genes, and Environments) Studies.

PubMed

Neophytou, Andreas M; White, Marquitta J; Oh, Sam S; Thakur, Neeta; Galanter, Joshua M; Nishimura, Katherine K; Pino-Yanes, Maria; Torgerson, Dara G; Gignoux, Christopher R; Eng, Celeste; Nguyen, Elizabeth A; Hu, Donglei; Mak, Angel C; Kumar, Rajesh; Seibold, Max A; Davis, Adam; Farber, Harold J; Meade, Kelley; Avila, Pedro C; Serebrisky, Denise; Lenoir, Michael A; Brigino-Buenaventura, Emerita; Rodriguez-Cintron, William; Bibbins-Domingo, Kirsten; Thyne, Shannon M; Williams, L Keoki; Sen, Saunak; Gilliland, Frank D; Gauderman, W James; Rodriguez-Santana, Jose R; Lurmann, Fred; Balmes, John R; Eisen, Ellen A; Burchard, Esteban G

2016-06-01

Adverse effects of exposures to ambient air pollution on lung function are well documented, but evidence in racial/ethnic minority children is lacking. To assess the relationship between air pollution and lung function in minority children with asthma and possible modification by global genetic ancestry. The study population consisted of 1,449 Latino and 519 African American children with asthma from five different geographical regions in the mainland United States and Puerto Rico. We examined five pollutants (particulate matter ≤10 μm and ≤2.5 μm in diameter, ozone, nitrogen dioxide, and sulfur dioxide), derived from participant residential history and ambient air monitoring data, and assessed over several time windows. We fit generalized additive models for associations between pollutant exposures and lung function parameters and tested for interaction terms between exposures and genetic ancestry. A 5 μg/m(3) increase in average lifetime particulate matter less than or equal to 2.5 μm in diameter exposure was associated with a 7.7% decrease in FEV1 (95% confidence interval = -11.8 to -3.5%) in the overall study population. Global genetic ancestry did not appear to significantly modify these associations, but percent African ancestry was a significant predictor of lung function. Early-life particulate exposures were associated with reduced lung function in Latino and African American children with asthma. This is the first study to report an association between exposure to particulates and reduced lung function in minority children in which racial/ethnic status was measured by ancestry-informative markers.

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

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.

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.

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.

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

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.

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

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.

Abnormalities in lung volumes and airflow in children with newly diagnosed connective tissue disease.

PubMed

Peradzyńska, Joanna; Krenke, Katarzyna; Szylling, Anna; Kołodziejczyk, Beata; Gazda, Agnieszka; Rutkowska-Sak, Lidia; Kulus, Marek

2016-01-01

Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. There were 98 children (mean age: 13 ± 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 ± 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. FEV₁, FEV₁/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs 9 (11%). 24-months observation didn't reveal progression in lung function impairment. Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality.

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.

Potential Role of Lung Ventilation Scintigraphy in the Assessment of COPD

PubMed Central

Cukic, Vesna; Begic, Amela

2014-01-01

Objective: To highlight the importance of the lung ventilation scintigraphy (LVS) to study the regional distribution of lung ventilation and to describe most frequent abnormal patterns of lung ventilation distribution obtained by this technique in COPD and to compare the information obtained by LVS with the that obtained by traditional lung function tests. Material and methods: The research was done in 20 patients with previously diagnosed COPD who were treated in Intensive care unit of Clinic for pulmonary diseases and TB “Podhrastovi” Clinical Center, University of Sarajevo in exacerbation of COPD during first three months of 2014. Each patient was undergone to testing of pulmonary function by body plethysmography and ventilation/perfusion lung scintigraphy with radio pharmaceutics Technegas, 111 MBq Tc -99m-MAA. We compared the results obtained by these two methods. Results: All patients with COPD have a damaged lung function tests examined by body plethysmography implying airflow obstruction, but LVS indicates not only airflow obstruction and reduced ventilation, but also indicates the disorders in distribution in lung ventilation. Conclusion: LVS may add further information to the functional evaluation of COPD to that provided by traditional lung function tests and may contribute to characterizing the different phenotypes of COPD. PMID:25132709

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.

Quantitative computed tomography of lung parenchyma in patients with emphysema: analysis of higher-density lung regions

NASA Astrophysics Data System (ADS)

Lederman, Dror; Leader, Joseph K.; Zheng, Bin; Sciurba, Frank C.; Tan, Jun; Gur, David

2011-03-01

Quantitative computed tomography (CT) has been widely used to detect and evaluate the presence (or absence) of emphysema applying the density masks at specific thresholds, e.g., -910 or -950 Hounsfield Unit (HU). However, it has also been observed that subjects with similar density-mask based emphysema scores could have varying lung function, possibly indicating differences of disease severity. To assess this possible discrepancy, we investigated whether density distribution of "viable" lung parenchyma regions with pixel values > -910 HU correlates with lung function. A dataset of 38 subjects, who underwent both pulmonary function testing and CT examinations in a COPD SCCOR study, was assembled. After the lung regions depicted on CT images were automatically segmented by a computerized scheme, we systematically divided the lung parenchyma into different density groups (bins) and computed a number of statistical features (i.e., mean, standard deviation (STD), skewness of the pixel value distributions) in these density bins. We then analyzed the correlations between each feature and lung function. The correlation between diffusion lung capacity (DLCO) and STD of pixel values in the bin of -910HU <= PV < -750HU was -0.43, as compared with a correlation of -0.49 obtained between the post-bronchodilator ratio (FEV1/FVC) measured by the forced expiratory volume in 1 second (FEV1) dividing the forced vital capacity (FVC) and the STD of pixel values in the bin of -1024HU <= PV < -910HU. The results showed an association between the distribution of pixel values in "viable" lung parenchyma and lung function, which indicates that similar to the conventional density mask method, the pixel value distribution features in "viable" lung parenchyma areas may also provide clinically useful information to improve assessments of lung disease severity as measured by lung functional tests.

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

PubMed

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

2017-01-01

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

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.

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 .

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

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

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.

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.

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.

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

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...

No mediating effects of glycemic control and inflammation on the association between vitamin D and lung function in the general population.

PubMed

Kaul, Anne; Gläser, Sven; Hannemann, Anke; Stubbe, Beate; Felix, Stefan B; Nauck, Matthias; Ewert, Ralf; Friedrich, Nele

2017-04-01

Vitamin D deficiency is discussed to be associated with lung health. While former studies focused on subjects suffering from pulmonary diseases, we aimed to investigate the association of 25-hydroxy vitamin D [25(OH)D] with lung function in the general population and examined whether mediating effects of inflammation, glycemic control or renal function exist. 1404 participants from the Study of Health in Pomerania with pulmonary function testing assessed by expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), total lung capacity and Krogh index were used. Adjusted analysis of variance, linear regression models and mediation analyses were performed. Significant positive associations between 25(OH)D levels and FEV 1 , FVC and Krogh index were found. Mediator analyses revealed no mediating effect of inflammation (fibrinogen), glycemic control (HbA1c) or renal function (eGFR) on associations with FEV 1 or FVC. With respect to Krogh-Index, the association to 25(OH)D was slightly mediated by fibrinogen with a proportion mediated of 9.7%. Significant positive associations of 25(OH)D with lung function were revealed in a general population. The proposed mediating effects of inflammation, glycemic control and renal function on these relations were not confirmed. Further studies examining the causality of the association between 25(OH)D and lung function are necessary. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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.

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.

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

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 muscle strength is not decreased in patients undergoing cardiac surgery.

PubMed

Urell, Charlotte; Emtner, Margareta; Hedenstrom, Hans; Westerdahl, Elisabeth

2016-03-31

Postoperative pulmonary impairments are significant complications after cardiac surgery. Decreased respiratory muscle strength could be one reason for impaired lung function in the postoperative period. The primary aim of this study was to describe respiratory muscle strength before and two months after cardiac surgery. A secondary aim was to describe possible associations between respiratory muscle strength and lung function. In this prospective observational study 36 adult cardiac surgery patients (67 ± 10 years) were studied. Respiratory muscle strength and lung function were measured before and two months after surgery. Pre- and postoperative respiratory muscle strength was in accordance with predicted values; MIP was 78 ± 24 cmH2O preoperatively and 73 ± 22 cmH2O at two months follow-up (p = 0.19). MEP was 122 ± 33 cmH2O preoperatively and 115 ± 38 cmH2O at two months follow-up (p = 0.18). Preoperative lung function was in accordance with predicted values, but was significantly decreased postoperatively. At two-months follow-up there was a moderate correlation between MIP and FEV1 (r = 0.43, p = 0.009). Respiratory muscle strength was not impaired, either before or two months after cardiac surgery. The reason for postoperative lung function alteration is not yet known. Interventions aimed at restore an optimal postoperative lung function should focus on other interventions then respiratory muscle strength training.

Lung function among 9- to 10-year-old Tibetan and Han Chinese schoolchildren living at different altitudes in Tibet.

PubMed

Yangzong; Berntsen, Sveinung; Bjertness, Espen; Stigum, Hein; Gonggalanzi; Bianba; Nafstad, Per

2013-03-01

Tibetans have lived at high altitude longer than any other high-altitude population. Still little is known about their lung function and especially among children. This study compared lung function values of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and forced expiratory flow at 50% of FVC (FEF50) in children living at various altitudes in Tibet and with different ancestries. A cross-sectional study of lung function was performed among 9-10-year-old native Tibetan and Han Chinese children living at 3700 meters above sea level, and among native Tibetan children living at 4300 meters above sea level. The adjusted FVC and FEV1 were significantly higher in Tibetan children living at 4300 m above sea level as compared to Tibetans living at 3700 m. Tibetans living at 3700 m had higher FVC and FEV1 than Han Chinese living at the same altitude. All Tibetan children had on average higher FEF50 than Han Chinese. Tibetan children living at an altitude of 4300 m had relatively higher lung function than those living at 3700 m, and there were differences in lung function between Tibetans and Han Chinese who live at the same altitude. It seems likely that genetic factors involved in long-term adaptation to high altitude and cultural attributes could have contributed to the study findings.

Explaining ethnic disparities in lung function among young adults: A pilot investigation

PubMed Central

Patel, Jaymini; Minelli, Cosetta; Burney, Peter G. J.

2017-01-01

Background Ethnic disparities in lung function have been linked mainly to anthropometric factors but have not been fully explained. We conducted a cross-sectional pilot study to investigate how best to study ethnic differences in lung function in young adults and evaluate whether these could be explained by birth weight and socio-economic factors. Methods We recruited 112 university students of White and South Asian British ethnicity, measured post-bronchodilator lung function, obtained information on respiratory symptoms and socio-economic factors through questionnaires, and acquired birth weight through data linkage. We regressed lung function against ethnicity and candidate predictors defined a priori using linear regression, and used penalised regression to examine a wider range of factors. We reviewed the implications of our findings for the feasibility of a larger study. Results There was a similar parental socio-economic environment and no difference in birth weight between the two ethnic groups, but the ethnic difference in FVC adjusted for sex, age, height, demi-span, father’s occupation, birth weight, maternal educational attainment and maternal upbringing was 0.81L (95%CI: -1.01 to -0.54L). Difference in body proportions did not explain the ethnic differences although parental immigration was an important predictor of FVC independent of ethnic group. Participants were comfortable with study procedures and we were able to link birth weight data to clinical measurements. Conclusion Studies of ethnic disparities in lung function among young adults are feasible. Future studies should recruit a socially more diverse sample and investigate the role of markers of acculturation in explaining such differences. PMID:28575113

Lung function in insulation workers.

PubMed Central

Clausen, J; Netterstrøm, B; Wolff, C

1993-01-01

To evaluate the effects of working with modern insulation materials (rock and glass wool), the members of the Copenhagen Union of Insulation Workers were invited to participate in a study based on a health examination that included lung function tests. Three hundred and forty men (74%) agreed to participate, and 166 bus drivers served as the control group. Age distribution, height, and smoking habits were similar in the two groups. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were used as tests for lung function. There were no differences in FVC between the study and control groups, but the insulation workers had significantly lower values of FEV1 (mean 2.51) compared with the controls (mean 3.4 1), independent of smoking habits. Six years before the present study, 114 of the insulation workers participated in a similar study, and eight years after the initial study, the lung function of 59 of the bus drivers was tested. The decline in FVC in insulation workers who smoked was significantly higher (7.7 cl/year) than in bus drivers who smoked (3.1 cl/year); the decline in FEV1 was significantly higher in insulation workers independent of smoking habits (17.0 cl/year v 2.9 cl/year). Self assessed former exposure to asbestos was not associated with lung function in insulation workers. The study concludes that working with modern insulation materials is associated with increased risk of developing obstructive lung disease. PMID:8457492

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

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.

Serum tocopherol levels and vitamin E intake are associated with lung function in the normative aging study.

PubMed

Hanson, Corrine; Lyden, Elizabeth; Furtado, Jeremy; Campos, Hannia; Sparrow, David; Vokonas, Pantel; Litonjua, Augusto A

2016-02-01

The results of studies assessing relationships between vitamin E intake and status and lung function are conflicting. This study aimed to evaluate the effect of vitamin E intake and serum levels of tocopherol isoforms on lung function in a cross-sectional sample of 580 men from the Normative Aging Study, a longitudinal aging study. Regression models were used to look at associations of serum tocopherol isoform levels and vitamin E intake with lung function parameters after adjustment for confounders. Vitamin E intake was measured using a food frequency questionnaire and serum levels of γ, α, and δ-tocopherol levels were measured using high-performance liquid chromatography. After adjustment for potential confounders, serum γ-tocopherol had a significant inverse association with forced vital capacity (β = -0.10, p = 0.05). Alpha and δ-tocopherol were not associated with any lung function parameter. After classifying COPD status according to Global Initiative for Obstructive Lung Disease (GOLD) stage criteria, serum levels of δ-tocopherol were lower in participants with more severe COPD (p = 0.01). Serum levels of δ-tocopherol were also lower in participants with greater levels of smoking (p = 0.02). Both vitamin E intake (β = 0.03, p = 0.02; β = 0.03, p = 0.01) and use of vitamin E supplements (β = 0.05, p = 0.03; β = 0.06. p = 0.02) were positively associated with FEV1 and FVC, after adjusting for confounders. Subjects who took vitamin E supplements had significantly higher α-tocopherol levels (p < 0.0001) and lower γ-tocopherol levels (p < 0.0001) than non-users. In this study, there is a positive association between dietary vitamin E intake and lung function, and evidence of an inverse relationship between serum levels of γ-tocopherol and lung function. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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

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

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.

Comprehensive outcomes after lung retransplantation: a single center review.

PubMed

Halloran, Kieran; Aversa, Meghan; Tinckam, Kathryn; Martinu, Tereza; Binnie, Matthew; Chaparro, Cecilia; Chow, Chung-Wai; Waddell, Tom; McRae, Karen; Pierre, Andrew; de Perrot, Marc; Yasufuku, Kazuhiro; Cypel, Marcelo; Keshavjee, Shaf; Singer, Lianne G

2018-05-13

Lung retransplantation is an important therapy for a growing population of lung transplant recipients with graft failure, but detailed outcome data are lacking. We conducted a retrospective cohort study of adult lung retransplant in the Toronto Lung Transplant Program from 2001 to 2013 (n=38). We analyzed the post-operative course, graft function, renal function, microbiology, donor specific antibodies (DSA), quality of life and survival compared to a control cohort of primary transplant recipients matched for age and era. Indication for retransplant was chronic lung allograft dysfunction in most retransplant recipients (35/38, 82%). The post-operative course was more complex after retransplant than primary (ventilation time, 8 vs. 2 days, p<0.01; ICU stay 14 vs. 4 days, 0<0.01) and peak lung function was lower (FEV1 2.2L vs. 3L, p<0.01). Quality of life scores were comparable, as were renal function, microbiology and donor specific antibody formation. Median survival was 1988 days after primary and 1475 days after retransplant (p=0.39). Lung retransplantation is associated with a more complex post-operative course and lower peak lung function, but the long term medical profile is similar to primary transplant. Lung retransplantation can be beneficial for carefully selected candidates with allograft failure. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

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.

Long-Term Exposure to Primary Traffic Pollutants and Lung Function in Children: Cross-Sectional Study and Meta-Analysis.

PubMed

Barone-Adesi, Francesco; Dent, Jennifer E; Dajnak, David; Beevers, Sean; Anderson, H Ross; Kelly, Frank J; Cook, Derek G; Whincup, Peter H

2015-01-01

There is widespread concern about the possible health effects of traffic-related air pollution. Nitrogen dioxide (NO2) is a convenient marker of primary pollution. We investigated the associations between lung function and current residential exposure to a range of air pollutants (particularly NO2, NO, NOx and particulate matter) in London children. Moreover, we placed the results for NO2 in context with a meta-analysis of published estimates of the association. Associations between primary traffic pollutants and lung function were investigated in 4884 children aged 9-10 years who participated in the Child Heart and Health Study in England (CHASE). A systematic literature search identified 13 studies eligible for inclusion in a meta-analysis. We combined results from the meta-analysis with the distribution of the values of FEV1 in CHASE to estimate the prevalence of children with abnormal lung function (FEV1<80% of predicted value) expected under different scenarios of NO2 exposure. In CHASE, there were non-significant inverse associations between all pollutants except ozone and both FEV1 and FVC. In the meta-analysis, a 10 μg/m3 increase in NO2 was associated with an 8 ml lower FEV1 (95% CI: -14 to -1 ml; p: 0.016). The observed effect was not modified by a reported asthma diagnosis. On the basis of these results, a 10 μg/m3 increase in NO2 level would translate into a 7% (95% CI: 4% to 12%) increase of the prevalence of children with abnormal lung function. Exposure to traffic pollution may cause a small overall reduction in lung function and increase the prevalence of children with clinically relevant declines in lung function.

[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.

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.

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.

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.

Asthma phenotypes modify the impact of environmetnal factors on lung function

EPA Science Inventory

Previous studies have examined the role of childhood asthma phenotypes based on clinical history on asthma severity and symptom aggravation by environmental risk factors. The current study focuses on the associations between lung function in childhood and environmental factors an...

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

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.

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

Rural-urban disparity in lung function parameters of Nigerian children: effects of socio-economic, nutritional and housing factors

PubMed Central

Kuti, Bankole Peter; Oladimeji, Oluwatoyin Ibukun; Kuti, Demilade Kehinde; Adeniyi, Adewuyi Temidayo; Adeniji, Emmanuel Oluwatosin; Osundare, Yetunde Justinah

2017-01-01

Introduction The effect of socio-demographic and nutritional factors on lung functions of African children is poorly studied. This study set out to determine the effects of these factors on lung functions of Nigerian school children. Methods Rural and urban secondary schools students in Ilesa, Nigeria were selected by multistage sampling. The socio-demographic, nutritional status as well as lung function parameters measured using incentive Spirometry (MIR Spirolab III srl, Italy) of the children were obtained and compared among the rural and urban children. Results A total of 250 children (128 rural and 122 urban) aged 9 to 17 years participated in the study over a 12 month period. Mean (SD) age was 12.6 (1.9) years and Male: Female 1:1.1. The urban children were heavier, taller and have larger lung volumes than their age and sex matched rural counterpart. Stunted rural males [Mean (SD) FVC 1.8 (0.3) L vs. 2.2 (0.6) L t-test = 2.360; p = 0.022], underweight females [Mean (SD) FVC 1.8 (0.4) L vs. 2.2 (0.6) L; t-test = 2.855; p = 0.006] and those exposed to unclean fuel [Mean (SD) FVC 2.1 (0.6) L vs. 2.4 (0.5) L; t-test = 2.079; p = 0.041] had significantly lower lung volumes compared to their counterparts without these conditions. Conclusion Undernutrition, low socio-economic class and use of unclean fuels adversely affect the lung functions of Nigerian children. Improved standard of living, use of clean fuel and adequate nutrition may ensure better lung health among these children. PMID:29629016

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.

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

The Association of Lung Function, Bronchial Hyperresponsiveness, and Exhaled Nitric Oxide Differs Between Atopic and Non-atopic Asthma in Children

PubMed Central

Shim, Eunhee; Lee, Eun; Yang, Song-I; Jung, Young-Ho; Park, Geun Mi; Kim, Hyung Young; Seo, Ju-Hee

2015-01-01

Purpose Although many previous studies have attempted to identify differences between atopic asthma (AA) and non-atopic asthma (NAA), they have mainly focused on the difference of each variable of lung function and airway inflammation. The aim of this study was to evaluate relationships between lung function, bronchial hyperresponsiveness (BHR), and the exhaled nitric oxide (eNO) levels in children with AA and NAA. Methods One hundred and thirty six asthmatic children aged 5-15 years and 40 normal controls were recruited. Asthma cases were classified as AA (n=100) or NAA (n=36) from skin prick test results. Lung function, BHR to methacholine and adenosine-5'-monophosphate (AMP), eNO, blood eosinophils, and serum total IgE were measured. Results The AA and NAA cases shared common features including a reduced small airway function and increased BHR to methacholine. However, children with AA showed higher BHR to AMP and eNO levels than those with NAA. When the relationships among these variables in the AA and NAA cases were evaluated, the AA group showed significant relationships between lung function, BHR to AMP or methacholine and eNO levels. However, the children in the NAA group showed an association between small airway function and BHR to methacholine only. Conclusions These findings suggest that the pathogenesis of NAA may differ from that of AA during childhood in terms of the relationship between lung function, airway inflammation and BHR. PMID:25749776

SU-E-J-149: Establishing the Relationship Between Pre-Treatment Lung Ventilation, Dose, and Toxicity Outcome

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

Mistry, N; D'Souza, W; Sornsen de Koste, J

2014-06-01

Purpose: Recently, there has been an interest in incorporating functional information in treatment planning especially in thoracic tumors. The rationale is that healthy lung regions need to be spared from radiation if possible to help achieve better control on toxicity. However, it is still unclear whether high functioning regions need to be spared or have more capacity to deal with the excessive radiation as compared to the compromised regions of the lung. Our goal with this work is to establish the tools by which we can establish a relationship between pre-treatment lung function, dose, and radiographic outcomes of lung toxicity.more » Methods: Treatment planning was performed using a single phase of a 4DCT scan, and follow-up anatomical CT scans were performed every 3 months for most patients. In this study, we developed the pipeline of tools needed to analyze such a large dataset, while trying to establish a relationship between function, dose, and outcome. Pre-treatment lung function was evaluated using a recently published technique that evaluates Fractional Regional Ventilation (FRV). All images including the FRV map and the individual follow-up anatomical CT images were all spatially matched to the planning CT using a diffusion based Demons image registration algorithm. Change in HU value was used as a metric to capture the effects of lung toxicity. To validate the findings, a radiologist evaluated the follow-up anatomical CT images and scored lung toxicity. Results: Initial experience in 1 patient shows a relationship between the pre-treatment lung function, dose and toxicity outcome. The results are also correlated to the findings by the radiologist who was blinded to the analysis or dose. Conclusion: The pipeline we have established to study this enables future studies in large retrospective studies. However, the tools are dependent on the fidelity of 4DCT reconstruction for accurate evaluation of regional ventilation. Patent Pending for the technique presented in this work to evaluate FRV incorporating mass correction.« less

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.

Spirometry (image)

MedlinePlus

Spirometry is a painless study of air volume and flow rate within the lungs. Spirometry is frequently used to evaluate lung function in people with obstructive or restrictive lung diseases such as asthma or cystic fibrosis.

Spirometric reference values in urban children in Madagascar: poverty is a risk factor for low lung function.

PubMed

Wolff, Peter Th; Arison, Lala; Rahajamiakatra, Abel; Raserijaona, Francis; Niggemann, Bodo

2014-01-01

Studies about children with respiratory diseases in Africa are impeded by the dearth of reliable data for the vast majority of countries on the continent. This study was conducted to establish representative reference values, therefore allowing a more accurate evaluation of lung function in Malagasy children. One thousand two hundred thirty-six students from three public and five private schools aged 8-12 years were recruited. A total of 1,093 children were healthy, had a valid lung function measurement and were thus deemed evaluable for this study. Lung function data were collected on consecutive days in Antananarivo, Madagascar's capital, using spirometry and a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The lung volumes found were substantially lower compared to Caucasian and African equations. The mean Z-score (Stanojevic) for the forced vital capacity (FVC) found was -1.45 and -0.93 for the forced expiratory volume in 1 sec (FEV1) with significant differences between private and public schools (FVC: P = 0.0023, FEV1: P = 0.0004). The equations established for school children in Madagascar's capital Antananarivo showed lung function values were lower than reference values for the same age group seen not only in European, but also in African American and African children. The unique ethnicity of the Malagasy people, which combines Southeast-Asian with substantial African influences, the heavy burden of pollution and poverty may explain these differences. © 2013 Wiley Periodicals, Inc.

Air pollution, airway inflammation and lung function in Mexico City school children

EPA Science Inventory

BACKGROUND: The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. OBJECTIVE: In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. METHODS: We studied a cohort...

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

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.

A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function.

PubMed

Sørli, Jorid B; Da Silva, Emilie; Bäckman, Per; Levin, Marcus; Thomsen, Birthe L; Koponen, Ismo K; Larsen, Søren T

2016-03-01

The lung surfactant (LS) lining is a thin liquid film covering the air-liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses--neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols--as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose--and albumin known to impair lung functionality by inhibiting LS function.

State-of-the-art radiological techniques improve the assessment of postoperative lung function in patients with non-small cell lung cancer.

PubMed

Ohno, Yoshiharu; Koyama, Hisanobu; Nogami, Munenobu; Takenaka, Daisuke; Onishi, Yumiko; Matsumoto, Keiko; Matsumoto, Sumiaki; Maniwa, Yoshimasa; Yoshimura, Masahiro; Nishimura, Yoshihiro; Sugimura, Kazuro

2011-01-01

The purpose of this study was to compare predictive capabilities for postoperative lung function in non-small cell lung cancer (NSCLC) patients of the state-of-the-art radiological methods including perfusion MRI, quantitative CT and SPECT/CT with that of anatomical method (i.e. qualitative CT) and traditional nuclear medicine methods such as planar imaging and SPECT. Perfusion MRI, CT, nuclear medicine study and measurements of %FEV(1) before and after lung resection were performed for 229 NSCLC patients (125 men and 104 women). For perfusion MRI, postoperative %FEV(1) (po%FEV(1)) was predicted from semi-quantitatively assessed blood volumes within total and resected lungs, for quantitative CT, it was predicted from the functional lung volumes within total and resected lungs, for qualitative CT, from the number of segments of total and resected lungs, and for nuclear medicine studies, from uptakes within total and resected lungs. All SPECTs were automatically co-registered with CTs for preparation of SPECT/CTs. Predicted po%FEV(1)s were then correlated with actual po%FEV(1)s, which were measured %FEV(1)s after operation. The limits of agreement were also evaluated. All predicted po%FEV(1)s showed good correlation with actual po%FEV(1)s (0.83≤r≤0.88, p<0.0001). Perfusion MRI, quantitative CT and SPECT/CT demonstrated better correlation than other methods. The limits of agreement of perfusion MRI (4.4±14.2%), quantitative CT (4.7±14.2%) and SPECT/CT (5.1±14.7%) were less than those of qualitative CT (6.0±17.4%), planar imaging (5.8±18.2%), and SPECT (5.5±16.8%). State-of-the-art radiological methods can predict postoperative lung function in NSCLC patients more accurately than traditional methods. Copyright © 2009 Elsevier Ireland Ltd. 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.).

Heritability of Lung Disease Severity in Cystic Fibrosis

PubMed Central

Vanscoy, Lori L.; Blackman, Scott M.; Collaco, Joseph M.; Bowers, Amanda; Lai, Teresa; Naughton, Kathleen; Algire, Marilyn; McWilliams, Rita; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Cutler, Dave; Cutting, Garry R.

2007-01-01

Rationale: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. Objectives: To quantify the contribution of modifier genes to variation in CF lung disease severity. Methods: Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV1 within the last year was used for cross-sectional analysis. FEV1 measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (∼ 100% gene sharing) with that of dizygous (DZ) twins/siblings (∼ 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. Measurements and Main Results: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82–0.91, p < 0.0001) were higher than for DZ twins and siblings (0.50–0.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). Conclusions: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype. PMID:17332481

Effects of Aspergillus fumigatus colonization on lung function in cystic fibrosis.

PubMed

Speirs, Jennifer J; van der Ent, Cornelis K; Beekman, Jeffrey M

2012-11-01

Aspergillus fumigatus is frequently isolated from cystic fibrosis (CF) patients and is notorious for its role in the debilitating condition of allergic bronchopulmonary aspergillosis (ABPA). Although CF patients suffer from perpetual microorganism-related lung disease, it is unclear whether A. fumigatus colonization has a role in causing accelerated lung function decline and whether intervention is necessary. A. fumigatus morbidity appears to be related to cystic fibrosis transmembrane conductance regulator-dependant function of the innate immune system. A. fumigatus-colonized patients have a lower lung capacity, more frequent hospitalizations and more prominent radiological abnormalities than noncolonized patients. Treatment with antifungal agents can be of value but has several drawbacks and a direct effect on lung function is yet to be shown. A. fumigatus appears to have an important role in CF lung disease, not exclusive to the context of ABPA. However, a causal relationship still needs to be confirmed. Study observations and trends indicate a need to further elucidate the mechanisms of A. fumigatus interactions with the host innate immune system and its role in CF lung morbidity.

Functional improvement in patients with idiopathic pulmonary fibrosis undergoing single lung transplantation *

PubMed Central

Rubin, Adalberto Sperb; Nascimento, Douglas Zaione; Sanchez, Letícia; Watte, Guilherme; Holand, Arthur Rodrigo Ronconi; Fassbind, Derrick Alexandre; Camargo, José Jesus

2015-01-01

Abstract Objective: To evaluate the changes in lung function in the first year after single lung transplantation in patients with idiopathic pulmonary fibrosis (IPF). Methods: We retrospectively evaluated patients with IPF who underwent single lung transplantation between January of 2006 and December of 2012, reviewing the changes in the lung function occurring during the first year after the procedure. Results: Of the 218 patients undergoing lung transplantation during the study period, 79 (36.2%) had IPF. Of those 79 patients, 24 (30%) died, and 11 (14%) did not undergo spirometry at the end of the first year. Of the 44 patients included in the study, 29 (66%) were men. The mean age of the patients was 57 years. Before transplantation, mean FVC, FEV1, and FEV1/FVC ratio were 1.78 L (50% of predicted), 1.48 L (52% of predicted), and 83%, respectively. In the first month after transplantation, there was a mean increase of 12% in FVC (400 mL) and FEV1 (350 mL). In the third month after transplantation, there were additional increases, of 5% (170 mL) in FVC and 1% (50 mL) in FEV1. At the end of the first year, the functional improvement persisted, with a mean gain of 19% (620 mL) in FVC and 16% (430 mL) in FEV1. Conclusions: Single lung transplantation in IPF patients who survive for at least one year provides significant and progressive benefits in lung function during the first year. This procedure is an important therapeutic alternative in the management of IPF. PMID:26398749

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.

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 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.

Tobacco use among designated air pollution victims and its association with lung function and respiratory symptoms: a retrospective cross-sectional study

PubMed Central

Kotaki, Kenji; Senjyu, Hideaki; Tanaka, Takako; Yano, Yudai; Miyamoto, Naomi; Nishinakagawa, Tsuyoshi; Yanagita, Yorihide; Asai, Masaharu; Kozu, Ryo; Tabusadani, Mitsuru; Sawai, Terumitsu; Honda, Sumihisa

2014-01-01

Objectives We sought to elucidate the long-term association of tobacco use and respiratory health in designated pollution victims with and without obstructive pulmonary defects. Design A retrospective cross-sectional study. Setting The register of pollution victims in Kurashiki, Japan. Participants 730 individuals over 65 years of age previously diagnosed with pollution-related respiratory disease. Patients were classified into four groups according to their smoking status and whether they had obstructive pulmonary disease. We then compared the prevalence of respiratory symptoms and lung function over time between groups. Primary outcome measures Spirometry was performed and a respiratory health questionnaire completed in the same season each year for up to 30 years. Results Rates of smoking and respiratory disease were high in our sample. Although respiratory function in non-smoking patients did not completely recover, the annual rate of change in lung function was within the normal range (p<0.01). However, smokers had worse lung function and were more likely to report more severe pulmonary symptoms (p<0.01). Conclusions Patients’ respiratory function did not fully recover despite improved air quality. Our results suggest that, in the context of exposure to air pollution, tobacco use causes additional loss of lung function and exacerbates respiratory symptoms. PMID:25082419

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.

Quantification of atopy, lung function and airway hypersensitivity in adults

PubMed Central

2011-01-01

Background Studies in children have shown that concentration of specific serum IgE (sIgE) and size of skin tests to inhalant allergens better predict wheezing and reduced lung function than the information on presence or absence of atopy. However, very few studies in adults have investigated the relationship of quantitative atopy with lung function and airway hyperresponsiveness (AHR). Objective To determine the association between lung function and AHR and quantitative atopy in a large sample of adults from the UK. Methods FEV1 and FVC (% predicted) were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma). Atopic status was assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant allergens). We also measured indoor allergen exposure in subjects' homes. Results Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV1 (mite p = 0.001, cat p = 0.0001, dog p = 2.95 × 10-8). Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 × 10-8, cat p = 3.93 × 10-10, dog p = 3.03 × 10-15, grass p = 2.95 × 10-9). The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control). Conclusions In the studied population, lung function decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to inhalant allergens, suggesting that atopy may not be a dichotomous outcome influencing lung function and AHR. PMID:22410099

Investigation of Hydrogen Sulfide Exposure and Lung Function, Asthma and Chronic Obstructive Pulmonary Disease in a Geothermal Area of New Zealand

PubMed Central

Bates, Michael N.; Crane, Julian; Balmes, John R.; Garrett, Nick

2015-01-01

Background Results have been conflicting whether long-term ambient hydrogen sulfide (H2S) affects lung function or is a risk factor for asthma or chronic obstructive pulmonary disease (COPD). Rotorua city, New Zealand, has the world’s largest population exposed to ambient H2S—from geothermal sources. Objectives We investigated associations of H2S with lung function, COPD and asthma in this population. Methods 1,204 of 1,639 study participants, aged 18–65 years during 2008–2010, provided satisfactory spirometry results. Residences, workplaces and schools over the last 30 years were geocoded. Exposures were estimated from data collected by summer and winter H2S monitoring networks across Rotorua. Four metrics for H2S exposure, representing both current and long-term (last 30 years) exposure, and also time-weighted average and peak exposures, were calculated. Departures from expected values for pre-bronchodilator lung function, calculated from prediction equations, were outcomes for linear regression models using quartiles of the H2S exposure metrics. Separate models examined participants with and without evidence of asthma or COPD, and never- and ever-smokers. Logistic regression was used to investigate associations of COPD (a post-bronchodilator FEV1/FVC < 70% of expected) and asthma (doctor-diagnosed or by FEV1 response to bronchodilator) with H2S exposure quartiles. Results None of the exposure metrics produced evidence of lung function decrement. The logistic regression analysis showed no evidence that long-term H2S exposure at Rotorua levels was associated with either increased COPD or asthma risk. Some results suggested that recent ambient H2S exposures were beneficially associated with lung function parameters. Conclusions The study found no evidence of reductions in lung function, or increased risk of COPD or asthma, from recent or long-term H2S exposure at the relatively high ambient concentrations found in Rotorua. Suggestions of improved lung function associated with recent ambient H2S exposures require confirmation in other studies. PMID:25822819

Investigation of hydrogen sulfide exposure and lung function, asthma and chronic obstructive pulmonary disease in a geothermal area of New Zealand.

PubMed

Bates, Michael N; Crane, Julian; Balmes, John R; Garrett, Nick

2015-01-01

Results have been conflicting whether long-term ambient hydrogen sulfide (H2S) affects lung function or is a risk factor for asthma or chronic obstructive pulmonary disease (COPD). Rotorua city, New Zealand, has the world's largest population exposed to ambient H2S-from geothermal sources. We investigated associations of H2S with lung function, COPD and asthma in this population. 1,204 of 1,639 study participants, aged 18-65 years during 2008-2010, provided satisfactory spirometry results. Residences, workplaces and schools over the last 30 years were geocoded. Exposures were estimated from data collected by summer and winter H2S monitoring networks across Rotorua. Four metrics for H2S exposure, representing both current and long-term (last 30 years) exposure, and also time-weighted average and peak exposures, were calculated. Departures from expected values for pre-bronchodilator lung function, calculated from prediction equations, were outcomes for linear regression models using quartiles of the H2S exposure metrics. Separate models examined participants with and without evidence of asthma or COPD, and never- and ever-smokers. Logistic regression was used to investigate associations of COPD (a post-bronchodilator FEV1/FVC < 70% of expected) and asthma (doctor-diagnosed or by FEV1 response to bronchodilator) with H2S exposure quartiles. None of the exposure metrics produced evidence of lung function decrement. The logistic regression analysis showed no evidence that long-term H2S exposure at Rotorua levels was associated with either increased COPD or asthma risk. Some results suggested that recent ambient H2S exposures were beneficially associated with lung function parameters. The study found no evidence of reductions in lung function, or increased risk of COPD or asthma, from recent or long-term H2S exposure at the relatively high ambient concentrations found in Rotorua. Suggestions of improved lung function associated with recent ambient H2S exposures require confirmation in other studies.

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.

Identification of rat lung-specific microRNAs by micoRNA microarray: valuable discoveries for the facilitation of lung research.

PubMed

Wang, Yang; Weng, Tingting; Gou, Deming; Chen, Zhongming; Chintagari, Narendranath Reddy; Liu, Lin

2007-01-24

An important mechanism for gene regulation utilizes small non-coding RNAs called microRNAs (miRNAs). These small RNAs play important roles in tissue development, cell differentiation and proliferation, lipid and fat metabolism, stem cells, exocytosis, diseases and cancers. To date, relatively little is known about functions of miRNAs in the lung except lung cancer. In this study, we utilized a rat miRNA microarray containing 216 miRNA probes, printed in-house, to detect the expression of miRNAs in the rat lung compared to the rat heart, brain, liver, kidney and spleen. Statistical analysis using Significant Analysis of Microarray (SAM) and Tukey Honestly Significant Difference (HSD) revealed 2 miRNAs (miR-195 and miR-200c) expressed specifically in the lung and 9 miRNAs co-expressed in the lung and another organ. 12 selected miRNAs were verified by Northern blot analysis. The identified lung-specific miRNAs from this work will facilitate functional studies of miRNAs during normal physiological and pathophysiological processes of the lung.

Differential respirable dust related lung function effects between current and former South African coal miners.

PubMed

Naidoo, Rajen N; Robins, Thomas G; Seixas, Noah; Lalloo, Umesh G; Becklake, Margaret

2005-05-01

Dust-related dose-response decrements in lung function among coal miners have been reported in several studies, with varying magnitudes across populations. Few studies have compared differences between current and former coal miners. No studies on dose response relationships with lung function have been conducted in South African coal mines, one of the top three producers of coal internationally. The objectives of this study were (1) to describe the relationship between respirable dust exposure and lung function among current and former South African coal miners and to determine whether differential dust related effects were present between these employment categories; (2) to examine dust related dose response relationships, controlling for potential confounding by smoking and a history of tuberculosis (TB). Six hundred and eighty-four current and 188 ex-miners from three bituminous coal mines in Mpumalanga Province were studied. Interviews assessing work histories, smoking profiles and other risk factors were conducted. Work histories were also obtained from company records. Standardised spirometry was performed by trained technicians. Cumulative respirable dust exposure (CDE) estimates were constructed from company-collected sampling and measurements conducted by the researchers. Regression models examined the associations of CDE with per cent predicted FEV(1) and FVC, controlling for smoking, past history of TB and employment status. A statistically significant decline in FEV(1) of 1.1 and 2.2 ml/mg-year/m(3) was found in representative 40-year-old, 1.7-m tall current and former miners, respectively. Significant differences were found between the highest and medium exposure categories. Ex-miners had a lower mean per cent predicted lung function than current miners for each cumulative exposure category, suggesting a "healthy worker" effect. Past history of TB contributed to 21 and 14% declines in per cent predicted FEV(1) and FVC, respectively. Thus, in this cohort, a dose-related decline in lung function was associated with respirable dust exposure, with a magnitude of effect similar to that seen in other studies and important differences between current and former employees. A "healthy worker" effect may have attenuated the magnitude of this relationship. TB was a significant contributor to lung function loss.

[K+ channels and lung epithelial physiology].

PubMed

Bardou, Olivier; Trinh, Nguyen Thu Ngan; Brochiero, Emmanuelle

2009-04-01

Transcripts of more than 30 different K(+) channels have been detected in the respiratory epithelium lining airways and alveoli. These channels belong to the 3 main classes of K(+) channels, i.e. i) voltage-dependent or calcium-activated, 6 transmembrane segments (TM), ii) 2-pores 4-TM and iii) inward-rectified 2-TM channels. The physiological and functional significance of this high molecular diversity of lung epithelial K(+) channels is not well understood. Surprisingly, relatively few studies are focused on K(+) channel function in lung epithelial physiology. Nevertheless, several studies have shown that KvLQT1, KCa and K(ATP) K(+) channels play a crucial role in ion and fluid transport, contributing to the control of airway and alveolar surface liquid composition and volume. K(+) channels are involved in other key functions, such as O(2) sensing or the capacity of the respiratory epithelia to repair after injury. This mini-review aims to discuss potential functions of lung K(+) channels.

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.

Long-term air pollution exposure, genome-wide DNA methylation and lung function in the LifeLines cohort study.

EPA Science Inventory

BACKGROUND: Long-term air pollution exposure is negatively associated with lung function, yet the mechanisms underlying this association are not·­ fully clear.Differential DNA methylation may explain this association. OBJECTIVES: Our main aim was to study the associati...

Association between right ventricular dysfunction and restrictive lung disease in childhood cancer survivors as measured by quantitative echocardiography.

PubMed

Patel, Amee; Weismann, Constance; Weiss, Pnina; Russell, Kerry; Bazzy-Asaad, Alia; Kadan-Lottick, Nina S

2014-11-01

Restrictive lung disease is a complication in childhood cancer survivors who received lung-toxic chemotherapy and/or thoracic radiation. Left ventricular dysfunction is documented in these survivors, but less is known about right ventricular (RV) function. Quantitative echocardiography may help detect subclinical RV dysfunction. The aim of this study was to assess RV function quantitatively in childhood cancer survivors after lung-toxic therapy. We identified records of 33 childhood cancer survivors who (1) were treated with lung-toxic therapy and/or radiation, (2) were cancer-free for ≥ one year after therapy, and (3) had pulmonary function tests and echocardiograms from their most recent follow-up visit. Participants' mean age was 11.6 ± 4.5 years at cancer diagnosis and 23 ± 8.6 years at evaluation. The most common diagnosis was lymphoma/leukemia (n = 27). Twenty-nine subjects had anthracycline exposure. Eleven of the 33 subjects demonstrated restrictive pulmonary impairment (total lung capacity 3.69 ± 1.5 L [69.3 ± 22.4% predicted]). Among quantitative measures of RV function, isovolumetric acceleration (IVA), a measure of contractility, was significantly lower in the group with restrictive lung disease (2.42 ± 0.56 vs. 1.83 ± 0.78 m/sec(2); P < 0.05). There was a trend towards lower tissue Doppler derived S' and tricuspid annular plane systolic excursion in the group with restrictive lung disease. Subjects with restrictive lung disease were found to have ≥ 2 abnormal parameters (P < 0.01). IVA may detect early RV dysfunction in childhood cancer survivors with restrictive lung disease. Our findings require confirmation in a larger study population and validation by cardiac MRI. © 2014 Wiley Periodicals, Inc.

Ex vivo administration of trimetazidine improves post-transplant lung function in pig model.

PubMed

Cosgun, Tugba; Iskender, Ilker; Yamada, Yoshito; Arni, Stephan; Lipiski, Miriam; van Tilburg, Koen; Weder, Walter; Inci, Ilhan

2017-07-01

Ex vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model. Pig lungs were retrieved and stored for 24 h at 4°C, followed by 4 h of EVLP. Allografts were randomly allocated to 2 groups ( n  = 5 each). TMZ (5 mg/kg) was added to the prime solution prior to EVLP. After EVLP, left lungs were transplanted and recipients were observed for 4 h. Allograft gas exchange function and lung mechanics were recorded hourly throughout reperfusion. Microscopic lung injury and inflammatory and biochemical parameters were assessed. There was a trend towards better oxygenation during EVLP in the TMZ group ( P  = 0.06). After transplantation, pulmonary gas exchange was significantly better during the 4-h reperfusion period and after isolation of the allografts for 10 min ( P  < 0.05). Tissue thiobarbituric acid levels, myeloperoxidase activity and protein concentrations in bronchoalveolar lavage samples were significantly lower in the TMZ group at the end of EVLP ( P  < 0.05). Ex vivo treatment of donor lungs with TMZ significantly improved immediate post-transplant lung function. Further studies are warranted to understand the effect of this strategy on long-term lung function. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Sensitization to sunflower pollen and lung functions in sunflower processing workers.

PubMed

Atis, S; Tutluoglu, B; Sahin, K; Yaman, M; Küçükusta, A R; Oktay, I

2002-01-01

This study aimed to investigate whether exposure to sunflower pollen (Helianthus annuus) increases both sensitization and respiratory symptoms, and whether or not it affects lung functions in sunflower processing workers. The largest sunflower processing factories in the Thrace region of Turkey participated in this study. Workers from the units directly exposed to sunflower seed enrolled as the study group (n = 102) and workers who were not directly exposed to Helianthus annuus pollen (n = 102) were the control group. Detailed questionnaires covering respiratory and allergic symptoms were completed, and skin prick tests and lung function tests were performed. We found a very high rate (23.5%) of sensitization to Helianthus annuus in the study group compared to the controls (P<0.001). Logistic regression analysis showed that the risk of sensitization to H. annuus was increased 4.7-fold (odds ratio = 4.17, 95%) confidence interval = 1.3-16.7) if subjects were exposed to sunflower pollen in the workplace. While asthmatic symptoms and allergic skin diseases were not different between the two groups, workers in the study group had a higher rate of allergic rhinitis and conjunctivitis (P<0.05). We found that pulmonary function was significantly impaired in the study group (P<0.01). Using a multivariate analysis model, inclusion in the study group was found to be a predictive factor for impairment of lung function (P=0.002). We conclude that sunflower pollen has high allergenic potential, especially when there is close contact, and exposure to sunflower pollen in the workplace can result in impairment in lung function.

Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two-way relationship.

PubMed

Noni, M; Katelari, A; Dimopoulos, G; Doudounakis, S-E; Tzoumaka-Bakoula, C; Spoulou, V

2015-11-01

Aspergillus fumigatus is commonly found in cystic fibrosis (CF) airways. Our aim was to assess the relationship between A. fumigatus chronic colonization and lung function in CF patients. A case-control study of CF patients born from 1989 to 2002 was performed. Medical records were reviewed from the time of initial diagnosis until December 2013. Chronic colonization was defined as two or more positive sputum cultures in a given year. Each patient chronically colonized with A. fumigatus was matched with three control patients (never colonized by A. fumigatus) for age, sex, and year of birth (±3 years). A number of parameters were recorded and analyzed prospectively. The primary outcome measure was the difference in forced expiratory volume in 1 s (FEV1) in percent predicted between groups. Linear mixed models were used for longitudinal analyses to evaluate the relationship between A. fumigatus chronic colonization and lung function during a 7-year period and study the lung function 4 years before the time of enrollment (t0). Twenty patients had chronic colonization and were matched with 60 controls. A significant difference in lung function was detected throughout the 7-year period after adjustment for confounders (est = 8.66, p = 0.020). Four years before t0, FEV1 baseline was the only factor associated with the course of lung function (est = 0.64, p < 0.001) and was significantly different between groups (p = 0.001). In conclusion, a decreased FEV1 baseline appears to be a risk factor for chronic colonization by A. fumigatus, which, in turn, may cause a faster deterioration of lung function.

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.

The alveolitis of pulmonary sarcoidosis. Evaluation of natural history and alveolitis-dependent changes in lung function

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

Keogh, B.A.; Hunninghake, G.W.; Line, B.R.

1983-08-01

Current concepts of the pathogenesis of pulmonary sarcoidosis suggest that a mononuclear cell alveolitis, comprised of activated T-lymphocytes and activated alveolar macrophages, precedes and modulates the formation of granuloma and fibrosis. To evaluate the natural history of this alveolitis and determine the relationship it has to subsequent changes in lung function, 19 untreated patients with pulmonary sarcoidosis without extrapulmonary manifestations were studied with bronchoalveolar lavage, /sup 67/Ga scanning, and pulmonary function tests to evaluate lung T-cells, lung alveolar macrophages, and lung function, respectively. In patients with sarcoidosis, low intensity alveolitis (lung T-cells less than or equal to 28% of allmore » lung effector cells and/or /sup 67/Ga scan negative) was much more common (80% of all observations) than high intensity alveolitis (lung T-cells greater than 28% and /sup 67/Ga scan positive, 20% of all observations). Conventional clinical, roentgenographic, or physiologic studies could not predict the alveolitis status. Interestingly, of the 51 alveolitis evaluations in the 19 patients, there were 24 occurrences (47%) where the alveolitis was ''split,'' i.e., /sup 67/Ga scans positive and T-cells low (39%) or /sup 67/Ga negative and T-cells high (8%). Most untreated patients with sarcoidosis without extrapulmonary symptoms may have some inflammatory processes ongoing in their alveolar structures. Overall, whenever a high intensity alveolitis episode occurred, it was followed by deterioration over the next 6 months in at least one lung function parameter. A low intensity alveolitis episode was followed by functional deterioration only 8% of the time. The alveolitis parameters (lavage and /sup 67/Ga scanning) clearly predicted prognosis. These observations should prove useful in understanding the natural history of pulmonary sarcoidosis, in staging patients with this disease, and in making rational therapy decisions.« less

Changes in Lung Function and Chylous Effusions in Patients With Lymphangioleiomyomatosis Treated With Sirolimus

PubMed Central

Taveira-DaSilva, Angelo M.; Hathaway, Olanda; Stylianou, Mario; Moss, Joel

2011-01-01

Background Lymphangioleiomyomatosis (LAM) is a disorder that affects women and is characterized by cystic lung destruction, chylous effusions, lymphangioleiomyomas, and angiomyolipomas. It is caused by proliferation of abnormal smooth muscle–like cells. Sirolimus is a mammalian target of rapamycin inhibitor that has been reported to decrease the size of neoplastic growths in animal models of tuberous sclerosis complex and to reduce the size of angiomyolipomas and stabilize lung function in humans. Objective To assess whether sirolimus therapy is associated with improvement in lung function and a decrease in the size of chylous effusions and lymphangioleiomyomas in patients with LAM. Design Observational study. Setting The National Institutes of Health Clinical Center. Patients 19 patients with rapidly progressing LAM or chylous effusions. Intervention Treatment with sirolimus. Measurements Lung function and the size of chylous effusions and lymphangioleiomyomas before and during sirolimus therapy. Results Over a mean of 2.5 years before beginning sirolimus therapy, the mean (±SE) FEV1 decreased by 2.8% ± 0.8% predicted and diffusing capacity of the lung for carbon monoxide (DLCO) decreased by 4.8% ± 0.9% predicted per year. In contrast, over a mean of 2.6 years of sirolimus therapy, the mean (± SE) FEV1 increased by 1.8% ± 0.5% predicted and DLCO increased by 0.8% ± 0.5% predicted per year (P < 0.001). After beginning sirolimus therapy, 12 patients with chylous effusions and 11 patients with lymphangioleiomyomas experienced almost complete resolution of these conditions. In 2 of the 12 patients, sirolimus therapy enabled discontinuation of pleural fluid drainage. Limitations This was an observational study. The resolution of effusions may have affected improvements in lung function. Conclusion Sirolimus therapy is associated with improvement or stabilization of lung function and reduction in the size of chylous effusions and lymphangioleiomyomas in patients with LAM. Primary Funding Source Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health. PMID:21690594

Effects of Bisphenol A Metabolite 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on Lung Function and Type 2 Pulmonary Alveolar Epithelial Cell Growth

PubMed Central

Liu, Shing-Hwa; Su, Chin-Chuan; Lee, Kuan-I; Chen, Ya-Wen

2016-01-01

Bisphenol A (BPA) is recognized as a major pollutant worldwide. 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is a major active metabolite of BPA. The epidemiological and animal studies have reported that BPA is harmful to lung function. The role of MBP in lung dysfunction after BPA exposure still remains unclear. This study investigated whether MBP would induce lung alveolar cell damage and evaluated the role of MBP in the BPA exposure-induced lung dysfunction. An in vitro type 2 alveolar epithelial cell (L2) model and an ex vivo isolated reperfused rat lung model were used to determine the effects of BPA or MBP on cell growth and lung function. MBP, but not BPA, dose-dependently increased the mean artery pressure (Pa), pulmonary capillary pressure (Pc), pulmonary capillary filtration coefficient (Kfc), and wet/dry weight ratio in isolated reperfused rat lungs. MBP significantly reduced cell viability and induced caspases-3/7 cleavage and apoptosis and increased AMP-activated protein kinas (AMPK) phosphorylation and endoplasmic reticulum (ER) stress-related molecules expression in L2 cells, which could be reversed by AMPK-siRNA transfection. These findings demonstrated for the first time that MBP exposure induced type 2 alveolar cell apoptosis and lung dysfunction through an AMPK-regulated ER stress signaling pathway. PMID:27982077

Effects of Bisphenol A Metabolite 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on Lung Function and Type 2 Pulmonary Alveolar Epithelial Cell Growth.

PubMed

Liu, Shing-Hwa; Su, Chin-Chuan; Lee, Kuan-I; Chen, Ya-Wen

2016-12-16

Bisphenol A (BPA) is recognized as a major pollutant worldwide. 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is a major active metabolite of BPA. The epidemiological and animal studies have reported that BPA is harmful to lung function. The role of MBP in lung dysfunction after BPA exposure still remains unclear. This study investigated whether MBP would induce lung alveolar cell damage and evaluated the role of MBP in the BPA exposure-induced lung dysfunction. An in vitro type 2 alveolar epithelial cell (L2) model and an ex vivo isolated reperfused rat lung model were used to determine the effects of BPA or MBP on cell growth and lung function. MBP, but not BPA, dose-dependently increased the mean artery pressure (Pa), pulmonary capillary pressure (Pc), pulmonary capillary filtration coefficient (K fc ), and wet/dry weight ratio in isolated reperfused rat lungs. MBP significantly reduced cell viability and induced caspases-3/7 cleavage and apoptosis and increased AMP-activated protein kinas (AMPK) phosphorylation and endoplasmic reticulum (ER) stress-related molecules expression in L2 cells, which could be reversed by AMPK-siRNA transfection. These findings demonstrated for the first time that MBP exposure induced type 2 alveolar cell apoptosis and lung dysfunction through an AMPK-regulated ER stress signaling pathway.

Effects of Exposure to Welding Fume on Lung Function: Results from the German WELDOX Study.

PubMed

Lehnert, M; Hoffmeyer, F; Gawrych, K; Lotz, A; Heinze, E; Berresheim, H; Merget, R; Harth, V; Van Gelder, R; Hahn, J-U; Hartwig, A; Weiß, T; Pesch, B; Brüning, T

2015-01-01

The association between exposure to welding fume and chronic obstructive pulmonary disease (COPD) has been insufficiently clarified. In this study we assessed the influence of exposure to welding fume on lung function parameters. We investigated forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and expiratory flow rates in 219 welders. We measured current exposure to respirable particles and estimated a worker's lifetime exposure considering welding techniques, working conditions and protective measures at current and former workplaces. Multiple regression models were applied to estimate the influence of exposure to welding fume, age, and smoking on lung function. We additionally investigated the duration of working as a welder and the predominant welding technique. The findings were that age- and smoking-adjusted lung function parameters showed no decline with increasing duration, current exposure level, and lifetime exposure to welding fume. However, 15% of the welders had FEV1/FVC below the lower limit of normal, but we could not substantiate the presence of an association with the measures of exposure. Adverse effects of cigarette smoking were confirmed. In conclusion, the study did not support the notion of a possible detrimental effect of exposure to welding fume on lung function in welders.

The role of respiratory tract infections and the microbiome in the development of asthma: A narrative review.

PubMed

van Meel, Evelien R; Jaddoe, Vincent W V; Bønnelykke, Klaus; de Jongste, Johan C; Duijts, Liesbeth

2017-10-01

Asthma is a common disease in childhood, and might predispose for chronic obstructive respiratory morbidity in adolescence and adulthood. Various early-life risk factors might influence the risk of wheezing, asthma, and lower lung function in childhood. Cohort studies demonstrated that lower respiratory tract infections in the first years of life are associated with an increased risk of wheezing and asthma, while the association with lung function is less clear. Additionally, the gut and airway microbiome might influence the risk of wheezing and asthma. The interaction between respiratory tract infections and the microbiome complicates studies of their associations with wheezing, asthma, and lung function. Furthermore, the causality behind these observations is still unclear, and several other factors such as genetic susceptibility and the immune system might be of importance. This review is focused on the association of early-life respiratory tract infections and the microbiome with wheezing, asthma, and lung function, it is possible influencing factors and perspectives for future studies. © 2017 Wiley Periodicals, Inc.

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.

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.

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.

Lung function, atopy, specific hypersensitivity, and smoking of workers in the enzyme detergent industry over 11 years.

PubMed

Flood, D F; Blofeld, R E; Bruce, C F; Hewitt, J I; Juniper, C P; Roberts, D M

1985-01-01

A study of 2800 workers employed in three factories of the two major manufacturers of enzymatic products in the United Kingdom covering 11 years of operation from 1969 to 1980 showed that 2344 workers had sufficient lung function data to meet the operational criteria and these were analysed in three separate groups by factory locations. Spirometry and prick tests for specific skin reactions to standardised enzyme were performed at six monthly intervals for the first six years of the study and then annually. Factory enzyme dust and total dust measurements were made to determine the degree of dust exposure of the subjects. The lung function of the factory groups was analysed for the effects of working in the detergent industry, the degree of exposure to enzymes, skin prick test positivity to enzymes, atopicity, and smoking. The 4.5% of workers who had experienced respiratory effects from enzymes were analysed separately. Exposure to the enzyme allergen has had no significant long term effect on the lung function of the detergent workers. A higher proportion of atopics than non-atopics became skin test positive to the allergen and more smokers than non-smokers were sensitised. The overall lung function of detergent workers showed 39 ml/year loss in FEV1 on the 11 year longitudinal study and 51 ml/year loss on the lateral (cross sectional) analysis with better lung function in the south east than the north west of England. In the development of the methodology for the study several potential problems were discovered that could remain unrecognised in a cross sectional analysis performed in isolation.

Long-term exposure to diesel engine exhaust induced lung function decline in a cross sectional study

PubMed Central

ZHANG, Li Ping; ZHANG, Xiao; DUAN, Hua Wei; MENG, Tao; NIU, Yong; HUANG, Chuan Feng; GAO, Wei Min; YU, Shan Fa; ZHENG, Yu Xin

2016-01-01

To clarify the effects of lung function following exposure to diesel engine exhaust (DEE), we recruited 137 diesel engine testing workers exposed to DEE and 127 non-DEE-exposed workers as study subjects. We performed lung function tests and measured cytokinesis-block micronucleus (CBMN) cytome index and levels of urinary polycyclic aromatic hydrocarbons (PAHs) metabolites. There was a significant decrease of forced expiratory volume in 1 second (FEV1), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/ FVC), maximal mid expiratory flow curve (MMF), forced expiratory flow at 50% of FVC (FEF50%), and forced expiratory flow at 75% of FVC (FEF75%) in the DEE-exposed workers than non-DEE-exposed workers (all p<0.05). Among all study subjects, the decreases of FEF75% were associated with the increasing levels of PAHs metabolites (p<0.05), and there were negative correlations between FEV1, FEV1/FVC, MMF, FEF50%, and FEF75% with CBMN cytome index (all p<0.05). Our results show that long-term exposure to DEE can induce lung function decline which shows mainly obstructive changes and influence of small airways function. The decreased lung function is associated with internal dosage of DEE exposure, and accompany with the increasing CBMN cytome index. PMID:27334424

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

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.

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

Influence of lung function on course of disease and response to antibiotic therapy in adult primary care patients with acute cough: a post hoc analysis of patients enrolled in a prospective multicentre study.

PubMed

van Erp, Nicole; Little, Paul; Stuart, Beth; Moore, Michael; Thomas, Mike; Butler, Chris C; Hood, Kerenza; Coenen, Samuel; Goossens, Herman; Leven, Margareta; Verheij, Theo J M

2014-09-25

In acute cough patients, impaired lung function as present in chronic lung conditions like asthma and chronic obstructive pulmonary disease (COPD) are often thought to negatively influence course of disease, but clear evidence is lacking. To investigate the influence of lung function abnormalities on course of disease and response to antibiotic therapy in primary care patients with acute cough. A total of 3,104 patients with acute cough (⩽28 days) were included in a prospective observational study with a within-nested trial, of which 2,427 underwent spirometry 28-35 days after inclusion. Influence of the lung function abnormalities fixed obstruction (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7) and bronchodilator responsiveness (FEV1 increase of ⩾12% or 200 ml after 400 μg salbutamol) on symptom severity, duration and worsening were evaluated using uni- and multivariable regression models. Antibiotic use was defined as the reported use of antibiotics ⩾5 days in the first week. Interaction terms were calculated to investigate modifying effects of lung function on antibiotic effect. The only significant association was the effect of severe airway obstruction on symptom severity on days 2-4 (difference=0.31, 95% confidence interval (CI)=0.03-0.60, P=0.03). No evidence of a differential effect of lung function on the effect of antibiotics was found. Prior use of inhaled steroids was associated with a 30% slower resolution of symptoms rated 'moderately bad' or worse (hazard ratio=0.75, 95% CI=0.63-0.90, P=0.00). In adult patients with acute cough, lung function abnormalities were neither significantly associated with course of disease nor did they modify the effect of antibiotics.

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.

Effects of obesity on lung volume and capacity in children and adolescents: a systematic review

PubMed Central

Winck, Aline Dill; Heinzmann-Filho, João Paulo; Soares, Rafaela Borges; da Silva, Juliana Severo; Woszezenki, Cristhiele Taís; Zanatta, Letiane Bueno

2016-01-01

Abstract Objective: To assess the effects of obesity on lung volume and capacity in children and adolescents. Data source: This is a systematic review, carried out in Pubmed, Lilacs, Scielo and PEDro databases, using the following Keywords: Plethysmography; Whole Body OR Lung Volume Measurements OR Total Lung Capacity OR Functional Residual Capacity OR Residual Volume AND Obesity. Observational studies or clinical trials that assessed the effects of obesity on lung volume and capacity in children and adolescents (0-18 years) without any other associated disease; in English; Portuguese and Spanish languages were selected. Methodological quality was assessed by the Agency for Healthcare Research and Quality. Data synthesis: Of the 1,030 articles, only four were included in the review. The studies amounted to 548 participants, predominantly males, with sample size ranging from 45 to 327 individuals. 100% of the studies evaluated nutritional status through BMI (z-score) and 50.0% reported the data on abdominal circumference. All demonstrated that obesity causes negative effects on lung volume and capacity, causing a reduction mainly in functional residual capacity in 75.0% of the studies; in the expiratory reserve volume in 50.0% and in the residual volume in 25.0%. The methodological quality ranged from moderate to high, with 75.0% of the studies classified as having high methodological quality. Conclusions: Obesity causes deleterious effects on lung volume and capacity in children and adolescents, mainly by reducing functional residual capacity, expiratory reserve volume and residual volume. PMID:27130483

Adverse Respiratory Health and Hematological Alterations among Agricultural Workers Occupationally Exposed to Organophosphate Pesticides: A Cross-Sectional Study in North India

PubMed Central

Fareed, Mohd.; Pathak, Manoj Kumar; Bihari, Vipin; Kamal, Ritul; Srivastava, Anup Kumar; Kesavachandran, Chandrasekharan Nair

2013-01-01

Background Non-protective work practices followed by farm workers during spraying of pesticides lead to occupational exposure among them. Objective This study is designed to explore the respiratory health and hematological profile of agricultural workers occupationally exposed to OP pesticides. Materials and Methods A cross sectional study was undertaken among 166 pesticide sprayers working in mango orchards of Lucknow district in North India compared with 77 controls to assess the respiratory illness, lung functions, cholinesterase levels and hematological profile. A questionnaire based survey and clinical examination for respiratory health were conducted among study subjects. Lung function test was conducted among study subjects by using spirometer. Cholinesterase level as biomarker of OP pesticides and hematological profile of study subjects were investigated in the laboratory by following the standard protocols. Results Overall respiratory morbidity observed among exposed subjects was 36.75%. Symptoms for respiratory illness like dry cough, productive cough, wheezing, irritation of throat and blood stained sputum were found to be significantly more (p<0.05) among pesticide sprayers than controls. Lung function parameters viz. PEFR, FEV1, %PEFR predicted, %FEV1 predicted and FEV1/FVC were found to be significantly decreased (p<0.05) among pesticide sprayers as compared to controls. Exposure wise distribution of respiratory illness and lung functions among pesticide sprayers show that the exposure duration significantly elevates (p<0.05) the respiratory problems and significantly decreases (p<0.001) lung functions among pesticide sprayers. Activities of acetylcholinesterase and butyrylcholinesterase were found to be significantly depleted (p<0.001) among pesticide sprayers as compared to controls which show the exposure of OP pesticides among them. The hematological profile viz. RBC, WBC, monocytes, neutrophils, MCV, MCH, MCHC and platelet count were significantly altered (p<0.001) in pesticide sprayers than controls. Conclusion This study shows that the unsafe occupational exposure of OP pesticides causes respiratory illness, decreased lung functions and hematological alterations among pesticide sprayers. PMID:23936093

Adverse respiratory health and hematological alterations among agricultural workers occupationally exposed to organophosphate pesticides: a cross-sectional study in North India.

PubMed

Fareed, Mohd; Pathak, Manoj Kumar; Bihari, Vipin; Kamal, Ritul; Srivastava, Anup Kumar; Kesavachandran, Chandrasekharan Nair

2013-01-01

Non-protective work practices followed by farm workers during spraying of pesticides lead to occupational exposure among them. This study is designed to explore the respiratory health and hematological profile of agricultural workers occupationally exposed to OP pesticides. A cross sectional study was undertaken among 166 pesticide sprayers working in mango orchards of Lucknow district in North India compared with 77 controls to assess the respiratory illness, lung functions, cholinesterase levels and hematological profile. A questionnaire based survey and clinical examination for respiratory health were conducted among study subjects. Lung function test was conducted among study subjects by using spirometer. Cholinesterase level as biomarker of OP pesticides and hematological profile of study subjects were investigated in the laboratory by following the standard protocols. Overall respiratory morbidity observed among exposed subjects was 36.75%. Symptoms for respiratory illness like dry cough, productive cough, wheezing, irritation of throat and blood stained sputum were found to be significantly more (p<0.05) among pesticide sprayers than controls. Lung function parameters viz. PEFR, FEV1, %PEFR predicted, %FEV1 predicted and FEV1/FVC were found to be significantly decreased (p<0.05) among pesticide sprayers as compared to controls. Exposure wise distribution of respiratory illness and lung functions among pesticide sprayers show that the exposure duration significantly elevates (p<0.05) the respiratory problems and significantly decreases (p<0.001) lung functions among pesticide sprayers. Activities of acetylcholinesterase and butyrylcholinesterase were found to be significantly depleted (p<0.001) among pesticide sprayers as compared to controls which show the exposure of OP pesticides among them. The hematological profile viz. RBC, WBC, monocytes, neutrophils, MCV, MCH, MCHC and platelet count were significantly altered (p<0.001) in pesticide sprayers than controls. This study shows that the unsafe occupational exposure of OP pesticides causes respiratory illness, decreased lung functions and hematological alterations among pesticide sprayers.

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

Biodistribution and Efficacy of Targeted Pulmonary Delivery of a Protein Kinase C-δ Inhibitory Peptide: Impact on Indirect Lung Injury

PubMed Central

Mondrinos, Mark J.; Knight, Linda C.; Kennedy, Paul A.; Wu, Jichuan; Kauffman, Matthew; Baker, Sandy T.; Wolfson, Marla R.

2015-01-01

Sepsis and sepsis-induced lung injury remain a leading cause of death in intensive care units. We identified protein kinase C-δ (PKCδ) as a critical regulator of the acute inflammatory response and demonstrated that PKCδ inhibition was lung-protective in a rodent sepsis model, suggesting that targeting PKCδ is a potential strategy for preserving pulmonary function in the setting of indirect lung injury. In this study, whole-body organ biodistribution and pulmonary cellular distribution of a transactivator of transcription (TAT)–conjugated PKCδ inhibitory peptide (PKCδ-TAT) was determined following intratracheal (IT) delivery in control and septic [cecal ligation and puncture (CLP)] rats to ascertain the impact of disease pathology on biodistribution and efficacy. There was negligible lung uptake of radiolabeled peptide upon intravenous delivery [<1% initial dose (ID)], whereas IT administration resulted in lung retention of >65% ID with minimal uptake in liver or kidney (<2% ID). IT delivery of a fluorescent-tagged (tetramethylrhodamine-PKCδ-TAT) peptide demonstrated uniform spatial distribution and cellular uptake throughout the peripheral lung. IT delivery of PKCδ-TAT at the time of CLP surgery significantly reduced PKCδ activation (tyrosine phosphorylation, nuclear translocation and cleavage) and acute lung inflammation, resulting in improved lung function and gas exchange. Importantly, peptide efficacy was similar when delivered at 4 hours post-CLP, demonstrating therapeutic relevance. Conversely, spatial lung distribution and efficacy were significantly impaired at 8 hours post-CLP, which corresponded to marked histopathological progression of lung injury. These studies establish a functional connection between peptide spatial distribution, inflammatory histopathology in the lung, and efficacy of this anti-inflammatory peptide. PMID:26243739

ACCOUNTING FOR THE ENDOGENEITY OF HEALTH AND ENVIRONMENTAL TOBACCO SMOKE EXPOSURE IN CHILDREN: AN APPLICATION TO CONTINUOUS LUNG FUNCTION

EPA Science Inventory

The goal of this study is to estimate an unbiased exposure effect of environmental tobacco smoke (ETS) exposure on children's continuous lung function. A majority of the evidence from health studies suggests that ETS exposure in early life contributes significantly to childhood ...

SUSD2 is frequently downregulated and functions as a tumor suppressor in RCC and lung cancer.

PubMed

Cheng, Yingying; Wang, Xiaolin; Wang, Pingzhang; Li, Ting; Hu, Fengzhan; Liu, Qiang; Yang, Fan; Wang, Jun; Xu, Tao; Han, Wenling

2016-07-01

Sushi domain containing 2 (SUSD2) is type I membrane protein containing domains inherent to adhesion molecules. There have been few reported studies on SUSD2, and they have mainly focused on breast cancer, colon cancer, and HeLa cells. However, the expression and function of SUSD2 in other cancers remain unclear. In the present study, we conducted an integrated bioinformatics analysis based on the array data from the GEO database and found a significant downregulation of SUSD2 in renal cell carcinoma (RCC) and lung cancer. Western blotting and quantitative RT-PCR (qRT-PCR) confirmed that SUSD2 was frequently decreased in RCC and lung cancer tissues compared with the corresponding levels in normal adjacent tissues. The restoration of SUSD2 expression inhibited the proliferation and clonogenicity of RCC and lung cancer cells, whereas the knockdown of SUSD2 promoted A549 cell growth. Our findings suggested that SUSD2 functions as a tumor suppressor gene (TSG) in RCC and lung cancer.

Pulmonary adverse effects of welding fume in automobile assembly welders.

PubMed

Sharifian, Seyed Akbar; Loukzadeh, Ziba; Shojaoddiny-Ardekani, Ahmad; Aminian, Omid

2011-01-01

Welding is one of the key components of numerous manufacturing industries, which has potential physical and chemical health hazards. Many components of welding fumes can potentially affect the lung function. This study investigates the effects of welding fumes on lung function and respiratory symptoms among welders of an automobile manufacturing plant in Iran. This historical cohort study assesses 43 male welders and 129 office workers by a questionnaire to record demographic data, smoking habits, work history and respiratory symptoms as well as lung function status by spirometry. The average pulmonary function values of welders were lower relative to controls with dose-effect relationship between work duration and pulmonary function impairment. The prevalence of chronic bronchitis was higher in welders than controls. Our findings suggest that welders are at risk for pulmonary disease.

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.

Periodontitis is related to lung volumes and airflow limitation: a cross-sectional study.

PubMed

Holtfreter, Birte; Richter, Stefanie; Kocher, Thomas; Dörr, Marcus; Völzke, Henry; Ittermann, Till; Obst, Anne; Schäper, Christoph; John, Ulrich; Meisel, Peter; Grotevendt, Anne; Felix, Stephan B; Ewert, Ralf; Gläser, Sven

2013-12-01

This study aimed to assess the potential association of periodontal diseases with lung volumes and airflow limitation in a general adult population. Based on a representative population sample of the Study of Health in Pomerania (SHIP), 1463 subjects aged 25-86 years were included. Periodontal status was assessed by clinical attachment loss (CAL), probing depth and number of missing teeth. Lung function was measured using spirometry, body plethysmography and diffusing capacity of the lung for carbon monoxide. Linear regression models using fractional polynomials were used to assess associations between periodontal disease and lung function. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP) were evaluated as potential intermediate factors. After full adjustment for potential confounders mean CAL was significantly associated with variables of mobile dynamic and static lung volumes, airflow limitation and hyperinflation (p<0.05). Including fibrinogen and hs-CRP did not change coefficients of mean CAL; associations remained statistically significant. Mean CAL was not associated with total lung capacity and diffusing capacity of the lung for carbon monoxide. Associations were confirmed for mean probing depth, extent measures of CAL/probing depth and number of missing teeth. Periodontal disease was significantly associated with reduced lung volumes and airflow limitation in this general adult population sample. Systemic inflammation did not provide a mechanism linking both diseases.

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.

The assessment and impact of sarcopenia in lung cancer: a systematic literature review.

PubMed

Collins, Jemima; Noble, Simon; Chester, John; Coles, Bernadette; Byrne, Anthony

2014-01-02

There is growing awareness of the relationship between sarcopenia (loss of muscle mass and function), and outcomes in cancer, making it a potential target for future therapies. In order to inform future research and practice, we undertook a systematic review of factors associated with loss of muscle mass, and the relationship between muscle function and muscle mass in lung cancer, a common condition associated with poor outcomes. We conducted a computerised systematic literature search on five databases. Studies were included if they explored muscle mass as an outcome measure in patients with lung cancer, and were published in English. Secondary care. Patients with lung cancer. Factors associated with loss of muscle mass and muscle function, or sarcopenia, and the clinical impact thereof in patients with lung cancer. We reviewed 5726 citations, and 35 articles were selected for analysis. Sarcopenia, as defined by reduced muscle mass alone, was found to be very prevalent in patients with lung cancer, regardless of body mass index, and where present was associated with poorer functional status and overall survival. There were diverse studies exploring molecular and metabolic factors in the development of loss of muscle mass; however, the precise mechanisms that contribute to sarcopenia and cachexia remain uncertain. The effect of nutritional supplements and ATP infusions on muscle mass showed conflicting results. There are very limited data on the correlation between degree of sarcopenia and muscle function, which has a non-linear relationship in older non-cancer populations. Loss of muscle mass is a significant contributor to morbidity in patients with lung cancer. Loss of muscle mass and function may predate clinically overt cachexia, underlining the importance of evaluating sarcopenia, rather than weight loss alone. Understanding this relationship and its associated factors will provide opportunities for focused intervention to improve clinical outcomes.

Pre- and postnatal exposure of mice to concentrated urban PM2.5 decreases the number of alveoli and leads to altered lung function at an early stage of life.

PubMed

de Barros Mendes Lopes, Thais; Groth, Espen E; Veras, Mariana; Furuya, Tatiane K; de Souza Xavier Costa, Natalia; Ribeiro Júnior, Gabriel; Lopes, Fernanda Degobbi; de Almeida, Francine M; Cardoso, Wellington V; Saldiva, Paulo Hilario Nascimento; Chammas, Roger; Mauad, Thais

2018-06-04

Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM 2.5 on lung development in mice. However, the means by which air pollution affects development of the lung have not yet been identified. In this study, we exposed pregnant BALB/c mice and their offspring to concentrated urban PM 2.5 (from São Paulo, Brazil; target dose 600 μg/m 3 for 1 h daily). Exposure was started on embryonic day 5.5 (E5.5, time of placental implantation). Lung tissue of fetuses and offspring was submitted to stereological and transcriptomic analyses at E14.5 (pseudoglandular stage of lung development), E18.5 (saccular stage) and P40 (postnatal day 40, alveolarized lung). Additionally, lung function and cellularity of bronchoalveolar lavage (BAL) fluid were studied in offspring animals at P40. Compared to control animals that were exposed to filtered air throughout gestation and postnatal life, PM-exposed mice exhibited higher lung elastance and a lower alveolar number at P40 whilst the total lung volume and cellularity of BAL fluid were not affected. Glandular and saccular structures of fetal lungs were not altered upon gestational exposure; transcriptomic signatures, however, showed changes related to DNA damage and its regulation, inflammation and regulation of cell proliferation. A differential expression was validated at E14.5 for the candidates Sox8, Angptl4 and Gas1. Our data substantiate the in utero biomolecular effect of gestational exposure to air pollution and provide first-time stereological evidence that pre- and early life-postnatal exposure compromise lung development, leading to a reduced number of alveoli and an impairment of lung function in the adult mouse. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Lung Function in Rural Guatemalan Women Before and After a Chimney Stove Intervention to Reduce Wood Smoke Exposure: Results From the Randomized Exposure Study of Pollution Indoors and Respiratory Effects and Chronic Respiratory Effects of Early Childhood Exposure to Respirable Particulate Matter Study.

PubMed

Guarnieri, Michael; Diaz, Esperanza; Pope, Daniel; Eisen, Ellen A; Mann, Jennifer; Smith, Kirk R; Smith-Sivertsen, Tone; Bruce, Nigel G; Balmes, John R

2015-11-01

COPD is the third most frequent cause of death globally, with much of this burden attributable to household biomass smoke exposure in developing countries. As biomass smoke exposure is also associated with cardiovascular disease, lower respiratory infection, lung cancer, and cataracts, it presents an important target for public health intervention. Lung function in Guatemalan women exposed to wood smoke from open fires was measured throughout the Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) stove intervention trial and continued during the Chronic Respiratory Effects of Early Childhood Exposure to Respirable Particulate Matter (CRECER) cohort study. In RESPIRE, early stove households received a chimney woodstove at the beginning of the 18-month trial, and delayed stove households received a stove at trial completion. Personal exposure to wood smoke was assessed with exhaled breath carbon monoxide (CO) and personal CO tubes. Change in lung function between intervention groups and as a function of wood smoke exposure was assessed using random effects models. Of 306 women participating in both studies, acceptable spirometry was collected in 129 early stove and 136 delayed stove households (n = 265), with a mean follow-up of 5.6 years. Despite reduced wood smoke exposures in early stove households, there were no significant differences in any of the measured spirometric variables during the study period (FEV1, FVC, FEV1/FVC ratio, and annual change) after adjustment for confounding. In these young Guatemalan women, there was no association between lung function and early randomization to a chimney stove or personal wood smoke exposure. Future stove intervention trials should incorporate cleaner stoves, longer follow-up, or potentially susceptible groups to identify meaningful differences in lung function.

Diverse Epitope Specificity, Immunodominance Hierarchy, and Functional Avidity of Effector CD4 T Cells Established During Priming Is Maintained in Lung After Influenza A Virus Infection.

PubMed

Richards, Katherine A; DiPiazza, Anthony T; Rattan, Ajitanuj; Knowlden, Zackery A G; Yang, Hongmei; Sant, Andrea J

2018-01-01

One of the major contributions to protective immunity to influenza viruses that is provided by virus-specific CD4 T cells is delivery of effector function to the infected lung. However, there is little known about the selection and breadth of viral epitope-specific CD4 T cells that home to the lung after their initial priming. In this study, using a mouse model of influenza A infection and an unbiased method of epitope identification, the viral epitope-specific CD4 T cells elicited after infection were identified and quantified. We found that a very diverse specificity of CD4 T cells is primed by infection, including epitopes from hemagglutinin, neuraminidase, matrix protein, nucleoprotein, and non-structural protein-1. Using peptide-specific cytokine EliSpots, the diversity and immunodominance hierarchies established in the lung-draining lymph node were compared with specificities of CD4 T cells that home to the lung. Our studies revealed that CD4 T cells of all epitope specificities identified in peripheral lymphoid tissue home back to the lung and that most of these lung-homing cells are localized within the tissue rather than the pulmonary vasculature. There is a striking shift of CD4 T cell functionality that enriches for IFN-γ production as cells are primed in the lymph node, enter the lung vasculature, and finally establish residency in the tissue, but with no apparent shifts in their functional avidity. We conclude that CD4 T cells of broad viral epitope specificity are recruited into the lung after influenza infection, where they then have the opportunity to encounter infected or antigen-bearing antigen-presenting cells.

Genome-wide association and network analysis of lung function in the Framingham Heart Study.

PubMed

Liao, Shu-Yi; Lin, Xihong; Christiani, David C

2014-09-01

Single nucleotide polymorphisms have been found to be associated with pulmonary function using genome-wide association studies. However, lung function is a complex trait that is likely to be influenced by multiple gene-gene interactions besides individual genes. Our goal is to build a cellular network to explore the relationship between pulmonary function and genotypes by combining SNP level and network analyses using longitudinal lung function data from the Framingham Heart Study. We analyzed 2,698 genotyped participants from the Offspring cohort that had an average of 3.35 spirometry measurements per person for a mean length of 13 years. Repeated forced expiratory volume in one second (FEV1 ) and the ratio of FEV1 to forced vital capacity (FVC) were used as outcomes. Data were analyzed using linear-mixed models for the association between lung function and alleles by accounting for the correlation among repeated measures over time within the same subject and within-family correlation. Network analyses were performed using dmGWAS and validated with data from the Third Generation cohort. Analyses identified SMAD3, TGFBR2, CD44, CTGF, VCAN, CTNNB1, SCGB1A1, PDE4D, NRG1, EPHB1, and LYN as contributors to pulmonary function. Most of these genes were novel that were not found previously using solely SNP-level analysis. These novel genes are involving the transforming growth factor beta (TGFB)-SMAD pathway, Wnt/beta-catenin pathway, etc. Therefore, combining SNP-level and network analyses using longitudinal lung function data is a useful alternative strategy to identify risk genes. © 2014 WILEY PERIODICALS, INC.

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.

Functional Assays to Screen and Dissect Genomic Hits: Doubling Down on the National Investment in Genomic Research.

PubMed

Musunuru, Kiran; Bernstein, Daniel; Cole, F Sessions; Khokha, Mustafa K; Lee, Frank S; Lin, Shin; McDonald, Thomas V; Moskowitz, Ivan P; Quertermous, Thomas; Sankaran, Vijay G; Schwartz, David A; Silverman, Edwin K; Zhou, Xiaobo; Hasan, Ahmed A K; Luo, Xiao-Zhong James

2018-04-01

The National Institutes of Health have made substantial investments in genomic studies and technologies to identify DNA sequence variants associated with human disease phenotypes. The National Heart, Lung, and Blood Institute has been at the forefront of these commitments to ascertain genetic variation associated with heart, lung, blood, and sleep diseases and related clinical traits. Genome-wide association studies, exome- and genome-sequencing studies, and exome-genotyping studies of the National Heart, Lung, and Blood Institute-funded epidemiological and clinical case-control studies are identifying large numbers of genetic variants associated with heart, lung, blood, and sleep phenotypes. However, investigators face challenges in identification of genomic variants that are functionally disruptive among the myriad of computationally implicated variants. Studies to define mechanisms of genetic disruption encoded by computationally identified genomic variants require reproducible, adaptable, and inexpensive methods to screen candidate variant and gene function. High-throughput strategies will permit a tiered variant discovery and genetic mechanism approach that begins with rapid functional screening of a large number of computationally implicated variants and genes for discovery of those that merit mechanistic investigation. As such, improved variant-to-gene and gene-to-function screens-and adequate support for such studies-are critical to accelerating the translation of genomic findings. In this White Paper, we outline the variety of novel technologies, assays, and model systems that are making such screens faster, cheaper, and more accurate, referencing published work and ongoing work supported by the National Heart, Lung, and Blood Institute's R21/R33 Functional Assays to Screen Genomic Hits program. We discuss priorities that can accelerate the impressive but incomplete progress represented by big data genomic research. © 2018 American Heart Association, Inc.

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.

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.

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

Welding, longitudinal lung function decline and chronic respiratory symptoms: a systematic review of cohort studies.

PubMed

Szram, Joanna; Schofield, Susie J; Cosgrove, Martin P; Cullinan, Paul

2013-11-01

While the acute respiratory risks of welding are well characterised, more chronic effects, including those on lung function, are less clear. We carried out a systematic review of published longitudinal studies of lung function decline in welders. Original cohort studies documenting two or more sequential measurements of lung function were reviewed. Meta-analysis was carried out on studies with suitable data on forced expiratory volume in 1 s (FEV1). Seven studies were included; their quality (measured on the Newcastle-Ottawa scale) was good, although exposure assessment was limited and the studies showed significant heterogeneity. Five had data suitable for meta-analysis; the pooled estimate of the difference in FEV1 decline between welders and nonwelders was -9.0 mL · year(-1) (95% CI -22.5-4.5; p=0.193). The pooled estimates of difference in annual FEV1 decline between welders and referents who smoked was -13.7 mL · year(-1) (95% CI -33.6-6.3; p=0.179). For welders and referents who did not smoke the estimated difference was -3.8 mL · year(-1) (95% CI -20.2-12.6; p=0.650). Symptom prevalence data were mainly narrative; smoking appeared to have the greatest effect on symptom evolution. Collectively, available longitudinal data on decline of lung function in welders and respiratory symptoms suggest a greater effect in those who smoke, supporting a focus on smoking cessation as well as control of fume exposure in this trade. Further prospective studies are required to confirm these findings.

Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia.

PubMed

Alanin, Mikkel Christian; Aanaes, Kasper; Høiby, Niels; Pressler, Tania; Skov, Marianne; Nielsen, Kim Gjerum; Johansen, Helle Krogh; von Buchwald, Christian

2017-03-01

Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs. We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway infections in PCD patients in a prospective single-arm intervention study of ESS with adjuvant therapy using nasal irrigation with saline, topical nasal steroids, and 2 weeks of systemic antibiotics. Additional treatment with local colistin for 6 months was instigated when P. aeruginosa was cultured at ESS. Twenty-four PCD patients underwent ESS to search for an infectious focus (n = 10), due to severe symptoms of CRS (n = 8), or both (n = 6). Bacteria were cultured from sinus samples in 21 patients (88%), and simultaneous sinus and lung colonization with identical pathogens were observed in 13 patients (62%). Four patients with preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow-up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12 months after ESS and we observed a trend toward better lung function after ESS. We demonstrated an improvement in CRS-related symptoms after ESS and adjuvant therapy. In selected PCD patients, the suggested regimen may postpone chronic lung infection with P. aeruginosa and stabilize lung function. © 2016 ARS-AAOA, LLC.

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.

Transfer factor, lung volumes, resistance and ventilation distribution in healthy adults.

PubMed

Verbanck, Sylvia; Van Muylem, Alain; Schuermans, Daniel; Bautmans, Ivan; Thompson, Bruce; Vincken, Walter

2016-01-01

Monitoring of chronic lung disease requires reference values of lung function indices, including putative markers of small airway function, spanning a wide age range.We measured spirometry, transfer factor of the lung for carbon monoxide (TLCO), static lung volume, resistance and ventilation distribution in a healthy population, studying at least 20 subjects per sex and per decade between the ages of 20 and 80 years.With respect to the Global Lung Function Initiative reference data, our subjects had average z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC of -0.12, 0.04 and -0.32, respectively. Reference equations were obtained which could account for a potential dependence of index variability on age and height. This was done for (but not limited to) indices that are pertinent to asthma and chronic obstructive pulmonary disease studies: forced expired volume in 6 s, forced expiratory flow, TLCO, specific airway conductance, residual volume (RV)/total lung capacity (TLC), and ventilation heterogeneity in acinar and conductive lung zones.Deterioration in acinar ventilation heterogeneity and lung clearance index with age were more marked beyond 60 years, and conductive ventilation heterogeneity showed the greatest increase in variability with age. The most clinically relevant deviation from published reference values concerned RV/TLC values, which were considerably smaller than American Thoracic Society/European Respiratory Society-endorsed reference values. Copyright ©ERS 2016.

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.

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

Elemental composition of particulate matter and the association with lung function.

PubMed

Eeftens, Marloes; Hoek, Gerard; Gruzieva, Olena; Mölter, Anna; Agius, Raymond; Beelen, Rob; Brunekreef, Bert; Custovic, Adnan; Cyrys, Josef; Fuertes, Elaine; Heinrich, Joachim; Hoffmann, Barbara; de Hoogh, Kees; Jedynska, Aleksandra; Keuken, Menno; Klümper, Claudia; Kooter, Ingeborg; Krämer, Ursula; Korek, Michal; Koppelman, Gerard H; Kuhlbusch, Thomas A J; Simpson, Angela; Smit, Henriëtte A; Tsai, Ming-Yi; Wang, Meng; Wolf, Kathrin; Pershagen, Göran; Gehring, Ulrike

2014-09-01

Negative effects of long-term exposure to particulate matter (PM) on lung function have been shown repeatedly. Spatial differences in the composition and toxicity of PM may explain differences in observed effect sizes between studies. We conducted a multicenter study in 5 European birth cohorts-BAMSE (Sweden), GINIplus and LISAplus (Germany), MAAS (United Kingdom), and PIAMA (The Netherlands)-for which lung function measurements were available for study subjects at the age of 6 or 8 years. Individual annual average residential exposure to copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM smaller than 2.5 μm (PM2.5) and smaller than 10 μm (PM10) was estimated using land-use regression models. Associations between air pollution and lung function were analyzed by linear regression within cohorts, adjusting for potential confounders, and then combined by random effects meta-analysis. We observed small reductions in forced expiratory volume in the first second, forced vital capacity, and peak expiratory flow related to exposure to most elemental pollutants, with the most substantial negative associations found for nickel and sulfur. PM10 nickel and PM10 sulfur were associated with decreases in forced expiratory volume in the first second of 1.6% (95% confidence interval = 0.4% to 2.7%) and 2.3% (-0.1% to 4.6%) per increase in exposure of 2 and 200 ng/m, respectively. Associations remained after adjusting for PM mass. However, associations with these elements were not evident in all cohorts, and heterogeneity of associations with exposure to various components was larger than for exposure to PM mass. Although we detected small adverse effects on lung function associated with annual average levels of some of the evaluated elements (particularly nickel and sulfur), lower lung function was more consistently associated with increased PM mass.

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

PubMed Central

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

2016-01-01

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

Transcriptome profile and unique genetic evolution of positively selected genes in yak lungs.

PubMed

Lan, DaoLiang; Xiong, XianRong; Ji, WenHui; Li, Jian; Mipam, Tserang-Donko; Ai, Yi; Chai, ZhiXin

2018-04-01

The yak (Bos grunniens), which is a unique bovine breed that is distributed mainly in the Qinghai-Tibetan Plateau, is considered a good model for studying plateau adaptability in mammals. The lungs are important functional organs that enable animals to adapt to their external environment. However, the genetic mechanism underlying the adaptability of yak lungs to harsh plateau environments remains unknown. To explore the unique evolutionary process and genetic mechanism of yak adaptation to plateau environments, we performed transcriptome sequencing of yak and cattle (Bos taurus) lungs using RNA-Seq technology and a subsequent comparison analysis to identify the positively selected genes in the yak. After deep sequencing, a normal transcriptome profile of yak lung that containing a total of 16,815 expressed genes was obtained, and the characteristics of yak lungs transcriptome was described by functional analysis. Furthermore, Ka/Ks comparison statistics result showed that 39 strong positively selected genes are identified from yak lungs. Further GO and KEGG analysis was conducted for the functional annotation of these genes. The results of this study provide valuable data for further explorations of the unique evolutionary process of high-altitude hypoxia adaptation in yaks in the Tibetan Plateau and the genetic mechanism at the molecular level.

Revascularization of decellularized lung scaffolds: principles and progress

PubMed Central

Stabler, Collin T.; Lecht, Shimon; Mondrinos, Mark J.; Goulart, Ernesto; Lazarovici, Philip

2015-01-01

There is a clear unmet clinical need for novel biotechnology-based therapeutic approaches to lung repair and/or replacement, such as tissue engineering of whole bioengineered lungs. Recent studies have demonstrated the feasibility of decellularizing the whole organ by removal of all its cellular components, thus leaving behind the extracellular matrix as a complex three-dimensional (3D) biomimetic scaffold. Implantation of decellularized lung scaffolds (DLS), which were recellularized with patient-specific lung (progenitor) cells, is deemed the ultimate alternative to lung transplantation. Preclinical studies demonstrated that, upon implantation in rodent models, bioengineered lungs that were recellularized with airway and vascular cells were capable of gas exchange for up to 14 days. However, the long-term applicability of this concept is thwarted in part by the failure of current approaches to reconstruct a physiologically functional, quiescent endothelium lining the entire vascular tree of reseeded lung scaffolds, as inferred from the occurrence of hemorrhage into the airway compartment and thrombosis in the vasculature in vivo. In this review, we explore the idea that successful whole lung bioengineering will critically depend on 1) preserving and/or reestablishing the integrity of the subendothelial basement membrane, especially of the ultrathin respiratory membrane separating airways and capillaries, during and following decellularization and 2) restoring vascular physiological functionality including the barrier function and quiescence of the endothelial lining following reseeding of the vascular compartment. We posit that physiological reconstitution of the pulmonary vascular tree in its entirety will significantly promote the clinical translation of the next generation of bioengineered whole lungs. PMID:26408553

Contemporary management of voice and swallowing disorders in patients with advanced lung cancer.

PubMed

Brady, Grainne C; Carding, Paul N; Bhosle, Jaishree; Roe, Justin W G

2015-06-01

Advanced lung cancer can cause changes to swallowing and communication function. Direct tumour invasion, dyspnoea and deconditioning can all impact on swallowing function and communication. Cancer treatment, if administered, may cause or compound symptoms. In this study, the nature of swallowing and communication difficulties in patients with advanced lung cancer will be discussed, and management options including medical management, speech and language therapy (SLT) intervention, and surgical interventions will be considered. Advanced lung cancer can result in voice and swallowing difficulties, which can increase symptom burden and significantly impact on quality of life (QOL). There is a growing evidence base to support the use of injection laryngoplasty under local anaesthetic to offer immediate improvement in voice, swallowing and overall QOL. There is limited literature on the nature and extent of voice and swallowing impairment in patients with lung cancer. Well designed studies with robust and sensitive multidimensional dysphagia and dysphonia assessments are required. Outcome studies examining interventions with clearly defined treatment goals are required. These studies should include both functional and patient-reported outcome measures to develop the evidence base and to ensure that interventions are both timely and appropriate.

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

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

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

Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com; School of Medicine, University Juarez of Durango, Gomez Palacio, Durango; Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatorymore » biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels • In 275 children chronically exposed to As, 3 biomarkers were measured. • Negative associations were found between DMA, %MMA and %DMA with sRAGE. • Positive associations were found between %DMA with MMP-9 and with the MMP-9/TIMP-1 ratio. • Chronic arsenic exposure-induced alterations in lung inflammatory biomarkers in children.« less

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.

Geriatric Assessment and Functional Decline in Older Patients with Lung Cancer.

PubMed

Decoster, L; Kenis, C; Schallier, D; Vansteenkiste, J; Nackaerts, K; Vanacker, L; Vandewalle, N; Flamaing, J; Lobelle, J P; Milisen, K; De Grève, J; Wildiers, H

2017-10-01

Older patients with lung cancer are a heterogeneous population making treatment decisions complex. This study aims to evaluate the value of geriatric assessment (GA) as well as the evolution of functional status (FS) in older patients with lung cancer, and to identify predictors associated with functional decline and overall survival (OS). At baseline, GA was performed in patients ≥70 years with newly diagnosed lung cancer. FS measured by activities of daily living (ADL) and instrumental activities of daily living (IADL) was reassessed at follow-up to define functional decline and OS was collected. Predictors for functional decline and OS were determined. Two hundred and forty-five patients were included in this study. At baseline, GA deficiencies were present in all domains and ADL and IADL were impaired in 51 and 63% of patients, respectively. At follow-up, functional decline in ADL was observed in 23% and in IADL in 45% of patients. In multivariable analysis, radiotherapy was predictive for ADL decline. No other predictors for ADL or IADL decline were identified. Stage and baseline performance status were predictive for OS. Older patients with lung cancer present with multiple deficiencies covering all geriatric domains. During treatment, functional decline is observed in almost half of the patients. None of the specific domains of the GA were predictive for functional decline or survival, probably because of the high impact of the aggressiveness of this tumor type leading to a poor prognosis.

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

Impaired functional vitamin B6 status is associated with increased risk of lung cancer.

PubMed

Theofylaktopoulou, Despoina; Midttun, Øivind; Ueland, Per M; Meyer, Klaus; Fanidi, Anouar; Zheng, Wei; Shu, Xiao-Ou; Xiang, Yong-Bing; Prentice, Ross; Pettinger, Mary; Thomson, Cynthia A; Giles, Graham G; Hodge, Allison; Cai, Qiuyin; Blot, William J; Wu, Jie; Johansson, Mikael; Hultdin, Johan; Grankvist, Kjell; Stevens, Victoria L; McCullough, Marjorie M; Weinstein, Stephanie J; Albanes, Demetrius; Ziegler, Regina; Freedman, Neal D; Langhammer, Arnulf; Hveem, Kristian; Naess, Marit; Sesso, Howard D; Gaziano, J Michael; Buring, Julie E; Lee, I-Min; Severi, Gianluca; Zhang, Xuehong; Stampfer, Meir J; Han, Jiali; Smith-Warner, Stephanie A; Zeleniuch-Jacquotte, Anne; Le Marchand, Loic; Yuan, Jian-Min; Wang, Renwei; Butler, Lesley M; Koh, Woon-Puay; Gao, Yu-Tang; Rothman, Nathaniel; Ericson, Ulrika; Sonestedt, Emily; Visvanathan, Kala; Jones, Miranda R; Relton, Caroline; Brennan, Paul; Johansson, Mattias; Ulvik, Arve

2018-06-15

Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR 4th vs. 1st ) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status. © 2017 UICC.

Rubberwood dust and lung function among Thai furniture factory workers.

PubMed

Thetkathuek, Anamai; Yingratanasuk, Tanongsak; Demers, Paul A; Thepaksorn, Phayong; Saowakhontha, Sastri; Keifer, Matthew C

2010-01-01

The objective of this study was to assess factors affecting lung function among 685 workers in the rubberwood (Hevea brasiliensis) furniture industry in the Chonburi and Rayung provinces of eastern Thailand. Study data were gathered using questionnaires, by sampling wood dust, and by spirometry. The mean wood dust exposure level in the factories was 4.08 mg/m3 (SD = 1.42, range: 1.15-11.17 mg/m3). The mean overall percent of predicted forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC values were 84 % (SD = 13.41), 86 % (SD = 14.40), and 99% (SD = 10.42), respectively. Significant negative correlations were found between mean dust exposure levels and FVC (p = 0.0008), and FEV1/FVC% (p < 0.001), but not FEV1 (p = 0.074). An association between decline in lung function and wood dust levels among wood workers suggests that rubberwood dust exposure negatively affects lung function.

Determinants of lung function and airway hyperresponsiveness in asthmatic children.

PubMed

Bisgaard, H; Pedersen, S; Anhøj, J; Agertoft, L; Hedlin, G; Gulsvik, A; Bjermer, L; Carlsen, K H; Nordvall, L; Lundbäck, B; Wennergren, G; Werner, S; Bønnelykke, K; Weiss, S T

2007-07-01

Asthma patients exhibit an increased rate of loss of lung function. Determinants to such decline are largely unknown and the modifying effect of steroid therapy is disputed. This cross-sectional study aimed to elucidate factors contributing to such decline and the possible modifying effect of steroid treatment. We analyzed determinants of lung function and airway hyperresponsiveness (AHR) in a Scandinavian study of 2390 subjects from 550 families. Families were selected for the presence of two or more asthmatic children as part of a genetic study, Scandinavian Asthma Genetic Study (SAGA). The primary analysis studied the association between the lung function and delay of inhaled corticosteroids (ICS) after asthma diagnosis among asthmatic children and young adults with a history of regular ICS treatment (N=919). FEV(1) percent predicted (FEV(1)% pred) was 0.25% lower per year of delay from diagnosis until treatment (p=0.039). This association was significantly greater in allergy skin prick test negative children. There was no significant influence of gender, age at asthma onset, or smoking. In the secondary analysis of the whole population of 2390 asthmatics and non-asthmatics, FEV(1)% pred was inversely related to having asthmatic siblings (-7.9%; p<0.0001), asthma diagnosis (-2.7%; p=0.0007), smoking (-3.5%; p=0.0027), and positive allergy skin prick test (-0.47% per test; p=0.012), while positively related to being of female gender (1.8%; p=0.0029). Risk of AHR was higher by having asthmatic siblings (OR 2.7; p<0.0001), being of female gender (OR 2.0; p<0.0001), and having asthma (OR 2.0; p<0.0001). These data suggest that lung function is lower in asthmatics with delayed introduction of ICS therapy, smoking, and positive allergy skin prick test. Lung function is lower and AHR higher in female asthmatics and subjects with asthmatic siblings or established asthma.

Effects of air pollution on lung function and symptoms of asthma, rhinitis and eczema in primary school children.

PubMed

Altuğ, Hicran; Gaga, Eftade O; Döğeroğlu, Tuncay; Ozden, Ozlem; Ornektekin, Sermin; Brunekreef, Bert; Meliefste, Kees; Hoek, Gerard; Van Doorn, Wim

2013-09-01

Health effects of ambient air pollution were studied in three groups of schoolchildren living in areas (suburban, urban and urban-traffic) with different air pollution levels in Eskişehir, Turkey. This study involved 1,880 students aged between 9 and 13 years from 16 public primary schools. This two-season study was conducted from January 2008 through March 2009. Symptoms of asthma, rhinitis and eczema were determined by the International Study of Asthma and Allergies in Childhood questionnaire in 2008. Two lung function tests were performed by each child for summer and winter seasons with simultaneous ambient air measurements of ozone (O3), nitrogen dioxide (NO2) and sulfur dioxide (SO2) by passive sampling. Effects of air pollution on impaired lung function and symptoms in schoolchildren were estimated by multivariate logistic regression analyses. Girls with impaired lung function (only for the summer season evaluation) were more observed in suburban and urban areas when compared to urban-traffic area ([odds ratio (OR) = 1.49; 95 % confidence interval (CI) 1.04-2.14] and [OR = 1.69 (95 % CI 1.06-2.71)] for suburban vs. urban-traffic and urban vs. urban-traffic, respectively). Significant association between ambient ozone concentrations and impaired lung function (for an increase of 10 μg m(-3)) was found only for girls for the summer season evaluation [OR = 1.11 (95 % CI 1.03-1.19)]. No association was found for boys and for the winter season evaluation. No association was found between any of the measured air pollutants and symptoms of current wheeze, current rhinoconjunctivitis and current itchy rash. The results of this study showed that increasing ozone concentrations may cause a sub-acute impairment in lung function of school aged children.

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

Lung function, atopy, and chronic exposure to air pollution in schoolchildren living in two cities of different air quality

NASA Astrophysics Data System (ADS)

Gurzau, Eugen S.; Gurzau, Anca; Muresan, Marius; Bodor, Ecaterina; Zehan, Zoe; Radulescu, Nicolae

1993-03-01

The question of a causative interrelation between air pollution and respiratory status has received considerable attention by the mass media in our country. Schoolchildren aged 7 to 11 living in two communities with different levels of air pollution were studied. The parents of these children filled out a health questionnaire. The prevalence of respiratory symptoms and pulmonary diseases was found to be significantly higher among children growing up in the polluted area (Tirnaveni) as compared with the low-pollution area (Dej). Lung function tests point out FEF25-75 disorders (and other lung disorders) at higher frequencies in schoolchildren living in the polluted area. Over 90% of schoolchildren living in the polluted area. Over 90% of schoolchildren with lung function disorders had a positive response to bronchodilatation. Of the schoolchildren with lung function disorders, 75.47% (p < 0,001) were atopic all of whom were sensitized to the down and house-dust.

Social integration and age-related decline in lung function.

PubMed

Crittenden, Crista N; Murphy, Michael L M; Cohen, Sheldon

2018-05-01

We tested the hypothesis that social integration, measured as number of social roles, is associated with less age-related loss of lung function, an important marker of health and longevity. We also investigated possible psychological factors through which social integration might influence lung health. Data were analyzed from the Health and Retirement Study (ages 52-94, n = 4,224). Each additional social role reported at baseline was associated with less of a decline in lung function between baseline and the follow-up assessment four years later. The association withstood controls for demographics, weight, and height and was mediated by more positive and less negative affect and lower rates of cigarette smoking and more physical activity. Roles were mostly substitutable, with both high (spouse, parent, friends, relatives) and low (employee, religious service attendee, volunteer, members of other groups) intimacy roles independently contributing to less age-related decline in lung function. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Recent lung imaging studies. [Effectiveness for diagnosis of chronic obstructive pulmonary disease

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

Taplin, G.V.; Chopra, S.K.

1976-01-01

Radionuclide lung imaging procedures have been available for 11 years but only the perfusion examination has been used extensively and mainly for the diagnosis of pulmonary embolism (P.E.). Its ability to reveal localized ischemia makes it a valuable test of regional lung function as well as a useful diagnostic aid in P.E. Although it had been recognized for several years that chronic obstructive pulmonary disease (COPD) can cause lung perfusion defects which may simulate pulmonary embolism, relatively little use has been made of either the radioxenon or the radioaerosol inhalation lung imaging procedures until the last few years as amore » means of distinguishing P.E. from COPD. In this review emphasis is placed on our recent experience with both of these inhalation procedures in comparison with pulmonary function tests and roentgenography for the early detection of COPD in population studies. Equal emphasis is given to simultaneous aerosol ventilation-perfusion (V/P) imaging for a functional diagnosis of P.E. Two new developments in regional lung diffusion imaging, performed after the inhalation of radioactive gases and/or rapidly absorbed radioaerosols are described. The experimental basis for their potential clinical application in pulmonary embolism detection is presented.« less

Effects of obesity on lung volume and capacity in children and adolescents: a systematic review.

PubMed

Winck, Aline Dill; Heinzmann-Filho, João Paulo; Soares, Rafaela Borges; da Silva, Juliana Severo; Woszezenki, Cristhiele Taís; Zanatta, Letiane Bueno

2016-12-01

To assess the effects of obesity on lung volume and capacity in children and adolescents. This is a systematic review, carried out in Pubmed, Lilacs, Scielo and PEDro databases, using the following Keywords: Plethysmography; Whole Body OR Lung Volume Measurements OR Total Lung Capacity OR Functional Residual Capacity OR Residual Volume AND Obesity. Observational studies or clinical trials that assessed the effects of obesity on lung volume and capacity in children and adolescents (0-18 years) without any other associated disease; in English; Portuguese and Spanish languages were selected. Methodological quality was assessed by the Agency for Healthcare Research and Quality. Of the 1,030 articles, only four were included in the review. The studies amounted to 548 participants, predominantly males, with sample size ranging from 45 to 327 individuals. 100% of the studies evaluated nutritional status through BMI (z-score) and 50.0% reported the data on abdominal circumference. All demonstrated that obesity causes negative effects on lung volume and capacity, causing a reduction mainly in functional residual capacity in 75.0% of the studies; in the expiratory reserve volume in 50.0% and in the residual volume in 25.0%. The methodological quality ranged from moderate to high, with 75.0% of the studies classified as having high methodological quality. Obesity causes deleterious effects on lung volume and capacity in children and adolescents, mainly by reducing functional residual capacity, expiratory reserve volume and residual volume. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

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

PubMed Central

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

2012-01-01

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

Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues.

PubMed

Kim, Bu-Yeo; Jin, Hee; Lee, Yoon-Jin; Kang, Ga-Young; Cho, Jaeho; Lee, Yun-Sil

2016-01-27

Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. Central areas of the mouse left lung were focally-irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions. Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non-irradiated neighboring areas of lung tissue, indicating a global lung response to focal high-dose irradiation.

Proteasome function is not impaired in healthy aging of the lung.

PubMed

Caniard, Anne; Ballweg, Korbinian; Lukas, Christina; Yildirim, Ali Ö; Eickelberg, Oliver; Meiners, Silke

2015-10-01

Aging is the progressive loss of cellular function which inevitably leads to death. Failure of proteostasis including the decrease in proteasome function is one hallmark of aging. In the lung, proteasome activity was shown to be impaired in age-related diseases such as chronic obstructive pulmonary disease. However, little is known on proteasome function during healthy aging. Here, we comprehensively analyzed healthy lung aging and proteasome function in wildtype, proteasome reporter and immunoproteasome knockout mice. Wildtype mice spontaneously developed senile lung emphysema while expression and activity of proteasome complexes and turnover of ubiquitinated substrates was not grossly altered in lungs of aged mice. Immunoproteasome subunits were specifically upregulated in the aged lung and the caspase-like proteasome activity concomitantly decreased. Aged knockout mice for the LMP2 or LMP7 immunoproteasome subunits showed no alteration in proteasome activities but exhibited typical lung aging phenotypes suggesting that immunoproteasome function is dispensable for physiological lung aging in mice. Our results indicate that healthy aging of the lung does not involve impairment of proteasome function. Apparently, the reserve capacity of the proteostasis systems in the lung is sufficient to avoid severe proteostasis imbalance during healthy aging.

Association between arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and lung function in a Korean population.

PubMed

Ro, M; Kim, S; Pyun, J-A; Shin, C; Cho, N H; Lee, J-Y; Koh, I; Kwack, K

2012-08-01

Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) plays a role in the 5-lipoxygenase (LO) pathway, which includes the LTC(4), LTD(4), LTE(4) and LTB(4). These leukotrienes are known causative factors of asthma, allergy, atopy and cardiovascular diseases. ALOX5AP lacks enzyme activity and acts by helping 5-LO function. In this study, healthy and general subjects who live in rural and urban areas of Korea were tested for the association of ALOX5AP polymorphisms with lung function. Lung function was also estimated by calculating the predicted values for forced expiratory volume in one second (FEV(1) _%PRED) and the proportion of the forced vital capacity exhaled in the first second (FEV(1) /FVC_PRED). The linear regression was adjusted for residence area, gender, age, height and smoking status. The analysis revealed associations between FEV(1) and the single-nucleotide polymorphism (SNP) rs9506352 and the haplotype TCAC (permuted P-value < 0.05). The linkage disequilibrium block that included the significant SNPs overlapped with SNPs that were revealed previously to associate with myocardial infarction and asthma and to affect lung function. This study is the first to demonstrate the association between lung function and ALOX5AP polymorphisms in a healthy and general population. © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd.

Excess longitudinal decline in lung function in grain farmers.

PubMed

Senthilselvan, Ambikaipakan; Chénard, Liliane; Grover, Vaneeta; Kirychuk, Shelley P; Hagel, Louise; Ulmer, Kendra; Hurst, Thomas S; Dosman, James A

2010-04-01

Workers in intensive agricultural operations are exposed to dust and endotoxin that are associated with respiratory effects. The authors investigated the longitudinal changes in lung function in male grain farmers. In this study, male grain farmers (n = 263) and male nonfarming control subjects (n = 261) studies initially in 1990/91 were followed-up in 1994/95 and 2003/04. After controlling for potential confounders, grain farmers had an excess annual decline of 9.2 ml/year (95% confidence interval [CI]: 2.7, 15.8, p = .006) in forced vital capacity (FVC) in comparison to control. Long-term exposure to grain dust and other substances in lifetime grain farmers results in progressive loss in lung function.

Budesonide ameliorates lung function of the cigarette smoke-exposed rats through reducing matrix metalloproteinase-1 content

PubMed Central

Sun, Jiawei; Zhang, Ping; Zhang, Bin; Li, Kang; Li, Zhu; Li, Junhong; Zhang, Yongjian; Sun, Wuzhuang

2015-01-01

Objectives: This study was conducted to investigate an effect of inhaled budesonide on cigarette smoke-exposed lungs with a possible mechanism involved in the event. Methods: Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of budesonide. Inflammatory cell count in bronchoalveolar lavage fluid (BALF), lung function testing, mean liner intercept (MLI) in lung tissue, mean alveolar number (MAN) and a ratio of bronchial wall thickness and external diameter (BWT/D) were determined in the grouped rats, respectively. Contents of matrix metalloproteinase (MMP)-1, MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 productions in BALF were examined as well. Results: There were significant changes in the above assessments in the smoking rats as compared to those in the control rats (all P < 0.01 and 0.05). Budesonide inhalation significantly decreased the numbers of the BALF cells and partly reversed lung function decline in the challenged rats (P < 0.01 and 0.05). However, this corticosteroid did not influence pathological changes in fine structures of the tobacco smoke-exposed lungs. Treatment with budesonide resulted in an obvious decrease in the MMP-1 but not MMP-2 and TIMP-2 productions (P < 0.05). Conclusion: Inhaled budesonide mitigates the ongoing inflammatory process in the smoked lungs and ameliorates declining lung function through reducing MMP-1 content. PMID:26191209

Budesonide ameliorates lung function of the cigarette smoke-exposed rats through reducing matrix metalloproteinase-1 content.

PubMed

Sun, Jiawei; Zhang, Ping; Zhang, Bin; Li, Kang; Li, Zhu; Li, Junhong; Zhang, Yongjian; Sun, Wuzhuang

2015-01-01

This study was conducted to investigate an effect of inhaled budesonide on cigarette smoke-exposed lungs with a possible mechanism involved in the event. Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of budesonide. Inflammatory cell count in bronchoalveolar lavage fluid (BALF), lung function testing, mean liner intercept (MLI) in lung tissue, mean alveolar number (MAN) and a ratio of bronchial wall thickness and external diameter (BWT/D) were determined in the grouped rats, respectively. Contents of matrix metalloproteinase (MMP)-1, MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 productions in BALF were examined as well. There were significant changes in the above assessments in the smoking rats as compared to those in the control rats (all P<0.01 and 0.05). Budesonide inhalation significantly decreased the numbers of the BALF cells and partly reversed lung function decline in the challenged rats (P<0.01 and 0.05). However, this corticosteroid did not influence pathological changes in fine structures of the tobacco smoke-exposed lungs. Treatment with budesonide resulted in an obvious decrease in the MMP-1 but not MMP-2 and TIMP-2 productions (P<0.05). Inhaled budesonide mitigates the ongoing inflammatory process in the smoked lungs and ameliorates declining lung function through reducing MMP-1 content.

GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer.

PubMed

Sheng, Xiumei; Bowen, Nathan; Wang, Zhengxin

2016-03-18

GLI pathogenesis-related 1 (GLIPR1) was originally identified in glioblastomas and its expression was also found to be down-regulated in prostate cancer. Functional studies revealed both growth suppression and proapoptotic activities for GLIPR1 in multiple cancer cell lines. GLIPR1's role in lung cancer has not been investigated. Protein arginine methyltransferase 5 (PRMT5) is a protein arginine methyltransferase and forms a stoichiometric complex with the WD repeat domain 77 (WDR77) protein. Both PRMT5 and WDR77 are essential for growth of lung epithelial and cancer cells. But additional gene products that interact genetically or biochemichally with PRMT5 and WDR77 in the control of lung cancer cell growth are not characterized. DNA microarray and immunostaining were used to detect GLIPR1 expression during lung development and lung tumorigenesis. GLIPR1 expression was also analyzed in the TCGA lung cancer cohort. The consequence of GLIPR1 on growth of lung cancer cells in the tissue culture and lung tumor xenografts in the nude mice was observed. We found that GLIPR1 expression is negatively associated with PRMT5/WDR77. GLIPR1 is absent in growing epithelial cells at the early stages of mouse lung development and highly expressed in the adult lung. Expression of GLIPR1 was down-regulated during lung tumorigenesis and its expression suppressed growth of lung cancer cells in the tissue culture and lung tumor xenografts in mice. GLIPR1 regulates lung cancer growth through the V-Erb-B avian erythroblastic leukemia viral oncogene homolog 3 (ErbB3). This study reveals a novel pathway that PRMT5/WDR77 regulates GLIPR1 expression to control lung cancer cell growth and GLIPR1 as a potential therapeutic agent for lung cancer.

Hypergravity Alters the Susceptibility of Cells to Anoxia-Reoxygenation Injury

NASA Technical Reports Server (NTRS)

McCloud, Henry; Pink, Yulondo; Harris-Hooker, Sandra A.; Melhado, Caroline D.; Sanford, Gary L.

1997-01-01

Gravity is a physical force, much like shear stress or mechanical stretch, and should affect organ and cellular function. Researchers have shown that gravity plays a role in ventilation and blood flow distribution, gas exchange, alveolar size and mechanical stresses within the lung. Short exposure to microgravity produced marked alterations in lung blood flow and ventilation distribution while hypergravity exaggerated the regional differences in lung structure and function resulting in reduced ventilation at the base and no ventilation of the upper half of the lung. Microgravity also decreased metabolic activity in cardiac cells, WI-38 embryonic lung cells, and human lymphocytes. Rats, in the tail-suspended head-down tilt model, experienced transient loss of lung water, contrary to an expected increase due to pooling of blood in the pulmonary vasculature. Hypergravity has also been found to increase the proliferation of several different cell lines (e.g., chick embryo fibroblasts) while decreasing cell motility and slowing liver regeneration following partial hepatectomy. These studies show that changes in the gravity environment will affect several aspects of organ and cellular function and produce major change in blood flow and tissue/organ perfusion. However, these past studies have not addressed whether ischemia-reperfusion injury will be exacerbated or ameliorated by changes in the gravity environment, e.g., space flight. Currently, nothing is known about how gravity will affect the susceptibility of different lung and vascular cells to this type of injury. We conducted studies that addressed the following question: Does the susceptibility of lung fibroblasts, vascular smooth muscle, and endothelial cells to anoxia/reoxygenation injury change following exposure to hypergravity conditions?

CD4 T Cell Epitope Specificity and Cytokine Potential Are Preserved as Cells Transition from the Lung Vasculature to Lung Tissue following Influenza Virus Infection.

PubMed

DiPiazza, Anthony; Laniewski, Nathan; Rattan, Ajitanuj; Topham, David J; Miller, Jim; Sant, Andrea J

2018-07-01

Pulmonary CD4 T cells are critical in respiratory virus control, both by delivering direct effector function and through coordinating responses of other immune cells. Recent studies have shown that following influenza virus infection, virus-specific CD4 T cells are partitioned between pulmonary vasculature and lung tissue. However, very little is known about the peptide specificity or functional differences of CD4 T cells within these two compartments. Using a mouse model of influenza virus infection in conjunction with intravascular labeling in vivo , the cell surface phenotype, epitope specificity, and functional potential of the endogenous polyclonal CD4 T cell response was examined by tracking nine independent CD4 T cell epitope specificities. These studies revealed that tissue-localized CD4 cells were globally distinct from vascular cells in expression of markers associated with transendothelial migration, residency, and micropositioning. Despite these differences, there was little evidence for remodeling of the viral epitope specificity or cytokine potential as cells transition from vasculature to the highly inflamed lung tissue. Our studies also distinguished cells in the pulmonary vasculature from peripheral circulating CD4 T cells, providing support for the concept that the pulmonary vasculature does not simply reflect circulating cells that are trapped within the narrow confines of capillary vessels but rather is enriched in transitional cells primed in the draining lymph node that have specialized potential to enter the lung tissue. IMPORTANCE CD4 T cells convey a multitude of functions in immunity to influenza, including those delivered in the lymph node and others conveyed by CD4 T cells that leave the lymph node, enter the blood, and extravasate into the lung tissue. Here, we show that the transition of recently primed CD4 cells detected in the lung vasculature undergo profound changes in expression of markers associated with tissue localization as they establish residence in the lung. However, this transition does not edit CD4 T cell epitope specificity or the cytokine potential of the CD4 T cells. Thus, CD4 T cells that enter the infected lung can convey diverse functions and have a sufficiently broad viral antigen specificity to detect the complex array of infected cells within the infected tissue, offering the potential for more effective protective function. Copyright © 2018 American Society for Microbiology.

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

PubMed Central

Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Alba, Cesar Gonzalez-De; Froines, John R.; Espinosa-Fematt, Jorge A.

2016-01-01

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero is associated with an increase in respiratory symptoms and diseases in adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that exposure to arsenic during early childhood or in utero was associated with impairment in the lung function in children and suggested that this adverse effect could be due to a chronic inflammatory response to the metalloid. Therefore, a cross-sectional study was designed in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their As levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the Soluble Receptor for Advanced Glycation Endproducts (sRAGE) sputum level was significantly lower and Matrix Metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsenic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/Tissue Inhibitor of Metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. PMID:26048584

Lung function impairment in women exposed to biomass fuels during cooking compared to cleaner fuels in Uttar Pradesh, India.

PubMed

Bihari, Vipin; Iqbal, S M; Srivastava, L P; Kesavachandran, C; Siddique, M J A

2013-11-01

A national survey has shown that approximately 75-80% use of fire wood and chips, 10% of dung cake rural women in Uttar Pradesh, India. Considering the respiratory health risk of biomass fuel exposure to women, a cross sectional study was conducted to elucidate the relationship between cooking smoke and lung function impairments. The present study showed significant decline in air flow limitation based on reduced PEFR (3.69 | sec(-1)) and FEV1 (1.34 | sec(-1)) in women cooking with biomass fuels compared to PEFR (4.26 | sec(-1)) and FEV1 (1.73 | sec(-1)) in women cooking with cleaner fuels. The noxious gases and particles generated from biomass fuels during cooking reported in earlier studies may be the reason for the slight decline in airway status PEFR (3.69 | sec(-1)) and lung volumes FEV1 (1.34 | sec(-1)). The higher mean bio-fuels exposure index (52.5 hr-yrs) can attribute to reduced lung function in rural women.

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

[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).

Tobacco use among designated air pollution victims and its association with lung function and respiratory symptoms: a retrospective cross-sectional study.

PubMed

Kotaki, Kenji; Senjyu, Hideaki; Tanaka, Takako; Yano, Yudai; Miyamoto, Naomi; Nishinakagawa, Tsuyoshi; Yanagita, Yorihide; Asai, Masaharu; Kozu, Ryo; Tabusadani, Mitsuru; Sawai, Terumitsu; Honda, Sumihisa

2014-07-31

We sought to elucidate the long-term association of tobacco use and respiratory health in designated pollution victims with and without obstructive pulmonary defects. A retrospective cross-sectional study. The register of pollution victims in Kurashiki, Japan. 730 individuals over 65 years of age previously diagnosed with pollution-related respiratory disease. Patients were classified into four groups according to their smoking status and whether they had obstructive pulmonary disease. We then compared the prevalence of respiratory symptoms and lung function over time between groups. Spirometry was performed and a respiratory health questionnaire completed in the same season each year for up to 30 years. Rates of smoking and respiratory disease were high in our sample. Although respiratory function in non-smoking patients did not completely recover, the annual rate of change in lung function was within the normal range (p<0.01). However, smokers had worse lung function and were more likely to report more severe pulmonary symptoms (p<0.01). Patients' respiratory function did not fully recover despite improved air quality. Our results suggest that, in the context of exposure to air pollution, tobacco use causes additional loss of lung function and exacerbates respiratory symptoms. 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.

Systems for lung volume standardization during static and dynamic MDCT-based quantitative assessment of pulmonary structure and function.

PubMed

Fuld, Matthew K; Grout, Randall W; Guo, Junfeng; Morgan, John H; Hoffman, Eric A

2012-08-01

Multidetector-row computed tomography (MDCT) has emerged as a tool for quantitative assessment of parenchymal destruction, air trapping (density metrics), and airway remodeling (metrics relating airway wall and lumen geometry) in chronic obstructive pulmonary disease (COPD) and asthma. Critical to the accuracy and interpretability of these MDCT-derived metrics is the assurance that the lungs are scanned during a breathhold at a standardized volume. A computer monitored turbine-based flow meter system was developed to control patient breathholds and facilitate static imaging at fixed percentages of the vital capacity. Because of calibration challenges with gas density changes during multibreath xenon CT, an alternative system was required. The design incorporated dual rolling seal pistons. Both systems were tested in a laboratory environment and human subject trials. The turbine-based system successfully controlled lung volumes in 32/37 subjects, having a linear relationship for CT measured air volume between repeated scans: for all scans, the mean and confidence interval of the differences (scan1-scan2) was -9 mL (-169, 151); for total lung capacity alone 6 mL (-164, 177); for functional residual capacity alone, -23 mL (-172, 126). The dual-piston system successfully controlled lung volume in 31/41 subjects. Study failures related largely to subject noncompliance with verbal instruction and gas leaks around the mouthpiece. We demonstrate the successful use of a turbine-based system for static lung volume control and demonstrate its inadequacies for dynamic xenon CT studies. Implementation of a dual-rolling seal spirometer has been shown to adequately control lung volume for multibreath wash-in xenon CT studies. These systems coupled with proper patient coaching provide the tools for the use of CT to quantitate regional lung structure and function. The wash-in xenon CT method for assessing regional lung function, although not necessarily practical for routine clinical studies, provides for a dynamic protocol against which newly emerging single breath, dual-energy xenon CT measures can be validated. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.

Determinants of early-life lung function in African infants

PubMed Central

Willemse, Lauren; Visagie, Ane; Czövek, Dorottya; Nduru, Polite; Vanker, Aneesa; Stein, Dan J; Koen, Nastassja; Sly, Peter D; Hantos, Zoltán; Hall, Graham L; Zar, Heather J

2017-01-01

Background Low lung function in early life is associated with later respiratory illness. There is limited data on lung function in African infants despite a high prevalence of respiratory disease. Aim To assess the determinants of early lung function in African infants. Method Infants enrolled in a South African birth cohort, the Drakenstein child health study, had lung function measured at 6–10 weeks of age. Measurements, made with the infant breathing via a facemask during natural sleep, included tidal breathing, sulfur hexafluoride multiple breath washout and the forced oscillation technique. Information on antenatal and early postnatal exposures was collected using questionnaires and urine cotinine. Household benzene exposure was measured antenatally. Results Successful tests were obtained in 645/675 (95%) infants, median (IQR) age of 51 (46–58) days. Infant size, age and male gender were associated with larger tidal volume. Infants whose mothers smoked had lower tidal volumes (−1.6 mL (95% CI −3.0 to −0.1), p=0.04) and higher lung clearance index (0.1 turnovers (95% CI 0.01 to 0.3), p=0.03) compared with infants unexposed to tobacco smoke. Infants exposed to alcohol in utero or household benzene had lower time to peak tidal expiratory flow over total expiratory time ratios, 10% (95% CI −15.4% to −3.7%), p=0.002) and 3.0% (95% CI −5.2% to −0.7%, p=0.01) lower respectively compared with unexposed infants. HIV-exposed infants had higher tidal volumes (1.7 mL (95% CI 0.06 to 3.3) p=0.04) compared with infants whose mothers were HIV negative. Conclusion We identified several factors including infant size, sex, maternal smoking, maternal alcohol, maternal HIV and household benzene associated with altered early lung function, many of which are factors amenable to public health interventions. Long-term study of lung function and respiratory disease in these children is a priority to develop strategies to strengthen child health. PMID:27856821

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

Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners

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

Leng, Shuguang; Thomas, Cynthia L.; Snider, Amanda M.

Background: High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development. Objectives: We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high occupational exposure to radon gas. Methods: Genetic associations were assessed in a case–control study of former uranium miners (242 cases and 336 controls). A replication study was performed usingmore » data from the Gene Environment Association Studies (GENEVA) Genome Wide Association Study (GWAS) of Lung Cancer and Smoking. Functional relevance of the SNPs was characterized using in vitro approaches. Results: We found that rs1800797 was associated with squamous cell carcinoma in miners and with a shorter time between the midpoint of the period of substantial exposure and diagnosis among the cases. Furthermore, rs1800797 was also associated with lung cancer among never smokers in the GENEVA dataset. Functional studies identified that the risk allele was associated with increased basal IL-6 mRNA level and greater promoter activity. Furthermore, fibroblasts with the risk allele showed greater induction of IL-6 secretion by hydrogen peroxide or benzo[a]pyrene diolepoxide treatments. Conclusions: An IL6 promoter variant was associated with lung cancer in uranium miners and never smokers in two external study populations. Lastly, the associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion« less

Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners

DOE PAGES

Leng, Shuguang; Thomas, Cynthia L.; Snider, Amanda M.; ...

2015-09-15

Background: High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development. Objectives: We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high occupational exposure to radon gas. Methods: Genetic associations were assessed in a case–control study of former uranium miners (242 cases and 336 controls). A replication study was performed usingmore » data from the Gene Environment Association Studies (GENEVA) Genome Wide Association Study (GWAS) of Lung Cancer and Smoking. Functional relevance of the SNPs was characterized using in vitro approaches. Results: We found that rs1800797 was associated with squamous cell carcinoma in miners and with a shorter time between the midpoint of the period of substantial exposure and diagnosis among the cases. Furthermore, rs1800797 was also associated with lung cancer among never smokers in the GENEVA dataset. Functional studies identified that the risk allele was associated with increased basal IL-6 mRNA level and greater promoter activity. Furthermore, fibroblasts with the risk allele showed greater induction of IL-6 secretion by hydrogen peroxide or benzo[a]pyrene diolepoxide treatments. Conclusions: An IL6 promoter variant was associated with lung cancer in uranium miners and never smokers in two external study populations. Lastly, the associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion« less

Lung function and respiratory symptoms among female hairdressers in Palestine: a 5-year prospective study

PubMed Central

Nemer, Maysaa; Kristensen, Petter; Nijem, Khaldoun; Bjertness, Espen; Skare, Øivind; Skogstad, Marit

2015-01-01

Objectives Hairdressers are exposed to chemicals at the workplace which are known to cause respiratory symptoms and asthma. This study aimed to examine changes in self-reported respiratory symptoms over 5 years, as well as to examine the lung function decline and determine whether it is within the expected range, to assess the dropout rate and reasons for leaving the profession, and to examine the associations between occupational factors and lung function changes at follow-up. Design Prospective study. Setting Female hairdressing salons in Hebron city, Palestine. Participants 170 female hairdressers who participated in a baseline survey in 2008 were followed up in 2013. A total of 161 participants participated in 2013. Outcome measures Change in reported respiratory symptoms and change in lung function over follow-up. Dropout from the profession and reasons for it. Differences between current and former hairdressers in respiratory symptoms and lung function at follow-up. Ambient air ammonia levels in 13 salons. Results Current hairdressers reported more respiratory symptoms in 2013 compared with baseline. Former hairdressers reported fewer symptoms at follow-up. At follow-up, current hairdressers showed a significant decrease in forced vital capacity of 35 mL/year (95% CI 26 to 44 mL/year) and of 31 mL/year (95% CI 25 to 36 mL/year) for forced expiratory volume in 1 s (FEV1). 28 (16%) of the hairdressers quit the job during the 5-year follow-up, 8 (28%) because of health problems. Hairdressers who had been working for 4 years or more at baseline showed a stronger decline in FEV1 compared with those who worked less than 4 years (difference 13, 95% CI 1 to 25). Conclusions Current hairdressers developed more respiratory symptoms and larger lung function decline than former hairdressers during follow-up. Few hairdressers left their profession because of respiratory health problems. Working for more years is associated with lung function decline among current hairdressers. PMID:26474935

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

Computed Tomography Studies of Lung Mechanics

PubMed Central

Simon, Brett A.; Christensen, Gary E.; Low, Daniel A.; Reinhardt, Joseph M.

2005-01-01

The study of lung mechanics has progressed from global descriptions of lung pressure and volume relationships to the high-resolution, three-dimensional, quantitative measurement of dynamic regional mechanical properties and displacements. X-ray computed tomography (CT) imaging is ideally suited to the study of regional lung mechanics in intact subjects because of its high spatial and temporal resolution, correlation of functional data with anatomic detail, increasing volumetric data acquisition, and the unique relationship between CT density and lung air content. This review presents an overview of CT measurement principles and limitations for the study of regional mechanics, reviews some of the early work that set the stage for modern imaging approaches and impacted the understanding and management of patients with acute lung injury, and presents evolving novel approaches for the analysis and application of dynamic volumetric lung image data. PMID:16352757

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.

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

PubMed

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

2017-07-26

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

Can Particulate Pollution Affect Lung Function in Healthy Adults?

EPA Science Inventory

Accompanying editorial to paper from Harvard by Rice et al. entitled "Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart StudyBy almost any measure the Clean Air Act and its amendments has to be considered as one...

Metal dust exposure and lung function deterioration among steel workers: an exposure-response relationship.

PubMed

Hamzah, Nurul Ainun; Mohd Tamrin, Shamsul Bahri; Ismail, Noor Hassim

2016-07-01

Metallic dust is a heterogeneous substance with respiratory sensitizing properties. Its long term exposure adversely affected lung function, thus may cause acute or chronic respiratory diseases. A cross-sectional study was conducted in a steel factory in Terengganu, Malaysia to assess the metal dust exposure and its relationship to lung function values among 184 workers. Metal dust concentrations values (Co, Cr, and Ni) for each worker were collected using air personal sampling. Lung function values (FEV 1 , FVC, and %FEV 1 /FVC) were determined using spirometer. Exposure to cobalt and chromium were 1-3 times higher than permissible exposure limit (PEL) while nickel was not exceeding the PEL. Cumulative of chromium was the predictor to all lung function values (FEV 1 , FVC, and %FEV 1 /FVC). Frequency of using mask was positively associated with FVC (Adj b = 0.263, P = 0.011) while past respiratory illnesses were negatively associated with %FEV 1 /FVC (Adj b = -1.452, P = 0.026). Only few workers (36.4%) were found to wear their masks all times during the working hours. There was an exposure-response relationship of cumulative metal dust exposure with the deterioration of lung function values. Improvement of control measures as well as proper and efficient use or personal protection equipment while at work could help to protect the respiratory health of workers.

Bronchopulmonary dysplasia: improvement in lung function between 7 and 10 years of age.

PubMed

Blayney, M; Kerem, E; Whyte, H; O'Brodovich, H

1991-02-01

To evaluate the natural history of bronchopulmonary dysplasia, we studied the same 32 patients at a mean age of 7 and 10 years. The group as a whole had normal height and weight percentiles, and each child grew along his or her established somatic growth curve. Although some children had abnormal values, the group maintained a normal mean total lung capacity and functional residual capacity. The mean residual volume and the residual volume/total lung capacity ratios were elevated at both ages. At age 7 years the 19 patients (59%) who had a forced expiratory volume in 1 second (FEV1) of less than 80% had "catch up" improvement by 10 years of age (65 +/- 11% to 72 +/- 16% of predicted value; p less than 0.05). All the children who had a normal FEV1 at 7 years of age continued to have a normal FEV1 at age 10 years. Resting single-breath carbon monoxide uptake by the lung was normal when measured at age 10 years. The majority of patients had a positive methacholine challenge test result at both ages, although there was a low incidence of clinically diagnosed asthma. This study demonstrates that patients with bronchopulmonary dysplasia who have normal lung function at age 7 have had normal lung growth and that those with evidence of mild to moderate lung disease have continued lung growth or repair, or both, during their school years.

Are Lung Disease and Function Related to Age-related Macular Degeneration?

PubMed Central

Moorthy, Sonia; Cheung, Ning; Klein, Ronald; Shahar, E; Wong, Tien Y

2010-01-01

Purpose To describe the relationship of lung disease and function with early age-related macular degeneration (AMD) in a population-based study. Design A population-based, cross-sectional study of 12,596 middle-aged participants from the Atherosclerosis Risk in Communities Study. Methods Lung function was assessed by spirometry. Physician diagnosis of asthma and lung disease was ascertained from a standardized questionnaire. AMD signs were graded from fundus photographs according to the Wisconsin grading protocol. Results Of our study population, 587 (4.7%) had early AMD, 638 (5.1%) had asthma and 581 (4.6%) had lung disease. After adjusting for age, gender, smoking and hypertension, each litre increase in predicted forced expiratory volume in one second (FEV1) (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 0.89, 1.80), forced vital capacity (FVC) (OR 1.18; 95% CI: 0.93, 1.51) and peak expiratory flow rate (OR 1.12; 95% CI: 0.95, 1.33) were not significantly associated with early AMD. FEV1/FVC ratio (second quartile OR 1.61; 95%CI 0.88–2.93, third quartile OR 1.65; CI 0.90–3.03, fourth quartile OR 1.28; 95%CI 0.68–2.40) was not significantly associated with early AMD. Similarly, asthma (OR 1.06; 95% CI: 0.86, 1.27) and other lung diseases (OR 1.08; 95% CI: 0.90, 1.29) were not associated with early AMD. Conclusion Our data do not support a cross-sectional association between lung disease and risk of early AMD. PMID:21168814

Association of growth and nutritional parameters with pulmonary function in cystic fibrosis: a literature review.

PubMed

Mauch, Renan Marrichi; Kmit, Arthur Henrique Pezzo; Marson, Fernando Augusto de Lima; Levy, Carlos Emilio; Barros-Filho, Antonio de Azevedo; Ribeiro, José Dirceu

2016-12-01

To review the literature addressing the relationship of growth and nutritional parameters with pulmonary function in pediatric patients with cystic fibrosis. A collection of articles published in the last 15 years in English, Portuguese and Spanish was made by research in electronic databases - PubMed, Cochrane, Medline, Lilacs and Scielo - using the keywords cystic fibrosis, growth, nutrition, pulmonary function in varied combinations. Articles that addressed the long term association of growth and nutritional parameters, with an emphasis on growth, with pulmonary disease in cystic fibrosis, were included, and we excluded those that addressing only the relationship between nutritional parameters and cystic fibrosis and those in which the aim was to describe the disease. Seven studies were included, with a total of 12,455 patients. Six studies reported relationship between growth parameters and lung function, including one study addressing the association of growth parameters, solely, with lung function, and all the seven studies reported relationship between nutritional parameters and lung function. The review suggests that the severity of the lung disease, determined by spirometry, is associated with body growth and nutritional status in cystic fibrosis. Thus, the intervention in these parameters can lead to the better prognosis and life expectancy for cystic fibrosis patients. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Prospective longitudinal evaluation of lung function during the first year of life after extracorporeal membrane oxygenation.

PubMed

Hofhuis, Ward; Hanekamp, Manon N; Ijsselstijn, Hanneke; Nieuwhof, Eveline M; Hop, Wim C J; Tibboel, Dick; de Jongste, Johan C; Merkus, Peter J F M

2011-03-01

To collect longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation and to evaluate relationships between lung function and perinatal factors. Longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation are lacking. Prospective longitudinal cohort study. Outpatient clinic of a tertiary level pediatric hospital. The cohort consisted of 64 infants; 33 received extracorporeal membrane oxygenation for meconium aspiration syndrome, 14 for congenital diaphragmatic hernia, four for sepsis, six for persistent pulmonary hypertension of the neonate, and seven for respiratory distress syndrome of infancy. Evaluation was at 6 mos and 12 mos; 39 infants were evaluated at both time points . None. Functional residual capacity and forced expiratory flow at functional residual capacity were measured and expressed as z score. Mean (sem) functional residual capacities in z score were 0.0 (0.2) and 0.2 (0.2) at 6 mos and 12 mos, respectively. Mean (sem) forced expiratory flow was significantly below average (z score = 0) (p < .001) at 6 mos and 12 mos: -1.1 (0.1) and -1.2 (0.1), respectively. At 12 mos, infants with diaphragmatic hernia had a functional residual capacity significantly above normal: mean (sem) z score = 1.2 (0.5). Infants treated with extracorporeal membrane oxygenation have normal lung volumes and stable forced expiratory flows within normal range, although below average, within the first year of life. There is reason to believe, therefore, that extracorporeal membrane oxygenation either ameliorates the harmful effects of mechanical ventilation or somehow preserves lung function in the very ill neonate.

Disparities in pulmonary function in healthy children across the Indian urban-rural continuum.

PubMed

Sonnappa, Samatha; Lum, Sooky; Kirkby, Jane; Bonner, Rachel; Wade, Angela; Subramanya, Vinita; Lakshman, Padmanabha T; Rajan, Babitha; Nooyi, Shalini C; Stocks, Janet

2015-01-01

Marked socioeconomic health-care disparities are recognized in India, but lung health inequalities between urban and rural children have not been studied. We investigated whether differences exist in spirometric pulmonary function in healthy children across the Indian urban-rural continuum and compared results with those from Indian children living in the UK. Indian children aged 5 to 12 years were recruited from Indian urban, semiurban, and rural schools, and as part of the Size and Lung Function in Children study, London. Anthropometric and spirometric assessments were undertaken. Acceptable spirometric data were obtained from 728 (58% boys) children in India and 311 (50% boys) UK-Indian children. As an entire group, the India-resident children had significantly lower z FEV1 and z FVC than UK-Indian children (P < 0.0005), when expressed using Global Lung Function Initiative-2012 equations. However, when India-resident children were categorized according to residence, there were no differences in z FEV1 and z FVC between Indian-urban and UK-Indian children. There were, however, significant reductions of ∼ 0.5 z scores and 0.9 z scores in both FEV1 and FVC (with no difference in FEV1/FVC) in Indian-semiurban and Indian-rural children, respectively, when compared with Indian-urban children (P < 0.0005). z Body mass index, socioeconomic circumstances, tobacco, and biomass exposure were individually significantly associated with z FEV1 and z FVC (P < 0.0005). The presence of an urban-rural continuum of lung function within a specific ethnic group emphasizes the impact of environmental factors on lung growth in emerging nations such as India, which must be taken into account when developing ethnic-specific reference values or designing studies to optimize lung health.

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.

Lung function and functional capacity among foundry workers using effective risk control measures.

PubMed

Bernardes, Rosane Andrea Bretas; Chiavegato, Luciana Dias; de Moraes, Mônica Vasconcelos; Negreiros, Alexandher; Padula, Rosimeire Simprini

2015-01-01

Inhaled dust in the environment can trigger specific reactions in the airways and cause various respiratory diseases. Evaluate the lung function and functional capacity of foundry workers who are exposed to metals and use effective control measures. A cross-sectional study was realized with 108 workers at a bronze foundry and machining plant and in maintenance at a private university, both in Brazil. The workers were divided into two groups: the study group exposed to metals but using risk control measues and a control group not exposed to metal work. The Medical Research Council Questionnaire on Respiratory Symptoms and the International Physical Activity Questionnaire were administered, and lung function and functional capacity were evaluated. Comparative statistics were used to identify differences in the outcome measures between the two groups. The groups had similar personal and anthropometric characteristics and time on the job. Spirometry and peak expiratory flow presented no significant differences between the groups. And there was also no statistically significant difference between groups in functional capacity as assessed by performance on the six-minute walk test. Foundry industry workers in Brazil who were exposed to metal but used risk control measures had similar lung function and functional capacity when compared to the control group who were not exposed to metal. This is a positive results and maybe related to age, time exposure and control of occupational hazards. However, these workers need to continue being monitored in longitudinal studies.

Role of pulmonary diseases and physical condition in the regulation of vasoactive hormones.

PubMed

Hietanen, E; Marniemi, J; Liippo, K; Seppänen, A; Hartiala, J; Viinamäki, O

1988-12-01

Lungs have many non-respiratory metabolic functions, of which some take place in the capillary endothelium, while others are in parenchymal lung tissue. We have studied the role of the lungs in the metabolism of vasoactive and some other hormones by comparing patients who have undergone lung resection to those having various obstructive or fibrotic lung diseases. We have also compared these groups with persons in good physical health. The data suggested that lung resection patients had low angiotensin II levels in plasma but the response of angiotensin II to exercise was normal. Also adrenalin concentration was low in the lung resection group while dopamine did not show any significant difference between the groups. When hormone levels were correlated to the exercise data, renin levels were especially related to physical condition. Serum post-exercise renin values were inversely related to the uneven distribution of lung perfusion, possibly thus reflecting the diminished pulmonary vascularization. A negative association was found between angiotensin II and diffusion capacity. Thus, the angiotensin II levels may preferably be controlled by the non-circulatory functions of the lungs.

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

Positive Rates and Factors Associated with Abnormal Lung Function of Greenhouse Workers in China: A Cross-Sectional Study.

PubMed

Zhu, Xiaojun; Gao, Panjun; Gu, Yishuo; Xiao, Pei; Liu, Mengxuan; Chen, Juan; Cen, Yacai; Ma, Wenjun; Li, Tao

2017-08-24

Since the number of greenhouse workers are increasing in China, this observational cross-sectional study was designed to evaluate lung function and discuss the potential risk factors, to provide evidence in the surveillance of greenhouse workers' health. 678 greenhouse workers in Gansu Province, China were enrolled. A questionnaire which included demographic and occupational information was used. Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁), and FEV₁:FVC ratios (FEV₁/FVC), maximal expiratory flow after 50% of the FVC has not been exhaled (MEF 50 ), maximal expiratory flow after 25% of the FVC has not been exhaled (MEF 25 ) and maximal mid-expiratory flow curve (MMEF) were measured as lung function indicators. The mean values and standard deviations (SDs) of VC% predicted, FVC% predicted, FEV₁% predicted and FEV₁/FVC ratio were 106.07 ± 13.36, 107.60 ± 13.95, 97.19 ± 14.80 and 89.76 ± 10.78 respectively. The positive rates of above four and abnormal lung ventilation function were 2.9%, 2.8%, 11.2%, 4.6% and 6.5% respectively. Gender, age, BMI and number of greenhouses owned were influence factors of lung ventilation function ( p < 0.05). The mean values and SDs of MEF 50 % predicted, MEF 25 % predicted and MMEF% predicted were 69.63 ± 24.95, 54.04 ± 24.94 and 66.81 ± 24.53. The positive rates of above three and abnormal small airway function were 45.0%, 72.1%, 47.2% and 49.4% respectively. Age, education and number of greenhouses owned were influence factors for small airway function ( p < 0.05). Working in a greenhouse might influence lung function of the workers. Small airway function indicators could be used as priority indicators for the surveillance of greenhouse workers' health.

Increased Risk of Interstitial Lung Disease in Children with a Single R288K Variant of ABCA3

PubMed Central

Wittmann, Thomas; Frixel, Sabrina; Höppner, Stefanie; Schindlbeck, Ulrike; Schams, Andrea; Kappler, Matthias; Hegermann, Jan; Wrede, Christoph; Liebisch, Gerhard; Vierzig, Anne; Zacharasiewicz, Angela; Kopp, Matthias Volkmar; Poets, Christian F; Baden, Winfried; Hartl, Dominik; van Kaam, Anton H; Lohse, Peter; Aslanidis, Charalampos; Zarbock, Ralf; Griese, Matthias

2016-01-01

The ABCA3 gene encodes a lipid transporter in type II pneumocytes critical for survival and normal respiratory function. The frequent ABCA3 variant R288K increases the risk for neonatal respiratory distress syndrome among term and late preterm neonates, but its role in children’s interstitial lung disease has not been studied in detail. In a retrospective cohort study of 228 children with interstitial lung disease related to the alveolar surfactant system, the frequency of R288K was assessed and the phenotype of patients carrying a single R288K variant further characterized by clinical course, lung histology, computed tomography and bronchoalveolar lavage phosphatidylcholine PC 32:0. Cell lines stably transfected with ABCA3-R288K were analyzed for intracellular transcription, processing and targeting of the protein. ABCA3 function was assessed by detoxification assay of doxorubicin, and the induction and volume of lamellar bodies. We found nine children with interstitial lung disease carrying a heterozygous R288K variant, a frequency significantly higher than in the general Caucasian population. All identified patients had neonatal respiratory insufficiency, recovered and developed chronic interstitial lung disease with intermittent exacerbations during early childhood. In vitro analysis showed normal transcription, processing, and targeting of ABCA3-R288K, but impaired detoxification function and smaller lamellar bodies. We propose that the R288K variant can underlie interstitial lung disease in childhood due to reduced function of ABCA3, demonstrated by decelerated detoxification of doxorubicin, reduced PC 32:0 content and decreased lamellar body volume. PMID:26928390

Immersing lungs in hydrogen-rich saline attenuates lung ischaemia-reperfusion injury.

PubMed

Takahashi, Mamoru; Chen-Yoshikawa, Toyofumi F; Saito, Masao; Tanaka, Satona; Miyamoto, Ei; Ohata, Keiji; Kondo, Takeshi; Motoyama, Hideki; Hijiya, Kyoko; Aoyama, Akihiro; Date, Hiroshi

2017-03-01

Anti-oxidant effects of hydrogen have been reported in studies examining ischaemia-reperfusion injury (IRI). In this study, we evaluated the therapeutic efficacy of immersing lungs in hydrogen-rich saline on lung IRI. Lewis rats were divided into three groups: (i) sham, (ii) normal saline and (iii) hydrogen-rich saline. In the first experiment, the left thoracic cavity was filled with either normal saline or hydrogen-rich saline for 1 h. Then, we measured the hydrogen concentration in the left lung using a sensor gas chromatograph ( N = 3 per group). In the second experiment, lung IRI was induced by occlusion of the left pulmonary hilum for 1 h, followed by reperfusion for 3 h. During the ischaemic period, the left thoracic cavity was filled with either normal saline or hydrogen-rich saline. After reperfusion, we assessed lung function, histological changes and cytokine production ( N = 5-7 per group). Immersing lungs in hydrogen-rich saline resulted in an elevated hydrogen concentration in the lung (6.9 ± 2.9 μmol/1 g lung). After IRI, pulmonary function (pulmonary compliance and oxygenation levels) was significantly higher in the hydrogen-rich saline group than in the normal saline group ( P  < 0.05). Similarly, pro-inflammatory cytokine levels (interleukin-1β and interleukin-6) in the left lung were significantly lower in the hydrogen-rich saline group than in the normal saline group ( P  < 0.05). Immersing lungs in hydrogen-rich saline delivered hydrogen into the lung and consequently attenuated lung IRI. Hydrogen-rich solution appears to be a promising approach to managing lung IRI. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Self-reported physical activity and lung function two months after cardiac surgery--a prospective cohort study.

PubMed

Jonsson, Marcus; Urell, Charlotte; Emtner, Margareta; Westerdahl, Elisabeth

2014-03-28

Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health's national survey. Formal lung function testing was performed preoperatively and two months postoperatively. The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results.

Cross-species functional analysis of cancer-associated fibroblasts identifies a critical role for CLCF1 and IL6 in non-small cell lung cancer in vivo

PubMed Central

Vicent, Silvestre; Sayles, Leanne C.; Vaka, Dedeepya; Khatri, Purvesh; Gevaert, Olivier; Chen, Ron; Zheng, Yanyan; Gillespie, Anna K.; Clarke, Nicole; Xu, Yue; Shrager, Joseph; Hoang, Chuong D.; Plevritis, Sylvia; Butte, Atul J.; Sweet-Cordero, E. Alejandro

2013-01-01

Cancer-associated fibroblasts (CAFs) have been reported to support tumor progression by a variety of mechanisms. However, their role in the progression of non-small cell lung cancer (NSCLC) remains poorly defined. In addition, the extent to which specific proteins secreted by CAFs contribute directly to tumor growth is unclear. To study the role of CAFs in NSCLC, a cross-species functional characterization of mouse and human lung CAFs was performed. CAFs supported the growth of lung cancer cells in vivo by secretion of soluble factors that directly stimulate the growth of tumor cells. Gene expression analysis comparing normal mouse lung fibroblasts (NFs) and mouse lung CAFs identified multiple genes that correlate with the CAF phenotype. A gene signature of secreted genes upregulated in CAFs was an independent marker of poor survival in NSCLC patients. This secreted gene signature was upregulated in NFs after long-term exposure to tumor cells, demonstrating that NFs are “educated” by tumor cells to acquire a CAF-like phenotype. Functional studies identified important roles for CLCF1-CNTFR and IL6-IL6R signaling, in promoting growth of NSCLC cells. This study identifies novel soluble factors contributing to the CAF protumorigenic phenotype in NSCLC and suggests new avenues for the development of therapeutic strategies. PMID:22962265

Lung Mass in Smokers

PubMed Central

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

2017-01-01

Rationale and Objective Emphysema is characterized by airspace dilation, inflammation, and irregular deposition of elastin and collagen in the interstitium. Computed tomographic (CT) studies have reported that lung mass (LM) may be increased in smokers, a finding attributed to inflammatory and parenchymal remodeling processes observed on histopathology. We sought to examine the epidemiologic and clinical associations of LM in smokers. Materials and Methods Baseline epidemiologic, clinical, and CT data (n=8,156) from smokers enrolled into the COPDGene Study were analyzed. LM was calculated from the CT scan. Changes in lung function at five-year follow-up were available from 1,623 subjects. Regression analysis was performed to assess for associations of LM with forced expiratory volume in 1 second (FEV1) and FEV1 decline. Results Subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 COPD had greater LM than either smokers with normal lung function or those with GOLD 2–4 COPD (P<0.001 for both comparisons). LM was predictive of rate of the decline in FEV1 (decline per 100 g, −4.7 ± 1.7 ml/yr, P=0.006). Conclusion Our cross sectional data suggest the presence of a biphasic radiologic remodeling process in smokers: the presence of such non-linearity must be accounted for in longitudinal CT studies. Baseline LM predicts the decline in lung function. PMID:27940230

A review of cetacean lung morphology and mechanics.

PubMed

Piscitelli, Marina A; Raverty, Stephen A; Lillie, Margo A; Shadwick, Robert E

2013-12-01

Cetaceans possess diverse adaptations in respiratory structure and mechanics that are highly specialized for an array of surfacing and diving behaviors. Some of these adaptations and air management strategies are still not completely understood despite over a century of study. We have compiled the historical and contemporary knowledge of cetacean lung anatomy and mechanics in regards to normal lung function during ventilation and air management while diving. New techniques are emerging utilizing pulmonary mechanics to measure lung function in live cetaceans. Given the diversity of respiratory adaptations in cetaceans, interpretations of these results should consider species-specific anatomy, mechanics, and behavior. Copyright © 2013 Wiley Periodicals, Inc.

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.

Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease

PubMed Central

Rodriguez-Roisin, Roberto; Tetzlaff, Kay; Watz, Henrik; Wouters, Emiel FM; Disse, Bernd; Finnigan, Helen; Magnussen, Helgo; Calverley, Peter MA

2016-01-01

The WISDOM study (NCT00975195) reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration. We subsequently determined the validity of home-based spirometry for detecting changes in lung function by comparing in-clinic and home-based forced expiratory volume in 1 second in patients who underwent stepwise fluticasone propionate withdrawal over 12 weeks versus patients remaining on fluticasone propionate for 52 weeks. Bland–Altman analysis of these data confirmed good agreement between in-clinic and home-based measurements, both across all visits and at the individual visits at study weeks 6, 12, 18, and 52. There was a measurable difference between the forced expiratory volume in 1 second values recorded at home and in the clinic (mean difference of −0.05 L), which may be due to suboptimal patient effort in performing unsupervised recordings. However, this difference remained consistent over time. Overall, these data demonstrate that home-based and in-clinic spirometric measurements were equally valid and reliable for assessing lung function in patients with COPD, and suggest that home-based spirometry may be a useful tool to facilitate analysis of changes in lung function on a day-to-day basis. PMID:27578972

Effect of a Gonadotrophin-Releasing Hormone Analogue on Lung Function in Lymphangioleiomyomatosis

PubMed Central

Harari, Sergio; Cassandro, Roberto; Chiodini, Jacopo; Taveira-DaSilva, Angelo M.; Moss, Joel

2010-01-01

Background Lymphangioleiomyomatosis (LAM), a multisystem disease occurring primarily in women, is characterized by cystic lung destruction, and kidney and lymphatic tumors, caused by the proliferation of abnormal-appearing cells (ie, LAM cells) with a smooth muscle cell phenotype that express melanoma antigens and are capable of metastasizing. Estrogen receptors are present in LAM cells, and this finding, along with reports of disease progression during pregnancy or following exogenous estrogen administration, suggest the involvement of estrogens in the pathogenesis of LAM. Consequently, antiestrogen therapies have been employed in treatment. The goal of this prospective study was to evaluate the efficacy of triptorelin, a gonadotrophin-releasing hormone analogue, in 11 premenopausal women with LAM. Methods Patients were evaluated at baseline and every 3 to 6 months thereafter, for a total of 36 months. Hormonal assays, pulmonary function tests, 6-min walk tests, high-resolution CT scans of the chest, and bone mineral density studies were performed. Results Gonadal suppression was achieved in all patients. Overall, a significant decline in lung function was observed; two patients underwent lung transplantation 1 year after study enrollment, and another patient was lost to follow-up. Treatment with triptorelin was associated with a decline in bone mineral density. Conclusions Triptorelin appears not to prevent a decline in lung function in patients with LAM. Its use, however, may be associated with the loss of bone mineral density. PMID:18071009

The respiratory health and lung function of Anglo-American children in a smelter town

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

Dodge, R.

1983-02-01

Cooper smelters are large, usually isolated, sources of air pollution. Arizona has several such plants on the periphery of small communities. The smelters emit predominantly sulfur oxides and particulates, and the residents of these communities intermittently are exposed to high concentrations (24-h sulfur dioxide (SO2) . 250 to 500 micrograms/m3) of smelter smoke but little other pollution. This study compared the respiratory health of Anglo-American school children who lived in one smelter community with children living in another small community in Arizona that was free of smelter air pollution. The prevalence of cough, as determined by questionnaire, was 25.6% inmore » the smelter town children and 14.3% in the nonsmelter town children (p less than 0.05). Pulmonary function at the study onset was equal in the two groups. Over the course of the 4 yr of study, lung function growth (measured as actual forced expiratory volume in one second (FEV1) after 4 yr of study minus predicted FEV1) was also equal in the smelter town and nonsmelter town children. These results suggest that children in smelter communities have slightly more cough when compared with children living in other communities, but no differences in initial lung function or lung function at yearly testing over the period of the study.« 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

Lung function association with outdoor temperature and relative humidity and its interaction with air pollution in the elderly.

PubMed

Lepeule, Johanna; Litonjua, Augusto A; Gasparrini, Antonio; Koutrakis, Petros; Sparrow, David; Vokonas, Pantel S; Schwartz, Joel

2018-04-21

While the effects of weather variability on cardio-respiratory mortality are well described, research examining the effects on morbidity, especially for vulnerable populations, is warranted. We investigated the associations between lung function and outdoor temperature (T in Celsius degrees (°C)) and relative humidity (RH), in a cohort of elderly men, the Normative Aging Study. Our study included 1103 participants whose forced vital capacity (FVC), forced expiratory volume in one second (FEV 1 ), and weather exposures were assessed one to five times during the period 1995-2011 (i.e. 3162 observations). Temperature and relative humidity were measured at one location 4 h to 7 days before lung function tests. We used linear mixed-effects models to examine the associations with outdoor T and RH. A 5-degree increase in the 3-day moving average T was associated with a significant 0.7% decrease (95%CI: -1.24, -0.20) in FVC and a 5% increase in the 7-day moving average RH was associated with a significant 0.2% decrease (95%CI: -0.40, -0.02) in FVC and FEV 1 . The associations with T were greater when combined with higher exposures of black carbon with a 1.6% decrease (95%CI -2.2; -0.9) in FVC and a 1% decrease (95%CI -1.7; -0.4) in FEV 1 . The relationships between T and RH and lung function were linear. No synergistic effect of T and RH was found. Heat and lung function are two predictors of mortality. Our findings suggest that increases in temperature and relative humidity are related to decreases in lung function, and such observations might be amplified by high black carbon levels. Copyright © 2018 Elsevier Inc. All rights reserved.

Lung function parameters of healthy Sri Lankan Tamil young adults.

PubMed

Balasubramaniam, M; Sivapalan, K; Thuvarathipan, R

2014-06-01

To establish reference norms of lung function parameters for healthy Sri Lankan Tamil young adults. Cross sectional study of Tamil students at the Faculty of Medicine, Jaffna. Healthy non smoking students of Sri Lankan Tamil ethnic group were enrolled. Age, height, weight, BMI and spirometric measurements (Micro Quark) were recorded in 267 participants (137 females and 130 males). Height was significantly correlated with (p<0.05) all the lung function parameters except FEV1%, PEFR and MEF75 in males. Prediction equations were derived by regression analysis based on the height as an independent variable. Predicted lung function values for a particular age and height were lower than values predicted for Pakistanis, Kelatanese Malaysians and eastern Indians. The values were comparable to south Indians in Madras. Our FVC values of males and VC of females were closer to Sri Lankan Sinhalese. FEV1 and FEF25-75 in males were slightly higher and FVC, FEV1 and FEF25-75 in females were slightly lower in Tamils. When mean values were compared, these parameters were significantly higher in Tamil males (p<0.001) and significantly lower in Tamil females (p<0.001). These values will be useful in interpreting lung function parameters of the particular age group as there are no published norms for Sri Lankan Tamils. However, our study sample was confined to medical students of 20-28 years which may explain the differences with Sinhalese.

Traffic-related Air Pollution, Lung Function, and Host Vulnerability. New Insights from the PARIS Birth Cohort.

PubMed

Bougas, Nicolas; Rancière, Fanny; Beydon, Nicole; Viola, Malika; Perrot, Xavier; Gabet, Stephan; Lezmi, Guillaume; Amat, Flore; De Blic, Jacques; Just, Jocelyne; Momas, Isabelle

2018-05-01

Although the effects of traffic-related air pollution on respiratory exacerbations have been well documented, its impact on lung function in childhood remains unclear. Our aim was to investigate the associations of prenatal, early, and lifetime traffic-related air pollution exposure with lung function at 8-9 years studying possible effect modification by sex, sensitization at 8-9 years, and early lower respiratory tract infections. We conducted this study among 788 children from the PARIS (Pollution and Asthma Risk: an Infant Study) birth cohort. Lung function tests were performed during the medical examination at 8-9 years. Traffic-related air pollution exposure during each trimester of pregnancy was estimated using nitrogen oxides background measurements. Postnatal traffic-related air pollution exposure was assessed by a nitrogen oxides air dispersion model at both residential and daycare/school addresses. Associations between lung function and traffic-related air pollution exposure were analyzed by multiple linear regression models. Higher prenatal nitrogen oxides levels, especially during the second trimester of pregnancy, were associated with a lower forced expiratory flow at 25-75% of the forced vital capacity, but there were no significant associations between prenatal nitrogen oxide levels and forced vital capacity, forced expiratory volume during 1 second, or the forced expiratory volume during 1 second/forced vital capacity ratio overall. Postnatal traffic-related air pollution exposure was associated with lower lung function among children with early lower respiratory tract infections or sensitization at 8-9 years, but not in the full cohort. In children with early repeated lower respiratory tract infections, an interquartile increase in lifetime nitrogen oxides exposure was associated with both a lower forced expiratory volume during 1 second (-62.6 ml; 95% confidence interval = -107.0 to -18.1) and forced vital capacity (-55.7 ml; 95% confidence interval = -109.5 to -1.8), but was not associated with the forced expiratory volume during 1 second/forced vital capacity ratio. There was an association between greater early postnatal nitrogen oxide exposure and a lower forced expiratory volume during 1 second/forced vital capacity ratio among sensitized children (-0.65%; 95% confidence interval = -1.25 to -0.05). This study sheds new light, suggesting associations between postnatal traffic-related air pollution exposure and reduced lung function may be enhanced by early, repeated lower respiratory tract infections or allergic sensitization.

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.

Relationship between linear and nonlinear dynamics of heart rate and impairment of lung function in COPD patients.

PubMed

Mazzuco, Adriana; Medeiros, Wladimir Musetti; Sperling, Milena Pelosi Rizk; de Souza, Aline Soares; Alencar, Maria Clara Noman; Arbex, Flávio Ferlin; Neder, José Alberto; Arena, Ross; Borghi-Silva, Audrey

2015-01-01

In chronic obstructive pulmonary disease (COPD), functional and structural impairment of lung function can negatively impact heart rate variability (HRV); however, it is unknown if static lung volumes and lung diffusion capacity negatively impacts HRV responses. We investigated whether impairment of static lung volumes and lung diffusion capacity could be related to HRV indices in patients with moderate to severe COPD. Sixteen sedentary males with COPD were enrolled in this study. Resting blood gases, static lung volumes, and lung diffusion capacity for carbon monoxide (DLCO) were measured. The RR interval (RRi) was registered in the supine, standing, and seated positions (10 minutes each) and during 4 minutes of a respiratory sinus arrhythmia maneuver (M-RSA). Delta changes (Δsupine-standing and Δsupine-M-RSA) of the standard deviation of normal RRi, low frequency (LF, normalized units [nu]) and high frequency (HF [nu]), SD1, SD2, alpha1, alpha2, and approximate entropy (ApEn) indices were calculated. HF, LF, SD1, SD2, and alpha1 deltas significantly correlated with forced expiratory volume in 1 second, DLCO, airway resistance, residual volume, inspiratory capacity/total lung capacity ratio, and residual volume/total lung capacity ratio. Significant and moderate associations were also observed between LF/HF ratio versus total gas volume (%), r=0.53; LF/HF ratio versus residual volume, %, r=0.52; and HF versus total gas volume (%), r=-0.53 (P<0.05). Linear regression analysis revealed that ΔRRi supine-M-RSA was independently related to DLCO (r=-0.77, r (2)=0.43, P<0.05). Responses of HRV indices were more prominent during M-RSA in moderate to severe COPD. Moreover, greater lung function impairment was related to poorer heart rate dynamics. Finally, impaired lung diffusion capacity was related to an altered parasympathetic response in these patients.

The Effect of Wood Aerosols and Bioaerosols on the Respiratory Systems of Wood Manufacturing Industry Workers in Golestan Province

PubMed Central

Badirdast, Phateme; Salehpour, Soussan; Ghadjari, Ali; Khodakarim, Soheila; Panahi, Davod; Fadaei, Moslem; Rahimi, Abolfazl

2017-01-01

Background: Occupational exposure to dust leads to acute and chronic respiratory diseases, occupational asthma, and depressed lung function. In the light of a lack of comprehensive studies on the exposure of Iranian workers to wood dusts, the objective of this study was to monitor the occupational exposure to wood dust and bioaerosol, and their correlation with the lung function parameters in chipboard manufacturing industry workers. Materials and Methods: A cross-sectional study was conducted on chipboard workers in Golestan Province; a total of 150 men (100 exposed cases and 50 controls) were assessed. Workers were monitored for inhalable wood dust and lung function parameters, i.e., FVC, FEV1, FEV1/FVC, and FEF25–75%. The workers’ exposure to bioaerosols was measured using a bacterial sampler; a total of 68 area samples were collected. The analysis was performed using the Mann-Whitney, Kruskal-Wallis, and regression statistical tests. Results: The geometric mean value and geometric standard deviation of inhalable wood dust for the exposed and control groups were 19 ± 2.00 mg/m3 and 0.008 ± 0.001 mg/m3, respectively. A statistically significant correlation was observed between the lung parameters and cumulative exposure to inhalable wood dust, whereas a statistically significant correlation was not observed between the lung parameters and bioaerosol exposure. However, the exposure of Iranian workers to bioaerosols was higher, compared to their foreign coworkers. Conclusion: Considering the high level of exposure among workers in this study along with their lung function results, long-term exposure to wood dust may be detrimental to the workers’ health and steps to limit their exposure should be considered seriously. PMID:28638425

Effects of indoor air pollution on lung function of primary school children in Kuala Lumpur

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

Azizi, B.H.; Henry, R.L.

1990-01-01

In a cross-sectional study of 7-12 year-old primary school children in Kuala Lumpur city, lung function was assessed by spirometric and peak expiratory flow measurements. Spirometric and peak expiratory flow measurements were successfully performed in 1,214 and 1,414 children, respectively. As expected, the main predictors of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and peak expiratory flow rate (PEFR) were standing height, weight, age, and sex. In addition, lung function values of Chinese and Malays were generally higher than those of Indians. In multiple regressionmore » models which included host and environmental factors, asthma was associated with significant decreases in FEV1, FEF25-75, and PEFR. However, family history of chest illness, history of allergies, low paternal education, and hospitalization during the neonatal period were not independent predictors of lung function. Children sharing rooms with adult smokers had significantly lower levels of FEF25-75. Exposures to wood or kerosene stoves were, but to mosquito repellents were not, associated with decreased lung function.« less

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.

Pilates Method for Lung Function and Functional Capacity in Obese Adults.

PubMed

Niehues, Janaina Rocha; Gonzáles, Inês; Lemos, Robson Rodrigues; Haas, Patrícia

2015-01-01

Obesity is defined as the condition in which the body mass index (BMI) is ≥ 30 kg/m2 and is responsible for decreased quality of life and functional limitations. The harmful effects on ventilatory function include reduced lung capacity and volume; diaphragmatic muscle weakness; decreased lung compliance and stiffness; and weakness of the abdominal muscles, among others. Pilates is a method of resistance training that works with low-impact muscle exercises and is based on isometric exercises. The current article is a review of the literature that aims to investigate the hypothesis that the Pilates method, as a complementary method of training, might be beneficial to pulmonary function and functional capacity in obese adults. The intent of the review was to evaluate the use of Pilates as an innovative intervention in the respiratory dysfunctions of obese adults. In studies with other populations, it has been observed that Pilates can be effective in improving chest capacity and expansion and lung volume. That finding is due to the fact that Pilates works through the center of force, made ​​up of the abdominal muscles and gluteus muscles lumbar, which are responsible for the stabilization of the static and dynamic body that is associated with breath control. It has been observed that different Pilates exercises increase the activation and recruitment of the abdominal muscles. Those muscles are important in respiration, both in expiration and inspiration, through the facilitation of diaphragmatic action. In that way, strengthening the abdominal muscles can help improve respiratory function, leading to improvements in lung volume and capacity. The results found in the current literature review support the authors' observations that Pilates promotes the strengthening of the abdominal muscles and that improvements in diaphragmatic function may result in positive outcomes in respiratory function, thereby improving functional capacity. However, the authors did not find specific studies with obese people, justifying the need for future studies.

Does current reporting of lung function by the UK cystic fibrosis registry allow a fair comparison of adult centres?

PubMed

Nightingale, Julia Anne; Osmond, Clive

2017-09-01

Outcome data for UK cystic fibrosis centres are publicly available in an annual report, which ranks centres by median FEV 1 % predicted. We wished to assess whether there are differences in lung function outcomes between adult centres that might imply differing standards of care. UK Registry data from 4761 subjects at 34 anonymised adult centres were used to calculate mean FEV 1 % and rate of change of lung function for 2007-13. These measures were used to rank centres and compare outcomes. There are minor differences between centres for mean FEV 1 % for some years of the study and for rate of change of lung function over the study period. However, rankings are critically dependent on the outcome measure chosen and centre variation becomes negligible once patient population characteristics are taken into account. We have demonstrated that the ranking of centres is biased and any apparent difference in respiratory outcomes is unlikely to be related to differing standards of care between centres. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Effects of occupational exposures and smoking on lung function in tile factory workers.

PubMed

Jaakkola, Maritta S; Sripaiboonkij, Penpatra; Jaakkola, Jouni J K

2011-02-01

The aims of this study were to investigate the relations of occupational exposures in tile industry to lung function and to evaluate potential interaction between smoking and tile dust exposure containing silica. A cross-sectional study of 232 workers (response rate 100%) in a tile factory and 76 office workers (response rate 73%) from four factories in Thailand was conducted in 2006-2007. Participants answered a questionnaire and performed spirometry. Factory workers had lower spirometric functions than office workers, especially those with high dust exposure. There was a dose-response relation between duration of dust exposure and FEV1 and FVC, the adjusted effect of ≥ 21 years of exposure on FEV1 being -240 ml (-100 to -380) and on FVC -300 ml (-140 to -460). The adverse effect of dust on lung function was larger in current smokers suggesting synergism between smoking and tile dust exposure. This study provides evidence that long-term exposure to dust in tile industry is related to lung function reduction. There was a suggestion of synergistic effect between dust exposure and smoking. Tile factories should consider measures to reduce dust exposure and arrange spirometry surveillance for workers with such exposure. Smoking cessation should be promoted to prevent harmful effects of occupational tile dust exposure.

Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology

PubMed Central

Hüttemann, Maik; Lee, Icksoo; Gao, Xiufeng; Pecina, Petr; Pecinova, Alena; Liu, Jenney; Aras, Siddhesh; Sommer, Natascha; Sanderson, Thomas H.; Tost, Monica; Neff, Frauke; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Naton, Beatrix; Rathkolb, Birgit; Rozman, Jan; Favor, Jack; Hans, Wolfgang; Prehn, Cornelia; Puk, Oliver; Schrewe, Anja; Sun, Minxuan; Höfler, Heinz; Adamski, Jerzy; Bekeredjian, Raffi; Graw, Jochen; Adler, Thure; Busch, Dirk H.; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Weissmann, Norbert; Doan, Jeffrey W.; Bassett, David J. P.; Grossman, Lawrence I.

2012-01-01

Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial electron transport chain. The purpose of this study was to analyze the function of lung-specific cytochrome c oxidase subunit 4 isoform 2 (COX4i2) in vitro and in COX4i2-knockout mice in vivo. COX was isolated from cow lung and liver as control and functionally analyzed. COX4i2-knockout mice were generated and the effect of the gene knockout was determined, including COX activity, tissue energy levels, noninvasive and invasive lung function, and lung pathology. These studies were complemented by a comprehensive functional screen performed at the German Mouse Clinic (Neuherberg, Germany). We show that isolated cow lung COX containing COX4i2 is about twice as active (88 and 102% increased activity in the presence of allosteric activator ADP and inhibitor ATP, respectively) as liver COX, which lacks COX4i2. In COX4i2-knockout mice, lung COX activity and cellular ATP levels were significantly reduced (−50 and −29%, respectively). Knockout mice showed decreased airway responsiveness (60% reduced Penh and 58% reduced airway resistance upon challenge with 25 and 100 mg methacholine, respectively), and they developed a lung pathology deteriorating with age that included the appearance of Charcot-Leyden crystals. In addition, there was an interesting sex-specific phenotype, in which the knockout females showed reduced lean mass (−12%), reduced total oxygen consumption rate (−8%), improved glucose tolerance, and reduced grip force (−14%) compared to wild-type females. Our data suggest that high activity lung COX is a central determinant of airway function and is required for maximal airway responsiveness and healthy lung function. Since airway constriction requires energy, we propose a model in which reduced tissue ATP levels explain protection from airway hyperresponsiveness, i.e., absence of COX4i2 leads to reduced lung COX activity and ATP levels, which results in impaired airway constriction and thus reduced airway responsiveness; long-term lung pathology develops in the knockout mice due to impairment of energy-costly lung maintenance processes; and therefore, we propose mitochondrial oxidative phosphorylation as a novel target for the treatment of respiratory diseases, such as asthma.—Hüttemann, M., Lee, I., Gao, X., Pecina, P., Pecinova, A., Liu, J., Aras, S., Sommer, N., Sanderson, T. H., Tost, M., Neff, F., Aguilar-Pimentel, J. A., Becker, L., Naton, B., Rathkolb, B., Rozman, J., Favor, J., Hans, W., Prehn, C., Puk, O., Schrewe, A., Sun, M., Höfler, H., Adamski, J., Bekeredjian, R., Graw, J., Adler, T., Busch, D. H., Klingenspor, M., Klopstock, T., Ollert, M., Wolf, E., Fuchs, H., Gailus-Durner, V., Hrabě de Angelis, M., Weissmann, N., Doan, J. W., Bassett, D. J. P., Grossman, L. I. Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology. PMID:22730437

Pulmonary preservation studies: effects on endothelial function and pulmonary adenine nucleotides.

PubMed

Paik, Hyo Chae; Hoffmann, Steven C; Egan, Thomas M

2003-02-27

Lung transplantation is an effective therapy plagued by a high incidence of early graft dysfunction, in part because of reperfusion injury. The optimal preservation solution for lung transplantation is unknown. We performed experiments using an isolated perfused rat lung model to test the effect of lung preservation with three solutions commonly used in clinical practice. Lungs were retrieved from Sprague-Dawley rats and flushed with one of three solutions: modified Euro-Collins (MEC), University of Wisconsin (UW), or low potassium dextran and glucose (LPDG), then stored cold for varying periods before reperfusion with Earle's balanced salt solution using the isolated perfused rat lung model. Outcome measures were capillary filtration coefficient (Kfc), wet-to-dry weight ratio, and lung tissue levels of adenine nucleotides and cyclic AMP. All lungs functioned well after 4 hr of storage. By 6 hr, UW-flushed lungs had a lower Kfc than LPDG-flushed lungs. After 8 hr of storage, only UW-flushed lungs had a measurable Kfc. Adenine nucleotide levels were higher in UW-flushed lungs after prolonged storage. Cyclic AMP levels correlated with Kfc in all groups. Early changes in endothelial permeability seemed to be better attenuated in lungs flushed with UW compared with LPDG or MEC; this was associated with higher amounts of adenine nucleotides. MEC-flushed lungs failed earlier than LPDG-flushed or UW-flushed lungs. The content of the solution may be more important for lung preservation than whether the ionic composition is intracellular or extracellular.

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

PubMed

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

2014-01-01

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

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

PubMed Central

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

2014-01-01

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

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.

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.

Lung Oxidative Damage by Hypoxia

PubMed Central

Araneda, O. F.; Tuesta, M.

2012-01-01

One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described. PMID:22966417

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.

The effect of lung volume reduction surgery on chronic obstructive pulmonary disease exacerbations.

PubMed

Washko, George R; Fan, Vincent S; Ramsey, Scott D; Mohsenifar, Zab; Martinez, Fernando; Make, Barry J; Sciurba, Frank C; Criner, Gerald J; Minai, Omar; Decamp, Malcolm M; Reilly, John J

2008-01-15

Lung volume reduction surgery (LVRS) has been demonstrated to provide a functional and mortality benefit to a select group of subjects with chronic obstructive pulmonary disease (COPD). The effect of LVRS on COPD exacerbations has not been as extensively studied, and whether improvement in postoperative lung function alters the risk of disease exacerbations is not known. To examine the effect, and mechanism of potential benefit, of LVRS on COPD exacerbations by comparing the medical and surgical cohorts of the National Emphysema Treatment Trial (NETT). A COPD exacerbation was defined using Centers for Medicare and Medicaid Services data and International Classification of Diseases, Ninth Revision, discharge diagnosis. There was no difference in exacerbation rate or time to first exacerbation between the medical and surgical cohorts during the year before study randomization (P = 0.58 and 0.85, respectively). Postrandomization, the surgical cohort experienced an approximate 30% reduction in exacerbation frequency (P = 0.0005). This effect was greatest in those subjects with the largest postoperative improvement in FEV(1) (P = 0.04) when controlling for changes in other spirometric measures of lung function, lung capacities, and room air arterial blood gas tensions. Finally, LVRS increased the time to first exacerbation in both those subjects with and those without a prior history of exacerbations (P = 0.0002 and P < 0.0001, respectively). LVRS reduces the frequency of COPD exacerbations and increases the time to first exacerbation. One explanation for this benefit may be the postoperative improvement in lung function.

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

PubMed

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

2014-11-01

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

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.

Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

PubMed Central

Ljungman, Petter L.; Wilker, Elissa H.; Gold, Diane R.; Schwartz, Joel D.; Koutrakis, Petros; Washko, George R.; O’Connor, George T.; Mittleman, Murray A.

2013-01-01

Rationale: Short-term exposure to ambient air pollution has been associated with lower lung function. Few studies have examined whether these associations are detectable at relatively low levels of pollution within current U.S. Environmental Protection Agency (EPA) standards. Objectives: To examine exposure to ambient air pollutants within EPA standards and lung function in a large cohort study. Methods: We included 3,262 participants of the Framingham Offspring and Third Generation cohorts living within 40 km of the Harvard Supersite monitor in Boston, Massachusetts (5,358 examinations, 1995–2011) who were not current smokers, with previous-day pollutant levels in compliance with EPA standards. We compared lung function (FEV1 and FVC) after previous-day exposure to particulate matter less than 2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in the “moderate” range of the EPA Air Quality Index to exposure in the “good” range. We also examined linear relationships between moving averages of pollutant concentrations 1, 2, 3, 5, and 7 days before spirometry and lung function. Measurements and Main Results: Exposure to pollutant concentrations in the “moderate” range of the EPA Air Quality Index was associated with a 20.1-ml lower FEV1 for PM2.5 (95% confidence interval [CI], −33.4, −6.9), a 30.6-ml lower FEV1 for NO2 (95% CI, −60.9, −0.2), and a 55.7-ml lower FEV1 for O3 (95% CI, −100.7, −10.8) compared with the “good” range. The 1- and 2-day moving averages of PM2.5, NO2, and O3 before testing were negatively associated with FEV1 and FVC. Conclusions: Short-term exposure to PM2.5, NO2, and O3 within current EPA standards was associated with lower lung function in this cohort of adults. PMID:24200465

A long term study of pulmonary function among US refractory ceramic fibre workers

PubMed Central

LeMasters, Grace K; Hilbert, Timothy J; Levin, Linda S; Rice, Carol H; Borton, Eric K; Lockey, James E

2010-01-01

Background Cross-sectional studies have shown declines in lung function among refractory ceramic fibre (RCF) workers with increasing fibre exposure. This study followed current and former workers (n=1396) for up to 17 years and collected 5243 pulmonary function tests. Methods Cumulative fibre exposure and production years were categorised into exposure levels at five manufacturing locations. Conventional longitudinal models did not adequately partition age-related changes from other time-dependent variables. Therefore, a restricted cubic spline model was developed to account for the non-linear decline with age. Results Cumulative fibre >60 fibre-months/cc showed a significant loss in lung function at the first test. When results were examined longitudinally, cumulative exposure was confounded with age as workers with the highest cumulative exposure were generally older. A longitudinal model adjusted by age groups was implemented to control for this confounding. No consistent longitudinal loss in lung function was observed with RCF exposure. Smoking, initial weight and weight increase were significant factors. Conclusion No consistent decline was observed longitudinally with exposure to RCF, although cross-sectional and longitudinal findings were discordant. Confounding and accelerated lung function declines with ageing and the correlation of multiple time-dependent variables should be considered in order to minimise error and maximise precision. An innovative statistical methodology for these types of data is described. PMID:20798015

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.

Effect of phrenic nerve palsy on early postoperative lung function after pneumonectomy: a prospective study.

PubMed

Kocher, Gregor J; Mauss, Karl; Carboni, Giovanni L; Hoksch, Beatrix; Kuster, Roland; Ott, Sebastian R; Schmid, Ralph A

2013-12-01

The issue of phrenic nerve preservation during pneumonectomy is still an unanswered question. So far, its direct effect on immediate postoperative pulmonary lung function has never been evaluated in a prospective trial. We conducted a prospective crossover study including 10 patients undergoing pneumonectomy for lung cancer between July 2011 and July 2012. After written informed consent, all consecutive patients who agreed to take part in the study and in whom preservation of the phrenic nerve during operation was possible, were included in the study. Upon completion of lung resection, a catheter was placed in the proximal paraphrenic tissue on the pericardial surface. After an initial phase of recovery of 5 days all patients underwent ultrasonographic assessment of diaphragmatic motion followed by lung function testing with and without induced phrenic nerve palsy. The controlled, temporary paralysis of the ipsilateral hemidiaphragm was achieved by local administration of lidocaine 1% at a rate of 3 mL/h (30 mg/h) via the above-mentioned catheter. Temporary phrenic nerve palsy was accomplished in all but 1 patient with suspected catheter dislocation. Spirometry showed a significant decrease in dynamic lung volumes (forced expiratory volume in 1 second and forced vital capacity; p < 0.05) with the paralyzed hemidiaphragm. Blood oxygen saturation levels did not change significantly. Our results show that phrenic nerve palsy causes a significant impairment of dynamic lung volumes during the early postoperative period after pneumonectomy. Therefore, in these already compromised patients, intraoperative phrenic nerve injury should be avoided whenever possible. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Gastroesophageal reflux symptoms are not sufficient to guide esophageal function testing in lung transplant candidates.

PubMed

Posner, S; Zheng, J; Wood, R K; Shimpi, R A; Hartwig, M G; Chow, S-C; Leiman, D A

2018-05-01

Gastroesophageal reflux disease and esophageal dysmotility are prevalent in patients with advanced lung disease and are associated with graft dysfunction following lung transplantation. As a result, many transplant centers perform esophageal function testing as part of the wait-listing process but guidelines for testing in this population are lacking. The aim of this study is to describe whether symptoms of gastroesophageal reflux correlate with abnormal results on pH-metry and high-resolution manometry and can be used to identify those who require testing. We performed a retrospective cohort study of 226 lung transplant candidates referred for high-resolution manometry and pH-metry over a 12-month period in 2015. Demographic data, results of a standard symptom questionnaire and details of esophageal function testing were obtained. Associations between the presence of symptoms and test results were analyzed using Fisher's exact tests and multivariable logistic regression. The most common lung disease diagnosis was interstitial lung disease (N = 131, 58%). Abnormal pH-metry was seen in 116 (51%) patients and the presence of symptoms was significantly associated with an abnormal study (p < 0.01). Dysmotility was found in 98 (43%) patients, with major peristaltic or esophageal outflow disorders in 45 (20%) patients. Symptoms were not correlated with findings on esophageal high-resolution manometry. Fifteen of 25 (60%) asymptomatic patients had an abnormal manometry or pH-metry. These results demonstrate that in patients with advanced lung disease, symptoms of gastroesophageal reflux increase the likelihood of elevated acid exposure on pH-metry but were not associated with dysmotility. Given the proportion of asymptomatic patients with abnormal studies and associated post-transplant risks, a practice of universal high-resolution manometry and pH-metry testing in this population is justifiable.

Metal dust exposure and lung function deterioration among steel workers: an exposure-response relationship

PubMed Central

Hamzah, Nurul Ainun; Mohd Tamrin, Shamsul Bahri; Ismail, Noor Hassim

2016-01-01

Background Metallic dust is a heterogeneous substance with respiratory sensitizing properties. Its long term exposure adversely affected lung function, thus may cause acute or chronic respiratory diseases. Methods A cross-sectional study was conducted in a steel factory in Terengganu, Malaysia to assess the metal dust exposure and its relationship to lung function values among 184 workers. Metal dust concentrations values (Co, Cr, and Ni) for each worker were collected using air personal sampling. Lung function values (FEV1, FVC, and %FEV1/FVC) were determined using spirometer. Results Exposure to cobalt and chromium were 1–3 times higher than permissible exposure limit (PEL) while nickel was not exceeding the PEL. Cumulative of chromium was the predictor to all lung function values (FEV1, FVC, and %FEV1/FVC). Frequency of using mask was positively associated with FVC (Adj b = 0.263, P = 0.011) while past respiratory illnesses were negatively associated with %FEV1/FVC (Adj b = –1.452, P = 0.026). Only few workers (36.4%) were found to wear their masks all times during the working hours. Conclusions There was an exposure-response relationship of cumulative metal dust exposure with the deterioration of lung function values. Improvement of control measures as well as proper and efficient use or personal protection equipment while at work could help to protect the respiratory health of workers. PMID:27392157

The significance and robustness of a plasma free amino acid (PFAA) profile-based multiplex function for detecting lung cancer

PubMed Central

2013-01-01

Background We have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a PFAA-based, multivariate discrimination index for the early detection of lung cancer. In this study, we aimed to verify the usefulness and robustness of PFAA profiling for detecting lung cancer using new test samples. Methods Plasma samples were collected from 171 lung cancer patients and 3849 controls without apparent cancer. PFAA levels were measured by high-performance liquid chromatography (HPLC)–electrospray ionization (ESI)–mass spectrometry (MS). Results High reproducibility was observed for both the change in the PFAA profiles in the lung cancer patients and the discriminating performance for lung cancer patients compared to previously reported results. Furthermore, multivariate discriminating functions obtained in previous studies clearly distinguished the lung cancer patients from the controls based on the area under the receiver-operator characteristics curve (AUC of ROC = 0.731 ~ 0.806), strongly suggesting the robustness of the methodology for clinical use. Moreover, the results suggested that the combinatorial use of this classifier and tumor markers improves the clinical performance of tumor markers. Conclusions These findings suggest that PFAA profiling, which involves a relatively simple plasma assay and imposes a low physical burden on subjects, has great potential for improving early detection of lung cancer. PMID:23409863

Unilateral lung transplantation for pulmonary fibrosis.

PubMed

1986-05-01

Improvements in immunosuppression and surgical techniques have made unilateral lung transplantation feasible in selected patients with end-stage interstitial lung disease. We report two cases of successful unilateral lung transplantation for end-stage respiratory failure due to pulmonary fibrosis. The patients, both oxygen-dependent, had progressive disease refractory to all treatment, with an anticipated life expectancy of less than one year on the basis of the rate of progression of the disease. Both patients were discharged six weeks after transplantation and returned to normal life. They are alive and well at 26 months and 14 months after the procedure. Pulmonary-function studies have shown substantial improvement in their lung volumes and diffusing capacities. For both patients, arterial oxygen tension is now normal and there is no arterial oxygen desaturation with exercise. This experience shows that unilateral lung transplantation, for selected patients with end-stage interstitial lung disease, provides a good functional result. Moreover, it avoids the necessity for cardiac transplantation, as required by the combined heart-lung procedure, and permits the use of the donor heart for another recipient.

No effect of artificial gravity on lung function with exercise training during head-down bed rest

NASA Astrophysics Data System (ADS)

Su, Longxiang; Guo, Yinghua; Wang, Yajuan; Wang, Delong; Liu, Changting

2016-04-01

The aim of this study is to explore the effectiveness of microgravity simulated by head-down bed rest (HDBR) and artificial gravity (AG) with exercise on lung function. Twenty-four volunteers were randomly divided into control and exercise countermeasure (CM) groups for 96 h of 6° HDBR. Comparisons of pulse rate, pulse oxygen saturation (SpO2) and lung function were made between these two groups at 0, 24, 48, 72, 96 h. Compared with the sitting position, inspiratory capacity and respiratory reserve volume were significantly higher than before HDBR (0° position) (P < 0.05). Vital capacity, expiratory reserve volume, forced vital capacity, forced expiratory volume in 1 s, forced inspiratory vital capacity, forced inspiratory volume in 1 s, forced expiratory flow at 25, 50, and 75%, maximal mid-expiratory flow and peak expiratory flow were all significantly lower than those before HDBR (P < 0.05). Neither control nor CM groups showed significant differences in pulse rate, SpO2, pulmonary volume and pulmonary ventilation function over the HDBR observation time. Postural changes can lead to variation in lung volume and ventilation function, but a HDBR model induced no changes in pulmonary function and therefore should not be used to study AG countermeasures.

A Psychometric Analysis of Quality of Life Tools in Lung Cancer Patients Who Smoke

PubMed Central

Browning, Kristine K.; Ferketich, Amy K.; Otterson, Gregory A.; Reynolds, Nancy R.; Wewers, Mary Ellen

2009-01-01

Lung cancer is the leading cause of cancer death for both men and women in the United States. Patient quality of life (QOL) prior to cancer treatment is known to be a strong predictor of survival and toleration of treatment toxicities. A lung cancer patient’s self-assessment of QOL is highly valued among clinicians as it guides treatment-related decisions and impacts clinical outcomes. Smokers are known to report a lower QOL. Limited research has been conducted on QOL outcomes in lung cancer patients who continue to smoke. To assess QOL, a reliable and valid QOL measure specific to lung cancer is required. The Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L) and Lung Cancer Symptom Scale (LCSS) are instruments that specifically examine QOL among lung cancer patients. The LCSS is a focused QOL instrument that includes physical and functional domains of QOL and disease symptomatology. The FACT-L is a broader QOL instrument that includes physical, functional, social and emotional domains and disease symptomatology. Both are psychometrically valid and are widely used in the literature, but have not been exclusively evaluated in smokers. Furthermore, there is no ‘gold standard’ instrument since there has never been a correlation study to compare estimates of reliability and validity between these instruments. The purpose of this study is to report the internal consistency and convergence validity of the FACT-L and the LCSS among newly diagnosed lung cancer patients who smoke. This data were collected and analyzed from a larger study examining smoking behavior among newly diagnosed lung cancer patients (n=51). Descriptive statistics were calculated on the FACT-L and LCSS scores, internal consistency was assessed by estimating Cronbach’s alpha coefficients, and Pearson correlation coefficients were estimated between the two scales. Internal consistency coefficients demonstrated good reliability for both scales, and the two instruments demonstrated a strong correlation, suggesting good convergence validity. Either of these instruments are appropriate measures for QOL in lung cancer patients who smoke. Given the conceptual difference between the two instruments, it is important to carefully consider the research aims when selecting the appropriate QOL measurement instrument. PMID:19181418

Evidence for a Cystic Fibrosis Enteropathy

PubMed Central

Adriaanse, Marlou P. M.; van der Sande, Linda J. T. M.; van den Neucker, Anita M.; Menheere, Paul P. C. A.; Dompeling, Edward; Buurman, Wim A.; Vreugdenhil, Anita C. E.

2015-01-01

Background Previous studies have suggested the existence of enteropathy in cystic fibrosis (CF), which may contribute to intestinal function impairment, a poor nutritional status and decline in lung function. This study evaluated enterocyte damage and intestinal inflammation in CF and studied its associations with nutritional status, CF-related morbidities such as impaired lung function and diabetes, and medication use. Methods Sixty-eight CF patients and 107 controls were studied. Levels of serum intestinal-fatty acid binding protein (I-FABP), a specific marker for enterocyte damage, were retrospectively determined. The faecal intestinal inflammation marker calprotectin was prospectively studied. Nutritional status, lung function (FEV1), exocrine pancreatic insufficiency (EPI), CF-related diabetes (CFRD) and use of proton pump inhibitors (PPI) were obtained from the medical charts. Results Serum I-FABP levels were elevated in CF patients as compared with controls (p<0.001), and correlated negatively with FEV1 predicted value in children (r-.734, p<0.05). Faecal calprotectin level was elevated in 93% of CF patients, and correlated negatively with FEV1 predicted value in adults (r-.484, p<0.05). No correlation was found between calprotectin levels in faeces and sputum. Faecal calprotectin level was significantly associated with the presence of CFRD, EPI, and PPI use. Conclusion This study demonstrated enterocyte damage and intestinal inflammation in CF patients, and provides evidence for an inverse correlation between enteropathy and lung function. The presented associations of enteropathy with important CF-related morbidities further emphasize the clinical relevance. PMID:26484665

Higher mobility scores in patients with cystic fibrosis are associated with better lung function.

PubMed

Thobani, Aneesha; Alvarez, Jessica A; Blair, Shaina; Jackson, Kaila; Gottlieb, Eric R; Walker, Seth; Tangpricha, Vin

2015-01-01

The purpose of this study was to determine whether mobility and physical activity were associated with lung function in adults with cystic fibrosis (CF). This was a prospective cohort observational study in an urban, academic, specialized care center. Participants were ambulatory, nonhospitalized adults with CF. Mobility was assessed monthly by the Life-Space Assessment (LSA) questionnaire and quarterly by pedometer. Lung function was assessed by spirometry. Twenty-seven subjects participated. Subjects recorded mean pedometer steps of 20,213 ± 11,331 over three days and FEV1% predicted of 77.48% ± 22.60% over one year. The LSA score at enrollment was correlated with initial pedometer steps (r = 0.42 and P = 0.03), and mean LSA score over one year was correlated with mean number of steps (r = 0.51 and P = 0.007). LSA mobility and pedometer scores were correlated with FEV1% predicted at enrollment and throughout the study. Mobility and physical activity measured by LSA questionnaire and pedometer are positively associated with lung function in adults with CF. This study confirms the importance of mobility and physical activity and supports the utility of a simple office-based questionnaire as a measure of mobility in adults with CF.

Association between spirometry controlled chest CT scores using computer-animated biofeedback and clinical markers of lung disease in children with cystic fibrosis.

PubMed

Kongstad, Thomas; Green, Kent; Buchvald, Frederik; Skov, Marianne; Pressler, Tania; Nielsen, Kim Gjerum

2017-01-01

Background : Computed tomography (CT) of the lungs is the gold standard for assessing the extent of structural changes in the lungs. Spirometry-controlled chest CT (SCCCT) has improved the usefulness of CT by standardising inspiratory and expiratory lung volumes during imaging. This was a single-centre cross-sectional study in children with cystic fibrosis (CF). Using SCCCT we wished to investigate the association between the quantity and extent of structural lung changes and pulmonary function outcomes, and prevalence of known CF lung pathogens. Methods : CT images were analysed by CF-CT scoring (expressed as % of maximum score) to quantify different aspects of structural lung changes including bronchiectasis, airway wall thickening, mucus plugging, opacities, cysts, bullae and gas trapping. Clinical markers consisted of outcomes from pulmonary function tests, microbiological cultures from sputum and serological samples reflecting anti-bacterial and anti-fungal antibodies. Results : Sixty-four children with CF, median age (range) of 12.7 (6.4-18.1) years, participated in the study. The median (range) CF-CT total score in all children was 9.3% (0.4-46.8) with gas trapping of 40.7% (3.7-100) as the most abundant finding. Significantly higher median CF-CT total scores (21.9%) were found in patients with chronic infections ( N  = 12) including Gram-negative infection and allergic bronchopulmonary aspergillosis (ABPA) exhibiting CF-CT total scores of 14.2% (ns) and 24.0% ( p  < 0.01), respectively, compared to 8.0% in patients with no chronic lung infection. Lung clearance index (LCI) derived from multiple breath washout exhibited closest association with total CF-CT scores, compared to other pulmonary function outcomes. Conclusions : The most prominent structural lung change was gas trapping, while CF-CT total scores were generally low, both showing close association with LCI. Chronic lung infections, specifically in the form of ABPA, were associated with increased scores in lung changes. Further investigation of impact of infections with different microorganisms on extent and progression of structural CF lung disease is needed.

WE-FG-206-07: Assessing the Lung Function of Patients with Non-Small Cell Lung Cancer Using Hyperpolarized Xenon-129 Dissolved-Phase MRI

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

Qing, K; Mugler, J; Chen, Q

Purpose: Hyperpolarized xenon-129 dissolved-phase MRI is the first imaging technique that allows 3-dimensional regional mapping of ventilation and gas uptake by tissue and blood the in human lung. Multiple outcome measures can be produced from this method. Existing studies in subjects with major lung diseases compared to healthy controls demonstrated high sensitivities of this method to pulmonary physiological factors including ventilation, alveolar tissue density, surface-to-volume ratio, pulmonary perfusion and gas-blood barrier thickness. The purpose of this study is to evaluate the utility of this new imaging tool to assess the lung function in patients with non-small cell lung cancer (NSCLC).more » Methods: Ten healthy controls (age: 63±10) and five patients (age: 62±13) with NSCLC underwent the xenon-129 dissolved-phase MRI, pulmonary function test (PFT) and CT for clinical purpose. Three outcome measures were produced from xenon-129 dissolved-phase MRI, including ventilation defect fraction (Vdef%) reflecting the airflow obstruction, tissue-to-gas ratio reflecting lung tissue density, and RBC-to-tissue ratio reflecting pulmonary perfusion and gas exchange. Results: Compared to healthy controls, patients with NSCLC showed more ventilation defects (NSCLC: 22±6%; control: 40±18%; P=0.01), lower tissue-to-gas (NSCLC: 0.82±0.31%; control: 1.07±0.13%; P=0.05) and RBC-to-tissue ratios (NSCLC: 0.82±0.31%; control: 1.07±0.13%; P=0.01). Maps for ventilation and gas uptake by tissue and blood were highly heterogeneous in the lungs of patients. Vdef% and RBC-to-tissue ratios in all 15 subjects correlated with corresponding global lung functional measures from PFT: FEV1/FVC (R=−0.91, P<0.001) and DLCO % predicted (R=0.54, P=0.03), respectively. The tissue-to-gas ratios correlated with tissue density (HU) measured by CT (R=0.88, P<0.001). Conclusion: With the unique ability to provide detailed information about lung function including ventilation, tissue density, perfusion and gas exchange with 3D resolution, hyperpolarized xenon-129 dissolved-phase MRI has high potential to be used as an important reference for radiotherapy treatment planning and for evaluating the side effects of the treatment. Receive research support and funding from Siemens.« less

Cavin1; a Regulator of Lung Function and Macrophage Phenotype

PubMed Central

Govender, Praveen; Romero, Freddy; Shah, Dilip; Paez, Jesus; Ding, Shi-Ying; Liu, Libin; Gower, Adam; Baez, Elizabeth; Aly, Sherif Shawky; Pilch, Paul; Summer, Ross

2013-01-01

Caveolae are cell membrane invaginations that are highly abundant in adipose tissue, endothelial cells and the lung. The formation of caveolae is dependent on the expression of various structural proteins that serve as scaffolding for these membrane invaginations. Cavin1 is a newly identified structural protein whose deficiency in mice leads to loss of caveolae formation and to development of a lipodystrophic phenotype. In this study, we sought to investigate the functional role of Cavin1 in the lung. Cavin1 deficient mice possessed dramatically altered distal lung morphology and exhibited significant physiological alterations, notably, increased lung elastance. The changes in distal lung architecture were associated with hypercellularity and the accumulation of lung macrophages. The increases in lung macrophages occurred without changes to circulating numbers of mononuclear cells and without evidence for increased proliferation. However, the increases in lung macrophages were associated with higher levels of macrophage chemotactic factors CXCL2 and CCL2 in BAL fluid from Cavin1−/− mice suggesting a possible mechanism by which these cells accumulate. In addition, lung macrophages from Cavin1−/− mice were larger and displayed measurable differences in gene expression when compared to macrophages from wild-type mice. Interestingly, macrophages were also increased in adipose tissue but not in liver, kidney or skeletal muscle from Cavin1−/− mice, and similar tissue specificity for macrophage accumulation was observed in lungs and adipose tissue from Caveolin1−/− mice. In conclusion, this study demonstrates an important role for Cavin1 in lung homeostasis and suggests that caveolae structural proteins are necessary for regulating macrophage number and phenotype in the lung. PMID:23634221

Lung function reductions associated with motor vehicle density in chronic obstructive pulmonary disease: a cross-sectional study.

PubMed

Nitschke, Monika; Appleton, Sarah L; Li, Qiaoyu; Tucker, Graeme R; Shah, Pushan; Bi, Peng; Pisaniello, Dino L; Adams, Robert J

2016-10-24

Motor vehicle-related air pollution can potentially impair lung function. The effect of pollution in people with compromised pulmonary function such as in COPD has not been previously investigated. To examine the association of lung function with motor vehicle density in people with spirometrically determined COPD in a cross-sectional study. In 2004-06, The North West Adelaide Health Study (NWAHS), a biomedical cohort of adults assessed pre and post-bronchodilator spirometry (n = 3,103). Traffic density, obtained from the motor vehicle inventory maintained by the South Australian Environment Protection Authority, was expressed as the daily numbers of vehicles travelling within a 200 m diameter zone around participants' geocoded residences. In subjects with COPD (FEV 1 /FVC <0.7, n = 221, 7.1 %), increasing daily vehicle density was associated with statistically significant decreases in lung function parameters after adjustment for smoking and socio-economic variables. Mean (95 % CI) post-bronchodilator % predicted FEV 1 was 81 % (76-87) in the low (≤7179/day) compared with 71 % (67-75) in the high (≥15,270/day) vehicle exposure group (p < 0.05). Linear regression analysis in all subjects with COPD showed significant decrements in post-bronchodilator FEV 1 /FVC ratio and % predicted FEV 1 of 0.03 and 0.05 % respectively per daily increase in 1000 vehicles. In men with COPD (n = 150), the corresponding reductions were 0.03 and 0.06 %. Smaller, non-significant decrements were seen in females. No difference was seen in those without COPD. Vehicle traffic density was associated with significant reductions in lung function in people with COPD. Urban planning should consider the health impacts for those with pre-existing respiratory conditions.

Self-reported physical activity and lung function two months after cardiac surgery – a prospective cohort study

PubMed Central

2014-01-01

Background Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Methods Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health’s national survey. Formal lung function testing was performed preoperatively and two months postoperatively. Results The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). Conclusions An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results. PMID:24678691

Farm environment during infancy and lung function at the age of 31: a prospective birth cohort study in Finland.

PubMed

Lampi, Jussi; Koskela, Heikki; Hartikainen, Anna-Liisa; Ramasamy, Adaikalavan; Couto Alves, Alexessander; Järvelin, Marjo-Riitta; Pekkanen, Juha

2015-07-22

Farming as an occupation is considered a risk factor for asthma and reduced lung function. By contrast, living on a farm during infancy has been reported to be associated with lower risk of asthma in adulthood. However, little is known about the association between farming environment during infancy and lung function in adulthood. We aimed to study the prospective longitudinal association between farming environment during infancy and lung function in adulthood. A prospective birth cohort study. Northern Finland. 5666 participants born in 1966 were followed up at the age of 31 years. Spirometry at the age of 31 years. To be born into a farmer's family was associated with higher forced expiratory volume in 1 s (FEV1) (36 mL; 95% CI 6 to 67 mL) and forced vital capacity (FVC) (40 mL; 95% CI 5 to 75 mL) at the age of 31 years. Contact with farm animals during infancy was associated with higher FEV1. No associations were seen with FEV1/FVC (FEV1/FVC ratio). Having dogs in childhood revealed similar associations. There was a suggestive dose-dependent association with the number of animal species during childhood and higher FEV1 and FVC at adulthood, especially among women. Farming environment in early life may have a positive impact on lung function in adulthood. 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.

The effects of indoor pollution on Arizona children

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

Dodge, R.

1982-05-01

The respiratory health of a large group of Arizona school children who have been exposed to indoor pollutants-tobacco smoke and home cooking fumes-is reported. A significant relationship was found between parental smoking and symptoms of cough, wheeze, and sputum production. Also, children in homes where gas cooking fuel was used had higher rates of cough than children in homes where electricity was used. No differences in pulmonary function or yearly lung growth rates occurred among subjects grouped by exposure to tobacco smoke or cooking fuel. Thus, parental smoking and home cooking fuel affected cross-sectional respiratory symptom rates in a largemore » group of Arizona school children. Study of pulmonary function, however, revealed no lung function or lung growth effects during 4 yr of study.« less

Genetic variant in the 3'-untranslated region of VEGFR1 gene influences chronic obstructive pulmonary disease and lung cancer development in Chinese population.

PubMed

Wang, Hui; Yang, Lei; Deng, Jieqiong; Wang, Bo; Yang, Xiaorong; Yang, Rongrong; Cheng, Mei; Fang, Wenxiang; Qiu, Fuman; Zhang, Xin; Ji, Weidong; Ran, Pixin; Zhou, Yifeng; Lu, Jiachun

2014-09-01

Lung inflammation and epithelial to mesenchymal transition (EMT) are two pathogenic features for the two contextual diseases: chronic obstructive pulmonary disease (COPD) and lung cancer. VEGFR1 (or FLT1) plays a certain role in promoting tumour growth, inflammation and EMT. To simultaneously test the association between the single nucleotide polymorphisms (SNPs) in VEGFR1 and risk of COPD and lung cancer would reveal genetic mechanisms shared by these two diseases and joint aetiology. We conducted a two-population hospital-based case-control study. Three potential functional SNPs (rs664393, rs7326277 and rs9554314) were genotyped in southern Chinese and validated in eastern Chinese to explore their associations with COPD risk in 1511 COPD patients and 1677 normal lung function controls, and with lung cancer risk in 1559 lung cancer cases and 1679 cancer-free controls. We also detected the function of the promising SNP. Individuals carrying the rs7326277C (CT+CC) variant genotypes of VEGFR1 had a significant decrease in risk of both COPD (OR = 0.78; 95% CI = 0.68-0.90) and lung cancer (OR = 0.79; 95% CI = 0.64-0.98), compared with those carrying the rs7326277TT genotype. Functional assays further showed that the rs7326277C genotypes had lower transcriptional activity and caused decreased VEGFR expression, compared with the rs7326277TT genotype. However, no significant association was observed for the other two SNPs (rs664393 and rs9554314) and either COPD or lung cancer risk. Our data suggested that the rs7326277C variant of VEGFR1 could reduce both COPD and lung cancer risk by lowering VEGFR1 mRNA expression; the SNP might be a common susceptible locus for both COPD and lung cancer. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Precision cut lung slices as an efficient tool for in vitro lung physio-pharmacotoxicology studies.

PubMed

Morin, Jean-Paul; Baste, Jean-Marc; Gay, Arnaud; Crochemore, Clément; Corbière, Cécile; Monteil, Christelle

2013-01-01

1.We review the specific approaches for lung tissue slices preparation and incubation systems and the research application fields in which lung slices proved to be a very efficient alternative to animal experimentation for biomechanical, physiological, pharmacological and toxicological approaches. 2.Focus is made on air-liquid interface dynamic organ culture systems that allow direct tissue exposure to complex aerosol and that best mimic in vivo lung tissue physiology. 3.A compilation of research applications in the fields of vascular and airway reactivity, mucociliary transport, polyamine transport, xenobiotic biotransformation, chemicals toxicology and complex aerosols supports the concept that precision cut lung slices are a very efficient tool maintaining highly differentiated functions similar to in vivo lung organ when kept under dynamic organ culture. They also have been successfully used for lung gene transfer efficiency assessment, for lung viral infection efficiency assessment, for studies of tissue preservation media and tissue post-conditioning to optimize lung tissue viability before grafting. 4.Taken all together, the reviewed studies point to a great interest for precision cut lung slices as an efficient and valuable alternative to in vivo lung organ experimentation.

Effect of prolonged bed rest on lung volume in normal individuals

NASA Technical Reports Server (NTRS)

Beckett, W. S.; Vroman, N. B.; Nigro, D.; Thompson-Gorman, S.; Wilkerson, J. E.

1986-01-01

The effect of prolonged bed rest on the lung function was studied by measuring forced vital capacity (FVC) and total lung capacity (TLC) in normal subjects before, during, and after 11- to 12-day rest periods. It was found that both FVC and TLC increased during bed rest (compared with the ambulatory controls), while residual volume and functional residual capacity of the respiratory system did not change. It is concluded that the increase in TLC by prolonged bed rest is not dependent on alterations in plasma volume.

Modeling pressure relationships of inspired air into the human lung bifurcations through simulations

NASA Astrophysics Data System (ADS)

Aghasafari, Parya; Ibrahim, Israr B. M.; Pidaparti, Ramana

2018-03-01

Applied pressure on human lung wall has great importance on setting up protective ventilatory strategies, therefore, estimating pressure relationships in terms of specific parameters would provide invaluable information specifically during mechanical ventilation (MV). A three-dimensional model from a healthy human lung MRI is analyzed by computational fluid dynamic (CFD), and results for pressure are curve fitted to estimate relationships that associate pressure to breathing time, cross section and generation numbers of intended locations. Among all possible functions, it is observed that exponential and polynomial pressure functions present most accurate results for normal breathing (NB) and MV, respectively. For validation, pressure-location curves from CFD and results from this study are compared and good correlations are found. Also, estimated pressure values are used to calculate pressure drop and airway resistance to the induced air into the lung bifurcations. It is concluded that maximum pressure drop appeared in generation number 2 and medium sized airways show higher resistance to air flow and that resistance decreased as cross sectional area increased through the model. Results from this study are in good agreement with previous studies and provide potentials for further studies on influence of air pressure on human lung tissue and reducing lung injuries during MV.

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

Outcome of influenza infection managed with oseltamivir in lung transplant recipients.

PubMed

Ison, Michael G; Sharma, Amita; Shepard, Jo-Anne O; Wain, John C; Ginns, Leo C

2008-03-01

Influenza causes significant morbidity and mortality in lung transplant recipients and likely predisposes to obliterative bronchiolitis. Neuraminidase inhibitors shorten the duration of symptoms and virus shedding and the number of antibiotic-requiring complications in ambulatory immunocompetent patients, although the efficacy of these agents in lung transplant recipients has not been assessed previously. In this study, 9 lung transplant patients who were treated with oseltamivir for influenza infections were identified and analyzed retrospectively. Oseltamivir was well tolerated. Infection resolved in all patients and there were no deaths. Two patients developed pneumonia shortly after their influenza infection and both responded to antibiotic therapy. None of the patients had persistent abnormalities noted on chest imaging and most did not show significant changes on pulmonary function testing. Two patients with the lowest pulmonary function test (PFT) values pre-infection had persistent defects after infection. Oseltamivir is well tolerated in lung transplant recipients and may reduce the risk of complications, although further studies are warranted.

Genome-Wide Study of Percent Emphysema on Computed Tomography in the General Population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study

PubMed Central

Manichaikul, Ani; Hoffman, Eric A.; Smolonska, Joanna; Gao, Wei; Cho, Michael H.; Baumhauer, Heather; Budoff, Matthew; Austin, John H. M.; Washko, George R.; Carr, J. Jeffrey; Kaufman, Joel D.; Pottinger, Tess; Powell, Charles A.; Wijmenga, Cisca; Zanen, Pieter; Groen, Harry J. M.; Postma, Dirkje S.; Wanner, Adam; Rouhani, Farshid N.; Brantly, Mark L.; Powell, Rhea; Smith, Benjamin M.; Rabinowitz, Dan; Raffel, Leslie J.; Hinckley Stukovsky, Karen D.; Crapo, James D.; Beaty, Terri H.; Hokanson, John E.; Silverman, Edwin K.; Dupuis, Josée; O’Connor, George T.; Boezen, H. Marike; Rich, Stephen S.

2014-01-01

Rationale: Pulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering. Objectives: To complete a genome-wide association study (GWAS) for the percentage of emphysema-like lung on computed tomography in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung/SNP Health Association Resource (SHARe) Study, a large, population-based cohort in the United States. Methods: We determined percent emphysema and upper-lower lobe ratio in emphysema defined by lung regions less than −950 HU on cardiac scans. Genetic analyses were reported combined across four race/ethnic groups: non-Hispanic white (n = 2,587), African American (n = 2,510), Hispanic (n = 2,113), and Chinese (n = 704) and stratified by race and ethnicity. Measurements and Main Results: Among 7,914 participants, we identified regions at genome-wide significance for percent emphysema in or near SNRPF (rs7957346; P = 2.2 × 10−8) and PPT2 (rs10947233; P = 3.2 × 10−8), both of which replicated in an additional 6,023 individuals of European ancestry. Both single-nucleotide polymorphisms were previously implicated as genes influencing lung function, and analyses including lung function revealed independent associations for percent emphysema. Among Hispanics, we identified a genetic locus for upper-lower lobe ratio near the α-mannosidase–related gene MAN2B1 (rs10411619; P = 1.1 × 10−9; minor allele frequency [MAF], 4.4%). Among Chinese, we identified single-nucleotide polymorphisms associated with upper-lower lobe ratio near DHX15 (rs7698250; P = 1.8 × 10−10; MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10−8; MAF, 2.6%), which acts on α-linked mannose. Among African Americans, a locus near a third α-mannosidase–related gene, MAN1C1 (rs12130495; P = 9.9 × 10−6; MAF, 13.3%) was associated with percent emphysema. Conclusions: Our results suggest that some genes previously identified as influencing lung function are independently associated with emphysema rather than lung function, and that genes related to α-mannosidase may influence risk of emphysema. PMID:24383474

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.

Lung Mass in Smokers.

PubMed

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

2017-04-01

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

Contribution of CT quantified emphysema, air trapping and airway wall thickness on pulmonary function in male smokers with and without COPD.

PubMed

Mohamed Hoesein, Firdaus A A; de Jong, Pim A; Lammers, Jan-Willem J; Mali, Willem P Th M; Mets, Onno M; Schmidt, Michael; de Koning, Harry J; Aalst, Carlijn van der; Oudkerk, Matthijs; Vliegenthart, Rozemarijn; Ginneken, Bram van; van Rikxoort, Eva M; Zanen, Pieter

2014-09-01

Emphysema, airway wall thickening and air trapping are associated with chronic obstructive pulmonary disease (COPD). All three can be quantified by computed tomography (CT) of the chest. The goal of the current study is to determine the relative contribution of CT derived parameters on spirometry, lung volume and lung diffusion testing. Emphysema, airway wall thickening and air trapping were quantified automatically on CT in 1,138 male smokers with and without COPD. Emphysema was quantified by the percentage of voxels below -950 Hounsfield Units (HU), airway wall thickness by the square root of wall area for a theoretical airway with 10 mm lumen perimeter (Pi10) and air trapping by the ratio of mean lung density at expiration and inspiration (E/I-ratio). Spirometry, residual volume to total lung capacity (RV/TLC) and diffusion capacity (Kco) were obtained. Standardized regression coefficients (β) were used to analyze the relative contribution of CT changes to pulmonary function measures. The independent contribution of the three CT measures differed per lung function parameter. For the FEV1 airway wall thickness was the most contributing structural lung change (β = -0.46), while for the FEV1/FVC this was emphysema (β = -0.55). For the residual volume (RV) air trapping was most contributing (β = -0.35). Lung diffusion capacity was most influenced by emphysema (β = -0.42). In a cohort of smokers with and without COPD the effect of different CT changes varies per lung function measure and therefore emphysema, airway wall thickness and air trapping need to be taken in account.

A Multicenter Study on Long-Term Outcomes After Lung Transplantation Comparing Donation After Circulatory Death and Donation After Brain Death.

PubMed

van Suylen, V; Luijk, B; Hoek, R A S; van de Graaf, E A; Verschuuren, E A; Van De Wauwer, C; Bekkers, J A; Meijer, R C A; van der Bij, W; Erasmus, M E

2017-10-01

The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the initial standard use of donation after brain death (DBD) lungs. From the three lung transplant centers in the Netherlands, 130 DCD3 recipients were one-to-one nearest neighbor propensity score matched with 130 DBD recipients. The primary end points were primary graft dysfunction (PGD), posttransplant lung function, freedom from chronic lung allograft dysfunction (CLAD), and overall survival. PGD did not differ between the groups. Posttransplant lung function was comparable after bilateral lung transplantation, but seemed worse after DCD3 single lung transplantation. The incidence of CLAD (p = 0.17) nor the freedom from CLAD (p = 0.36) nor the overall survival (p = 0.40) were significantly different between both groups. The presented multicenter results are derived from a national context where one third of the lung transplantations are performed with DCD3 lungs. We conclude that the long-term outcome after lung transplantation with DCD3 donors is similar to that of DBD donors and that DCD3 donation can substantially enlarge the donor pool. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Post-9/11/2001 lung function trajectories by sex and race in World Trade Center-exposed New York City emergency medical service workers.

PubMed

Vossbrinck, Madeline; Zeig-Owens, Rachel; Hall, Charles B; Schwartz, Theresa; Moir, William; Webber, Mayris P; Cohen, Hillel W; Nolan, Anna; Weiden, Michael D; Christodoulou, Vasilios; Kelly, Kerry J; Aldrich, Thomas K; Prezant, David J

2017-03-01

To determine whether lung function trajectories after 9/11/2001 (9/11) differed by sex or race/ethnicity in World Trade Center-exposed Fire Department of the City of New York emergency medical service (EMS) workers. Serial cross-sectional study of pulmonary function tests (PFTs) taken between 9/11 and 9/10/2015. We used data from routine PFTs (forced expiratory volume in 1 s (FEV 1 ) and FEV 1 % predicted), conducted at 12-18 month intervals. FEV 1 and FEV 1 % predicted were assessed over time, stratified by sex, and race/ethnicity. We also assessed FEV 1 and FEV 1 % predicted in current, former and never-smokers. Among 1817 EMS workers, 334 (18.4%) were women, 979 (53.9%) self-identified as white and 939 (51.6%) were never-smokers. The median follow-up was 13.1 years (IQR 10.5-13.6), and the median number of PFTs per person was 11 (IQR 7-13). After large declines associated with 9/11, there was no discernible recovery in lung function. In analyses limited to never-smokers, the trajectory of decline in adjusted FEV 1 and FEV 1 % predicted was relatively parallel for men and women in the 3 racial/ethnic groups. Similarly, small differences in FEV 1 annual decline between groups were not clinically meaningful. Analyses including ever-smokers were essentially the same. 14 years after 9/11, most EMS workers continued to demonstrate a lack of lung function recovery. The trajectories of lung function decline, however, were parallel by sex and by race/ethnicity. These findings support the use of routine, serial measures of lung function over time in first responders and demonstrate no sex or racial sensitivity to exposure-related lung function decline. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Incidental lung volume reduction following fulminant pulmonary hemorrhage in a patient with severe emphysema.

PubMed

Hetzel, Juergen; Spengler, Werner; Horger, Marius; Boeckeler, Michael

2015-06-01

Endoscopic lung volume reduction is an emerging technique meant to improve lung function parameters, quality of life, and exercise tolerance in patients with severe lung emphysema. This is the first report of lung volume reduction by autologous blood in a patient with non-bullous lung emphysema. A 74-year-old woman with heterogeneous lung emphysema developed accidentally diffuse lobar bleeding immediately after valve placement. Due to persistent hemorrhage, the valves had to be removed shortly thereafter. Despite extraction of the valves, respiratory function of the patient improved rapidly indicated also by a drop in the COPD assessment test questionnaire, 3 months later. This was consistent with both improvement of lung function tests and six-minute walking test.

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

Identification of TRA2B-DNAH5 fusion as a novel oncogenic driver in human lung squamous cell carcinoma

PubMed Central

Li, Fei; Fang, Zhaoyuan; Zhang, Jian; Li, Chen; Liu, Hongyan; Xia, Jufeng; Zhu, Hongwen; Guo, Chenchen; Qin, Zhen; Li, Fuming; Han, Xiangkun; Wang, Yuetong; Feng, Yan; Wang, Ye; Zhang, Wenjing; Wang, Zuoyun; Jin, Yujuan; Sun, Yihua; Wei, Wenyi; Zeng, Rong; Chen, Haiquan; Ji, Hongbin

2016-01-01

Lung squamous cell carcinoma (SCC) is one of the major subtypes of lung cancer. Our current knowledge of oncogenic drivers in this specific subtype of lung cancer is largely limited compared with lung adenocarcinoma (ADC). Through exon array analyses, molecular analyses and functional studies, we here identify the TRA2B-DNAH5 fusion as a novel oncogenic driver in lung SCC. We found that this gene fusion occurs exclusively in lung SCC (3.1%, 5/163), but not in lung ADC (0/119). Through mechanistic studies, we further revealed that this TRA2B-DNAH5 fusion promotes lung SCC malignant progression through regulating a SIRT6-ERK1/2-MMP1 signaling axis. We show that inhibition of ERK1/2 activation using selumetinib efficiently inhibits the growth of lung SCC with TRA2B-DNAH5 fusion expression. These findings improve our current knowledge of oncogenic drivers in lung SCC and provide a potential therapeutic strategy for lung SCC patients with TRA2B-DNAH5 fusion. PMID:27670699

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.

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.

Extracorporeal membrane oxygenation as a bridge to lung transplantation: A single-center experience in the present era.

PubMed

Todd, Emily M; Biswas Roy, Sreeja; Hashimi, A Samad; Serrone, Rosemarie; Panchanathan, Roshan; Kang, Paul; Varsch, Katherine E; Steinbock, Barry E; Huang, Jasmine; Omar, Ashraf; Patel, Vipul; Walia, Rajat; Smith, Michael A; Bremner, Ross M

2017-11-01

Extracorporeal membrane oxygenation has been used as a bridge to lung transplantation in patients with rapid pulmonary function deterioration. The reported success of this modality and perioperative and functional outcomes are varied. We retrospectively reviewed all patients who underwent lung transplantation at our institution over 1 year (January 1, 2015, to December 31, 2015). Patients were divided into 2 groups depending on whether they required extracorporeal membrane oxygenation support as a bridge to transplant; preoperative characteristics, lung transplantation outcomes, and survival were compared between groups. Of the 93 patients, 12 (13%) received bridge to transplant, and 81 (87%) did not. Patients receiving bridge to transplant were younger, had higher lung allocation scores, had lower functional status, and were more often on mechanical ventilation at listing. Most patients who received bridge to transplant (n = 10, 83.3%) had pulmonary fibrosis. Mean pretransplant extracorporeal membrane oxygenation support was 103.6 hours in duration (range, 16-395 hours). All patients who received bridge to transplant were decannulated immediately after lung transplantation but were more likely to return to the operating room for secondary chest closure or rethoracotomy. Grade 3 primary graft dysfunction within 72 hours was similar between groups. Lung transplantation success and hospital discharge were 100% in the bridge to transplant group; however, these patients experienced longer hospital stays and higher rates of discharge to acute rehabilitation. The 1-year survival was 100% in the bridge to transplant group and 91% in the non-bridge to transplant group (log-rank, P = .24). The 1-year functional status was excellent in both groups. Extracorporeal membrane oxygenation can be used to safely bridge high-acuity patients with end-stage lung disease to lung transplantation with good 30-day, 90-day, and 1-year survival and excellent 1-year functional status. Long-term outcomes are being studied. Copyright © 2017. Published by Elsevier Inc.

[Lung involvement in systemic connective tissue diseases].

PubMed

Plavec, Goran; Tomić, Ilija; Bihorac, Sanela; Kovacević, Gordana; Pavlica, Ljiljana; Cvetković, Gordana; Sikimić, Stevan; Milić, Rade

2008-09-01

Systemic connective tissue diseases (SCTD) are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory sistem. The aim of this study was to find out the frequency of respiratory simptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT) abnormalities, and their correlation with the duration of the disease and the applied treatment. In 47 non-randomised consecutive patients standard chest radiography, HRCT, and lung function tests were done. Hypoxemia was present in nine of the patients with respiratory simptoms (20%). In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had simptoms of lung involment. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung functin disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro). Pulmonary fibrosis occures in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

Measurement of lung volumes from supine portable chest radiographs.

PubMed

Ries, A L; Clausen, J L; Friedman, P J

1979-12-01

Lung volumes in supine nonambulatory patients are physiological parameters often difficult to measure with current techniques (plethysmograph, gas dilution). Existing radiographic methods for measuring lung volumes require standard upright chest radiographs. Accordingly, in 31 normal supine adults, we determined helium-dilution functional residual and total lung capacities and measured planimetric lung field areas (LFA) from corresponding portable anteroposterior and lateral radiographs. Low radiation dose methods, which delivered less than 10% of that from standard portable X-ray technique, were utilized. Correlation between lung volume and radiographic LFA was highly significant (r = 0.96, SEE = 10.6%). Multiple-step regressions using height and chest diameter correction factors reduced variance, but weight and radiographic magnification factors did not. In 17 additional subjects studied for validation, the regression equations accurately predicted radiographic lung volume. Thus, this technique can provide accurate and rapid measurement of lung volume in studies involving supine patients.

Carcinogenesis From Inhaled (PuO2)-Pu-239 in Beagles: Evidence for Radiation Homeostasis at Low Doses?

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

Fisher, Darrell R.; Weller, Richard E.

From the early 1970s to the late 1980s, Pacific Northwest National Laboratory conducted life-span studies in beagle dogs on the biological effects of inhaled plutonium (239PuO2, 238PuO2, and 239Pu[NO3]4) to help predict risks associated with accidental intakes in workers. Years later, the purpose of the present follow-up study is to reassess the dose-response relationship for lung cancer induction in the 239PuO2 dogs compared to controls, with particular focus on the dose-response at low lung doses. A 239PuO2 aerosol (2.3 μm AMAD, 1.9 μm GSD) was administered to six groups of 20 young (18-month old) beagle dogs (10 males and 10more » females) by inhalation at six different activity levels, as previously described in Laboratory reports. Control dogs were sham-exposed. In dose level 1, initial pulmonary lung depositions were 130 ± 48 Bq (3.5 ± 1.3 nCi), corresponding to 1 Bq g-1 lung tissue (0.029 ± 0.001 nCi g-1. Groups 2 through 6 received initial lung depositions (mean values) of 760, 2724, 10345, 37900, and 200000 Bq (22, 79, 300, 1100, and 5800 nCi) 239PuO2, respectively. For each dog, the absorbed dose to lungs was calculated from the initial lung burden and the final lung burden at time of death and lung mass, assuming a single, long-term retention function. Insoluble plutonium oxide exhibited long retention times in the lungs. Increased dose-dependent mortality due to lung cancer (bronchiolar-alveolar carcinoma, adenocarcinoma, epidermoid carcinoma) and radiation pneumonitis (highest exposures group) was observed in dogs exposed to 239PuO2. Calculated lung doses ranged from a few cGy in early-sacrificed dogs to 7764 cGy in dogs that experienced early deaths from radiation pneumonitis. Data were regrouped by lifetime lung dose and plotted as a function of lung tumor incidence. Lung tumor incidence in controls and zero-dose exposed dogs was 18% (5/28). However, no lung tumors were observed in 16 dogs with the lowest lung doses (8 to 22 cGy, mean 14.4 ± 7.6 cGy), and only one lung tumor was observed in 10 dogs with lung doses ranging from 27 to 48 cGy (mean 37.5 ± 10.9 cGy). By least-squares analysis, a quadratic function represented the overall dose-response (n = 137, r = 0.96) with no dose threshold. Reducing this function to three linear dose-response components, risk coefficients were calculated for each. The incidence of lung tumors at zero dose was significantly greater than the incidence at low dose (at the p ≤ 0.053 confidence level), suggesting a protective effect (radiation homeostasis) of alpha-particle radiation from 239PuO2. If a threshold for lung cancer incidence exists, it will be observed in the range 15 to 40 cGy.« less

Emodin mitigates diesel exhaust particles-induced increase in airway resistance, inflammation and oxidative stress in mice.

PubMed

Nemmar, Abderrahim; Al-Salam, Suhail; Yuvaraju, Priya; Beegam, Sumaya; Ali, Badreldin H

2015-08-15

Clinical and experimental studies have reported that short-term exposure to particulate air pollution is associated with inflammation, oxidative stress and impairment of lung function. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) has a strong antioxidant and anti-inflammatory actions. Therefore, in the present study, we evaluated the possible ameliorative effect of emodin on diesel exhaust particles (DEP)-induced impairment of lung function, inflammation and oxidative stress in mice. Mice were intratracheally instilled with DEP (20 μg/mouse) or saline (control). Emodin was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty-four hours following DEP exposure, we evaluated airway resistance measured by forced oscillation technique, lung inflammation and oxidative stress. Emodin treatment abated the DEP-induced increase in airway resistance, and prevented the influx of neutrophils in bronchoalveolar lavage fluid. Similarly, lung histopathology confirmed the protective effect of emodin on DEP-induced lung inflammation. DEP induced a significant increase of proinflammatory cytokines in the lung including tumor necrosis factor α, interleukin 6 and interleukin 1β. The latter effect was significantly ameliorated by emodin. DEP caused a significant increase in lung lipid peroxidation, reactive oxygen species and a significant decrease of reduced glutathione concentration. These effects were significantly mitigated by emodin. We conclude that emodin significantly mitigated DEP-induced increase of airway resistance, lung inflammation and oxidative stress. Pending further pharmacological and toxicological studies, emodin may be considered a potentially useful pulmonary protective agent against particulate air pollution-induced lung toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Leptin does not influence surfactant synthesis in fetal sheep and mice lungs

PubMed Central

Sato, Atsuyasu; Schehr, Angelica

2011-01-01

In the fetus, leptin in the circulation increases at late gestation and likely influences fetal organ development. Increased surfactant by leptin was previously demonstrated in vitro using fetal lung explant. We hypothesized that leptin treatment given to fetal sheep and pregnant mice might increase surfactant synthesis in the fetal lung in vivo. At 122–124 days gestational age (term: 150 days), fetal sheep were injected with 5 mg of leptin or vehicle using ultrasound guidance. Three and a half days after injection, preterm lambs were delivered, and lung function was studied during 30-min ventilation, followed by pulmonary surfactant components analyses. Pregnant A/J mice were given 30 or 300 mg of leptin or vehicle by intraperitoneal injection according to five study protocols with different doses, number of treatments, and gestational ages to treat. Surfactant components were analyzed in fetal lung 24 h after the last maternal treatment. Leptin injection given to fetal sheep increased fetal body weight. Control and leptin-treated groups were similar in lung function (preterm newborn lamb), surfactant components pool sizes (lamb and fetal mice), and expression of genes related to surfactant synthesis in the lung (fetal mice). Likewise, saturated phosphatidylcholine and phospholipid were normal in mice lungs with absence of circulating leptin (ob/ob mice) at all ages. These studies coincided in findings that neither exogenously given leptin nor deficiency of leptin influenced fetal lung maturation or surfactant pool sizes in vivo. Furthermore, the key genes critically required for surfactant synthesis were not affected by leptin treatment. PMID:21216976

Lung and Intestine: A Specific Link in an Ulcerative Colitis Rat Model

PubMed Central

Liu, Yuan; Wang, Xin-Yue; Yang, Xue; Jing, Shan; Zhu, Li; Gao, Si-Hua

2013-01-01

Background. To investigate the link and mechanisms between intestine and lung in the ulcerative colitis (UC) rat model. Materials and Methods. We used the UC rat model by immunological sensitization combined with local 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol enema, observed dynamically animal general state and body weight, examined the histological and functional changes in the colon, lung, liver, and kidney tissues, and detected microvascular endothelium response towards inflammation characterized with the expression of iNOS, TXB2, P-selectin, ICAM-1, and vascular endothelial growth factor A (VEGF-A) in the colon and lung tissue. Results. Pulmonary function results suggested ventilator disorder, and pathological findings showed interstitial pneumonia. There were no significant changes in the liver and kidney function and histopathology. The colon and lung tissue iNOS, TXB2, P-selectin, ICAM-1, and VEGF-A expression of the model rats was significantly higher than the normal rats at both time points. Conclusions. Our study is the first to demonstrate the close association between the large intestine and lung in the immune-TNBS-ethanol-induced UC rat model. Different organs and tissues with the same embryonic origin may share the same pathological specificities in a disease. The present study provided a new way of thinking for pathological changes in clinical complex diseases manifested with multiorgan damage. PMID:23606829

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

Coexistence of Chronic Bronchitis in Chronic Obstructive Lung Disease.

PubMed

Mejza, Filip; Nastałek, Paweł; Mastalerz-Migas, Agnieszka; Doniec, Zbigniew; Skucha, Wojciech

2018-05-12

The incidence of chronic obstructive pulmonary disease (COPD) is on the rise worldwide. Chronic bronchitis is a frequent accompaniment of COPD, which increases the burden of COPD in affected individuals. The aim of this study was to characterize the phenotype of chronic bronchitis in COPD patients. The study was based on the survey data retrospectively retrieved from the Action Health-Lung Cancer Prophylaxis and Health Care Improvement screening program that concerned all the inhabitants, aged over 40, of the Proszowice administrative region situated in the Lesser Poland Voivodeship in southern Poland. Participants with the symptoms suggestive of a lung disease were subject to further evaluation. The findings were that 546 (13.3%) out of the 4105 individuals displayed spirometry features of COPD. Symptoms of chronic bronchitis were present in 92 (16.8%) out of the COPD afflicted persons. Chronic bronchitis was commoner in current smokers and its incidence increased with increasing severity of airway obstruction. In multivariate analysis, chronic bronchitis was independently related to lower FEV1, FVC, FEV1/FVC, and to dyspnea. In regression model, factors related to increased risk of chronic bronchitis were current smoking, asthma, and lower lung function. We conclude that COPD with coexisting chronic bronchitis is linked to severer dyspnea and worse lung function. Current smoking, asthma, and lower lung function are related to increased risk of chronic bronchitis accompanying COPD.

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.

Lung VITAL: Rationale, design, and baseline characteristics of an ancillary study evaluating the effects of vitamin D and/or marine omega-3 fatty acid supplements on acute exacerbations of chronic respiratory disease, asthma control, pneumonia and lung function in adults

PubMed Central

Gold, Diane R; Litonjua, Augusto A.; Carey, Vincent J.; Manson, JoAnn E.; Buring, Julie E; Lee, I-Min; Gordon, David; Walter, Joseph; Friedenberg, Georgina; Hankinson, John L; Copeland, Trisha; Luttmann-Gibson, Heike

2016-01-01

Laboratory and observational research studies suggest that vitamin D and marine omega-3 fatty acids may reduce risk for pneumonia, acute exacerbations of respiratory diseases including chronic obstructive lung disease (COPD) or asthma, and decline of lung function, but prevention trials with adequate dosing, adequate power, and adequate time to follow-up are lacking. The ongoing Lung VITAL study is taking advantage of a large clinical trial—the VITamin D and OmegA-3 TriaL (VITAL)—to conduct the first major evaluation of the influences of vitamin D and marine omega-3 fatty acid supplementation on pneumonia risk, respiratory exacerbation episodes, asthma control and lung function in adults. VITAL is a 5-year U.S.-wide randomized, double-blind, placebo-controlled, 2×2 factorial trial of supplementation with vitamin D3 ([cholecalciferol], 2000 IU/day) and marine omega-3 FA (Omacor® fish oil, eicosapentaenoic acid [EPA] +docosahexaenoic acid [DHA], 1 g/day) for primary prevention of CVD and cancer among men and women, at baseline aged ≥50 and ≥55, respectively, with 5107 African Americans. In a subset of 1973 participants from 11 urban U.S. centers, lung function is measured before and two years after randomization. Yearly follow-up questionnaires assess incident pneumonia in the entire randomized population, and exacerbations of respiratory disease, asthma control and dyspnea in a subpopulation of 4314 randomized participants enriched, as shown in presentation of baseline characteristics, for respiratory disease, respiratory symptoms, and history of cigarette smoking. Self-reported pneumonia hospitalization will be confirmed by medical record review, and exacerbations will be confirmed by Center for Medicare and Medicaid Services data review. PMID:26784651

Lung VITAL: Rationale, design, and baseline characteristics of an ancillary study evaluating the effects of vitamin D and/or marine omega-3 fatty acid supplements on acute exacerbations of chronic respiratory disease, asthma control, pneumonia and lung function in adults.

PubMed

Gold, Diane R; Litonjua, Augusto A; Carey, Vincent J; Manson, JoAnn E; Buring, Julie E; Lee, I-Min; Gordon, David; Walter, Joseph; Friedenberg, Georgina; Hankinson, John L; Copeland, Trisha; Luttmann-Gibson, Heike

2016-03-01

Laboratory and observational research studies suggest that vitamin D and marine omega-3 fatty acids may reduce risk for pneumonia, acute exacerbations of respiratory diseases including chronic obstructive lung disease (COPD) or asthma, and decline of lung function, but prevention trials with adequate dosing, adequate power, and adequate time to follow-up are lacking. The ongoing Lung VITAL study is taking advantage of a large clinical trial-the VITamin D and OmegA-3 TriaL (VITAL)--to conduct the first major evaluation of the influences of vitamin D and marine omega-3 fatty acid supplementation on pneumonia risk, respiratory exacerbation episodes, asthma control and lung function in adults. VITAL is a 5-year U.S.-wide randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of supplementation with vitamin D3 ([cholecalciferol], 2000 IU/day) and marine omega-3 FA (Omacor® fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) for primary prevention of CVD and cancer among men and women, at baseline aged ≥50 and ≥55, respectively, with 5107 African Americans. In a subset of 1973 participants from 11 urban U.S. centers, lung function is measured before and two years after randomization. Yearly follow-up questionnaires assess incident pneumonia in the entire randomized population, and exacerbations of respiratory disease, asthma control and dyspnea in a subpopulation of 4314 randomized participants enriched, as shown in presentation of baseline characteristics, for respiratory disease, respiratory symptoms, and history of cigarette smoking. Self-reported pneumonia hospitalization will be confirmed by medical record review, and exacerbations will be confirmed by Center for Medicare and Medicaid Services data review. Copyright © 2016 Elsevier Inc. All rights reserved.

A non-randomized confirmatory trial of segmentectomy for clinical T1N0 lung cancer with dominant ground glass opacity based on thin-section computed tomography (JCOG1211).

PubMed

Aokage, Keiju; Saji, Hisashi; Suzuki, Kenji; Mizutani, Tomonori; Katayama, Hiroshi; Shibata, Taro; Watanabe, Syunichi; Asamura, Hisao

2017-05-01

Lobectomy has been the standard surgery for even stage I lung cancer since the validity of limited resection for stage I lung cancer was denied by the randomized study reported in 1995. The aim of this non-randomized confirmatory going on since September 2013 is to confirm the efficacy of a segmentectomy for clinical T1N0 lung cancer with dominant ground glass opacity based on thin-slice computed tomography. A total of 390 patients from 42 Japanese institutions are recruited within 4 years. The primary endpoint of this study is a 5-year relapse-free survival in all of the patients who undergo a segmentectomy for a lung nodule. The secondary endpoints are overall survival, annual relapse-free survival, disease-free survival, proportion of local relapse, postoperative pulmonary function, proportion of segmentectomy completion, proportion of R0 resection completion by segmentectomy, adverse events, and serious adverse events. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000011819 ( http://www.umin.ac.jp/ctr/ ). Patient's accrual has been already finished in November, 2015 and the primary analysis will be performed in 2021. This study is one of the pivotal trial of lung segmentectomy for early lung cancer. The result will provide a clear evidence for our daily clinics and will be possible contribution to preserving pulmonary function for lung cancer patients.

Ozone Exposure, Cardiopulmonary Health, and Obesity: A Substantive Review.

PubMed

Koman, Patricia D; Mancuso, Peter

2017-07-17

From 1999-2014, obesity prevalence increased among adults and youth. Obese individuals may be uniquely susceptible to the proinflammatory effects of ozone because obese humans and animals have been shown to experience a greater decline in lung function than normal-weight subjects. Obesity is independently associated with limitations in lung mechanics with increased ozone dose. However, few epidemiologic studies have examined the interaction between excess weight and ozone exposure among adults. Using PubMed keyword searches and reference lists, we reviewed epidemiologic evidence to identify potential response-modifying factors and determine if obese or overweight adults are at increased risk of ozone-related health effects. We initially identified 170 studies, of which seven studies met the criteria of examining the interaction of excess weight and ozone exposure on cardiopulmonary outcomes in adults, including four short-term ozone exposure studies in controlled laboratory settings and three community epidemiologic studies. In the studies identified, obesity was associated with decreased lung function and increased inflammatory mediators. Results were inconclusive about the effect modification when data were stratified by sex. Obese and overweight populations should be considered as candidate at-risk groups for epidemiologic studies of cardiopulmonary health related to air pollution exposures. Air pollution is a modifiable risk factor that may decrease lung function among obese individuals with implications for environmental and occupational health policy.

Assessing lung function and respiratory health in schoolchildren as a means to improve local environmental conditions.

PubMed

Hutter, Hans-Peter; Borsoi, Livia; Wallner, Peter; Moshammer, Hanns; Kundi, Michael

2009-07-01

In response to the World Health Organization Children's Environment and Health Action Plan for Europe (CEHAPE), a town near Vienna initiated a health survey of schoolchildren. To create recommendations for the community's decision makers, the health survey tried to identify the environmental factors influencing the respiratory health of children. The survey consisted of a questionnaire and spirometry. For 186 of 207 children of first and second grade, parents consented to include their children and answered a questionnaire. Spirometry was performed in 177 children. Results of lung function testing revealed that lung function was significantly reduced in children with visible mould infestation at home and living on a street with frequent lorry traffic. Larger family size and living in a rural area had positive effects on lung function. Our study provides an example for a feasible strategy to provide local decision makers with recommendations based on scientific evidence and actual observations and to help them implement measures in accordance with CEHAPE.

First Danish experience with ex vivo lung perfusion of donor lungs before transplantation.

PubMed

Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold; Zemtsovski, Mikhail; Nilsson, Jens Christian; Seidelin, Casper Tobias; Perch, Michael; Iversen, Martin; Steinbrüchel, Daniel

2014-03-01

The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its introduction. The study was conducted by prospective registration of donor offers and lung transplantations in Denmark from 1 May 2012 to 30 April 2013. Donor lungs without any contraindications were transplanted in the traditional manner. Taken for EVLP were donor lungs that were otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died of non-EVLP-related causes, but all other recipients were alive with normal graft function at the end of our registration period. All lungs showed an improved PaO2/FiO2 ratio from a median 23.1 kPa (8.8-38.9) within the donor to 58.8 kPa (34.9-76.5) (FiO2 = 1.0) after EVLP, which corresponds to a 155% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted as a result of their improved function. EVLP seems to be a safe way to increase the use of marginal donor lungs. no funding was granted for the present paper. not relevant.

Acute effects of summer air pollution on respiratory function in primary school children in southern England.

PubMed Central

Scarlett, J F; Abbott, K J; Peacock, J L; Strachan, D P; Anderson, H R

1996-01-01

BACKGROUND: There is growing concern about health effects of air pollution in the UK. Studies in the USA have reported adverse effects on lung function among children but no comparable studies have been published in the UK. This study investigates the relationship between daily changes in ambient air pollution and short term variations in lung function in a panel of school children. METHODS: One hundred and fifty four children aged 7-11 attending a primary school adjacent to a major motorway in Surrey, south-east England, were studied. Bellows spirometry was performed daily on 31 schooldays between 6 June and 21 July 1994. Levels of ozone, nitrogen dioxide, and particulates of less than 10 microns in diameter (PM10) were measured continuously at the school and the pollen count was measured six miles away. Relationships between daily changes in forced expiratory volume in 0.75 seconds (FEV0.75), forced vital capacity (FVC), the FEV0.75/FVC ratio and pollutants were analysed using separate autoregressive models for each child. A weighted average of the resulting slopes was then calculated. RESULTS: There was a significant inverse relationship between daily mean PM10 levels lagged one day and FVC, with a reduction in lung function of 1% (95% CI 0.3% to 2%) across the whole range of PM10 levels (20-150 micrograms/m3). The effect on FEV0.75 was similar (-0.5%) but was not significant when weighted by 1/SE2 (95% CI -1.2% to 0.2%). There was no effect of PM10 levels on the FEV0.75/FVC ratio. No significant association was seen between FEV0.75, FVC, or the FEV0.75/FVC ratio and either ozone or nitrogen dioxide levels. There was no evidence that wheezy children were more affected than healthy children. Pollen levels on the previous day had no effect on lung function and did not change the air pollution results. CONCLUSIONS: There is a very small, but statistically significant, adverse effect of airborne respirable particulate matter, measured as PM10, on lung function in this study group. There is no evidence for an inverse association of lung function with levels of ozone or NO2 measured on the previous day. PMID:8958894

Lung volume, breathing pattern and ventilation inhomogeneity in preterm and term infants.

PubMed

Latzin, Philipp; Roth, Stefan; Thamrin, Cindy; Hutten, Gerard J; Pramana, Isabelle; Kuehni, Claudia E; Casaulta, Carmen; Nelle, Matthias; Riedel, Thomas; Frey, Urs

2009-01-01

Morphological changes in preterm infants with bronchopulmonary dysplasia (BPD) have functional consequences on lung volume, ventilation inhomogeneity and respiratory mechanics. Although some studies have shown lower lung volumes and increased ventilation inhomogeneity in BPD infants, conflicting results exist possibly due to differences in sedation and measurement techniques. We studied 127 infants with BPD, 58 preterm infants without BPD and 239 healthy term-born infants, at a matched post-conceptional age of 44 weeks during quiet natural sleep according to ATS/ERS standards. Lung function parameters measured were functional residual capacity (FRC) and ventilation inhomogeneity by multiple breath washout as well as tidal breathing parameters. Preterm infants with BPD had only marginally lower FRC (21.4 mL/kg) than preterm infants without BPD (23.4 mL/kg) and term-born infants (22.6 mL/kg), though there was no trend with disease severity. They also showed higher respiratory rates and lower ratios of time to peak expiratory flow and expiratory time (t(PTEF)/t(E)) than healthy preterm and term controls. These changes were related to disease severity. No differences were found for ventilation inhomogeneity. Our results suggest that preterm infants with BPD have a high capacity to maintain functional lung volume during natural sleep. The alterations in breathing pattern with disease severity may reflect presence of adaptive mechanisms to cope with the disease process.

Lung function in post-poliomyelitis syndrome: a cross-sectional study*

PubMed Central

de Lira, Claudio Andre Barbosa; Minozzo, Fábio Carderelli; Sousa, Bolivar Saldanha; Vancini, Rodrigo Luiz; Andrade, Marília dos Santos; Quadros, Abrahão Augusto Juviniano; Oliveira, Acary Souza Bulle; da Silva, Antonio Carlos

2013-01-01

OBJECTIVE: To compare lung function between patients with post-poliomyelitis syndrome and those with sequelae of paralytic poliomyelitis (without any signs or symptoms of post-poliomyelitis syndrome), as well as between patients with post-poliomyelitis syndrome and healthy controls. METHODS: Twenty-nine male participants were assigned to one of three groups: control; poliomyelitis (comprising patients who had had paralytic poliomyelitis but had not developed post-poliomyelitis syndrome); and post-poliomyelitis syndrome. Volunteers underwent lung function measurements (spirometry and respiratory muscle strength assessment). RESULTS: The results of the spirometric assessment revealed no significant differences among the groups except for an approximately 27% lower mean maximal voluntary ventilation in the post-poliomyelitis syndrome group when compared with the control group (p = 0.0127). Nevertheless, the maximal voluntary ventilation values for the post-poliomyelitis group were compared with those for the Brazilian population and were found to be normal. No significant differences were observed in respiratory muscle strength among the groups. CONCLUSIONS: With the exception of lower maximal voluntary ventilation, there was no significant lung function impairment in outpatients diagnosed with post-poliomyelitis syndrome when compared with healthy subjects and with patients with sequelae of poliomyelitis without post-poliomyelitis syndrome. This is an important clinical finding because it shows that patients with post-poliomyelitis syndrome can have preserved lung function. PMID:24068267

Technical Advance: Live-imaging analysis of human dendritic cell migrating behavior under the influence of immune-stimulating reagents in an organotypic model of lung

PubMed Central

Nguyen Hoang, Anh Thu; Chen, Puran; Björnfot, Sofia; Högstrand, Kari; Lock, John G.; Grandien, Alf; Coles, Mark; Svensson, Mattias

2014-01-01

This manuscript describes technical advances allowing manipulation and quantitative analyses of human DC migratory behavior in lung epithelial tissue. DCs are hematopoietic cells essential for the maintenance of tissue homeostasis and the induction of tissue-specific immune responses. Important functions include cytokine production and migration in response to infection for the induction of proper immune responses. To design appropriate strategies to exploit human DC functional properties in lung tissue for the purpose of clinical evaluation, e.g., candidate vaccination and immunotherapy strategies, we have developed a live-imaging assay based on our previously described organotypic model of the human lung. This assay allows provocations and subsequent quantitative investigations of DC functional properties under conditions mimicking morphological and functional features of the in vivo parental tissue. We present protocols to set up and prepare tissue models for 4D (x, y, z, time) fluorescence-imaging analysis that allow spatial and temporal studies of human DCs in live epithelial tissue, followed by flow cytometry analysis of DCs retrieved from digested tissue models. This model system can be useful for elucidating incompletely defined pathways controlling DC functional responses to infection and inflammation in lung epithelial tissue, as well as the efficacy of locally administered candidate interventions. PMID:24899587

The European Respiratory Society and European Society of Thoracic Surgeons clinical guidelines for evaluating fitness for radical treatment (surgery and chemoradiotherapy) in patients with lung cancer.

PubMed

Brunelli, Alessandro; Charloux, Anne; Bolliger, Chris T; Rocco, Gaetano; Sculier, Jean-Paul; Varela, Gonzalo; Licker, Marc; Ferguson, Mark K; Faivre-Finn, Corinne; Huber, Rudolf Maria; Clini, Enrico M; Win, Thida; De Ruysscher, Dirk; Goldman, Lee

2009-07-01

The European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) established a joint task force with the purpose to develop clinical evidence-based guidelines on evaluation of fitness for radical therapy in patients with lung cancer. The following topics were discussed, and are summarized in the final report along with graded recommendations: Cardiologic evaluation before lung resection; lung function tests and exercise tests (limitations of ppoFEV1; DLCO: systematic or selective?; split function studies; exercise tests: systematic; low-tech exercise tests; cardiopulmonary (high tech) exercise tests); future trends in preoperative work-up; physiotherapy/rehabilitation and smoking cessation; scoring systems; advanced care management (ICU/HDU); quality of life in patients submitted to radical treatment; combined cancer surgery and lung volume reduction surgery; compromised parenchymal sparing resections and minimally invasive techniques: the balance between oncological radicality and functional reserve; neoadjuvant chemotherapy and complications; definitive chemo and radiotherapy: functional selection criteria and definition of risk; should surgical criteria be re-calibrated for radiotherapy?; the patient at prohibitive surgical risk: alternatives to surgery; who should treat thoracic patients and where these patients should be treated?

Real-time imaging of inflation-induced ATP release in the ex vivo rat lung.

PubMed

Furuya, Kishio; Tan, Ju Jing; Boudreault, Francis; Sokabe, Masahiro; Berthiaume, Yves; Grygorczyk, Ryszard

2016-11-01

Extracellular ATP and other nucleotides are important autocrine/paracrine mediators that regulate diverse processes critical for lung function, including mucociliary clearance, surfactant secretion, and local blood flow. Cellular ATP release is mechanosensitive; however, the impact of physical stimuli on ATP release during breathing has never been tested in intact lungs in real time and remains elusive. In this pilot study, we investigated inflation-induced ATP release in rat lungs ex vivo by real-time luciferin-luciferase (LL) bioluminescence imaging coupled with simultaneous infrared tissue imaging to identify ATP-releasing sites. With LL solution introduced into air spaces, brief inflation of such edematous lung (1 s, ∼20 cmH 2 O) induced transient (<30 s) ATP release in a limited number of air-inflated alveolar sacs during their recruitment/opening. Released ATP reached concentrations of ∼10 -6 M, relevant for autocrine/paracrine signaling, but it remained spatially restricted to single alveolar sacs or their clusters. ATP release was stimulus dependent: prolonged (100 s) inflation evoked long-lasting ATP release that terminated upon alveoli deflation/derecruitment while cyclic inflation/suction produced cyclic ATP release. With LL introduced into blood vessels, inflation induced transient ATP release in many small patchlike areas the size of alveolar sacs. Findings suggest that inflation induces ATP release in both alveoli and the surrounding blood capillary network; the functional units of ATP release presumably consist of alveolar sacs or their clusters. Our study demonstrates the feasibility of real-time ATP release imaging in ex vivo lungs and provides the first direct evidence of inflation-induced ATP release in lung air spaces and in pulmonary blood capillaries, highlighting the importance of purinergic signaling in lung function. Copyright © 2016 the American Physiological Society.

South African and international reference values for lung function and its relationship with blood pressure in Africans.

PubMed

van Rooyen, Yolandi; Huisman, Hugo W; Schutte, Aletta E; Eloff, Fritz C; Du Plessis, Johan L; Kruger, Annamarie; Van Rooyen, Johannes M

2015-06-01

In South Africa respiratory diseases are highly prevalent, with cardiovascular disease being a manifestation. However, international reference values for lung function are commonly used, which may not be appropriate to correctly identify reduced lung function. An inverse relationship exists between lung function and blood pressure (BP) but is not investigated extensively in black South Africans. We included 2010 Africans from the PURE (Prospective Urban Rural Epidemiology) study (aged > 35 years) in the North West Province. Spirometry was performed and predicted values for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were calculated from South African, European and United States prediction equations. With the exception of the European predicted values, all other predicted mean FEV1 and FVC were above 80%. South African reference values displayed the highest percentages of the predicted values for FEV1 and FVC (87.9 and 99.7%, respectively.) BP increased from quintiles five to one for both FEV1 and FVC, (p for trend <0.001). After adjustment the differences remained (p<0.05). South African reference values yielded higher percentages of predicted FEV1 and FVC values than European and US equations suggesting that South African prediction equations may be more useful when investigating lung function in black South Africans. Elevated BP is related to reduced lung function, highlighting the importance in managing both respiratory- and cardiovascular disease. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Lung transplantation in adults and children: putting lung function into perspective.

PubMed

Thompson, Bruce Robert; Westall, Glen Philip; Paraskeva, Miranda; Snell, Gregory Ian

2014-11-01

The number of lung transplants performed globally continues to increase year after year. Despite this growing experience, long-term outcomes following lung transplantation continue to fall far short of that described in other solid-organ transplant settings. Chronic lung allograft dysfunction (CLAD) remains common and is the end result of exposure to a multitude of potentially injurious insults that include alloreactivity and infection among others. Central to any description of the clinical performance of the transplanted lung is an assessment of its physiology by pulmonary function testing. Spirometry and the evaluation of forced expiratory volume in 1 s and forced vital capacity, remain core indices that are measured as part of routine clinical follow-up. Spirometry, while reproducible in detecting lung allograft dysfunction, lacks specificity in differentiating the different complications of lung transplantation such as rejection, infection and bronchiolitis obliterans. However, interpretation of spirometry is central to defining the different 'chronic rejection' phenotypes. It is becoming apparent that the maximal lung function achieved following transplantation, as measured by spirometry, is influenced by a number of donor and recipient factors as well as the type of surgery performed (single vs double vs lobar lung transplant). In this review, we discuss the wide range of variables that need to be considered when interpreting lung function testing in lung transplant recipients. Finally, we review a number of novel measurements of pulmonary function that may in the future serve as better biomarkers to detect and diagnose the cause of the failing lung allograft. © 2014 Asian Pacific Society of Respirology.

Personality and Lung Function in Older Adults.

PubMed

Terracciano, Antonio; Stephan, Yannick; Luchetti, Martina; Gonzalez-Rothi, Ricardo; Sutin, Angelina R

2017-10-01

Lung disease is a leading cause of disability and death among older adults. We examine whether personality traits are associated with lung function and shortness of breath (dyspnea) in a national cohort with and without chronic obstructive pulmonary disease (COPD). Participants (N = 12,670) from the Health and Retirement Study were tested for peak expiratory flow (PEF) and completed measures of personality, health behaviors, and a medical history. High neuroticism and low extraversion, openness, agreeableness, and conscientiousness were associated with lower PEF, and higher likelihood of COPD and dyspnea. Conscientiousness had the strongest and most consistent associations, including lower risk of PEF less than 80% of the predicted value (OR = 0.67; 0.62-0.73) and dyspnea (OR = 0.52; 0.47-0.57). Although attenuated, the associations remained significant when accounting for smoking, physical activity, and chronic diseases including cardiovascular and psychiatric disorders. The associations between personality and PEF or dyspnea were similar among those with or without COPD, suggesting that psychological links to lung function are not disease dependent. In longitudinal analyses, high neuroticism (β = -0.019) and low conscientiousness (β = 0.027) predicted steeper declines in PEF. A vulnerable personality profile is common among individuals with limited lung function and COPD, predicts shortness of breath and worsening lung function. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

Clinical and Radiographic Predictors of GOLD–Unclassified Smokers in the COPDGene Study

PubMed Central

Hokanson, John E.; Murphy, James R.; Regan, Elizabeth A.; Make, Barry J.; Lynch, David A.; Crapo, James D.; Silverman, Edwin K.

2011-01-01

Rationale: A significant proportion of smokers have lung function impairment characterized by a reduced FEV1 with a preserved FEV1/FVC ratio. These smokers are a poorly characterized group due to their systematic exclusion from chronic obstructive pulmonary disease (COPD) studies. Objectives: To characterize the clinical, functional, and radiographic features of Global Initiative for Chronic Obstructive Lung Disease (GOLD)-Unclassified (FEV1/FVC ≥ 0.7 and FEV1 < 80% predicted) and lower limits of normal (LLN)-unclassified (FEV1/FVC ≥ LLN and FEV1 < LLN) subjects compared to smokers with normal lung function and subjects with COPD. Methods: Data from the first 2,500 subjects enrolled in the COPDGene study were analyzed. All subjects had 10 or more pack-years of smoking and were between the ages of 45 and 80 years. Multivariate regression models were constructed to determine the clinical and radiological variables associated with GOLD-Unclassified (GOLD-U) and LLN-Unclassified status. Separate multivariate regressions were performed in the subgroups of subjects with complete radiologic measurement variables available. Measurements and Main Results: GOLD-U smokers account for 9% of smokers in COPDGene and have increased body mass index (BMI), a disproportionately reduced total lung capacity, and a higher proportion of nonwhite subjects and subjects with diabetes. GOLD-U subjects exhibit increased airway wall thickness compared to smoking control subjects and decreased gas trapping and bronchodilator responsiveness compared to subjects with COPD. When LLN criteria were used to define the “unclassified” group, African American subjects were no longer overrepresented. Both GOLD-U and LLN-Unclassified subjects demonstrated a wide range of lung function impairment, BMI, and percentage of total lung emphysema. Conclusions: Subjects with reduced FEV1 and a preserved FEV1/FVC ratio are a heterogeneous group with significant symptoms and functional limitation who likely have a variety of underlying etiologies beyond increased BMI. Clinical trial registered with www.clinicaltrials.gov (NCT000608764). PMID:21493737

The relationship between respiratory system impedance and lung function in asthmatics: A prospective observational study.

PubMed

Kamada, Takahiro; Kaneko, Masahiro; Tomioka, Hiromi

2017-05-01

The aim was to elucidate the relationship between the annual changes in respiratory system impedance, measured by FOT, and lung function tests in patients with asthma. Between March 2011 and March 2012, asthma outpatients who attended Kobe City Medical Center West Hospital were recruited. Lung function tests, FOT were conducted every 6 months until March 2016. The relationships between annual parameter changes were evaluated. Sixty-four patients were completed this study. The median follow-up period was 55 months. At enrollment, although resistance showed no relationship with forced expiratory volume in one second (%FEV 1 ), the reactance was moderately correlated with X5 (r=0.524, r 2 =0.275, <0.001), Fres (r=-0.498, r 2 =0.248, <0.001) and ALX (r=-0.416, r 2 =0.173, p=<0.001). By contrast, the annual resistance change at 5Hz (R5) was highly and significantly associated with%FEV 1 change (r=-0.564, r 2 =0.318, p<0.001). Longitudinal changes in airway resistance and reactance measured by FOT might be useful for the assessment of lung function in patients with asthma. Copyright © 2017 Elsevier B.V. All rights reserved.

Responses of Six-Weeks Aquatic Exercise on the Autonomic Nervous System, Peak Nasal Inspiratory Flow and Lung Functions in Young Adults with Allergic Rhinitis.

PubMed

Janyacharoen, Taweesak; Kunbootsri, Narupon; Arayawichanon, Preeda; Chainansamit, Seksun; Sawanyawisuth, Kittisak

2015-06-01

Allergic rhinitis is a chronic respiratory disease. Sympathetic hypofunction is identified in all of the allergic rhinitis patients. Moreover, allergic rhinitis is associated with decreased peak nasal inspiratory flow (PNIF) and impaired lung functions. The aim of this study was to investigate effects of six-week of aquatic exercise on the autonomic nervous system function, PNIF and lung functions in allergic rhinitis patients. Twenty-six allergic rhinitis patients, 12 males and 14 females were recruited in this study. Subjects were diagnosed by a physician based on history, physical examination, and positive reaction to a skin prick test. Subjects were randomly assigned to two groups. The control allergic rhinitis group received education and maintained normal life. The aquatic group performed aquatic exercise for 30 minutes a day, three days a week for six weeks. Heart rate variability, PNIF and lung functions were measured at the beginning, after three weeks and six weeks. There were statistically significant increased low frequency normal units (LF n.u.), PNIF and showed decreased high frequency normal units (HF n.u.) at six weeks after aquatic exercise compared with the control group. Six weeks of aquatic exercise could increase sympathetic activity and PNIF in allergic rhinitis patients.

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.

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

The triterpenoid CDDO-Me inhibits bleomycin-induced lung inflammation and fibrosis.

PubMed

Kulkarni, Ajit A; Thatcher, Thomas H; Hsiao, Hsi-Min; Olsen, Keith C; Kottmann, Robert Matthew; Morrissette, Jason; Wright, Terry W; Phipps, Richard P; Sime, Patricia J

2013-01-01

Pulmonary Fibrosis (PF) is a devastating progressive disease in which normal lung structure and function is compromised by scarring. Lung fibrosis can be caused by thoracic radiation, injury from chemotherapy and systemic diseases such as rheumatoid arthritis that involve inflammatory responses. CDDO-Me (Methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate, Bardoxolone methyl) is a novel triterpenoid with anti-fibrotic and anti-inflammatory properties as shown by our in vitro studies. Based on this evidence, we hypothesized that CDDO-Me would reduce lung inflammation, fibrosis and lung function impairment in a bleomycin model of lung injury and fibrosis. To test this hypothesis, mice received bleomycin via oropharyngeal aspiration (OA) on day zero and CDDO-Me during the inflammatory phase from days -1 to 9 every other day. Bronchoalveolar lavage fluid (BALF) and lung tissue were harvested on day 7 to evaluate inflammation, while fibrosis and lung function were evaluated on day 21. On day 7, CDDO-Me reduced total BALF protein by 50%, alveolar macrophage infiltration by 40%, neutrophil infiltration by 90% (p≤0.01), inhibited production of the inflammatory cytokines KC and IL-6 by over 90% (p≤0.001), and excess production of the pro-fibrotic cytokine TGFβ by 50%. CDDO-Me also inhibited α-smooth muscle actin and fibronectin mRNA by 50% (p≤0.05). On day 21, CDDO-Me treatment reduced histological fibrosis, collagen deposition and αSMA production. Lung function was significantly improved at day 21 by treatment with CDDO-Me, as demonstrated by respiratory rate and dynamic compliance. These new findings reveal that CDDO-Me exhibits potent anti-fibrotic and anti-inflammatory properties in vivo. CDDO-Me is a potential new class of drugs to arrest inflammation and ameliorate fibrosis in patients who are predisposed to lung injury and fibrosis incited by cancer treatments (e.g. chemotherapy and radiation) and by systemic autoimmune diseases.

The Triterpenoid CDDO-Me Inhibits Bleomycin-Induced Lung Inflammation and Fibrosis

PubMed Central

Kulkarni, Ajit A.; Thatcher, Thomas H.; Hsiao, Hsi-Min; Olsen, Keith C.; Kottmann, Robert Matthew; Morrissette, Jason; Wright, Terry W.; Phipps, Richard P.; Sime, Patricia J.

2013-01-01

Pulmonary Fibrosis (PF) is a devastating progressive disease in which normal lung structure and function is compromised by scarring. Lung fibrosis can be caused by thoracic radiation, injury from chemotherapy and systemic diseases such as rheumatoid arthritis that involve inflammatory responses. CDDO-Me (Methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate, Bardoxolone methyl) is a novel triterpenoid with anti-fibrotic and anti-inflammatory properties as shown by our in vitro studies. Based on this evidence, we hypothesized that CDDO-Me would reduce lung inflammation, fibrosis and lung function impairment in a bleomycin model of lung injury and fibrosis. To test this hypothesis, mice received bleomycin via oropharyngeal aspiration (OA) on day zero and CDDO-Me during the inflammatory phase from days -1 to 9 every other day. Bronchoalveolar lavage fluid (BALF) and lung tissue were harvested on day 7 to evaluate inflammation, while fibrosis and lung function were evaluated on day 21. On day 7, CDDO-Me reduced total BALF protein by 50%, alveolar macrophage infiltration by 40%, neutrophil infiltration by 90% (p≤0.01), inhibited production of the inflammatory cytokines KC and IL-6 by over 90% (p≤0.001), and excess production of the pro-fibrotic cytokine TGFβ by 50%. CDDO-Me also inhibited α-smooth muscle actin and fibronectin mRNA by 50% (p≤0.05). On day 21, CDDO-Me treatment reduced histological fibrosis, collagen deposition and αSMA production. Lung function was significantly improved at day 21 by treatment with CDDO-Me, as demonstrated by respiratory rate and dynamic compliance. These new findings reveal that CDDO-Me exhibits potent anti-fibrotic and anti-inflammatory properties in vivo. CDDO-Me is a potential new class of drugs to arrest inflammation and ameliorate fibrosis in patients who are predisposed to lung injury and fibrosis incited by cancer treatments (e.g. chemotherapy and radiation) and by systemic autoimmune diseases. PMID:23741300

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

PubMed

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

2016-11-01

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

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

PubMed Central

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

2016-01-01

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

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.

Neurobehavioral Functioning and Survival Following Lung Transplantation

PubMed Central

Blumenthal, James A.; Carney, Robert M.; Freedland, Kenneth E.; O’Hayer, C. Virginia F.; Trulock, Elbert P.; Martinu, Tereza; Schwartz, Todd A.; Hoffman, Benson M.; Koch, Gary G.; Davis, R. Duane; Palmer, Scott M.

2014-01-01

Background: Neurobehavioral functioning is widely recognized as being an important consideration in lung transplant candidates, but little is known about whether these factors are related to clinical outcomes. The present study examined the relationship of neurobehavioral functioning, including measures of executive function and memory, depression, and anxiety, to long-term survival among lung transplant recipients. Methods: The sample was drawn from 201 patients who underwent transplantation at Duke University and Washington University who participated in a dual-site clinical trial investigating medical and psychosocial outcomes in transplant candidates with end-stage lung disease. All patients completed the Beck Depression Inventory-II (BDI-II) and Spielberger State-Trait Anxiety Inventory at baseline and again after 12 weeks, while a subset of 86 patients from Duke University also completed neurocognitive testing. Patients were followed for survival up to 12 years after completing baseline assessments. Results: One hundred eleven patients died over a mean follow-up of 10.8 years (SD = 0.8). Baseline depression, anxiety, and neurocognitive function were examined as predictors of posttransplant survival, controlling for age, 6-min walk distance, FEV, and native disease; education and cardiovascular risk factors were also included in the model for neurocognition. Lower executive function (hazard ratio [HR] = 1.09, P = .012) and memory performance (HR = 1.11, P = .030) were independently associated with greater mortality following lung transplant. Although pretransplant depression and anxiety were not predictive of mortality, patients who scored > 13 on the BDI-II at baseline and after 3 months pretransplant had greater mortality (HR = 1.85 [95% CI, 1.04, 3.28], P = .036). Conclusions: Neurobehavioral functioning, including persistently elevated depressive symptoms and lower neurocognitive performance, was associated with reduced survival after lung transplantation. Trial registry: ClinicalTrials.gov; No.: NCT00113139; URL: www.clinicaltrials.gov PMID:24233282

Lung function status of some Nigerian men and women chronically exposed to fish drying using burning firewood.

PubMed

Peters, E J; Esin, R A; Immananagha, K K; Siziya, S; Osim, E E

1999-05-01

To determine the lung function status of some Nigerian men and women chronically exposed to fish drying using burning firewood. Case control study. Ibaka, Utaewa and Ikanga fishing settlements. 183 males and 192 females engaged in fishing, aged 20 to 45 years who have been exposed for a minimum of five years as cases. The control group comprised sex matched male (142) and female (152) Nigerians from the same area who were not exposed to any known air pollutant. Lung function indices: FVC, FEV1, FEV1% and PEFR. Lung function indices were significantly lower in men engaged in fishing than in their controls: FVC [mean (SD): 2.98 (0.20) vs 3.52 (0.29), p < 0.001]; FEV1 [2.08 (0.18) vs 2.82 (0.25), p < 0.001]; FEV1% [69.8 (3.1) vs 80.2 (6.7), p < 0.001]; and PEFR [335 (22) vs 592 (99), p < 0.001], respectively. Similarly, lung function indices were lower in females in the fishing industry than in their controls; FVC [2.42 (0.17) vs 3.02 (0.24), p < 0.001]; FEV1 [1.70 (0.19) vs 2.55 (0.21), p < 0.001]; FEV1% [72.9 (3.2) vs 84.4 (6.7), p < 0.001]; and PEFR [298 (22) vs 418 (34), p < 0.001]. All the lung function indices (except FEV1%) of the fishermen and women declined significantly (p < 0.001) with their duration of exposure. The results showed a predominantly mixed pattern (restrictive and obstructive) of respiratory defect. There were higher prevalences of respiratory and other symptoms among the cases than the controls. The respiratory symptoms included cough with sputum, chest pain, dyspnoea catarrh and sneezing and unproductive cough. Other symptoms were eye and skin irritation, internal heat and headache. Chronic exposure to fish drying using burning firewood can impair lung function and cause respiratory and other symptoms.

Effect of cannabis smoking on lung function and respiratory symptoms: a structured literature review

PubMed Central

Ribeiro, Luis IG; Ind, Philip W

2016-01-01

As cannabis use increases, physicians need to be familiar with the effects of both cannabis and tobacco on the lungs. However, there have been very few long-term studies of cannabis smoking, mostly due to legality issues and the confounding effects of tobacco. It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC. The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant. Bullous lung disease, barotrauma and cannabis smoking have been recognised in case reports and small series. More work is needed to address the effects of cannabis on lung function, imaging and histological changes. PMID:27763599

Characteristics of elderly patients with COPD and newly diagnosed lung cancer, and factors associated with treatment decision.

PubMed

Qin, Jianwen; Li, Guangsheng; Zhou, Jingmin

2016-01-01

To investigate the clinical features, diagnosis, and treatment status of elderly patients with chronic obstructive pulmonary disease (COPD) complicated with lung cancer. This was a retrospective study of 206 patients aged >60 years with COPD and newly diagnosed lung cancer at the Tianjin Chest Hospital Respiratory Centre between September 2008 and September 2013. Lung function, radiology, and clinical data were retrieved. Among all patients, 57% (117/206) were hospitalized due to acute COPD aggravation, 47% (96/206) had COPD grade III or IV, 95% (195/206), showed diffusion dysfunction in pulmonary function examination, 90% (185/206) had a history of smoking, and 26% (54/206) were treated with inhaled corticosteroids for COPD treatment. Ninety-eight patients suffered from squamous carcinoma, 73 from adenocarcinoma, and 35 from small-cell carcinoma. Clinical staging was I in 36 patients, II in 47 patients, III in 78 patients, and IV in 45 patients. Initial treatments were surgery in 59 patients, chemotherapy in 30 patients, and no treatment in 117 patients. Multivariate analysis showed that age (P<0.001), COPD grades (P=0.01), clinical staging (P<0.001), and pulmonary diffusion function (P=0.007) were independent factors associated with patients with COPD being given treatments for lung cancer. Younger patients with lower COPD grades, earlier lung cancer stage, and better pulmonary diffusion function are more likely to receive treatments.

Functional and prognostic effects when emphysema complicates idiopathic pulmonary fibrosis.

PubMed

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

2017-07-01

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

Effects of an anti-inflammatory VAP-1/SSAO inhibitor, PXS-4728A, on pulmonary neutrophil migration.

PubMed

Schilter, Heidi C; Collison, Adam; Russo, Remo C; Foot, Jonathan S; Yow, Tin T; Vieira, Angelica T; Tavares, Livia D; Mattes, Joerg; Teixeira, Mauro M; Jarolimek, Wolfgang

2015-03-20

The persistent influx of neutrophils into the lung and subsequent tissue damage are characteristics of COPD, cystic fibrosis and acute lung inflammation. VAP-1/SSAO is an endothelial bound adhesion molecule with amine oxidase activity that is reported to be involved in neutrophil egress from the microvasculature during inflammation. This study explored the role of VAP-1/SSAO in neutrophilic lung mediated diseases and examined the therapeutic potential of the selective inhibitor PXS-4728A. Mice treated with PXS-4728A underwent intra-vital microscopy visualization of the cremaster muscle upon CXCL1/KC stimulation. LPS inflammation, Klebsiella pneumoniae infection, cecal ligation and puncture as well as rhinovirus exacerbated asthma models were also assessed using PXS-4728A. Selective VAP-1/SSAO inhibition by PXS-4728A diminished leukocyte rolling and adherence induced by CXCL1/KC. Inhibition of VAP-1/SSAO also dampened the migration of neutrophils to the lungs in response to LPS, Klebsiella pneumoniae lung infection and CLP induced sepsis; whilst still allowing for normal neutrophil defense function, resulting in increased survival. The functional effects of this inhibition were demonstrated in the RV exacerbated asthma model, with a reduction in cellular infiltrate correlating with a reduction in airways hyperractivity. This study demonstrates that the endothelial cell ligand VAP-1/SSAO contributes to the migration of neutrophils during acute lung inflammation, pulmonary infection and airway hyperractivity. These results highlight the potential of inhibiting of VAP-1/SSAO enzymatic function, by PXS-4728A, as a novel therapeutic approach in lung diseases that are characterized by neutrophilic pattern of inflammation.

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

PubMed

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

2010-11-01

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

Enhanced Heme Function and Mitochondrial Respiration Promote the Progression of Lung Cancer Cells

PubMed Central

Alam, Md Maksudul; Shah, Ajit; Cao, Thai M.; Sullivan, Laura A.; Brekken, Rolf; Zhang, Li

2013-01-01

Lung cancer is the leading cause of cancer-related mortality, and about 85% of the cases are non-small-cell lung cancer (NSCLC). Importantly, recent advance in cancer research suggests that altering cancer cell bioenergetics can provide an effective way to target such advanced cancer cells that have acquired mutations in multiple cellular regulators. This study aims to identify bioenergetic alterations in lung cancer cells by directly measuring and comparing key metabolic activities in a pair of cell lines representing normal and NSCLC cells developed from the same patient. We found that the rates of oxygen consumption and heme biosynthesis were intensified in NSCLC cells. Additionally, the NSCLC cells exhibited substantially increased levels in an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins HRG1 and HCP1 that are involved in heme uptake, and various types of oxygen-utilizing hemoproteins such as cytoglobin and cytochromes. Several types of human tumor xenografts also displayed increased levels of such proteins. Furthermore, we found that lowering heme biosynthesis and uptake, like lowering mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. In contrast, lowering heme degradation does not have an effect on lung cancer cells. These results show that increased heme flux and function are a key feature of NSCLC cells. Further, increased generation and supply of heme and oxygen-utilizing hemoproteins in cancer cells will lead to intensified oxygen consumption and cellular energy production by mitochondrial respiration, which would fuel cancer cell proliferation and progression. The results show that inhibiting heme and respiratory function can effectively arrest the progression of lung cancer cells. Hence, understanding heme function can positively impact on research in lung cancer biology and therapeutics. PMID:23704904

A Major Population of Functional KLRG1- ILC2s in Female Lungs Contributes to a Sex Bias in ILC2 Numbers.

PubMed

Kadel, Sapana; Ainsua-Enrich, Erola; Hatipoglu, Ibrahim; Turner, Sean; Singh, Simar; Khan, Sohaib; Kovats, Susan

2018-02-01

Humans show significant sex differences in the incidence and severity of respiratory diseases, including asthma and virus infection. Sex hormones contribute to the female sex bias in type 2 inflammation associated with respiratory diseases, consistent with recent reports that female lungs harbor greater numbers of GATA-3-dependent group 2 innate lymphoid cells (ILC2s). In this study, we determined whether sex hormone levels govern sex differences in the numbers, phenotype, and function of ILC2s in the murine lung and bone marrow (BM). Our data show that lungs of female mice harbor significantly greater ILC2 numbers in homeostasis, in part due to a major subset of ILC2s lacking killer-cell lectin like receptor G1 (KLRG1), a population largely absent in male lungs. The KLRG1 - ILC2s were capable of type 2 cytokine production and increased with age after sexual maturity, suggesting that a unique functional subset exists in females. Experiments with gonadectomized mice or mice bearing either global or lymphocyte restricted estrogen receptor α ( Esr1 ) deficiency showed that androgens rather than estrogens regulated numbers of the KLRG1 - ILC2 subset and ILC2 functional capacity in the lung and BM, as well as levels of GATA-3 expression in BM ILC2s. Furthermore, the frequency of BM PLZF + ILC precursors was higher in males and increased by excess androgens, suggesting that androgens act to inhibit the transition of ILC precursors to ILC2s. Taken together, these data show that a functional subset of KLRG1 - ILC2s in females contributes to the sex bias in lung ILC2s that is observed after reproductive age.

Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

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

Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.

2006-02-15

Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs.more » On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-{alpha} levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later.« less

Obesity disproportionately impacts lung volumes, airflow and exhaled nitric oxide in children.

PubMed

Yao, Tsung-Chieh; Tsai, Hui-Ju; Chang, Su-Wei; Chung, Ren-Hua; Hsu, Jing-Ya; Tsai, Ming-Han; Liao, Sui-Ling; Hua, Man-Chin; Lai, Shen-Hao; Chen, Li-Chen; Yeh, Kuo-Wei; Tseng, Yu-Lun; Lin, Wan-Chen; Chang, Su-Ching; Huang, Jing-Long

2017-01-01

The current literature focusing on the effect of obesity and overweight on lung function and fraction of exhaled nitric oxide (FeNO) in children, particularly among healthy children of non-European descent, remains controversial. Furthermore, whether the relationship of obesity and overweight with lung function and FeNO in children is modified by atopy is unclear. The objective of this study was to examine the effect of excess weight on lung function parameters and FeNO among Asian children, with a particular focus on exploring the potential effect modification by atopy. We investigated the effect of excess weight on lung function and FeNO in a population sample of 1,717 children aged 5 to 18 years and explored the potential modifying effect of atopy. There were positive associations of body mass index (BMI) z-score with forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), and forced expiratory flow at 25-75% (FEF25-75) (all P<0.001), after controlling for confounders. The beta coefficient for FEV1 (0.084) was smaller than that for FVC (0.111). In contrast, a negative association was found between BMI z-score and FEV1/FVC ratio (P<0.001) and FeNO (P = 0.03). A consistent pattern of association for lung function variables was observed when stratifying by atopy. There was a negative association of BMI z-score with FeNO in atopic subjects (P = 0.006), but not in non-atopic subjects (P = 0.46). Excess weight disproportionately impacts lung volumes and airflow in children from the general population, independent of atopic status. Excess weight inversely affects FeNO in atopic but not in non-atopic children.

Renal function preservation with the mTOR inhibitor, Everolimus, after lung transplant.

PubMed

Schneer, Sonia; Kramer, Mordechai R; Fox, Benjamin; Rusanov, Viktoria; Fruchter, Oren; Rosengarten, Dror; Bakal, Ilana; Medalion, Benjamin; Raviv, Yael

2014-06-01

Chronic kidney disease (CKD) is a common complication of calcineurin inhibitors (CNIs) in solid organ transplantation. Previous data suggest that the use of everolimus as an immunosuppressant drug leads to improvement in renal function. The aim of our study was to establish the effect of everolimus in combination with lower doses of CNIs on renal function among lung transplant recipients. Data regarding renal function and pulmonary function were collected from 41 lung transplanted patients in whom treatment was converted to a combination of everolimus with lower doses of CNIs. Patients transferred to everolimus and low dose CNIs showed an improvement in renal function. Patients who continued treatment with everolimus showed improvement in renal function, as opposed to patients who discontinued the treatment. Subjects without proteinuria at baseline showed a better improvement compared with subjects with proteinuria. The incidence of graft rejection did not increase. We concluded that a protocol that includes everolimus and lower doses of CNIs is effective for preserving renal function in lung transplant recipients with CKD. We also believe that an early implementation of everolimus, before proteinuria occurs or creatinine clearance is reduced, could lead to better outcomes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed Central

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

2013-01-01

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

WE-AB-202-02: Incorporating Regional Ventilation Function in Predicting Radiation Fibrosis After Concurrent Chemoradiotherapy for Lung Cancer

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

Lan, F; Jeudy, J; Tseng, H

Purpose: To investigate the incorporation of pre-therapy regional ventilation function in predicting radiation fibrosis (RF) in stage III non-small-cell lung cancer (NSCLC) patients treated with concurrent thoracic chemoradiotherapy. Methods: 37 stage III NSCLC patients were retrospectively studied. Patients received one cycle of cisplatin-gemcitabine, followed by two to three cycles of cisplatin-etoposide concurrently with involved-field thoracic radiotherapy between 46 and 66 Gy (2 Gy per fraction). Pre-therapy regional ventilation images of the lung were derived from 4DCT via a density-change-based image registration algorithm with mass correction. RF was evaluated at 6-months post-treatment using radiographic scoring based on airway dilation and volumemore » loss. Three types of ipsilateral lung metrics were studied: (1) conventional dose-volume metrics (V20, V30, V40, and mean-lung-dose (MLD)), (2) dose-function metrics (fV20, fV30, fV40, and functional mean-lung-dose (fMLD) generated by combining regional ventilation and dose), and (3) dose-subvolume metrics (sV20, sV30, sV40, and subvolume mean-lung-dose (sMLD) defined as the dose-volume metrics computed on the sub-volume of the lung with at least 60% of the quantified maximum ventilation status). Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to evaluate the predictability of these metrics for RF. Results: In predicting airway dilation, the area under the ROC curve (AUC) values for (V20, MLD), (fV20, fMLD), and (sV20, and sMLD) were (0.76, 0.70), (0.80, 0.74) and (0.82, 0.80), respectively. The logistic regression p-values were (0.09, 0.18), (0.02, 0.05) and (0.004, 0.006), respectively. With regard to volume loss, the corresponding AUC values for these metrics were (0.66, 0.57), (0.67, 0.61) and (0.71, 0.69), and p-values were (0.95, 0.90), (0.43, 0.64) and (0.08, 0.12), respectively. Conclusion: The inclusion of regional ventilation function improved predictability of radiation fibrosis. Dose-subvolume metrics provided a promising method for incorporating functional information into the conventional dose-volume parameters for outcome assessment.« less

Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life.

PubMed

Bui, Dinh S; Lodge, Caroline J; Burgess, John A; Lowe, Adrian J; Perret, Jennifer; Bui, Minh Q; Bowatte, Gayan; Gurrin, Lyle; Johns, David P; Thompson, Bruce R; Hamilton, Garun S; Frith, Peter A; James, Alan L; Thomas, Paul S; Jarvis, Deborah; Svanes, Cecilie; Russell, Melissa; Morrison, Stephen C; Feather, Iain; Allen, Katrina J; Wood-Baker, Richard; Hopper, John; Giles, Graham G; Abramson, Michael J; Walters, Eugene H; Matheson, Melanie C; Dharmage, Shyamali C

2018-04-05

Lifetime lung function is related to quality of life and longevity. Over the lifespan, individuals follow different lung function trajectories. Identification of these trajectories, their determinants, and outcomes is important, but no study has done this beyond the fourth decade. We used six waves of the Tasmanian Longitudinal Health Study (TAHS) to model lung function trajectories measured at 7, 13, 18, 45, 50, and 53 years. We analysed pre-bronchodilator FEV 1 z-scores at the six timepoints using group-based trajectory modelling to identify distinct subgroups of individuals whose measurements followed a similar pattern over time. We related the trajectories identified to childhood factors and risk of chronic obstructive pulmonary disease (COPD) using logistic regression, and estimated population-attributable fractions of COPD. Of the 8583 participants in the original cohort, 2438 had at least two waves of lung function data at age 7 years and 53 years and comprised the study population. We identified six trajectories: early below average, accelerated decline (97 [4%] participants); persistently low (136 [6%] participants); early low, accelerated growth, normal decline (196 [8%] participants); persistently high (293 [12%] participants); below average (772 [32%] participants); and average (944 [39%] participants). The three trajectories early below average, accelerated decline; persistently low; and below average had increased risk of COPD at age 53 years compared with the average group (early below average, accelerated decline: odds ratio 35·0, 95% CI 19·5-64·0; persistently low: 9·5, 4·5-20·6; and below average: 3·7, 1·9-6·9). Early-life predictors of the three trajectories included childhood asthma, bronchitis, pneumonia, allergic rhinitis, eczema, parental asthma, and maternal smoking. Personal smoking and active adult asthma increased the impact of maternal smoking and childhood asthma, respectively, on the early below average, accelerated decline trajectory. We identified six potential FEV 1 trajectories, two of which were novel. Three trajectories contributed 75% of COPD burden and were associated with modifiable early-life exposures whose impact was aggravated by adult factors. We postulate that reducing maternal smoking, encouraging immunisation, and avoiding personal smoking, especially in those with smoking parents or low childhood lung function, might minimise COPD risk. Clinicians and patients with asthma should be made aware of the potential long-term implications of non-optimal asthma control for lung function trajectory throughout life, and the role and benefit of optimal asthma control on improving lung function should be investigated in future intervention trials. National Health and Medical Research Council of Australia; European Union's Horizon 2020; The University of Melbourne; Clifford Craig Medical Research Trust of Tasmania; The Victorian, Queensland & Tasmanian Asthma Foundations; The Royal Hobart Hospital; Helen MacPherson Smith Trust; and GlaxoSmithKline. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development of Welding Fumes Health Index (WFHI) for Welding Workplace's Safety and Health Assessment.

PubMed

Hariri, Azian; Paiman, Nuur Azreen; Leman, Abdul Mutalib; Md Yusof, Mohammad Zainal

2014-08-01

This study aimed to develop an index that can rank welding workplace that associate well with possible health risk of welders. Welding Fumes Health Index (WFHI) were developed based on data from case studies conducted in Plant 1 and Plant 2. Personal sampling of welding fumes to assess the concentration of metal constituents along with series of lung function tests was conducted. Fifteen metal constituents were investigated in each case study. Index values were derived from aggregation analysis of metal constituent concentration while significant lung functions were recognized through statistical analysis in each plant. The results showed none of the metal constituent concentration was exceeding the permissible exposure limit (PEL) for all plants. However, statistical analysis showed significant mean differences of lung functions between welders and non-welders. The index was then applied to one of the welding industry (Plant 3) for verification purpose. The developed index showed its promising ability to rank welding workplace, according to the multiple constituent concentrations of welding fumes that associates well with lung functions of the investigated welders. There was possibility that some of the metal constituents were below the detection limit leading to '0' value of sub index, thus the multiplicative form of aggregation model was not suitable for analysis. On the other hand, maximum or minimum operator forms suffer from compensation issues and were not considered in this study.

Indoor exposure to formaldehyde and relation to asthma ...

EPA Pesticide Factsheets

Formaldehyde exposure is associated with asthma-like symptoms in occupational settings, but does exposure at lower concentrations in residential settings contribute to the current high burden of this respiratory disease? We conducted a systematic review and meta-analysis of asthma and lung function in humans, focusing on effects from long-term exposures. Our literature search through August 2013 identified 20 studies of asthma or asthma symptoms and 11 studies of lung function in PubMed and Web of Science meeting our inclusion criteria. For the asthma analysis, significant heterogeneity was present in the entire set of studies (p 0.051 mg/m3) and high occupational (> 0.1 mg/m3). Risk ratios (95% confidence interval) for these three categories, respectively, were 0.99 (0.93, 1.06), 1.5 (1.04, 2.1) and 6.3 (3.8, 10.6). The studies of lung function reported results as percent of predicted accounting for gender, age and height. These were occupational exposures with time-weighted formaldehyde concentrations of 0.1 – 1.5 mg/m3, primarily involving woodworking or chemical production. Overall, mean differences in lung function (95% confidence interval) between exposed and referent groups were -4.48 percent (-6.88, -2.09) for forced expiratory volume 1 second (FEV1), -4.08 percent (-6.33, -1.82) for forced vital capacity (FVC) and -7.29 percent (-11.

Association of ambient air quality with children's lung function in urban and rural Iran.

PubMed

Asgari, M M; DuBois, A; Asgari, M; Gent, J; Beckett, W S

1998-01-01

During the summer of 1994, a cross-sectional epidemiological study, in which the pulmonary function of children in Tehran was compared with pulmonary function in children in a rural town in Iran, was conducted. Four hundred children aged 5-11 y were studied. Daytime ambient nitrogen dioxide, sulfur dioxide, and particulate matter were measured with portable devices, which were placed in the children's neighborhoods on the days of study. Levels of these ambient substances were markedly higher in urban Tehran than in rural areas. Children's parents were questioned about home environmental exposures (including heating source and environmental tobacco smoke) and the children's respiratory symptoms. Pulmonary function was assessed, both by spirometry and peak expiratory flow meter. Forced expiratory volume in 1 s and forced vital capacity-as a percentage of predicted for age, sex and height-were significantly lower in urban children than in rural children. Both measurements evidenced significant reverse correlations with levels of sulfur dioxide, nitrogen dioxide, and particulate matter. Differences in spirometric lung function were not explained by nutritional status, as assessed by height and weight for age, or by home environmental exposures. Reported airway symptoms (i.e., cough, phlegm, and wheeze) were higher among rural children, whereas reported physician diagnosis of bronchitis and asthma were higher among urban children. The association between higher pollutant concentrations and reduced pulmonary function in this urban-rural comparison suggests that there is an effect of urban air pollution on short-term lung function and/or lung growth and development during the preadolescent years.

Association of ambient air quality with children`s lung function in urban and rural Iran

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

Asgari, M.M.; Dubois, A.; Beckett, W.S.

During the summer of 1994, a cross-sectional epidemiological study, in which the pulmonary function of children in Tehran was compared with pulmonary function in children in a rural town in Iran, was conducted. Four hundred children aged 5--11 y were studied. Daytime ambient nitrogen dioxide, sulfur dioxide, and particulate matter were measured with portable devices, which were placed in the children`s neighborhoods on the days of study. Levels of these ambient substances were markedly higher in urban Tehran than in rural areas. Children`s parents were questioned about home environmental exposures (including heating source and environmental tobacco smoke) and the children`smore » respiratory symptoms. Pulmonary function was assessed, both by spirometry and peak expiratory flow meter. Forced expiratory volume in 1 s and forced vital capacity--as a percentage of predicted for age, sex and height--were significantly lower in urban children than in rural children. Both measurements evidenced significant reverse correlations with levels of sulfur dioxide, nitrogen dioxide, and particulate matter. Differences in spirometric lung function were not explained by nutritional status, as assessed by height and weight for age, or by home environmental exposures. Reported airway symptoms were higher among rural children, whereas reported physician diagnosis of bronchitis and asthma were higher among urban children. The association between higher pollutant concentrations and reduced pulmonary function in this urban-rural comparison suggests that there is an effect of urban air pollution on short-term lung function and/or lung growth and development during the preadolescent years.« less

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

PubMed

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

2017-02-01

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

Depletion of tissue plasminogen activator attenuates lung ischemia-reperfusion injury via inhibition of neutrophil extravasation.

PubMed

Zhao, Yunge; Sharma, Ashish K; LaPar, Damien J; Kron, Irving L; Ailawadi, Gorav; Liu, Yuan; Jones, David R; Laubach, Victor E; Lau, Christine L

2011-05-01

Ischemia-reperfusion (IR) injury following lung transplantation remains a major source of early morbidity and mortality. Histologically, this inflammatory process is characterized by neutrophil infiltration and activation. We previously reported that lung IR injury was significantly attenuated in plasminogen activator inhibitor-1-deficient mice. In this study, we explored the potential role of tissue plasminogen activator (tPA) in a mouse lung IR injury model. As a result, tPA knockout (KO) mice were significantly protected from lung IR injury through several mechanisms. At the cellular level, tPA KO specifically blocked neutrophil extravasation into the interstitium, and abundant homotypic neutrophil aggregation (HNA) was detected in the lung microvasculature of tPA KO mice after IR. At the molecular level, inhibition of neutrophil extravasation was associated with reduced expression of platelet endothelial cell adhesion molecule-1 mediated through the tPA/ LDL receptor-related protein/NF-κB signaling pathway, whereas increased P-selectin triggered HNA. At the functional level, tPA KO mice incurred significantly decreased vascular permeability and improved lung function following IR. Protection from lung IR injury in tPA KO mice occurs through a fibrinolysis-independent mechanism. These results suggest that tPA could serve as an important therapeutic target for the prevention and treatment of acute IR injury after lung transplantation.

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

PubMed

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

2015-12-01

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

The alpha2-adrenoreceptor agonist dexmedetomidine protects against lipopolysaccharide-induced apoptosis via inhibition of gap junctions in lung fibroblasts.

PubMed

Zhang, Yuan; Tan, Xiaoming; Xue, Lianfang

2018-01-01

The α2-adrenoceptor inducer dexmedetomidine protects against acute lung injury (ALI), but the mechanism of this effect is largely unknown. The present study investigated the effect of dexmedetomidine on apoptosis induced by lipopolysaccharide (LPS) and the relationship between this effect and gap junction intercellular communication in human lung fibroblast cell line. Flow cytometry was used to detect apoptosis induced by LPS. Parachute dye coupling assay was used to measure gap junction function, and western blot analysis was used to determine the expression levels of connexin43 (Cx43). The results revealed that exposure of human lung fibroblast cell line to LPS for 24 h increased the apoptosis, and pretreatment of dexmedetomidine and 18α-GA significantly reduced LPS-induced apoptosis. Dexmedetomidine exposure for 1 h inhibited gap junction function mainly via a decrease in Cx43 protein levels in human lung fibroblast cell line. These results demonstrated that the inhibition of gap junction intercellular communication by dexmedetomidine affected the LPS-induced apoptosis through inhibition of gap junction function by reducing Cx43 protein levels. The present study provides evidence of a novel mechanism underlying the effects of analgesics in counteracting ALI. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome-wide assessment of gene-by-smoking interactions in COPD.

PubMed

Park, Boram; Koo, So-My; An, Jaehoon; Lee, MoonGyu; Kang, Hae Yeon; Qiao, Dandi; Cho, Michael H; Sung, Joohon; Silverman, Edwin K; Yang, Hyeon-Jong; Won, Sungho

2018-06-18

Cigarette smoke exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) and its interactions with genetic variants could affect lung function. However, few gene-smoking interactions have been reported. In this report, we evaluated the effects of gene-smoking interactions on lung function using Korea Associated Resource (KARE) data with the spirometric variables-forced expiratory volume in 1 s (FEV 1 ). We found that variations in FEV 1 were different among smoking status. Thus, we considered a linear mixed model for association analysis under heteroscedasticity according to smoking status. We found a previously identified locus near SOX9 on chromosome 17 to be the most significant based on a joint test of the main and interaction effects of smoking. Smoking interactions were replicated with Gene-Environment of Interaction and phenotype (GENIE), Multi-Ethnic Study of Atherosclerosis-Lung (MESA-Lung), and COPDGene studies. We found that individuals with minor alleles, rs17765644, rs17178251, rs11870732, and rs4793541, tended to have lower FEV 1 values, and lung function decreased much faster with age for smokers. There have been very few reports to replicate a common variant gene-smoking interaction, and our results revealed that statistical models for gene-smoking interaction analyses should be carefully selected.

[Variations of respiratory parameters in healthy men].

PubMed

Shishkin, G S; Ustiuzhaninova, N V

2006-01-01

The subjects of the study were 656 healthy men living in the south of West Siberia, in whom the basic parameters of gas exchange, lung ventilation, static lung volumes, and bronchial permeability were measured. The significance and incidence of non-pathological changes in the system of external respiration were defined on the basis of statistical and cluster analysis of these parameters. The study shows that individuals with functional changes can be divided into four groups with different characteristics: 1. Steady mobilization of the reserve tissue of the respiratory parts of the lungs as a physiological defense reaction to unfavorable ecological factors; 2. An increased airiness of the respiratory tissue as a sign of a compensatory reaction directed towards maintaining gas homeostasis in frequent and prominent overload of the system of external respiration; 3. Steady hyperventilation as a direct functional response of the organism to the slowing down of oxygen mass transfer in the respiratory parts of the lungs; 4. Restriction of external respiration due to respiratory diseases in the past. Despite differences in the origin, all the studied functional changes have one common feature, i.e. their association with a decrease in external respiratory reserve; all of them should be considered pulmonological risk manifestations.

Emphysema and soluble CD14 are associated with pulmonary nodules in HIV-infected patients: implications for lung cancer screening.

PubMed

Triplette, Matthew; Sigel, Keith M; Morris, Alison; Shahrir, Shahida; Wisnivesky, Juan P; Kong, Chung Y; Diaz, Phillip T; Petraglia, Alycia; Crothers, Kristina

2017-07-31

Lung cancer screening may benefit HIV-infected (HIV) smokers because of an elevated risk of lung cancer, but may have unique harms because of HIV-specific risk factors for false-positive screens. This study seeks to understand whether inflammatory biomarkers and markers of chronic lung disease are associated with noncalcified nodules at least 4 mm (NCN) in HIV compared with uninfected patients. This is a cohort study of Examinations of HIV-Associated Lung Emphysema (EXHALE), including 158 HIV and 133 HIV-uninfected participants. Participants underwent a laboratory assessment [including measurement of D-dimer, interleukin 6, and soluble CD14 (sCD14)], chest computed tomography (CT), and pulmonary function testing. We created multivariable logistic regression models to determine predictors of NCN in the participants stratified by HIV status, with attention to semiqualitative scoring of radiographic emphysema, markers of pulmonary function, and inflammatory biomarkers. Of the 291 participants, 69 had NCN on chest CT. As previously reported, there was no difference in prevalence of these nodules by HIV status. Emphysema and elevated sCD14 demonstrated an association with NCN in HIV participants independent of smoking status, CD4 cell count, HIV viral load, and pulmonary function. Emphysema and sCD14, a marker of immune activation, was associated with a higher prevalence of NCN on chest CT in HIV participants. Patients with chronic immune activation and emphysema may be at higher risk for both false-positive findings and incident lung cancer, thus screening in this group requires further study to understand the balance of benefits and harms.

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.

Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide.

PubMed

Tourkina, Elena; Bonner, Michael; Oates, James; Hofbauer, Ann; Richard, Mathieu; Znoyko, Sergei; Visconti, Richard P; Zhang, Jing; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley

2011-07-01

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD) peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and phenotype and that the hyperaccumulation of fibrocytes in SSc-ILD may result from the altered phenotype and migratory activity of their monocyte precursors.

Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide

PubMed Central

2011-01-01

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD) peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and phenotype and that the hyperaccumulation of fibrocytes in SSc-ILD may result from the altered phenotype and migratory activity of their monocyte precursors. PMID:21722364

Nonintrusive gas monitoring in neonatal lungs using diode laser spectroscopy: feasibility study.

PubMed

Lewander, Märta; Bruzelius, Anders; Svanberg, Sune; Svanberg, Katarina; Fellman, Vineta

2011-12-01

A feasibility study on noninvasive, real-time monitoring of gases in lungs of preterm infants is reported, where a laser-spectroscopic technique using diode lasers tuned to oxygen and water vapor absorption lines was employed on realistic tissue phantoms. Our work suggests that the technique could provide a new possibility for surveillance of the lung function of preterm infants, in particular the oxygenation, which is of prime importance in this patient group.

The role of the occupational therapist in the care of people living with lung cancer.

PubMed

White, Kahren M

2016-06-01

This paper aims to explore the vital role occupational therapists play in enabling people living with lung cancer to continue to actively live. Core assessments and interventions employed by occupational therapists are described in a case study. It will demonstrate how people living with lung cancer can continue to participate in meaningful and chosen life roles, even in the face of functional decline. Skilled management by the occupational therapist of the refractory symptoms of advanced lung cancer supports this participation.

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

Distinct quantitative computed tomography emphysema patterns are associated with physiology and function in smokers.

PubMed

Castaldi, Peter J; San José Estépar, Raúl; Mendoza, Carlos S; Hersh, Craig P; Laird, Nan; Crapo, James D; Lynch, David A; Silverman, Edwin K; Washko, George R

2013-11-01

Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. Compared with percentage of low-attenuation area less than -950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures.

Reference Equations for Static Lung Volumes and TLCO from a Population Sample in Northern Greece.

PubMed

Michailopoulos, Pavlos; Kontakiotis, Theodoros; Spyratos, Dionisios; Argyropoulou-Pataka, Paraskevi; Sichletidis, Lazaros

2015-02-14

Background: The most commonly used reference equations for the measurement of static lung volumes/capacities and transfer factor of the lung for CO (TL CO ) are based on studies around 30-40 years old with significant limitations. Objectives: Our aim was to (1) develop reference equations for static lung volumes and TL CO using the current American Thoracic Society/European Respiratory Society guidelines, and (2) compare the equations derived with those most commonly used. Methods: Healthy Caucasian subjects (234 males and 233 females) aged 18-91 years were recruited. All of them were healthy never smokers with a normal chest X-ray. Static lung volumes and TL CO were measured with a single-breath technique according to the latest guidelines. Results: Curvilinear regression prediction equations derived from the present study were compared with those that are most commonly used. Our reference equations in accordance with the latest studies show lower values for all static lung volume parameters and TL CO as well as a different way of deviation of those parameters (i.e. declining with age total lung capacity, TL CO age decline in both sex and functional residual capacity age rise in males). Conclusions: We suggest that old reference values of static lung volumes and TL CO should be updated, and our perception of deviation of some spirometric parameters should be revised. Our new reference curvilinear equations derived according to the latest guidelines could contribute to the updating by respiratory societies of old existing reference values and result in a better estimation of the lung function of contemporary populations with similar Caucasian characteristics. © 2015 S. Karger AG, Basel.

Effect on lung function of continuous positive airway pressure administered either by infant flow driver or a single nasal prong.

PubMed

Kavvadia, V; Greenough, A; Dimitriou, G

2000-04-01

The aim of this study was to assess if continuous positive airways pressure (CPAP) delivered by an infant flow driver (IFD) was a more effective method of improving lung function than delivering CPAP by a single nasal prong. A total of 36 infants (median gestational age 29 weeks, range 25-35 weeks) were studied, 12 who received CPAP via an IFD, 12 who received CPAP via a single nasal prong and 12 without CPAP. CPAP was administered post extubation if apnoeas and bradycardias or a respiratory acidosis developed or electively if the infant was of birth weight <1.0 kg. Lung function was assessed by the supplementary oxygen requirement and measurement of compliance of the respiratory system using an occlusion technique. Assessments were made immediately prior to and after 24 h of CPAP administration and at similar postnatal ages in the non-CPAP group. The infants who did not require CPAP had better lung function (non significant) than the other two groups before they received CPAP. After 24 h, lung function had improved in both CPAP groups to the level of the non CPAP infants. The supplementary oxygen requirements of all three groups decreased over the 24 h period, but this only reached significance in the single nasal prong group (P<0.05). Four infants supported by the IFD, but none with a single nasal prong, became hyperoxic. Continuous positive airways pressure administration via the infant flow driver appears to offer no short-term advantage over a single nasal prong system when used after extubation in preterm infants.

Lung function changes in coke oven workers during 12 years of follow up

PubMed Central

Wu, J; Griffiths, D; Kreis, I; Darling, C

2004-01-01

Aims: To investigate the effect of exposure to coke oven emissions on the lung function of coke oven workers. Methods: The study population, followed from 1978 and 1990, was 580 male workers with at least two sets of lung function measurements (FVC, FEV1, FEV1/FVC, and FEF25–75%). An annual rate of change (time slope) for age and height adjusted lung function index was estimated for each subject. This "time slope" was then treated as the response variable in a weighted multiple regression analysis with selected predictors. Results: For all 580 subjects, each year of working in the "operation" group (the most exposed) was found to increase the FVC decline by around 0.7 ml/year (95% CI 0.1 to 1.3 ml/year). After the exclusion of 111 subjects without detailed work history, the above finding was confirmed and each year of exposure in "operation" was also found to increase the FEV1 decline by around 0.8 ml/year (95% CI 0.1 to 1.4 ml/year). Conclusions: These findings are consistent with the results of previous cross-sectional studies. Work duration in the most exposed position in the coke ovens was associated with increased annual decline for FVC and FEV1. The estimated effect of one year of work exposure in "operation" is equivalent, in terms of the reduction in lung function, to an estimated 2.1 pack-years of smoking for FVC and 1.2 pack-years of smoking for FEV1. PMID:15258275

Air pollution and environmental risk factors for altered lung function among adult women of an urban slum area of Delhi: A prevalence study.

PubMed

Arora, Shweta; Rasania, S K; Bachani, D; Gandhi, Asha; Chhabra, S K

2018-01-01

Household and ambient air pollution are jointly responsible for about 7 million premature deaths annually. Women living in slums, with unhealthy environment, both indoors and outdoors, particularly those living close to industrial and/or vehicular pollution zones due to multiple sources of air pollution, are at the higher risk of having impaired lung function tests. The aim of this study was to estimate the prevalence of abnormal lung functions and to identify the environmental risk factors associated with them among adult women of 18-59 years. A total of 550 women aged 18-59 years were approached in a representative urban slum. Five hundred consented to participate and 299 had prebronchodilator spirometry satisfying ATS standards. House visits to assess environmental conditions were conducted to determine their association with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Chi-square test was used to test the association of risk factors with lung functions. ANOVA was used to test the association of mean values of FEV1 and FVC with age. Out of 299 participants with acceptable spirometric curves, 5% had reduced FEV1/FVC ratio than the normal and 26.8% and 17.4% had lower values than predicted for FVC and FEV1, respectively. Altered lung function was related to age, tobacco smoking, and history of respiratory disease. Both ambient and household air pollution have a deleterious pulmonary effect on long-term women residents of a representative urban slum in Delhi.

Associations of interleukin-1 gene cluster polymorphisms with C-reactive protein concentration and lung function decline in smoking-induced chronic obstructive pulmonary disease

PubMed Central

Wang, Yu; Shumansky, Karey; Sin, Don D; Man, SF Paul; Akhabir, Loubna; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Sandford, Andrew J; He, Jian-Qing

2015-01-01

Objective: We reported association of haplotypes formed by IL-1b (IL1B)-511C/T (rs16944) and a variable number of tandem repeats (rs2234663) in intron 3 of IL-1 receptor antagonist (IL1RN) with rate of lung function decline in smoking-induced COPD. The aim of current study was to further investigate this association. Methods: We genotyped an additional 19 polymorphisms in IL1 cluster (including IL1A, IL1B and IL1RN) in non-Hispanic whites who had the fastest (n = 268) and the slowest (n = 292) decline of FEV1% predicted in the same study. We also analyzed the association of all 21 polymorphisms with serum CRP levels. Results: None of 21 polymorphisms showed significant association with rate of decline of lung function or CRP levels after adjusting for multiple comparisons. Before adjusting for multiple comparisons, only IL1RN_19327 (rs315949) showed significant association with lung function decline (P = 0.03, additive model). The frequencies of genotypes containing the IL1RN_19327A allele were 71.9% and 62.2%, respectively in the fast and slow decline groups (P = 0.02, odds ratio = 1.6, 95% confidence interval = 1.1-2.3); the IL1B_5200 (rs1143633) and rs2234663 in IL1RN were associated with serum CRP levels (P=0.04 and 0.03, respectively). Conclusions: No single marker was significantly associated with either rate of lung function decline or serum CRP levels. PMID:26722511

miR‐34b‐5p inhibition attenuates lung inflammation and apoptosis in an LPS‐induced acute lung injury mouse model by targeting progranulin

PubMed Central

Xie, Wang; Lu, Qingchun; Wang, Kailing; Lu, Jingjing; Gu, Xia; Zhu, Dongyi; Liu, Fanglei

2018-01-01

Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS‐induced ALI. Here, we have investigated the potential roles of PGRN‐targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. LPS‐induced lung injury and the protective roles of PGRN in ALI were first confirmed. The function of miR‐34b‐5p in ALI was determined by transfection of a miR‐34b‐5p mimic or inhibitor in intro and in vivo. The PGRN level gradually increased and subsequently significantly decreased, reaching its lowest value by 24 hr; PGRN was still elevated compared to the control. The change was accompanied by a release of inflammatory mediators and accumulation of inflammatory cells in the lungs. Using bioinformatics analysis and RT‐PCR, we demonstrated that, among 12 putative miRNAs, the kinetics of the miR‐34b‐5p levels were closely associated with PGRN expression in the lung homogenates. The gain‐ and loss‐of‐function analysis, dual‐luciferase reporter assays, and rescue experiments confirmed that PGRN was the functional target of miR‐34b‐5p. Intravenous injection of miR‐34b‐5p antagomir in vivo significantly inhibited miR‐34b‐5p up‐regulation, reduced inflammatory cytokine release, decreased alveolar epithelial cell apoptosis, attenuated lung inflammation, and improved survival by targeting PGRN during ALI. miR‐34b‐5p knockdown attenuates lung inflammation and apoptosis in an LPS‐induced ALI mouse model by targeting PGRN. This study shows that miR‐34b‐5p and PGRN may be potential targets for ALI treatments. PMID:29150939

In utero and early childhood exposure to arsenic decreases lung function in children

PubMed Central

Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R. Clark; Gandolfi, A. Jay; Gonzalez-De Alba, Cesar

2016-01-01

Background The lung is a target organ for adverse health outcomes following exposure to arsenic. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to arsenic through drinking water, however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of arsenic and its metabolites with lung function in children exposed in utero and in early childhood to high arsenic levels through drinking water. Methods A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic arsenic. Lung function was assessed by spirometry. Results Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 μg/L. The mean urinary arsenic level registered in the studied subjects was 141.2 μg/L and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percent of inorganic arsenic. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Conclusion Exposure to arsenic through drinking water during in utero and early life was associated with a decrease in FVC and with a restrictive spirometric pattern in the children evaluated. PMID:25131850

In utero and early childhood exposure to arsenic decreases lung function in children.

PubMed

Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R Clark; Gandolfi, A Jay; Gonzalez-De Alba, Cesar

2015-04-01

The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⁻¹. The mean urinary As level registered in the studied subjects was 141.2 µg l⁻¹ and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated. Copyright © 2014 John Wiley & Sons, Ltd.

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.

Association of High-Dose Ibuprofen Use, Lung Function Decline, and Long-Term Survival in Children with Cystic Fibrosis.

PubMed

Konstan, Michael W; VanDevanter, Donald R; Sawicki, Gregory S; Pasta, David J; Foreman, Aimee J; Neiman, Evgueni A; Morgan, Wayne J

2018-04-01

Cystic fibrosis deaths result primarily from lung function loss, so chronic respiratory therapies, intended to preserve lung function, are cornerstones of cystic fibrosis care. Although treatment-associated reduction in rate of lung function loss should ultimately improve cystic fibrosis survival, no such relationship has been described for any chronic cystic fibrosis therapy. In part, this is because the ages of most rapid lung function decline-early adolescence-precede the median age of cystic fibrosis deaths by more than a decade. To study associations of high-dose ibuprofen treatment with the rate of forced expiratory volume in 1 second decline and mortality among children followed in the Epidemiologic Study of Cystic Fibrosis and subsequently in the U.S. Cystic Fibrosis Foundation Patient Registry. We performed a matched cohort study using data from Epidemiologic Study of Cystic Fibrosis. Exposure was defined as high-dose ibuprofen use reported at ≥80% of encounters over 2 years. Unexposed children were matched to exposed children 5:1 using propensity scores on the basis of demographic, clinical, and treatment covariates. The rate of decline of percent predicted forced expiratory volume in 1 second during the 2-year follow-up period was estimated by mixed-effects modeling with random slopes and intercepts. Survival over 16 follow-up years in the U.S. Cystic Fibrosis Foundation Patient Registry was compared between treatment groups by using proportional hazards modeling controlling for matching and covariates. We included 775 high-dose ibuprofen users and 3,665 nonusers who were well matched on demographic, clinical, and treatment variables. High-dose ibuprofen users declined on average 1.10 percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 0.51, 1.69) during the 2-year treatment period, whereas nonusers declined at a rate of 1.76% percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 1.48, 2.04) during the corresponding 2-year period, a 37.5% slower decline among users compared with nonusers (95% confidence interval; 0.4%, 71.3%; P = 0.046). The users had better subsequent survival (P < 0.001): the unadjusted and adjusted hazard ratios for mortality (high-dose ibuprofen/non-high-dose ibuprofen) (95% confidence interval) were 0.75 (0.64, 0.87) and 0.82 (0.69, 0.96). In a propensity-score matched cohort study of children with cystic fibrosis, we observed an association between high-dose ibuprofen use and both slower lung function decline and improved long-term survival. These results are consistent with the hypothesis that treatment-associated reduction of lung function decline in children with cystic fibrosis leads to improved survival.

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.

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.

Pulmonary function tests as outcomes for systemic sclerosis interstitial lung disease.

PubMed

Caron, Melissa; Hoa, Sabrina; Hudson, Marie; Schwartzman, Kevin; Steele, Russell

2018-06-30

Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc). We performed a systematic review to characterise the use and validation of pulmonary function tests (PFTs) as surrogate markers for systemic sclerosis-associated interstitial lung disease (SSc-ILD) progression.Five electronic databases were searched to identify all relevant studies. Included studies either used at least one PFT measure as a longitudinal outcome for SSc-ILD progression ( i.e. outcome studies) and/or reported at least one classical measure of validity for the PFTs in SSc-ILD ( i.e. validation studies).This systematic review included 169 outcome studies and 50 validation studies. Diffusing capacity of the lung for carbon monoxide ( D LCO ) was cumulatively the most commonly used outcome until 2010 when it was surpassed by forced vital capacity (FVC). FVC (% predicted) was the primary endpoint in 70.4% of studies, compared to 11.3% for % predicted D LCO Only five studies specifically aimed to validate the PFTs: two concluded that D LCO was the best measure of SSc-ILD extent, while the others did not favour any PFT. These studies also showed respectable validity measures for total lung capacity (TLC).Despite the current preference for FVC, available evidence suggests that D LCO and TLC should not yet be discounted as potential surrogate markers for SSc-ILD progression. Copyright ©ERS 2018.

Intrapulmonary percussive ventilation improves lung function in cystic fibrosis patients chronically colonized with Pseudomonas aeruginosa: a pilot cross-over study.

PubMed

Dingemans, Jozef; Eyns, Hanneke; Willekens, Julie; Monsieurs, Pieter; Van Houdt, Rob; Cornelis, Pierre; Malfroot, Anne; Crabbé, Aurélie

2018-06-01

High levels of shear stress can prevent and disrupt Pseudomonas aeruginosa biofilm formation in vitro. Intrapulmonary percussive ventilation (IPV) could be used to introduce shear stress into the lungs of cystic fibrosis (CF) patients to disrupt biofilms in vivo. We performed a first-of-its-kind pilot clinical study to evaluate short-term IPV therapy at medium (200 bursts per minute, bpm) and high frequency (400 bpm) as compared to autogenic drainage (AD) on lung function and the behavior of P. aeruginosa in the CF lung in four patients who are chronically colonized by P. aeruginosa. A significant difference between the three treatment groups was observed for both the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) (p < 0.05). More specifically, IPV at high frequency significantly increased FEV1 and FVC compared to AD (p < 0.05) and IPV at medium frequency (p < 0.001). IPV at high frequency enhanced the expression levels of P. aeruginosa planktonic marker genes, which was less pronounced with IPV at medium frequency or AD. In conclusion, IPV at high frequency could potentially alter the behavior of P. aeruginosa in the CF lung and improve lung function. The trail was retrospectively registered at the ISRCTN registry on 6 June 2013, under trial registration number ISRCTN75391385.

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

Retinoblastoma function is essential for establishing lung epithelial quiescence after injury.

PubMed

Mason-Richie, Nicole A; Mistry, Meenakshi J; Gettler, Caitlin A; Elayyadi, Asmaa; Wikenheiser-Brokamp, Kathryn A

2008-06-01

The retinoblastoma gene product (RB) regulates cell cycle, quiescence, and survival in a cell type-dependent and environment-dependent manner. RB function is critical in the pulmonary epithelium, as evidenced by nearly universal RB inactivation in lung cancer and increased lung cancer risk in persons with germline RB gene mutations. Lung carcinomas occur in the context of epithelial remodeling induced by cytotoxic damage. Whereas the role of RB in development and normal organ homeostasis has been extensively studied, RB function in the context of cellular injury and repair has remained largely unexplored. In the current studies, the RB gene was selectively deleted in the respiratory epithelium of the mouse. Although RB was not required for establishing or maintaining quiescence during lung homeostasis, RB was essential for establishing quiescence during epithelial repair after injury. Notably, aberrant cell cycle progression was sustained for 9 months after injury in RB-deficient lungs. Prenatal and postnatal RB ablation had similar effects, providing evidence that timing of RB loss was not critical to the outcome and that the injury-induced phenotype was not secondary to compensatory alterations occurring during development. These data show that RB is essential for repair of the respiratory epithelium after cytotoxic damage and support a critical unique role for RB in the context of epithelial remodeling after injury. Because human cancers are associated with chronic cellular damage, these findings have important new implications for RB-mediated tumor suppression.

Bayesian modelling of lung function data from multiple-breath washout tests.

PubMed

Mahar, Robert K; Carlin, John B; Ranganathan, Sarath; Ponsonby, Anne-Louise; Vuillermin, Peter; Vukcevic, Damjan

2018-05-30

Paediatric respiratory researchers have widely adopted the multiple-breath washout (MBW) test because it allows assessment of lung function in unsedated infants and is well suited to longitudinal studies of lung development and disease. However, a substantial proportion of MBW tests in infants fail current acceptability criteria. We hypothesised that a model-based approach to analysing the data, in place of traditional simple empirical summaries, would enable more efficient use of these tests. We therefore developed a novel statistical model for infant MBW data and applied it to 1197 tests from 432 individuals from a large birth cohort study. We focus on Bayesian estimation of the lung clearance index, the most commonly used summary of lung function from MBW tests. Our results show that the model provides an excellent fit to the data and shed further light on statistical properties of the standard empirical approach. Furthermore, the modelling approach enables the lung clearance index to be estimated by using tests with different degrees of completeness, something not possible with the standard approach. Our model therefore allows previously unused data to be used rather than discarded, as well as routine use of shorter tests without significant loss of precision. Beyond our specific application, our work illustrates a number of important aspects of Bayesian modelling in practice, such as the importance of hierarchical specifications to account for repeated measurements and the value of model checking via posterior predictive distributions. Copyright © 2018 John Wiley & Sons, Ltd.

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).

Physical activity levels early after lung transplantation.

PubMed

Wickerson, Lisa; Mathur, Sunita; Singer, Lianne G; Brooks, Dina

2015-04-01

Little is known of the early changes in physical activity after lung transplantation. The purposes of this study were: (1) to describe physical activity levels in patients up to 6 months following lung transplantation and (2) to explore predictors of the change in physical activity in that population. This was a prospective cohort study. Physical activity (daily steps and time spent in moderate-intensity activity) was measured using an accelerometer before and after transplantation (at hospital discharge, 3 months, and 6 months). Additional functional measurements included submaximal exercise capacity (measured with the 6-Minute Walk Test), quadriceps muscle torque, and health-related quality of life (measured with the Medical Outcomes Study 36-Item Short-Form Health Survey 36 [SF-36] and the St George's Respiratory Questionnaire). Thirty-six lung transplant recipients (18 men, 18 women; mean age=49 years, SD=14) completed posttransplant measurements. Before transplant, daily steps were less than a third of the general population. By 3 months posttransplant, the largest improvement in physical activity had occurred, and level of daily steps reached 55% of the general population. The change in daily steps (pretransplant to 3 months posttransplant) was inversely correlated with pretransplant 6-minute walk distance (r=-.48, P=.007), daily steps (r=-.36, P=.05), and SF-36 physical functioning (SF-36 PF) score (r=-.59, P=.0005). The SF-36 PF was a significant predictor of the change in physical activity, accounting for 35% of the variation in change in daily steps. Only individuals who were ambulatory prior to transplant and discharged from the hospital in less than 3 months were included in the study. Physical activity levels improve following lung transplantation, particularly in individuals with low self-reported physical functioning. However, the majority of lung transplant recipients remain sedentary between 3 to 6 months following transplant. The role of exercise training, education, and counseling in further improving physical activity levels in lung transplant recipients should be further explored. © 2015 American Physical Therapy Association.

Childhood pneumonia increases risk for chronic obstructive pulmonary disease: the COPDGene study.

PubMed

Hayden, Lystra P; Hobbs, Brian D; Cohen, Robyn T; Wise, Robert A; Checkley, William; Crapo, James D; Hersh, Craig P

2015-09-21

Development of adult respiratory disease is influenced by events in childhood. The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined. We hypothesize that childhood pneumonia is a risk factor for reduced lung function and COPD in adult smokers. COPD cases and control smokers between 45-80 years old from the United States COPDGene Study were included. Childhood pneumonia was defined by self-report of pneumonia at <16 years. Subjects with lung disease other than COPD or asthma were excluded. Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans. Of 10,192 adult smokers, 854 (8.4%) reported pneumonia in childhood. Childhood pneumonia was associated with COPD (OR 1.40; 95% CI 1.17-1.66), chronic bronchitis, increased COPD exacerbations, and lower lung function: post-bronchodilator FEV1 (69.1 vs. 77.1% predicted), FVC (82.7 vs. 87.4% predicted), FEV1/FVC ratio (0.63 vs. 0.67; p < 0.001 for all comparisons). Childhood pneumonia was associated with increased airway wall thickness on CT, without significant difference in emphysema. Having both pneumonia and asthma in childhood further increased the risk of developing COPD (OR 1.85; 95% CI 1.10-3.18). Children with pneumonia are at increased risk for future smoking-related lung disease including COPD and decreased lung function. This association is supported by airway changes on chest CT scans. Childhood pneumonia may be an important factor in the early origins of COPD, and the combination of pneumonia and asthma in childhood may pose the greatest risk. ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).

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.

Nutrition Status Parameters and Hydration Status by Bioelectrical Impedance Vector Analysis Were Associated With Lung Function Impairment in Children and Adolescents With Cystic Fibrosis.

PubMed

Hauschild, Daniela Barbieri; Barbosa, Eliana; Moreira, Emilia Addison Machado; Ludwig Neto, Norberto; Platt, Vanessa Borges; Piacentini Filho, Eduardo; Wazlawik, Elisabeth; Moreno, Yara Maria Franco

2016-06-01

(1) To compare nutrition and hydration status between a group of children/adolescents with cystic fibrosis (CFG; n = 46; median age, 8.5 years) and a control group without cystic fibrosis (CG). (2) To examine the association of nutrition and hydration status with lung function in the CFG. A cross-sectional study. Nutrition screening, anthropometric parameters, and bioelectrical impedance analysis (BIA) were assessed. The z scores for body mass index for age, height for age, mid upper arm circumference, triceps and subscapular skinfold thickness, mid upper arm muscle area, resistance/height, and reactance/height were calculated. Bioelectrical impedance vector analysis was conducted. Forced expiratory volume in 1 second <80% was considered lung function impairment. An adjusted logistic regression was applied (P < .05). In the CFG, lung function impairment was observed in 51.1%. All anthropometric parameters were lower, and the mean z-resistance/height and z-reactance/height were higher in the CFG (P < .05) compared with the CG. In the CFG, 43% were severely/mildly dehydrated, while none were in the CG (P = .007). In the CFG, there was an association between high nutrition risk-via nutrition screening (odds ratio [OR], 22.28; P < .05), lower values of anthropometric parameters, higher z-resistance/height (OR, 2.23; P < .05) and z-reactance/height (OR, 1.81; P < .05), and dehydration (OR, 4.94; P < .05)-and lung function impairment. The CFG exhibited a compromised nutrition status assessed by anthropometric and BIA parameters. Nutrition screening, anthropometric and BIA parameters, and hydration status were associated with lung function. © 2016 American Society for Parenteral and Enteral Nutrition.

Influence of stapling the intersegmental planes on lung volume and function after segmentectomy.

PubMed

Tao, Hiroyuki; Tanaka, Toshiki; Hayashi, Tatsuro; Yoshida, Kumiko; Furukawa, Masashi; Yoshiyama, Koichi; Okabe, Kazunori

2016-10-01

Dividing the intersegmental planes with a stapler during pulmonary segmentectomy leads to volume loss in the remnant segment. The aim of this study was to assess the influence of segment division methods on preserved lung volume and pulmonary function after segmentectomy. Using image analysis software on computed tomography (CT) images of 41 patients, the ratio of remnant segment and ipsilateral lung volume to their preoperative values (R-seg and R-ips) was calculated. The ratio of postoperative actual forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) per those predicted values based on three-dimensional volumetry (R-FEV1 and R-FVC) was also calculated. Differences in actual/predicted ratios of lung volume and pulmonary function for each of the division methods were analysed. We also investigated the correlations of the actual/predicted ratio of remnant lung volume with that of postoperative pulmonary function. The intersegmental planes were divided by either electrocautery or with a stapler in 22 patients and with a stapler alone in 19 patients. Mean values of R-seg and R-ips were 82.7 (37.9-140.2) and 104.9 (77.5-129.2)%, respectively. The mean values of R-FEV1 and R-FVC were 103.9 (83.7-135.1) and 103.4 (82.2-125.1)%, respectively. There were no correlations between the actual/predicted ratio of remnant lung volume and pulmonary function based on the division method. Both R-FEV1 and R-FVC were correlated not with R-seg, but with R-ips. Stapling does not lead to less preserved volume or function than electrocautery in the division of the intersegmental planes. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Technical advance: live-imaging analysis of human dendritic cell migrating behavior under the influence of immune-stimulating reagents in an organotypic model of lung.

PubMed

Nguyen Hoang, Anh Thu; Chen, Puran; Björnfot, Sofia; Högstrand, Kari; Lock, John G; Grandien, Alf; Coles, Mark; Svensson, Mattias

2014-09-01

This manuscript describes technical advances allowing manipulation and quantitative analyses of human DC migratory behavior in lung epithelial tissue. DCs are hematopoietic cells essential for the maintenance of tissue homeostasis and the induction of tissue-specific immune responses. Important functions include cytokine production and migration in response to infection for the induction of proper immune responses. To design appropriate strategies to exploit human DC functional properties in lung tissue for the purpose of clinical evaluation, e.g., candidate vaccination and immunotherapy strategies, we have developed a live-imaging assay based on our previously described organotypic model of the human lung. This assay allows provocations and subsequent quantitative investigations of DC functional properties under conditions mimicking morphological and functional features of the in vivo parental tissue. We present protocols to set up and prepare tissue models for 4D (x, y, z, time) fluorescence-imaging analysis that allow spatial and temporal studies of human DCs in live epithelial tissue, followed by flow cytometry analysis of DCs retrieved from digested tissue models. This model system can be useful for elucidating incompletely defined pathways controlling DC functional responses to infection and inflammation in lung epithelial tissue, as well as the efficacy of locally administered candidate interventions. © 2014 Society for Leukocyte Biology.

Increased lung function decline in blue-collar workers exposed to welding fumes.

PubMed

Thaon, Isabelle; Demange, Valérie; Herin, Fabrice; Touranchet, Annie; Paris, Christophe

2012-07-01

There is no consensus at the present time about the effect of welding on lung function decline. This study compared lung function decline between blue-collar workers exposed and not exposed to welding fumes in a French longitudinal cohort of 21,238 subjects aged 37 to 52 years at inclusion. Medical data, occupation, sector of activity, and spirometry were recorded twice by occupational physicians in 1990 and 1995. A job-exposure matrix was used to identify 503 male blue-collar workers exposed to welding fumes and 709 control subjects and to define the weekly duration of exposure to welding fumes. Baseline lung function parameters were higher in workers exposed to welding fumes than in control subjects. After a 5-year follow-up, welding-fume exposure was associated with a nonsignificant decline in FVC (P = .06) and FEV(1) (P = .07) after adjustment for age, pack-years, BMI, and baseline value of the parameter. A significant accelerated decline in FEV(1) (P = .046) was also observed in never smokers exposed to welding fumes. An “exposure-response” relationship was observed between FEV(1) decline and weekly duration of exposure to welding fumes in nonsmokers but not in smokers. Blue-collar workers exposed to welding fumes showed accelerated decline in lung function, which, in nonsmokers, was related to weekly duration of exposure.

Hyperpolarized Xenon-129 Gas-Exchange Imaging of Lung Microstructure: First Case Studies in Subjects with Obstructive Lung Disease

PubMed Central

Dregely, Isabel; Mugler, John P.; Ruset, Iulian C.; Altes, Talissa A.; Mata, Jaime F.; Miller, G. Wilson; Ketel, Jeffrey; Ketel, Steve; Distelbrink, Jan; Hersman, F.W.; Ruppert, Kai

2011-01-01

Purpose To develop and test a method to non-invasively assess the functional lung microstructure. Materials and Methods The Multiple exchange time Xenon polarization Transfer Contrast technique (MXTC) encodes xenon gas-exchange contrast at multiple delay times permitting two lung-function parameters to be derived: 1) MXTC-F, the long exchange-time depolarization value, which is proportional to the tissue to alveolar-volume ratio and 2) MXTC-S, the square root of the xenon exchange-time constant, which characterizes thickness and composition of alveolar septa. Three healthy volunteers, one asthmatic and two COPD (GOLD stage I and II) subjects were imaged with MXTC MRI. In a subset of subjects, hyperpolarized xenon-129 ADC MRI and CT imaging were also performed. Results The MXTC-S parameter was found to be elevated in subjects with lung disease (p-value = 0.018). In the MXTC-F parameter map it was feasible to identify regional loss of functional tissue in a COPD patient. Further, the MXTC-F map showed excellent regional correlation with CT and ADC (ρ ≥ 0.90) in one COPD subject. Conclusion The functional tissue-density parameter MXTC-F showed regional agreement with other imaging techniques. The newly developed parameter MXTC-S, which characterizes the functional thickness of alveolar septa, has potential as a novel biomarker for regional parenchymal inflammation or thickening. PMID:21509861

Longitudinal analysis of respiratory outcomes among bauxite exposed workers in Western Australia.

PubMed

Dennekamp, Martine; de Klerk, Nicholas Hubert; Reid, Alison; Abramson, Michael John; Cui, Jisheng; Del Monaco, Anthony; Fritschi, Lin; Benke, Geza Paul; Sim, Malcolm Ross; Musk, Arthur William

2015-08-01

Occupational exposure to bauxite is common in the aluminium industry but little is known about the associated health effects. This study investigates respiratory health in relation to respirable bauxite dust exposure longitudinally over a 13 year period. An inception cohort study recruited 91 male bauxite miners and 363 male alumina refinery workers. Annual measurements of respiratory symptoms and lung function were made. Cumulative exposure to bauxite was derived from job histories and air monitoring data. Mixed-effects modeling was used. No associations were found between cumulative bauxite exposure and respiratory symptoms or lung function. However, when analysis was restricted to the first three rounds, FEV1 was significantly lower in all exposure groups than in those unexposed but with no significant trend. Increasing exposure to bauxite dust in the aluminum industry was not associated with respiratory symptoms or consistent decrements in lung function. © 2015 Wiley Periodicals, Inc.

Longitudinal and Cross-sectional Analyses of Lung Function in Toluene Diisocyanate Production Workers.

PubMed

Wang, Mei Lin; Storey, Eileen; Cassidy, Laura D; Doney, Brent; Conner, Patrick R; Collins, James J; Carson, Michael; Molenaar, Don

2017-12-01

The aim of this study was to investigate lung function among toluene diisocyanate (TDI) production workers. One hundred ninety-seven U.S workers performed spirometry from 2006 through 2012. Results were compared within the study cohort and with U.S. population measures. A mixed-effects model assessed factors affecting repeated forced expiratory volume in 1 second (FEV1) measurements. The cohort's mean FEV1 and forced vital capacity (FVC) percent reference values, although greater than 90%, were significantly lower and the prevalence of abnormal spirometry (predominantly restrictive pattern) was significantly higher than in the U.S. Differences in lung function among workers with higher cumulative TDI exposure were in the direction of an exposure effect, but not significant. We found little evidence of an adverse effect of TDI exposure on longitudinal spirometry in these workers. The association between TDI exposure and the increasing prevalence of a restrictive pattern needs further exploration.

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.

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.

Long-term sequelae after lung abscess in children - Two tertiary centers' experience.

PubMed

Wojsyk-Banaszak, I; Krenke, K; Jończyk-Potoczna, K; Ksepko, K; Wielebska, A; Mikoś, M; Bręborowicz, A

2018-05-01

The aim of the study was to describe the epidemiology and clinical characteristic of children hospitalized with pneumonia complicated by lung abscess, as well as to evaluate the long-term sequelae of the disease. A retrospective review of medical records of all patients treated for pulmonary abscess in two tertiary centers was undertaken. Pulmonary function tests and lung ultrasound were performed at a follow-up. During the study period, 5151 children with pneumonia were admitted, and 49 (0.95%) cases were complicated with lung abscess. In 38 (77.5%) patients, lung abscess was treated solely with antibiotics, and in nine cases (16.3%) surgically. In 21 (51.21%) children complete radiological regression was documented. The mean time for radiological abnormalities regression was 84.14 ± 51.57 days, regardless of the treatment mode. Fifteen patients were followed up at 61.6 ± 28.3 months after discharge. Lung ultrasound revealed minor residual abnormalities: pleural thickening, subpleural consolidations and line B artefacts in 11 (73.3%) children. Pulmonary function tests results were abnormal in eight (53.3%) patients, the most frequent abnormality being hyperinflation. We did not find a restrictive disorder in any of the children. There were no deaths in our study. Lung abscess is a rare but severe complication of pneumonia in children. Most children recover uneventfully with no significant long-term pulmonary sequelae. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

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

Hyperpolarized (3)He magnetic resonance imaging: comparison with four-dimensional x-ray computed tomography imaging in lung cancer.

PubMed

Mathew, Lindsay; Wheatley, Andrew; Castillo, Richard; Castillo, Edward; Rodrigues, George; Guerrero, Thomas; Parraga, Grace

2012-12-01

Pulmonary functional imaging using four-dimensional x-ray computed tomographic (4DCT) imaging and hyperpolarized (3)He magnetic resonance imaging (MRI) provides regional lung function estimates in patients with lung cancer in whom pulmonary function measurements are typically dominated by tumor burden. The aim of this study was to evaluate the quantitative spatial relationship between 4DCT and hyperpolarized (3)He MRI ventilation maps. Eleven patients with lung cancer provided written informed consent to 4DCT imaging and MRI performed within 11 ± 14 days. Hyperpolarized (3)He MRI was acquired in breath-hold after inhalation from functional residual capacity of 1 L hyperpolarized (3)He, whereas 4DCT imaging was acquired over a single tidal breath of room air. For hyperpolarized (3)He MRI, the percentage ventilated volume was generated using semiautomated segmentation; for 4DCT imaging, pulmonary function maps were generated using the correspondence between identical tissue elements at inspiratory and expiratory phases to generate percentage ventilated volume. After accounting for differences in image acquisition lung volumes ((3)He MRI: 1.9 ± 0.5 L ipsilateral, 2.3 ± 0.7 L contralateral; 4DCT imaging: 1.2 ± 0.3 L ipsilateral, 1.3 ± 0.4 L contralateral), there was no significant difference in percentage ventilated volume between hyperpolarized (3)He MRI (72 ± 11% ipsilateral, 79 ± 12% contralateral) and 4DCT imaging (74 ± 3% ipsilateral, 75 ± 4% contralateral). Spatial correspondence between 4DCT and (3)He MRI ventilation was evaluated using the Dice similarity coefficient index (ipsilateral, 86 ± 12%; contralateral, 88 ± 12%). Despite rather large differences in image acquisition breathing maneuvers, good spatial and significant quantitative agreement was observed for ventilation maps on hyperpolarized (3)He MRI and 4DCT imaging, suggesting that pulmonary regions with good lung function are similar between modalities in this small group of patients with lung cancer. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.

Genetic regulation of gene expression in the lung identifies CST3 and CD22 as potential causal genes for airflow obstruction.

PubMed

Lamontagne, Maxime; Timens, Wim; Hao, Ke; Bossé, Yohan; Laviolette, Michel; Steiling, Katrina; Campbell, Joshua D; Couture, Christian; Conti, Massimo; Sherwood, Karen; Hogg, James C; Brandsma, Corry-Anke; van den Berge, Maarten; Sandford, Andrew; Lam, Stephen; Lenburg, Marc E; Spira, Avrum; Paré, Peter D; Nickle, David; Sin, Don D; Postma, Dirkje S

2014-11-01

COPD is a complex chronic disease with poorly understood pathogenesis. Integrative genomic approaches have the potential to elucidate the biological networks underlying COPD and lung function. We recently combined genome-wide genotyping and gene expression in 1111 human lung specimens to map expression quantitative trait loci (eQTL). To determine causal associations between COPD and lung function-associated single nucleotide polymorphisms (SNPs) and lung tissue gene expression changes in our lung eQTL dataset. We evaluated causality between SNPs and gene expression for three COPD phenotypes: FEV(1)% predicted, FEV(1)/FVC and COPD as a categorical variable. Different models were assessed in the three cohorts independently and in a meta-analysis. SNPs associated with a COPD phenotype and gene expression were subjected to causal pathway modelling and manual curation. In silico analyses evaluated functional enrichment of biological pathways among newly identified causal genes. Biologically relevant causal genes were validated in two separate gene expression datasets of lung tissues and bronchial airway brushings. High reliability causal relations were found in SNP-mRNA-phenotype triplets for FEV(1)% predicted (n=169) and FEV(1)/FVC (n=80). Several genes of potential biological relevance for COPD were revealed. eQTL-SNPs upregulating cystatin C (CST3) and CD22 were associated with worse lung function. Signalling pathways enriched with causal genes included xenobiotic metabolism, apoptosis, protease-antiprotease and oxidant-antioxidant balance. By using integrative genomics and analysing the relationships of COPD phenotypes with SNPs and gene expression in lung tissue, we identified CST3 and CD22 as potential causal genes for airflow obstruction. This study also augmented the understanding of previously described COPD pathways. 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.

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

Heterodimerization controls localization of Duox-DuoxA NADPH oxidases in airway cells.

PubMed

Luxen, Sylvia; Noack, Deborah; Frausto, Monika; Davanture, Suzel; Torbett, Bruce E; Knaus, Ulla G

2009-04-15

Duox NADPH oxidases generate hydrogen peroxide at the air-liquid interface of the respiratory tract and at apical membranes of thyroid follicular cells. Inactivating mutations of Duox2 have been linked to congenital hypothyroidism, and epigenetic silencing of Duox is frequently observed in lung cancer. To study Duox regulation by maturation factors in detail, its association with these factors, differential use of subunits and localization was analyzed in a lung cancer cell line and undifferentiated or polarized lung epithelial cells. We show here that Duox proteins form functional heterodimers with their respective DuoxA subunits, in close analogy to the phagocyte NADPH oxidase. Characterization of novel DuoxA1 isoforms and mispaired Duox-DuoxA complexes revealed that heterodimerization is a prerequisite for reactive oxygen species production. Functional Duox1 and Duox2 localize to the leading edge of migrating cells, augmenting motility and wound healing. DuoxA subunits are responsible for targeting functional oxidases to distinct cellular compartments in lung epithelial cells, including Duox2 expression in ciliated cells in an ex vivo differentiated lung epithelium. As these locations probably define signaling specificity of Duox1 versus Duox2, these findings will facilitate monitoring Duox isoform expression in lung disease, a first step for early screening procedures and rational drug development.

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.

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

Dysregulated Functions of Lung Macrophage Populations in COPD.

PubMed

Kapellos, Theodore S; Bassler, Kevin; Aschenbrenner, Anna C; Fujii, Wataru; Schultze, Joachim L

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD.

Dysregulated Functions of Lung Macrophage Populations in COPD

PubMed Central

Bassler, Kevin; Aschenbrenner, Anna C.

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. PMID:29670919

Dynamic dual-energy chest radiography: a potential tool for lung tissue motion monitoring and kinetic study

PubMed Central

Xu, Tong; Ducote, Justin L.; Wong, Jerry T.; Molloi, Sabee

2011-01-01

Dual-energy chest radiography has the potential to provide better diagnosis of lung disease by removing the bone signal from the image. Dynamic dual-energy radiography is now possible with the introduction of digital flat panel detectors. The purpose of this study is to evaluate the feasibility of using dynamic dual-energy chest radiography for functional lung imaging and tumor motion assessment. The dual energy system used in this study can acquire up to 15 frame of dual-energy images per second. A swine animal model was mechanically ventilated and imaged using the dual-energy system. Sequences of soft-tissue images were obtained using dual-energy subtraction. Time subtracted soft-tissue images were shown to be able to provide information on regional ventilation. Motion tracking of a lung anatomic feature (a branch of pulmonary artery) was performed based on an image cross-correlation algorithm. The tracking precision was found to be better than 1 mm. An adaptive correlation model was established between the above tracked motion and an external surrogate signal (temperature within the tracheal tube). This model is used to predict lung feature motion using the continuous surrogate signal and low frame rate dual-energy images (0.1 to 3.0 frames /sec). The average RMS error of the prediction was (1.1 ± 0.3) mm. The dynamic dual-energy was shown to be potentially useful for lung functional imaging such as regional ventilation and kinetic studies. It can also be used for lung tumor motion assessment and prediction during radiation therapy. PMID:21285477

Dynamic dual-energy chest radiography: a potential tool for lung tissue motion monitoring and kinetic study.

PubMed

Xu, Tong; Ducote, Justin L; Wong, Jerry T; Molloi, Sabee

2011-02-21

Dual-energy chest radiography has the potential to provide better diagnosis of lung disease by removing the bone signal from the image. Dynamic dual-energy radiography is now possible with the introduction of digital flat-panel detectors. The purpose of this study is to evaluate the feasibility of using dynamic dual-energy chest radiography for functional lung imaging and tumor motion assessment. The dual-energy system used in this study can acquire up to 15 frames of dual-energy images per second. A swine animal model was mechanically ventilated and imaged using the dual-energy system. Sequences of soft-tissue images were obtained using dual-energy subtraction. Time subtracted soft-tissue images were shown to be able to provide information on regional ventilation. Motion tracking of a lung anatomic feature (a branch of pulmonary artery) was performed based on an image cross-correlation algorithm. The tracking precision was found to be better than 1 mm. An adaptive correlation model was established between the above tracked motion and an external surrogate signal (temperature within the tracheal tube). This model is used to predict lung feature motion using the continuous surrogate signal and low frame rate dual-energy images (0.1-3.0 frames per second). The average RMS error of the prediction was (1.1 ± 0.3) mm. The dynamic dual energy was shown to be potentially useful for lung functional imaging such as regional ventilation and kinetic studies. It can also be used for lung tumor motion assessment and prediction during radiation therapy.

Relationship of the functional movement screen in-line lunge to power, speed, and balance measures.

PubMed

Hartigan, Erin H; Lawrence, Michael; Bisson, Brian M; Torgerson, Erik; Knight, Ryan C

2014-05-01

The in-line lunge of the Functional Movement Screen (FMS) evaluates lateral stability, balance, and movement asymmetries. Athletes who score poorly on the in-line lunge should avoid activities requiring power or speed until scores are improved, yet relationships between the in-line lunge scores and other measures of balance, power, and speed are unknown. (1) Lunge scores will correlate with center of pressure (COP), maximum jump height (MJH), and 36.6-meter sprint time and (2) there will be no differences between limbs on lunge scores, MJH, or COP. Descriptive laboratory study. Level 3. Thirty-seven healthy, active participants completed the first 3 tasks of the FMS (eg, deep squat, hurdle step, in-line lunge), unilateral drop jumps, and 36.6-meter sprints. A 3-dimensional motion analysis system captured MJH. Force platforms measured COP excursion. A laser timing system measured 36.6-m sprint time. Statistical analyses were used to determine whether a relationship existed between lunge scores and COP, MJH, and 36.6-m speed (Spearman rho tests) and whether differences existed between limbs in lunge scores (Wilcoxon signed-rank test), MJH, and COP (paired t tests). Lunge scores were not significantly correlated with COP, MJH, or 36.6-m sprint time. Lunge scores, COP excursion, and MJH were not statistically different between limbs. Performance on the FMS in-line lunge was not related to balance, power, or speed. Healthy participants were symmetrical in lunging measures and MJH. Scores on the FMS in-line lunge should not be attributed to power, speed, or balance performance without further examination. However, assessing limb symmetry appears to be clinically relevant.

Systems for Lung Volume Standardization during Static and Dynamic MDCT-based Quantitative Assessment of Pulmonary Structure and Function

PubMed Central

Fuld, Matthew K.; Grout, Randall; Guo, Junfeng; Morgan, John H.; Hoffman, Eric A.

2013-01-01

Rationale and Objectives Multidetector-row Computed Tomography (MDCT) has emerged as a tool for quantitative assessment of parenchymal destruction, air trapping (density metrics) and airway remodeling (metrics relating airway wall and lumen geometry) in chronic obstructive pulmonary disease (COPD) and asthma. Critical to the accuracy and interpretability of these MDCT-derived metrics is the assurance that the lungs are scanned during a breath-hold at a standardized volume. Materials and Methods A computer monitored turbine-based flow meter system was developed to control patient breath-holds and facilitate static imaging at fixed percentages of the vital capacity. Due to calibration challenges with gas density changes during multi-breath xenon-CT an alternative system was required. The design incorporated dual rolling seal pistons. Both systems were tested in a laboratory environment and human subject trials. Results The turbine-based system successfully controlled lung volumes in 32/37 subjects, having a linear relationship for CT measured air volume between repeated scans: for all scans, the mean and confidence interval of the differences (scan1-scan2) was −9 ml (−169, 151); for TLC alone 6 ml (−164, 177); for FRC alone, −23 ml (−172, 126). The dual-piston system successfully controlled lung volume in 31/41 subjects. Study failures related largely to subject non-compliance with verbal instruction and gas leaks around the mouthpiece. Conclusion We demonstrate the successful use of a turbine-based system for static lung volume control and demonstrate its inadequacies for dynamic xenon-CT studies. Implementation of a dual-rolling seal spirometer has been shown to adequately control lung volume for multi-breath wash-in xenon-CT studies. These systems coupled with proper patient coaching provide the tools for the use of CT to quantitate regional lung structure and function. The wash-in xenon-CT method for assessing regional lung function, while not necessarily practical for routine clinical studies, provides for a dynamic protocol against which newly emerging single breath, dual-energy xenon-CT measures can be validated. PMID:22555001

Should regional ventilation function be considered during radiation treatment planning to prevent radiation-induced complications?

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

Lan, Fujun; Jeudy, Jean; D’Souza, Warren

Purpose: To investigate the incorporation of pretherapy regional ventilation function in predicting radiation fibrosis (RF) in stage III nonsmall cell lung cancer (NSCLC) patients treated with concurrent thoracic chemoradiotherapy. Methods: Thirty-seven patients with stage III NSCLC were retrospectively studied. Patients received one cycle of cisplatin–gemcitabine, followed by two to three cycles of cisplatin–etoposide concurrently with involved-field thoracic radiotherapy (46–66 Gy; 2 Gy/fraction). Pretherapy regional ventilation images of the lung were derived from 4D computed tomography via a density change–based algorithm with mass correction. In addition to the conventional dose–volume metrics (V{sub 20}, V{sub 30}, V{sub 40}, and mean lung dose),more » dose–function metrics (fV{sub 20}, fV{sub 30}, fV{sub 40}, and functional mean lung dose) were generated by combining regional ventilation and radiation dose. A new class of metrics was derived and referred to as dose–subvolume metrics (sV{sub 20}, sV{sub 30}, sV{sub 40}, and subvolume mean lung dose); these were defined as the conventional dose–volume metrics computed on the functional lung. Area under the receiver operating characteristic curve (AUC) values and logistic regression analyses were used to evaluate these metrics in predicting hallmark characteristics of RF (lung consolidation, volume loss, and airway dilation). Results: AUC values for the dose–volume metrics in predicting lung consolidation, volume loss, and airway dilation were 0.65–0.69, 0.57–0.70, and 0.69–0.76, respectively. The respective ranges for dose–function metrics were 0.63–0.66, 0.61–0.71, and 0.72–0.80 and for dose–subvolume metrics were 0.50–0.65, 0.65–0.75, and 0.73–0.85. Using an AUC value = 0.70 as cutoff value suggested that at least one of each type of metrics (dose–volume, dose–function, dose–subvolume) was predictive for volume loss and airway dilation, whereas lung consolidation cannot be accurately predicted by any of the metrics. Logistic regression analyses showed that dose–function and dose–subvolume metrics were significant (P values ≤ 0.02) in predicting volume airway dilation. Likelihood ratio test showed that when combining dose–function and/or dose–subvolume metrics with dose–volume metrics, the achieved improvements of prediction accuracy on volume loss and airway dilation were significant (P values ≤ 0.04). Conclusions: The authors’ results demonstrated that the inclusion of regional ventilation function improved accuracy in predicting RF. In particular, dose–subvolume metrics provided a promising method for preventing radiation-induced pulmonary complications.« less

The Lung Microbiome After Lung Transplantation

PubMed Central

Becker, Julia B.; Poroyko, Valeriy

2014-01-01

Summary Lung transplantation survival remains significantly impacted by infections and the development of chronic rejection manifesting as bronchiolitis obliterans syndrome (BOS). Traditional microbiologic data has provided insight into the role of infections in BOS. Now, new non-culture-based techniques have been developed to characterize the entire population of microbes resident on the surfaces of the body, also known as the human microbiome. Early studies have identified that lung transplant patients have a different lung microbiome and have demonstrated the important finding that the transplant lung microbiome changes over time. Furthermore, both unique bacterial populations and longitudinal changes in the lung microbiome have now been suggested to play a role in the development of BOS. In the future, this technology will need to be combined with functional assays and assessment of the immune responses in the lung to help further explain the microbiome’s role in the failing lung allograft. PMID:24601662

New insights into saccular development and vascular formation in lung allografts under the renal capsule

PubMed Central

Vu, Thiennu H.; Alemayehu, Yemisrach; Werb, Zena

2009-01-01

The study of distal lung morphogenesis and vascular development would be greatly facilitated by an in vitro or ex vivo experimental model. In this study we show that the growth of mouse embryonic day 12.5 lung rudiments implanted underneath the kidney capsules of syngeneic or immunodeficient hosts follows closely lung development in utero. The epithelium develops extensively with both proximal and distal differentiation to the saccular stage. The vasculature also develops extensively. Large blood vessels accompany large airways and capillaries develop within the saccular walls. Interestingly, vessels in the lung grafts develop from endothelial progenitor cells endogenous to the explants and host vessels do not vascularize the grafts independently. This suggests that embryonic lungs possess mechanisms to prevent the inappropriate ingrowth of surrounding vessels. However, vessels in the lung grafts do connect to host vessels, showing that embryonic lungs have the ability to stimulate host angiogenesis and recruit host vessel connections. These data support the hypothesis that the lung vasculature develops by both vasculogenic and angiogenic processes: a vascular network develops in situ in lung mesenchyme, which is then connected to angiogenic processes from central vessels. The lung renal capsule allograft is thus an excellent model to study the development of the pulmonary vasculature and of late fetal lung development that requires a functional blood supply. PMID:12591600

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.

Respirator triggering of electron beam computed tomography (EBCT): evaluation of dynamic changes during mechanical expiration in the traumatized patient

NASA Astrophysics Data System (ADS)

Recheis, Wolfgang A.; Kleinsasser, Axel; Hatschenberger, Robert; Knapp, Rudolf; zur Nedden, Dieter; Hoermann, Christoph

1999-05-01

The purpose of this project is to evaluate the dynamic changes during expiration at different levels of positive end- expiratory pressure (PEEP) in the ventilated patient. We wanted to discriminate between normal lung function and acute respiratory distress syndrome (ARDS). After approval by the local Ethic Committee we studied two ventilated patients: (1) with normal lung function; (2) ARDS). We used the 50 ms scan mode of the EBCT. The beam was positioned 1 cm above the diaphragm. The table position remained unchanged. An electronic trigger was developed, that utilizes the respirators synchronizing signal to start the EBCT at the onset of expiration. During controlled mechanical expiration at two levels of PEEP (0 and 15 cm H2O), pulmonary aeration was rated as: well-aerated (-900HU/-500HU), poorly- aerated (-500HU/-100HU) and non-aerated (-100HU/+100HU). Pathological and normal lung function showed different dynamic changes (FIG.4-12). The different PEEP levels resulted in a significant change of pulmonary aeration in the same patient. Although we studied only a very limited number of patients, respirator triggered EBCT may be accurate in discriminating pathological changes due to the abnormal lung function in the mechanically ventilated patient.

Matrix metalloproteinases and airway remodeling and function in primary ciliary dyskinesia.

PubMed

Pifferi, Massimo; Bush, Andrew; Caramella, Davide; Metelli, Maria Rita; Di Cicco, Maria; Piras, Martina; Gherarducci, Giulia; Capristo, Carlo; Maggi, Fabrizio; Peroni, Diego; Boner, Attilio L

2017-03-01

The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is important in the regulation of airway damage. To evaluate whether they are important in the pathophysiology of primary and secondary ciliary dyskinesia (PCD, SCD). We measured sputum bacteriology, lung CT changes, MMPs, TIMPs and lung function in 86 patients (51 PCD, 35 SCD) in a cross-sectional study; the 10 controls studied did not have HRCT or sputum cultures. MMPs, TIMPs and lung function were evaluated longitudinally for up to one year in 38 PCD patients. At baseline, there were no differences in MMPs, TIMPs and MMPs/TIMPs, between PCD and SCD but lower levels were found in controls. There was an association between poorer lung function with increasing levels of MMPs in PCD, while in SCD only MMP-9/TIMP-1 values correlated with FRC z-scores. Levels of MMPs and TIMPs significantly correlated with severity HRCT changes. Longitudinally, there were significant correlations between slope of changes in spirometric parameters and slope of change in sputum MMPs in PCD patients. In conclusion, we report for the first time that increased MMPs are associated with worse airway damage in PCD and SCD, and thus are potential therapeutic targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of cooking fuel smoke on respiratory symptoms and lung function in semi-rural women in Cameroon

PubMed Central

Mbatchou Ngahane, Bertrand Hugo; Afane Ze, Emmanuel; Chebu, Cyrille; Mapoure, Njankouo Yacouba; Temfack, Elvis; Nganda, Malea; Luma, Namme Henry

2015-01-01

Background: Indoor air pollution is a major health problem in the developing world. In sub-Saharan Africa more than 90% of people rely on biomass to meet their domestic energy demands. Pollution from biomass fuel ranks 10th among preventable risk factors contributing to the global burden of diseases. Objectives: The present study aimed to determine the prevalence of respiratory symptoms and the factors associated with reduced lung function in a population of women exposed to cooking fuel smoke. Methods: A cross-sectional study was conducted in a semi-rural area in Cameroon. We compared forced respiratory volume between women using wood (n = 145) and women using alternative sources of energy (n = 155) for cooking. Results: Chronic bronchitis was found in 7·6% of the wood smoke group and 0·6% in the alternative fuels group. We observed two cases of airflow obstruction in the wood smoke group. Factors associated with lung function impairment were chronic bronchitis, use of wood as cooking fuel, age, and height. Conclusion: Respiratory symptoms and reduced lung function are more pronounced among women using wood as cooking fuel. Improved stoves technology should be developed to reduce the effects of wood smoke on respiratory health. PMID:25384259

A brief review of chronic obstructive pulmonary disease.

PubMed

Hogg, James C

2012-01-01

A recent study, based on a combination of multidetector computed tomography scanning of an intact specimen with microcomputed tomography and histological analysis of lung tissue samples, reported that the number of terminal bronchioles were reduced from approximately 44,500/lung pair in control (donor) lungs to approximately 4800/lung pair in lungs donated by individuals with very severe (Global initiative for chronic Obstructive Lung Disease stage 4) chronic obstructive pulmonary disease (COPD) treated by lung transplantation. The present short review discusses the hypothesis that a rapid rate of terminal bronchiolar destruction causes the rapid decline in lung function leading to advanced COPD. With respect to why the terminal bronchioles are targeted for destruction, the postulated mechanisms of this destruction and the possibility that new treatments are able to either prevent or reverse the underlying cause of airway obstruction in COPD are addressed.

Effects of particulate air pollution on nasal and lung function development among Greek children: a 19-year cohort study.

PubMed

Spyratos, Dionisios; Sioutas, Constantinos; Tsiotsios, Anastasios; Haidich, Anna-Bettina; Chloros, Diamantis; Triantafyllou, Georgios; Sichletidis, Lazaros

2015-01-01

The aim was to investigate respiratory symptoms, lung function and nasal airflow development among a cohort of children who were exposed to particulate air pollution. We used questionnaires, spirometry and rhinomanometry, while central-monitored PM10 concentrations were used for exposure assessment. We initially examined 1046 children (10-12 year old) in the heavily polluted town of Ptolemaida, Greece, and 379 children in the cleaner town of Grevena (control group). We re-evaluated 312 of the former and 119 of the latter after 19 years. PM10 concentrations were above permissible levels in Ptolemaida during all study period. At both visits, nasal flow was significantly lower in the study sample. At the follow-up visit, 34.3% had severe nasal obstruction (< 500 ml/s) and 38.5% reported chronic nasal symptoms. Spirometric parameters did not differ compared to the control group. Particulate air pollution had significant and negative effects on nasal but not on lung function development.

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

Enhanced Re-Endothelialization of Decellularized Rat Lungs

PubMed Central

Stabler, Collin T.; Caires, Luiz C.; Mondrinos, Mark J.; Marcinkiewicz, Cezary; Lazarovici, Philip; Wolfson, Marla R.

2016-01-01

Decellularized lung tissue has been recognized as a potential platform to engineer whole lung organs suitable for transplantation or for modeling a variety of lung diseases. However, many technical hurdles remain before this potential may be fully realized. Inability to efficiently re-endothelialize the pulmonary vasculature with a functional endothelium appears to be the primary cause of failure of recellularized lung scaffolds in early transplant studies. Here, we present an optimized approach for enhanced re-endothelialization of decellularized rodent lung scaffolds with rat lung microvascular endothelial cells (ECs). This was achieved by adjusting the posture of the lung to a supine position during cell seeding through the pulmonary artery. The supine position allowed for significantly more homogeneous seeding and better cell retention in the apex regions of all lobes than the traditional upright position, especially in the right upper and left lobes. Additionally, the supine position allowed for greater cell retention within large diameter vessels (proximal 100–5000 μm) than the upright position, with little to no difference in the small diameter distal vessels. EC adhesion in the proximal regions of the pulmonary vasculature in the decellularized lung was dependent on the binding of EC integrins, specifically α1β1, α2β1, and α5β1 integrins to, respectively, collagen type-I, type-IV, and fibronectin in the residual extracellular matrix. Following in vitro maturation of the seeded constructs under perfusion culture, the seeded ECs spread along the vascular wall, leading to a partial reestablishment of endothelial barrier function as inferred from a custom-designed leakage assay. Our results suggest that attention to cellular distribution within the whole organ is of paramount importance for restoring proper vascular function. PMID:26935764

Susceptibility loci of CNOT6 in the general mRNA degradation pathway and lung cancer risk - a re-analysis of eight GWASs

PubMed Central

Zhou, Fei; Wang, Yanru; Liu, Hongliang; Ready, Neal; Han, Younghun; Hung, Rayjean J.; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; Bickeböller, Heike; Rosenberger, Albert; Houlston, Richard S.; Caporaso, Neil; Landi, Maria Teresa; Brüske, Irene; Risch, Angela; Ye, Yuanqing; Wu, Xifeng; Christiani, David C.; Goodman, Gary; Chen, Chu; Amos, Christopher I.; Qingyi, Wei

2017-01-01

Purpose mRNA degradation is an important regulatory step for controlling gene expression and cell functions. Genetic abnormalities of the genes involved in mRNA degradation were found to be associated with cancer risks. Therefore, we systematically investigated the roles of genetic variants of genes in the general mRNA degradation pathway in lung cancer risk. Experimental design Meta-analyses were conducted in six lung cancer genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung and additional two GWASs from Harvard University and deCODE in the International Lung Cancer Consortium. Expression quantitative trait loci analysis (eQTL) was used for in silico functional validation of the identified significant susceptibility loci. Results This pathway-based analysis included 4,603 single nucleotide polymorphisms (SNP) in 68 genes in 14,463 lung cancer cases and 44,188 controls, of which 20 SNPs were found to be associated with lung cancer risk with a false discovery rate threshold of <0.05. Among the 11 newly identified SNPs in CNOT6, which were in high linkage disequilibrium, the rs2453176 with a RegulomDB score “1f” was chosen as the tag SNP for further analysis. We found that the rs2453176 T allele was significantly associated with lung cancer risk (odds ratio=1.11, 95% confidence interval=1.04–1.18, P=0.001) in the eight GWASs. In the eQTL analysis, we found that levels of CNOT6 mRNA expression were significantly correlated with the rs2453176 T allele, which provided additional biological basis for the observed positive association. Conclusion The CNOT6 rs2453176 SNP may be a new functional susceptible locus for lung cancer risk. PMID:27805284

Susceptibility loci of CNOT6 in the general mRNA degradation pathway and lung cancer risk-A re-analysis of eight GWASs.

PubMed

Zhou, Fei; Wang, Yanru; Liu, Hongliang; Ready, Neal; Han, Younghun; Hung, Rayjean J; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; Bickeböller, Heike; Rosenberger, Albert; Houlston, Richard S; Caporaso, Neil; Landi, Maria Teresa; Brüske, Irene; Risch, Angela; Ye, Yuanqing; Wu, Xifeng; Christiani, David C; Goodman, Gary; Chen, Chu; Amos, Christopher I; Wei, Qingyi

2017-04-01

mRNA degradation is an important regulatory step for controlling gene expression and cell functions. Genetic abnormalities involved in mRNA degradation genes were found to be associated with cancer risks. Therefore, we systematically investigated the roles of genetic variants in the general mRNA degradation pathway in lung cancer risk. Meta-analyses were conducted using summary data from six lung cancer genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung and additional two GWASs from Harvard University and deCODE in the International Lung Cancer Consortium. Expression quantitative trait loci analysis (eQTL) was used for in silico functional validation of the identified significant susceptibility loci. This pathway-based analysis included 6816 single nucleotide polymorphisms (SNP) in 68 genes in 14 463 lung cancer cases and 44 188 controls. In the single-locus analysis, we found that 20 SNPs were associated with lung cancer risk with a false discovery rate threshold of <0.05. Among the 11 newly identified SNPs in CNOT6, which were in high linkage disequilibrium, the rs2453176 with a RegulomDB score "1f" was chosen as the tagSNP for further analysis. We found that the rs2453176 T allele was significantly associated with lung cancer risk (odds ratio = 1.11, 95% confidence interval = 1.04-1.18) in the eight GWASs. In the eQTL analysis, we found that levels of CNOT6 mRNA expression were significantly correlated with the rs2453176 T allele, which provided additional biological basis for the observed positive association. The CNOT6 rs2453176 SNP may be a new functional susceptible locus for lung cancer risk. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Exposure to household air pollution from wood combustion and association with respiratory symptoms and lung function in nonsmoking women: results from the RESPIRE trial, Guatemala.

PubMed

Pope, Daniel; Diaz, Esperanza; Smith-Sivertsen, Tone; Lie, Rolv T; Bakke, Per; Balmes, John R; Smith, Kirk R; Bruce, Nigel G

2015-04-01

With 40% of the world's population relying on solid fuel, household air pollution (HAP) represents a major preventable risk factor for COPD (chronic obstructive pulmonary disease). Meta-analyses have confirmed this relationship; however, constituent studies are observational, with virtually none measuring exposure directly. We estimated associations between HAP exposure and respiratory symptoms and lung function in young, nonsmoking women in rural Guatemala, using measured carbon monoxide (CO) concentrations in exhaled breath and personal air to assess exposure. The Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) Guatemala study was a trial comparing respiratory outcomes among 504 women using improved chimney stoves versus traditional cookstoves. The present analysis included 456 women with data from postintervention surveys including interviews at 6, 12, and 18 months (respiratory symptoms) and spirometry and CO (ppm) in exhaled breath measurements. Personal CO was measured using passive diffusion tubes at variable times during the study. Associations between CO concentrations and respiratory health were estimated using random intercept regression models. Respiratory symptoms (cough, phlegm, wheeze, or chest tightness) during the previous 6 months were positively associated with breath CO measured at the same time of symptom reporting and with average personal CO concentrations during the follow-up period. CO in exhaled breath at the same time as spirometry was associated with lower lung function [average reduction in FEV1 (forced expiratory volume in 1 sec) for a 10% increase in CO was 3.33 mL (95% CI: -0.86, -5.81)]. Lung function measures were not significantly associated with average postintervention personal CO concentrations. Our results provide further support for the effects of HAP exposures on airway inflammation. Further longitudinal research modeling continuous exposure to particulate matter against lung function will help us understand more fully the impact of HAP on COPD.

Synchrotron-based dynamic computed tomography of tissue motion for regional lung function measurement

PubMed Central

Dubsky, Stephen; Hooper, Stuart B.; Siu, Karen K. W.; Fouras, Andreas

2012-01-01

During breathing, lung inflation is a dynamic process involving a balance of mechanical factors, including trans-pulmonary pressure gradients, tissue compliance and airway resistance. Current techniques lack the capacity for dynamic measurement of ventilation in vivo at sufficient spatial and temporal resolution to allow the spatio-temporal patterns of ventilation to be precisely defined. As a result, little is known of the regional dynamics of lung inflation, in either health or disease. Using fast synchrotron-based imaging (up to 60 frames s−1), we have combined dynamic computed tomography (CT) with cross-correlation velocimetry to measure regional time constants and expansion within the mammalian lung in vivo. Additionally, our new technique provides estimation of the airflow distribution throughout the bronchial tree during the ventilation cycle. Measurements of lung expansion and airflow in mice and rabbit pups are shown to agree with independent measures. The ability to measure lung function at a regional level will provide invaluable information for studies into normal and pathological lung dynamics, and may provide new pathways for diagnosis of regional lung diseases. Although proof-of-concept data were acquired on a synchrotron, the methodology developed potentially lends itself to clinical CT scanning and therefore offers translational research opportunities. PMID:22491972

Na,K-ATPase is a target of cigarette smoke and reduced expression predicts poor patient outcome of smokers with lung cancer

PubMed Central

Huynh, Thu P.; Mah, Vei; Sampson, Valerie B.; Chia, David; Fishbein, Michael C.; Horvath, Steve; Alavi, Mohammad; Wu, Debbie C.; Harper, Jeffrey; Sarafian, Ted; Dubinett, Steven M.; Langhans, Sigrid A.; Goodglick, Lee

2012-01-01

Diminished Na,K-ATPase expression has been reported in several carcinomas and has been linked to tumor progression. However, few studies have determined whether Na,K-ATPase function and expression are altered in lung malignancies. Because cigarette smoke (CS) is a major factor underlying lung carcinogenesis and progression, we investigated whether CS affects Na,K-ATPase activity and expression in lung cell lines. Cells exposed to CS in vitro showed a reduction of Na,K-ATPase activity. We detected the presence of reactive oxygen species (ROS) in cells exposed to CS before Na,K-ATPase inhibition, and neutralization of ROS restored Na,K-ATPase activity. We further determined whether Na,K-ATPase expression correlated with increasing grades of lung adenocarcinoma and survival of patients with smoking history. Immunohistochemical analysis of lung adenocarcinoma tissues revealed reduced Na,K-ATPase expression with increasing tumor grade. Using tissue microarray containing lung adenocarcinomas of patients with known smoking status, we found that high expression of Na,K-ATPase correlated with better survival. For the first time, these data demonstrate that CS is associated with loss of Na,K-ATPase function and expression in lung carcinogenesis, which might contribute to disease progression. PMID:22345575

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

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.

Metabolic Syndrome Biomarkers Predict Lung Function Impairment

PubMed Central

Naveed, Bushra; Weiden, Michael D.; Kwon, Sophia; Gracely, Edward J.; Comfort, Ashley L.; Ferrier, Natalia; Kasturiarachchi, Kusali J.; Cohen, Hillel W.; Aldrich, Thomas K.; Rom, William N.; Kelly, Kerry; Prezant, David J.

2012-01-01

Rationale: Cross-sectional studies demonstrate an association between metabolic syndrome and impaired lung function. Objectives: To define if metabolic syndrome biomarkers are risk factors for loss of lung function after irritant exposure. Methods: A nested case-control study of Fire Department of New York personnel with normal pre–September 11th FEV1 and who presented for subspecialty pulmonary evaluation before March 10, 2008. We correlated metabolic syndrome biomarkers obtained within 6 months of World Trade Center dust exposure with subsequent FEV1. FEV1 at subspecialty pulmonary evaluation within 6.5 years defined disease status; cases had FEV1 less than lower limit of normal, whereas control subjects had FEV1 greater than or equal to lower limit of normal. Measurements and Main Results: Clinical data and serum sampled at the first monitoring examination within 6 months of September 11, 2001, assessed body mass index, heart rate, serum glucose, triglycerides and high-density lipoprotein (HDL), leptin, pancreatic polypeptide, and amylin. Cases and control subjects had significant differences in HDL less than 40 mg/dl with triglycerides greater than or equal to 150 mg/dl, heart rate greater than or equal to 66 bpm, and leptin greater than or equal to 10,300 pg/ml. Each increased the odds of abnormal FEV1 at pulmonary evaluation by more than twofold, whereas amylin greater than or equal to 116 pg/ml decreased the odds by 84%, in a multibiomarker model adjusting for age, race, body mass index, and World Trade Center arrival time. This model had a sensitivity of 41%, a specificity of 86%, and a receiver operating characteristic area under the curve of 0.77. Conclusions: Abnormal triglycerides and HDL and elevated heart rate and leptin are independent risk factors of greater susceptibility to lung function impairment after September 11, 2001, whereas elevated amylin is protective. Metabolic biomarkers are predictors of lung disease, and may be useful for assessing risk of impaired lung function in response to particulate inhalation. PMID:22095549

Detecting regional lung properties using audio transfer functions of the respiratory system.

PubMed

Mulligan, K; Adler, A; Goubran, R

2009-01-01

In this study, a novel instrument has been developed for measuring changes in the distribution of lung fluid the respiratory system. The instrument consists of a speaker that inputs a 0-4kHz White Gaussian Noise (WGN) signal into a patient's mouth and an array of 4 electronic stethoscopes, linked via a fully adjustable harness, used to recover signals on the chest surface. The software system for processing the data utilizes the principles of adaptive filtering in order to obtain a transfer function that represents the input-output relationship for the signal as the volume of fluid in the lungs is varied. A chest phantom model was constructed to simulate the behavior of fluid related diseases within the lungs through the injection of varying volumes of water. Tests from the phantom model were compared to healthy subjects. Results show the instrument can obtain similar transfer functions and sound propagation delays between both human and phantom chests.

Early fundoplication is associated with slower decline in lung function after lung transplantation in patients with gastroesophageal reflux disease.

PubMed

Biswas Roy, Sreeja; Elnahas, Shaimaa; Serrone, Rosemarie; Haworth, Cassandra; Olson, Michael T; Kang, Paul; Smith, Michael A; Bremner, Ross M; Huang, Jasmine L

2018-06-01

Gastroesophageal reflux disease (GERD) is prevalent after lung transplantation. Fundoplication slows lung function decline in patients with GERD, but the optimal timing of fundoplication is unknown. We retrospectively reviewed patients who underwent fundoplication after lung transplantion at our center from April 2007 to July 2014. Patients were divided into 2 groups: early fundoplication (<6 months after lung transplantation) and late fundoplication (≥6 months after lung transplantation). Annual decline in percent predicted forced expiratory volume in 1 second (FEV 1 ) was analyzed. Of the 251 patients who underwent lung transplantation during the study period with available pH data, 86 (34.3%) underwent post-transplantation fundoplication for GERD. Thirty of 86 (34.9%) had early fundoplication and 56 of 86 (65.1%) had late fundoplication. Median time from lung transplantation to fundoplication was 4.6 months (interquartile range, 2.0-5.2) and 13.8 months (interquartile range, 9.0-16.1) for the early and late groups, respectively. The median DeMeester score was comparable between groups. One-, 3-, and 5-year actuarial survival rates in the early group were 90%, 70%, and 70%, respectively; in the late group, these rates were 91%, 66%, and 66% (log rank P = .60). Three- and 5-year percent predicted FEV 1 was lower in the late group by 8.9% (95% confidence interval, -30.2 to 12.38; P = .46) and 40.7% (95% confidence interval, -73.66 to -7.69; P = .019). A linear mixed model showed a 5.7% lower percent predicted FEV 1 over time in the late fundoplication group (P < .001). In this study, patients with early fundoplication had a higher FEV 1 5 years after lung transplantation. Early fundoplication might protect against GERD-induced lung damage in lung transplant recipients with GERD. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

Grating-based X-ray Dark-field Computed Tomography of Living Mice.

PubMed

Velroyen, A; Yaroshenko, A; Hahn, D; Fehringer, A; Tapfer, A; Müller, M; Noël, P B; Pauwels, B; Sasov, A; Yildirim, A Ö; Eickelberg, O; Hellbach, K; Auweter, S D; Meinel, F G; Reiser, M F; Bech, M; Pfeiffer, F

2015-10-01

Changes in x-ray attenuating tissue caused by lung disorders like emphysema or fibrosis are subtle and thus only resolved by high-resolution computed tomography (CT). The structural reorganization, however, is of strong influence for lung function. Dark-field CT (DFCT), based on small-angle scattering of x-rays, reveals such structural changes even at resolutions coarser than the pulmonary network and thus provides access to their anatomical distribution. In this proof-of-concept study we present x-ray in vivo DFCTs of lungs of a healthy, an emphysematous and a fibrotic mouse. The tomographies show excellent depiction of the distribution of structural - and thus indirectly functional - changes in lung parenchyma, on single-modality slices in dark field as well as on multimodal fusion images. Therefore, we anticipate numerous applications of DFCT in diagnostic lung imaging. We introduce a scatter-based Hounsfield Unit (sHU) scale to facilitate comparability of scans. In this newly defined sHU scale, the pathophysiological changes by emphysema and fibrosis cause a shift towards lower numbers, compared to healthy lung tissue.

Grating-based X-ray Dark-field Computed Tomography of Living Mice

PubMed Central

Velroyen, A.; Yaroshenko, A.; Hahn, D.; Fehringer, A.; Tapfer, A.; Müller, M.; Noël, P.B.; Pauwels, B.; Sasov, A.; Yildirim, A.Ö.; Eickelberg, O.; Hellbach, K.; Auweter, S.D.; Meinel, F.G.; Reiser, M.F.; Bech, M.; Pfeiffer, F.

2015-01-01

Changes in x-ray attenuating tissue caused by lung disorders like emphysema or fibrosis are subtle and thus only resolved by high-resolution computed tomography (CT). The structural reorganization, however, is of strong influence for lung function. Dark-field CT (DFCT), based on small-angle scattering of x-rays, reveals such structural changes even at resolutions coarser than the pulmonary network and thus provides access to their anatomical distribution. In this proof-of-concept study we present x-ray in vivo DFCTs of lungs of a healthy, an emphysematous and a fibrotic mouse. The tomographies show excellent depiction of the distribution of structural – and thus indirectly functional – changes in lung parenchyma, on single-modality slices in dark field as well as on multimodal fusion images. Therefore, we anticipate numerous applications of DFCT in diagnostic lung imaging. We introduce a scatter-based Hounsfield Unit (sHU) scale to facilitate comparability of scans. In this newly defined sHU scale, the pathophysiological changes by emphysema and fibrosis cause a shift towards lower numbers, compared to healthy lung tissue. PMID:26629545

High-Resolution Computed Tomography and Pulmonary Function Findings of Occupational Arsenic Exposure in Workers.

PubMed

Ergün, Recai; Evcik, Ender; Ergün, Dilek; Ergan, Begüm; Özkan, Esin; Gündüz, Özge

2017-05-05

The number of studies where non-malignant pulmonary diseases are evaluated after occupational arsenic exposure is very few. To investigate the effects of occupational arsenic exposure on the lung by high-resolution computed tomography and pulmonary function tests. Retrospective cross-sectional study. In this study, 256 workers with suspected respiratory occupational arsenic exposure were included, with an average age of 32.9±7.8 years and an average of 3.5±2.7 working years. Hair and urinary arsenic levels were analysed. High-resolution computed tomography and pulmonary function tests were done. In workers with occupational arsenic exposure, high-resolution computed tomography showed 18.8% pulmonary involvement. In pulmonary involvement, pulmonary nodule was the most frequently seen lesion (64.5%). The other findings of pulmonary involvement were 18.8% diffuse interstitial lung disease, 12.5% bronchiectasis, and 27.1% bullae-emphysema. The mean age of patients with pulmonary involvement was higher and as they smoked more. The pulmonary involvement was 5.2 times higher in patients with skin lesions because of arsenic. Diffusing capacity of lung for carbon monoxide was significantly lower in patients with pulmonary involvement. Besides lung cancer, chronic occupational inhalation of arsenic exposure may cause non-malignant pulmonary findings such as bronchiectasis, pulmonary nodules and diffuse interstitial lung disease. So, in order to detect pulmonary involvement in the early stages, workers who experience occupational arsenic exposure should be followed by diffusion test and high-resolution computed tomography.

Development of Welding Fumes Health Index (WFHI) for Welding Workplace’s Safety and Health Assessment

PubMed Central

HARIRI, Azian; PAIMAN, Nuur Azreen; LEMAN, Abdul Mutalib; MD. YUSOF, Mohammad Zainal

2014-01-01

Abstract Background This study aimed to develop an index that can rank welding workplace that associate well with possible health risk of welders. Methods Welding Fumes Health Index (WFHI) were developed based on data from case studies conducted in Plant 1 and Plant 2. Personal sampling of welding fumes to assess the concentration of metal constituents along with series of lung function tests was conducted. Fifteen metal constituents were investigated in each case study. Index values were derived from aggregation analysis of metal constituent concentration while significant lung functions were recognized through statistical analysis in each plant. Results The results showed none of the metal constituent concentration was exceeding the permissible exposure limit (PEL) for all plants. However, statistical analysis showed significant mean differences of lung functions between welders and non-welders. The index was then applied to one of the welding industry (Plant 3) for verification purpose. The developed index showed its promising ability to rank welding workplace, according to the multiple constituent concentrations of welding fumes that associates well with lung functions of the investigated welders. Conclusion There was possibility that some of the metal constituents were below the detection limit leading to ‘0’ value of sub index, thus the multiplicative form of aggregation model was not suitable for analysis. On the other hand, maximum or minimum operator forms suffer from compensation issues and were not considered in this study. PMID:25927034

Depletion of tissue plasminogen activator attenuates lung ischemia-reperfusion injury via inhibition of neutrophil extravasation

PubMed Central

Zhao, Yunge; Sharma, Ashish K.; LaPar, Damien J.; Kron, Irving L.; Ailawadi, Gorav; Liu, Yuan; Jones, David R.; Laubach, Victor E.

2011-01-01

Ischemia-reperfusion (IR) injury following lung transplantation remains a major source of early morbidity and mortality. Histologically, this inflammatory process is characterized by neutrophil infiltration and activation. We previously reported that lung IR injury was significantly attenuated in plasminogen activator inhibitor-1-deficient mice. In this study, we explored the potential role of tissue plasminogen activator (tPA) in a mouse lung IR injury model. As a result, tPA knockout (KO) mice were significantly protected from lung IR injury through several mechanisms. At the cellular level, tPA KO specifically blocked neutrophil extravasation into the interstitium, and abundant homotypic neutrophil aggregation (HNA) was detected in the lung microvasculature of tPA KO mice after IR. At the molecular level, inhibition of neutrophil extravasation was associated with reduced expression of platelet endothelial cell adhesion molecule-1 mediated through the tPA/ LDL receptor-related protein/NF-κB signaling pathway, whereas increased P-selectin triggered HNA. At the functional level, tPA KO mice incurred significantly decreased vascular permeability and improved lung function following IR. Protection from lung IR injury in tPA KO mice occurs through a fibrinolysis-independent mechanism. These results suggest that tPA could serve as an important therapeutic target for the prevention and treatment of acute IR injury after lung transplantation. PMID:21378024

The Impact of a Multidimensional Exercise Intervention on Physical and Functional Capacity, Anxiety, and Depression in Patients With Advanced-Stage Lung Cancer Undergoing Chemotherapy.

PubMed

Quist, Morten; Adamsen, Lis; Rørth, Mikael; Laursen, Jørgen H; Christensen, Karl B; Langer, Seppo W

2015-07-01

Patients with advanced-stage lung cancer face poor survival and experience co-occurring chronic physical and psychosocial symptoms. Despite several years of research in exercise oncology, few exercise studies have targeted advanced lung cancer patients undergoing chemotherapy. The aim of the present study was to investigate the benefits of a 6-week supervised group exercise intervention and to outline the effect on aerobic capacity, strength, health-related quality of life (HRQoL), anxiety, and depression. VO2peak was assessed using an incremental exercise test. Muscle strength was measured with one repetition maximum test (1RM). HRQoL, anxiety, and depression were assessed using Functional Assessment of Cancer Therapy-Lung (FACT-L) scale and the Hospital Anxiety and Depression Scale (HADS). One hundred and forthteen patients with advanced stage lung cancer were recruited. Forty-three patients dropped out. No serious adverse events were reported. Exercise adherence in the group training was 68%. Improvements in VO2peak (P < .001) and 6-minute walk distance (P < .001) and muscle strength measurements (P < .05) were seen. There was a reduction in anxiety level (P = .0007) and improvement in the emotional well-being parameter (FACT-L) but no statistically significant changes in HRQoL were observed. The results of the present study show that during a 6-week hospital-based supervised, structured, and group-based exercise program, patients with advanced-stage lung cancer (NSCLC IIIb-IV, ED-SCLC) improve their physical capacity (VO2peak, 1RM), functional capacity, anxiety level, and emotional well-being, but not their overall HRQoL. A randomized controlled trial testing the intervention including 216 patients is currently being carried out. © The Author(s) 2015.

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

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

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

Distinct Quantitative Computed Tomography Emphysema Patterns Are Associated with Physiology and Function in Smokers

PubMed Central

San José Estépar, Raúl; Mendoza, Carlos S.; Hersh, Craig P.; Laird, Nan; Crapo, James D.; Lynch, David A.; Silverman, Edwin K.; Washko, George R.

2013-01-01

Rationale: Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. Objectives: To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. Methods: Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. Measurements and Main Results: Compared with percentage of low-attenuation area less than −950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). Conclusions: Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures. PMID:23980521

Lung matrix and vascular remodeling in mechanically ventilated elastin haploinsufficient newborn mice

PubMed Central

Hilgendorff, Anne; Parai, Kakoli; Ertsey, Robert; Navarro, Edwin; Jain, Noopur; Carandang, Francis; Peterson, Joanna; Mokres, Lucia; Milla, Carlos; Preuss, Stefanie; Alcazar, Miguel Alejandre; Khan, Suleman; Masumi, Juliet; Ferreira-Tojais, Nancy; Mujahid, Sana; Starcher, Barry; Rabinovitch, Marlene

2014-01-01

Elastin plays a pivotal role in lung development. We therefore queried if elastin haploinsufficient newborn mice (Eln+/−) would exhibit abnormal lung structure and function related to modified extracellular matrix (ECM) composition. Because mechanical ventilation (MV) has been linked to dysregulated elastic fiber formation in the newborn lung, we also asked if elastin haploinsufficiency would accentuate lung growth arrest seen after prolonged MV of neonatal mice. We studied 5-day-old wild-type (Eln+/+) and Eln+/− littermates at baseline and after MV with air for 8–24 h. Lungs of unventilated Eln+/− mice contained ∼50% less elastin and ∼100% more collagen-1 and lysyl oxidase compared with Eln+/+ pups. Eln+/− lungs contained fewer capillaries than Eln+/+ lungs, without discernible differences in alveolar structure. In response to MV, lung tropoelastin and elastase activity increased in Eln+/+ neonates, whereas tropoelastin decreased and elastase activity was unchanged in Eln+/− mice. Fibrillin-1 protein increased in lungs of both groups during MV, more in Eln+/− than in Eln+/+ pups. In both groups, MV caused capillary loss, with larger and fewer alveoli compared with unventilated controls. Respiratory system elastance, which was less in unventilated Eln+/− compared with Eln+/+ mice, was similar in both groups after MV. These results suggest that elastin haploinsufficiency adversely impacts pulmonary angiogenesis and that MV dysregulates elastic fiber integrity, with further loss of lung capillaries, lung growth arrest, and impaired respiratory function in both Eln+/+ and Eln+/− mice. Paucity of lung capillaries in Eln+/− newborns might help explain subsequent development of pulmonary hypertension previously reported in adult Eln+/− mice. PMID:25539853

Quantitative evaluation of native lung hyperinflation after single lung transplantation for emphysema using three-dimensional computed tomography volumetry.

PubMed

Motoyama, H; Chen, F; Ohsumi, A; Hijiya, K; Takahashi, M; Ohata, K; Yamada, T; Sato, M; Aoyama, A; Bando, T; Date, H

2014-04-01

Although double lung transplantation is performed more frequently for emphysema, single lung transplantation (SLT) continues to be performed owing to limited donor organ availability. Native lung hyperinflation (NLH) is a unique complication following SLT for emphysema. Three-dimensional computed tomography (3D-CT) volumetry has been introduced into the field of lung transplantation, which we used to assess NLH in emphysema patients undergoing SLT. The primary purpose of this study was to confirm the effectiveness of 3D-CT volumetry in the evaluation of NLH following SLT for emphysema. In 5 emphysema patients undergoing SLT at Kyoto University Hospital, 3D-CT volumetry data, pulmonary function test results, and clinical and radiological findings were retrospectively evaluated. Three patients did not develop a significant mediastinal shift, whereas the other 2 patients developed a mediastinal shift. In the 3 patients without a mediastinal shift, 3D-CT volumetry did not show a significant increase in native lung volume. These patients had a history of sternotomy prior to lung transplantation and firm adhesion on the mediastinal side was detected during lung transplantation. One of 2 patients with a mediastinal shift developed severe dyspnea with significantly decreased pulmonary function, and 3D-CT volumetry showed a significant increase in the native lung volume. However, the other patient did not show any dyspnea and his native lung volume decreased postoperatively (preoperatively to 6 months postoperatively: +981 mL and -348 mL, respectively). Although bilateral lung transplantation has become preferable for emphysema patients owing to postoperative NLH with SLT, patients with a history of sternotomy prior to lung transplantation might be good candidates for SLT. 3D-CT volumetry may be a useful method for detection of NLH. Copyright © 2014 Elsevier Inc. All rights reserved.

Associations of Pet Ownership with Wheezing and Lung Function in Childhood: Findings from a UK Birth Cohort.

PubMed

Collin, Simon M; Granell, Raquel; Westgarth, Carri; Murray, Jane; Paul, Elizabeth S; Sterne, Jonathan A C; Henderson, A John

2015-01-01

Asthma is a heterogeneous condition and differential effects of pet ownership on non-atopic versus atopic asthma have been reported. The aim of this study was to investigate whether pet ownership during pregnancy and early childhood was associated with wheezing from birth to age 7 years and with lung function at age 8 years in a UK population-based birth cohort. Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to investigate associations of pet ownership at six time-points from pregnancy to age 7 years with concurrent episodes of wheezing, wheezing trajectories (phenotypes) and lung function at age 8 years using logistic regression models adjusted for child's sex, maternal history of asthma/atopy, maternal smoking during pregnancy, and family adversity. 4,706 children had complete data on pet ownership and wheezing. From birth to age 7 years, cat ownership was associated with an overall 6% lower odds of wheezing (OR=0.94 (0.89-0.99)). Rabbit and rodent ownership was associated with 21% (OR=1.21 (1.12-1.31)) and 11% (OR=1.11 (1.02-1.21)) higher odds of wheezing, respectively, with strongest effects evident during infancy. Rabbit and rodent ownership was positively associated with a 'persistent wheeze' phenotype. Pet ownership was not associated with lung function at age 8 years, with the exception of positive associations of rodent and bird ownership with better lung function. Cat ownership was associated with reduced risk, and rabbit and rodent ownership with increased risk, of wheezing during childhood. The mechanisms behind these differential effects warrant further investigation.

Acute changes in lung function associated with proximity to a steel plant: a randomized study.

PubMed

Dales, Robert; Kauri, Lisa Marie; Cakmak, Sabit; Mahmud, Mamun; Weichenthal, Scott A; Van Ryswyk, Keith; Kumarathasan, Premkumari; Thomson, Errol; Vincent, Renaud; Broad, Gayle; Liu, Ling

2013-05-01

Steel production is a major industry worldwide yet there is relatively little information on the pulmonary effects of air quality near steel manufacturing plants. The aim of this study was to examine how lung function changes acutely when healthy subjects are situated near a steel plant which is adjacent to a residential area. Sixty-one subjects were randomly assigned to spend 5 consecutive, 8-hour days in a residential neighborhood approximately 0.9km from a steel plant, or approximately 4.5km away at a college campus. Subjects crossed-over between sites after a nine-day washout period. Lung function was measured daily at both sites along with air pollutants including SO2, NO2, O3, PM2.5, and ultrafine particles. Diffusion capacity and pulse oximetry were also examined. Compared with the college site, the forced expiratory volume in 1-second/forced vital capacity, forced expiratory flow between 25% and 75% of the FVC, total lung capacity, functional residual capacity, and residual volume were lower near the steel plant by 0.67% (95% CI: 0.28, 1.06),1.62% (95% CI: 0.50, 2.75), 1.54% (95% CI: 0.68, 2.39), 3.54% (95% CI: 1.95, 5.13) and 11.3% (95% CI: 4.92, 17.75), respectively. Diffusion capacity, forced expiratory volume in 1s, and pulse oximetry were also lower near the plant but these effects were not statistically significant. Sulfur dioxide, ultrafine particulates, and oxides of nitrogen were greater near the steel plant site compared to the college site. Spending short periods of time near a steel plant is associated with a decrease in lung function. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Cleaning at Home and at Work in Relation to Lung Function Decline and Airway Obstruction.

PubMed

Svanes, Øistein; Bertelsen, Randi J; Lygre, Stein H L; Carsin, Anne E; Antó, Josep M; Forsberg, Bertil; García-García, José M; Gullón, José A; Heinrich, Joachim; Holm, Mathias; Kogevinas, Manolis; Urrutia, Isabel; Leynaert, Bénédicte; Moratalla, Jesús M; Le Moual, Nicole; Lytras, Theodore; Norbäck, Dan; Nowak, Dennis; Olivieri, Mario; Pin, Isabelle; Probst-Hensch, Nicole; Schlünssen, Vivi; Sigsgaard, Torben; Skorge, Trude D; Villani, Simona; Jarvis, Debbie; Zock, Jan P; Svanes, Cecilie

2018-05-01

Cleaning tasks may imply exposure to chemical agents with potential harmful effects to the respiratory system, and increased risk of asthma and respiratory symptoms among professional cleaners and in persons cleaning at home has been reported. Long-term consequences of cleaning agents on respiratory health are, however, not well described. This study aimed to investigate long-term effects of occupational cleaning and cleaning at home on lung function decline and airway obstruction. The European Community Respiratory Health Survey (ECRHS) investigated a multicenter population-based cohort at three time points over 20 years. A total of 6,235 participants with at least one lung function measurement from 22 study centers, who in ECRHS II responded to questionnaire modules concerning cleaning activities between ECRHS I and ECRHS II, were included. The data were analyzed with mixed linear models adjusting for potential confounders. As compared with women not engaged in cleaning (ΔFEV 1  = -18.5 ml/yr), FEV 1 declined more rapidly in women responsible for cleaning at home (-22.1; P = 0.01) and occupational cleaners (-22.4; P = 0.03). The same was found for decline in FVC (ΔFVC = -8.8 ml/yr; -13.1, P = 0.02; and -15.9, P = 0.002; respectively). Both cleaning sprays and other cleaning agents were associated with accelerated FEV 1 decline (-22.0, P = 0.04; and -22.9, P = 0.004; respectively). Cleaning was not significantly associated with lung function decline in men or with FEV 1 /FVC decline or airway obstruction. Women cleaning at home or working as occupational cleaners had accelerated decline in lung function, suggesting that exposures related to cleaning activities may constitute a risk to long-term respiratory health.

Associations of Pet Ownership with Wheezing and Lung Function in Childhood: Findings from a UK Birth Cohort

PubMed Central

Collin, Simon M.; Granell, Raquel; Westgarth, Carri; Murray, Jane; Paul, Elizabeth S.; Sterne, Jonathan A. C.; Henderson, A. John

2015-01-01

Background Asthma is a heterogeneous condition and differential effects of pet ownership on non-atopic versus atopic asthma have been reported. The aim of this study was to investigate whether pet ownership during pregnancy and early childhood was associated with wheezing from birth to age 7 years and with lung function at age 8 years in a UK population-based birth cohort. Methods Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to investigate associations of pet ownership at six time-points from pregnancy to age 7 years with concurrent episodes of wheezing, wheezing trajectories (phenotypes) and lung function at age 8 years using logistic regression models adjusted for child’s sex, maternal history of asthma/atopy, maternal smoking during pregnancy, and family adversity. Results 4,706 children had complete data on pet ownership and wheezing. From birth to age 7 years, cat ownership was associated with an overall 6% lower odds of wheezing (OR=0.94 (0.89-0.99)). Rabbit and rodent ownership was associated with 21% (OR=1.21 (1.12-1.31)) and 11% (OR=1.11 (1.02–1.21)) higher odds of wheezing, respectively, with strongest effects evident during infancy. Rabbit and rodent ownership was positively associated with a ‘persistent wheeze’ phenotype. Pet ownership was not associated with lung function at age 8 years, with the exception of positive associations of rodent and bird ownership with better lung function. Conclusions Cat ownership was associated with reduced risk, and rabbit and rodent ownership with increased risk, of wheezing during childhood. The mechanisms behind these differential effects warrant further investigation. PMID:26061067

Association of lung function and chronic obstructive pulmonary disease with American Heart Association's Life's Simple 7 cardiovascular health metrics.

PubMed

Fan, Wenjun; Lee, Hwa; Lee, Angela; Kieu, Chi; Wong, Nathan D

2017-10-01

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the U.S. There is a strong association between COPD and cardiovascular (CV) disease; however, the relation between COPD and CV health factors is not well defined. We examined the relation between lung function and CV health factors defined by American Heart Association's (AHA) Life's Simple 7 (LS7). We studied 6352 adults aged ≥20 from the National Health and Nutrition Examination Survey (NHANES) 2009-2012. Analysis of variance was used to compare mean FEV1% of predicted across levels of each LS7 metric and population attributable risk was calculated based on COPD prevalence. We also conducted linear regression and logistic regression analyses to determine the association between lung function, COPD and LS7 score. Overall 19.9% of subjects were defined as having COPD. Subjects in the highest categories of the LS7 metrics had the highest mean values of FEV1% of predicted (p < 0.0001 except for total cholesterol). Current smoking and hypertension had a population attributed risk of 21.8% and 21.1% of COPD, respectively. Compared to subjects with 0 ideal health factors, the gender and ethnicity-adjusted odds (95% CI) for COPD were 0.45 (0.22-0.93), 0.22 (0.11-0.43) for those with 4 and 5-7 factors, but adjustment for age attenuated this relation. LS7 score is associated with lung function as well as the odds of COPD that is largely explained by age. Studies are needed to show if promotion of CV health will preserve healthy lung function. Copyright © 2017 Elsevier Ltd. All rights reserved.

The mammalian respiratory system and critical windows of exposure for children's health.

PubMed Central

Pinkerton, K E; Joad, J P

2000-01-01

The respiratory system is a complex organ system composed of multiple cell types involved in a variety of functions. The development of the respiratory system occurs from embryogenesis to adult life, passing through several distinct stages of maturation and growth. We review embryonic, fetal, and postnatal phases of lung development. We also discuss branching morphogenesis and cellular differentiation of the respiratory system, as well as the postnatal development of xenobiotic metabolizing systems within the lungs. Exposure of the respiratory system to a wide range of chemicals and environmental toxicants during perinatal life has the potential to significantly affect the maturation, growth, and function of this organ system. Although the potential targets for exposure to toxic factors are currently not known, they are likely to affect critical molecular signals expressed during distinct stages of lung development. The effects of exposure to environmental tobacco smoke during critical windows of perinatal growth are provided as an example leading to altered cellular and physiological function of the lungs. An understanding of critical windows of exposure of the respiratory system on children's health requires consideration that lung development is a multistep process and cannot be based on studies in adults. Images Figure 1 Figure 4 PMID:10852845

Impact of exacerbations on respiratory system impedance measured by a forced oscillation technique in COPD: a prospective observational study.

PubMed

Kamada, Takahiro; Kaneko, Masahiro; Tomioka, Hiromi

2017-01-01

Forced oscillation technique (FOT) has been reported to be useful in the evaluation and management of obstructive lung disease, including COPD. To date, no data are available concerning long-term changes in respiratory system impedance measured by FOT. Additionally, although exacerbations have been reported to be associated with excessive lung function decline in COPD, the impact of exacerbations on the results of FOT has not been demonstrated. The aim of this study was to investigate the longitudinal changes in respiratory system impedance and the influence of exacerbations thereon. Between March 2011 and March 2012, outpatients who attended Kobe City Medical Center West Hospital with a diagnosis of COPD were assessed for eligibility. Baseline patient characteristics (age, sex, body mass index, smoking history, current smoking status, COPD stage), lung function (post-bronchodilator forced expiratory volume in 1 second [FEV 1 ]), blood tests (neutrophils and eosinophils), FOT, and COPD assessment test results were collected at enrollment. Lung function and FOT were examined every 6 months until March 2016. Annual changes in FEV 1 and FOT parameters were obtained from the slope of the linear regression curve. The patients were divided into 2 groups based on exacerbation history. Fifty-one of 58 patients with COPD were enrolled in this study. The median follow-up period was 57 (52-59) months. Twenty-five (49%) patients experienced exacerbations. A significant annual decline in FEV 1 and respiratory system impedance were shown. Additionally, annual changes in FEV 1 , respiratory system resistance at 5 Hz, respiratory system reactance at 5 Hz, and resonant frequency were greater in patients with exacerbations than in those without exacerbations. Exacerbations of COPD lead not only to a decline in lung function but also to an increase in respiratory system impedance.

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.

Animal Models of Fibrotic Lung Disease

PubMed Central

Lawson, William E.; Oury, Tim D.; Sisson, Thomas H.; Raghavendran, Krishnan; Hogaboam, Cory M.

2013-01-01

Interstitial lung fibrosis can develop as a consequence of occupational or medical exposure, as a result of genetic defects, and after trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can develop in an idiopathic manner. The pathogenesis of each form of lung fibrosis remains poorly understood. They each result in a progressive loss of lung function with increasing dyspnea, and most forms ultimately result in mortality. To better understand the pathogenesis of lung fibrotic disorders, multiple animal models have been developed. This review summarizes the common and emerging models of lung fibrosis to highlight their usefulness in understanding the cell–cell and soluble mediator interactions that drive fibrotic responses. Recent advances have allowed for the development of models to study targeted injuries of Type II alveolar epithelial cells, fibroblastic autonomous effects, and targeted genetic defects. Repetitive dosing in some models has more closely mimicked the pathology of human fibrotic lung disease. We also have a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis. Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease. PMID:23526222

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

PubMed

Morris, Christopher J; Aljayyoussi, Ghaith; Mansour, Omar; Griffiths, Peter; Gumbleton, Mark

2017-12-01

Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

Correlation between thoracolumbar curvatures and respiratory function in older adults.

PubMed

Rahman, Nor Najwatul Akmal Ab; Singh, Devinder Kaur Ajit; Lee, Raymond

2017-01-01

Aging is associated with alterations in thoracolumbar curvatures and respiratory function. Research information regarding the correlation between thoracolumbar curvatures and a comprehensive examination of respiratory function parameters in older adults is limited. The aim of the present study was to examine the correlation between thoracolumbar curvatures and respiratory function in community-dwelling older adults. Thoracolumbar curvatures (thoracic and lumbar) were measured using a motion tracker. Respiratory function parameters such as lung function, respiratory rate, respiratory muscle strength and respiratory muscle thickness (diaphragm and intercostal) were measured using a spirometer, triaxial accelerometer, respiratory pressure meter and ultrasound imaging, respectively. Sixty-eight community-dwelling older males and females from Kuala Lumpur, Malaysia, with mean (standard deviation) age of 66.63 (5.16) years participated in this cross-sectional study. The results showed that mean (standard deviation) thoracic curvature angle and lumbar curvature angles were -46.30° (14.66°) and 14.10° (10.58°), respectively. There was a significant negative correlation between thoracic curvature angle and lung function (forced expiratory volume in 1 second: r =-0.23, P <0.05; forced vital capacity: r =-0.32, P <0.05), quiet expiration intercostal thickness ( r =-0.22, P <0.05) and deep expiration diaphragm muscle thickness ( r =-0.21, P <0.05). The lumbar curvature angle had a significant negative correlation with respiratory muscle strength ( r =-0.29, P <0.05) and diaphragm muscle thickness at deep inspiration ( r =-0.22, P <0.05). However, respiratory rate was correlated neither with thoracic nor with lumbar curvatures. The findings of this study suggest that increase in both thoracic and lumbar curvatures is correlated with decrease in respiratory muscle strength, respiratory muscle thickness and some parameters of lung function. Clinically, both thoracic and lumbar curvatures, respiratory muscles and lung function should be taken into consideration in the holistic management of respiratory function among older adults.

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.

HIF Oxygen Sensing Pathways in Lung Biology.

PubMed

Urrutia, Andrés A; Aragonés, Julián

2018-06-06

Cellular responses to oxygen fluctuations are largely mediated by hypoxia-inducible factors (HIFs). Upon inhalation, the first organ inspired oxygen comes into contact with is the lungs, but the understanding of the pulmonary HIF oxygen-sensing pathway is still limited. In this review we will focus on the role of HIF1α and HIF2α isoforms in lung responses to oxygen insufficiency. In particular, we will discuss novel findings regarding their role in the biology of smooth muscle cells and endothelial cells in the context of hypoxia-induced pulmonary vasoconstriction. Moreover, we will also discuss recent studies into HIF-dependent responses in the airway epithelium, which have been even less studied than the HIF-dependent vascular responses in the lungs. In summary, we will review the biological functions executed by HIF1 or HIF2 in the pulmonary vessels and epithelium to control lung responses to oxygen fluctuations as well as their pathological consequences in the hypoxic lung.

Nonlinear dimensionality reduction of CT histogram based feature space for predicting recurrence-free survival in non-small-cell lung cancer

NASA Astrophysics Data System (ADS)

Kawata, Y.; Niki, N.; Ohmatsu, H.; Aokage, K.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.

2015-03-01

Advantages of CT scanners with high resolution have allowed the improved detection of lung cancers. In the recent release of positive results from the National Lung Screening Trial (NLST) in the US showing that CT screening does in fact have a positive impact on the reduction of lung cancer related mortality. While this study does show the efficacy of CT based screening, physicians often face the problems of deciding appropriate management strategies for maximizing patient survival and for preserving lung function. Several key manifold-learning approaches efficiently reveal intrinsic low-dimensional structures latent in high-dimensional data spaces. This study was performed to investigate whether the dimensionality reduction can identify embedded structures from the CT histogram feature of non-small-cell lung cancer (NSCLC) space to improve the performance in predicting the likelihood of RFS for patients with NSCLC.

The Significance of MMP-1 in EGFR-TKI-Resistant Lung Adenocarcinoma: Potential for Therapeutic Targeting.

PubMed

Saito, Ryoko; Miki, Yasuhiro; Ishida, Naoya; Inoue, Chihiro; Kobayashi, Masayuki; Hata, Shuko; Yamada-Okabe, Hisafumi; Okada, Yoshinori; Sasano, Hironobu

2018-02-18

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance is one of the most important problems in lung cancer therapy. Lung adenocarcinoma with EGFR-TKI resistance was reported to have higher abilities of invasion and migration than cancers sensitive to EGFR-TKI, but the function of matrix metalloproteinases (MMPs) has not been explored in EGFR-TKI-resistant lung adenocarcinoma. This study aims to clarify the significance of MMP-1 in EGFR-TKI-resistant lung adenocarcinoma. From the results of in vitro studies of migration and invasion assays using EGFR-TKI-sensitive and -resistant cell lines and phosphorylation antibody arrays using EGF and rapamycin, we first demonstrate that overexpression of MMP-1, which might follow activation of a mammalian target of rapamycin (mTOR) pathway, plays an important role in the migration and invasion abilities of EGFR-TKI-resistant lung adenocarcinoma. Additionally, immunohistochemical studies using 89 cases of lung adenocarcinoma demonstrate that high expression of MMP-1 is significantly correlated with poor prognosis and factors such as smoking history and the subtype of invasive mucinous adenocarcinoma. These are consistent with the results of this in vitro study. To conclude, this study provides insights into the development of a possible alternative therapy manipulating MMP-1 and the mTOR signaling pathway in EGFR-TKI-resistant lung adenocarcinoma.

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

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.

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.

Role of CYP1A2 polymorphisms on lung cancer risk in a prospective study.

PubMed

Pavanello, Sofia; Fedeli, Ugo; Mastrangelo, Giuseppe; Rota, Federica; Overvad, Kim; Raaschou-Nielsen, Ole; Tjønneland, Anne; Vogel, Ulla

2012-06-01

Cytochrome P4501A2 (CYP1A2) is a key enzyme for lung carcinogen activation and lung inflammation. We studied the interactions of the CYP1A2 functional variants -3860G/A(rs2069514),-2467T/delT(rs3569413),-163C/A(rs762551)] with occupational/environmental carcinogenic exposures in the development of lung cancer in a case-control study nested in the Danish prospective cohort "Diet, Cancer and Health." At enrollment (1993-1997), blood samples for genotype analyses and information on lifestyle were collected 5 (mean value) years before the onset of the disease. The study population included 425 lung cancer cases and 786 subcohort members, who were gender- and age-matched. We found that -163A carriers were at increased risk of lung cancer (P=0.035) in a multivariate COX regression model, which was adjusted for personal habits (i.e., cumulative smoking, passive smoke at home, alcohol intake, and fruit intake) and occupational exposure. Additionally, the interaction between -2467delT and smoking increases lung cancer risk in males, especially light smokers (<21.5 pack-years, P=0.004). The increased lung cancer risk found in -163C carriers, independent of smoking status, and in -2467delT male smokers, suggests that these variants could influence lung cancer development through different mechanisms (i.e. lung carcinogen activation and lung inflammation). Copyright © 2012 Elsevier Inc. All rights reserved.

Considering the effects of ambient particulate matter on the lung function of motorcycle taxi drivers in Bangkok, Thailand.

PubMed

Arphorn, Sara; Ishimaru, Tomohiro; Hara, Kunio; Mahasandana, Suwisa

2018-02-01

The motorcycle taxi drivers of Bangkok have been heavily exposed to high concentrations of PM 10 (particulate matter with an aerodynamic diameter ≤10 μm), and the impact of this on their lungs has been neither documented nor studied. This study examines the association between exposure to PM 10 and lung function decline among motorcycle taxi drivers. A cross-sectional study was conducted in Bangkok between two groups: a subject group of motorcycle taxi drivers and control group of enclosed vehicle taxi drivers. The findings of the Thailand Pollution Control Department were used to estimate the annual ambient PM 10 concentration levels in the metropolis. Pulmonary functions of motorcycle taxi drivers and enclosed vehicle taxi drivers were measured and compared using the Mann-Whitney test. Multiple linear regression analysis was applied to estimate the effects of PM 10 exposure on the lung function of motorcycle taxi drivers. A total of 1283 motorcycle taxi drivers and 600 taxi drivers were investigated. The mean forced expiratory volume in 1 sec/forced vital capacity (FEV 1 /FVC) of the motorcycle taxi drivers was significantly lower than that of the taxi drivers (P < 0.001). The mean FEV 1 /FVC of motorcycle taxi drivers exposed to ≥50 µg/m 3 PM 10 was statistically lower (-2.82%; 95% confidence interval [CI]: -4.54% to -1.09%) and the mean % vital capacity (%VC) of those exposed to 40-49.9 µg/m 3 PM 10 was statistically lower than that of motorcycle taxi drivers exposed to <30 µg/m 3 PM 10 (-3.33%; 95% CI: -5.79% to -0.87%). Motorcycle taxi drivers were directly exposed to air pollution in their working environment. As a result, their lung function might decrease more than that of enclosed vehicle taxi drivers. With the possible exposure to ≥50 µg/m 3 PM 10 , the vehicular emission standards should be vigorously enforced. Further investigation is warranted to clarify the effect of lung dysfunction on the work and lifestyle of motorcycle taxi drivers. Motorcycle taxi drivers are directly exposed to air pollution in their work environment; therefore, their lung function might decrease more than that of enclosed vehicle taxi drivers, especially when exposed to ≥50 µg/m 3 PM 10 . World Health Organization (WHO) vehicular emission standards should be recognized and eventually enforced.

Reduced survival in adult cystic fibrosis despite attenuated lung function decline.

PubMed

Keating, Claire; Poor, Armeen D; Liu, Xinhua; Chiuzan, Codruta; Backenroth, Daniel; Zhang, Yuan; DiMango, Emily

2017-01-01

There is limited data on disease progression and survival in adult diagnosis cystic fibrosis (CF). This study evaluates change of lung function over time and rates of death/lung transplant in adult diagnosis CF. The CF Foundation Patient Registry was reviewed for patients diagnosed 1993-2003. Rate of FEV1 decline was calculated up to 2010 for age groups 6-11, 12-17, and 18 and above. Kaplan Meier method was used for 10 and 15year survival rate calculations for patients diagnosed as adults. Cox Proportional hazards models using predictors affecting disease progression and survival without transplant were run. Between 1993 and 2003, 11,884 patients were diagnosed with CF, of which 2848 were ages 6 and older. Annual rate of change of FEV1% predicted over 5years differed by diagnosis age group: -1.42% per year for ages 6-11, -2.04% for ages 12-17 and -1.13% for ages 18-65 (p<0.0001). Pseudomonas aeruginosa infection was associated with faster rates of lung function decline in all age groups. Survival without transplant for CF patients diagnosed at ≥18years were 76% and 65% by 10 and 15years, respectively. Of adults with FEV1 of >70% predicted at diagnosis, 95% were alive without transplant at 10years, whereas of those with FEV1<40% predicted at diagnosis, 31% were alive without transplant at 10years. Lung function declines at a slower rate in adult diagnosis CF. However, particularly in those with low lung function at diagnosis, rates of death or transplant in adult diagnosis CF after 10 and 15years is not negligible. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Lung function in infants with cystic fibrosis diagnosed by newborn screening.

PubMed

Linnane, Barry M; Hall, Graham L; Nolan, Gary; Brennan, Siobhan; Stick, Stephen M; Sly, Peter D; Robertson, Colin F; Robinson, Philip J; Franklin, Peter J; Turner, Stephen W; Ranganathan, Sarath C

2008-12-15

Progressive lung damage in cystic fibrosis (CF) starts in infancy, and early detection may aid preventative strategies. To measure lung function in infants with CF diagnosed by newborn screening and describe its association with pulmonary infection and inflammation. Infants with CF (n = 68, 6 weeks to 30 months of age) and healthy infants without CF (n = 49) were studied. Forced vital capacity, FEV(0.5), and forced expiratory flows at 75% of exhaled vital capacity (FEF(75)) were measured using the raised-volume rapid thoracoabdominal compression technique. Forty-eight hours later, infants with CF had bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation. In the CF group, the deficit in FEV(0.5) z score increased by -0.77 (95% confidence interval, -1.14 to -0.41; P < 0.001) with each year of age. The mean FEV(0.5) z score did not differ between infants with CF and healthy control subjects less than 6 months of age (-0.06 and 0.02, respectively; P = 0.87). However, the mean FEV(0.5) z score was lower by 1.15 in infants with CF who were older than 6 months of age compared with healthy infants (P < 0.001). FVC and FEF(75) followed a similar pattern. Pulmonary infection and inflammation in BAL samples did not explain the lung function results. Lung function, measured by forced expiration, is normal in infants with CF at the time of diagnosis by newborn screening but is diminished in older infants. These findings suggest that in CF the optimal timing of therapeutic interventions aimed at preserving lung function may be within the first 6 months of life.

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

Gender and respiratory findings in workers occupationally exposed to organic aerosols: a meta analysis of 12 cross-sectional studies.

PubMed

Schachter, E Neil; Zuskin, Eugenija; Moshier, Erin L; Godbold, James; Mustajbegovic, Jadranka; Pucarin-Cvetkovic, Jasna; Chiarelli, Angelo

2009-01-12

Gender related differences in respiratory disease have been documented. The aim of this study was to investigate gender related differences in respiratory findings by occupation. We analyzed data from 12 of our previously published studies. Three thousand and eleven (3011) workers employed in "organic dust" industries (1379 female and 1632 male) were studied. A control group of 806 workers not exposed to any kind of dust were also investigated (male = 419, female = 387). Acute and chronic respiratory symptoms and lung function were measured. The weighted average method and the Mantel-Haentszel method were used to calculate the odds ratios of symptoms. Hedge's unbiased estimations were used to measure lung function differences between men and women. There were high prevalences of acute and chronic respiratory symptoms in all the "dusty" studied groups compared to controls. Significantly less chronic cough, chronic phlegm as well as chronic bronchitis were found among women than among men after the adjustments for smoking, age and duration of employment. Upper respiratory tract symptoms by contrast were more frequent in women than in men in these groups. Significant gender related lung function differences occurred in the textile industry but not in the food processing industry or among farmers. The results of this study suggest that in industries processing organic compounds there are gender differences in respiratory symptoms and lung function in exposed workers. Whether these findings represent true physiologic gender differences, gender specific workplace exposures or other undefined gender variables not defined in this study cannot be determined. These data do not suggest that special limitations for women are warranted for respiratory health reasons in these industries, but the issue of upper respiratory irritation and disease warrants further study.

IL-10 Gene Polymorphisms Are Associated with Post-Bronchiolitis Lung Function Abnormalities at Six Years of Age

PubMed Central

Lauhkonen, Eero; Koponen, Petri; Teräsjärvi, Johanna; Gröndahl-Yli-Hannuksela, Kirsi; Vuononvirta, Juho; Nuolivirta, Kirsi; Toikka, Jyri O.; Helminen, Merja; He, Qiushui; Korppi, Matti

2015-01-01

Aim Interleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age. Methods We performed baseline and post-exercise IOS on 103 former bronchiolitis patients. Data on single nucleotide polymorphisms (SNP) of IL10 rs1800896 (–1082G/A), rs1800871 (–819C/T), rs1800872 (–592C/A) were available for 99 children and of IL10 rs1800890 (–3575T/A) for 98 children. Results IL10 rs1800896, rs1800871 and rs1800872 combined genotype AA+CT+CA and carriage of haplotype ATA, respectively, were associated with higher resistance and lower reactance in baseline IOS in adjusted analyses. At IL10 rs1800890, the A/A-genotype and carriers of A-allele were associated with lower reactance in baseline IOS. There were no significant associations between the studied SNPs and airway hyper-reactivity to exercise. Conclusion Low-IL-10-producing polymorphisms in the IL-10 encoding gene were associated with obstructive lung function parameters, suggesting an important role for IL-10 in development of lung function deficit in early bronchiolitis patients. PMID:26473365

Longitudinal follow-up study of smoking-induced emphysema progression in low-dose CT screening of lung cancer

NASA Astrophysics Data System (ADS)

Suzuki, H.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, Masahiro; Moriyama, N.

2014-03-01

Chronic obstructive pulmonary disease is a major public health problem that is predicted to be third leading cause of death in 2030. Although spirometry is traditionally used to quantify emphysema progression, it is difficult to detect the loss of pulmonary function by emphysema in early stage, and to assess the susceptibility to smoking. This study presents quantification method of smoking-induced emphysema progression based on annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in lung cancer screening. The method consists of three steps. First, lung lobes are segmented using extracted interlobar fissures by enhancement filter based on fourdimensional curvature. Second, LAV of each lung lobe is segmented. Finally, smoking-induced emphysema progression is assessed by statistical analysis of the annual changes represented by linear regression of LAV percentage in each lung lobe. This method was applied to 140 participants in lung cancer CT screening for six years. The results showed that LAV progressions of nonsmokers, past smokers, and current smokers are different in terms of pack-year and smoking cessation duration. This study demonstrates effectiveness in diagnosis and prognosis of early emphysema in lung cancer CT screening.

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.

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.

Non-invasive assessment of respiratory muscle function and its relationship to exercise tolerance in patients with chronic obstructive pulmonary disease.

PubMed

Chlumský, J; Filipova, P; Terl, M

2006-01-01

Most patients with chronic obstructive pulmonary disease (COPD) have impaired respiratory muscle function. Maximal oesophageal pressure correlates closely with exercise tolerance and seems to predict the distance walked during the 6-min walk test. This study assessed the non-invasive parameters of respiratory muscle function in 41 patients with COPD to investigate their relationship to pulmonary function tests and exercise tolerance. The COPD patients, who demonstrated the full range of airway obstruction severity, had a mean forced expiratory volume in 1 s of 42.5% predicted (range, 20 - 79% predicted). Both the maximal inspiratory muscle strength and non-invasive tension-time index were significantly correlated with the degree of lung hyperinflation, as expressed by the ratio of residual volume to total lung capacity, and the distance walked in 6 min. We conclude that respiratory muscle function was influenced mainly by lung hyperinflation and that it had an important effect on exercise tolerance in COPD patients.

POSITIVE study: physical exercise program in non-operable lung cancer patients undergoing palliative treatment.

PubMed

Wiskemann, Joachim; Hummler, Simone; Diepold, Christina; Keil, Melanie; Abel, Ulrich; Steindorf, Karen; Beckhove, Philipp; Ulrich, Cornelia M; Steins, Martin; Thomas, Michael

2016-07-19

Patients with advanced stage non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) often experience multidimensional impairments, affecting quality of life during their course of disease. In lung cancer patients with operable disease, several studies have shown that exercise has a positive impact on quality of life and physical functioning. There is limited evidence regarding efficacy for advanced lung cancer patients undergoing palliative treatment. Therefore, the POSITIVE study aims to evaluate the benefit of a 24-week exercise intervention during palliative treatment in a randomized controlled setting. The POSITIVE study is a randomized, controlled trial investigating the effects of a 24-week exercise intervention during palliative treatment on quality of life, physical performance and immune function in advanced, non-operable lung cancer patients. 250 patients will be recruited in the Clinic for Thoracic Diseases in Heidelberg, enrolment begun in November 2013. Main inclusion criterion is histologically confirmed NSCLC (stage IIIa, IIIb, IV) or SCLC (Limited Disease-SCLC, Extensive Disease-SCLC) not amenable to surgery. Patients are randomized into two groups. Both groups receive weekly care management phone calls (CMPCs) with the goal to assess symptoms and side effects. Additionally, one group receives a combined resistance and endurance training (3x/week). Primary endpoints are quality of life assessed by the Functional Assessment of Cancer Therapy for patients with lung cancer (FACT-L, subcategory Physical Well-Being) and General Fatigue measured by the Multidimensional Fatigue Inventory (MFI-20). Secondary endpoints are physical performance (maximal voluntary isometric contraction, 6-min walk distance), psychosocial (depression and anxiety) and immunological parameters and overall survival. The aim of the POSITIVE trial is the evaluation of effects of a 24-week structured and guided exercise intervention during palliative treatment stages. Analysis of various outcomes (such as quality of life, physical performance, self-efficacy, psychosocial and immunological parameters) will contribute to a better understanding of the potential of exercise in advanced lung cancer patients. In contrast to other studies with advanced oncological patients the POSITIVE trial provides weekly phone calls to support patients both in the intervention and control group and to segregate the impact of physical activity on quality of life. ClinicalTrials.gov NCT02055508 (Date: December 12, 2013).

Factors Associated with Life Expectancy in Patients with Metastatic Spine Disease from Adenocarcinoma of the Lung

PubMed Central

Goodwin, C. Rory; Khattab, Mohamed H.; Sankey, Eric W.; Elder, Benjamin D.; Kosztowski, Thomas A.; Sarabia-Estrada, Rachel; Bydon, Ali; Witham, Timothy F.; Wolinsky, Jean-Paul; Gokaslan, Ziya L.; Sciubba, Daniel M.

2015-01-01

Study Design Retrospective study. Objective Our objective was to identify preoperative prognostic factors associated with survival in patients with spinal metastasis from lung carcinoma. Methods A retrospective analysis of 26 patients diagnosed with lung carcinoma metastatic to the spinal column was performed to determine factors associated with survival. We used 3 months survival as the clinical cutoff for whether surgical intervention should be performed. We analyzed patients who survived less than 3 months compared with those who survived more than 3 months. Demographic, preoperative, operative, and postoperative factors including functional scores were collected for analysis. Results The median survival for all patients in our study was 3.5 months. We found a statistically significant difference between the group that survived less than 3 months and the group that survived greater than 3 months in terms of extrathoracic metastasis, visceral metastasis, and average postoperative modified Rankin score. Conclusion Determining which patients with lung cancer spinal metastases will benefit from surgical intervention is often dictated by the patient's predicted life expectancy. Factors associated with poorer prognosis include age, functional status, visceral metastases, and extrathoracic metastases. Although the prognosis for patients with lung cancer spinal metastases is poor, some patients may experience long-term benefit from surgical intervention. PMID:26430597

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.

Immune function monitoring in lung transplantation using adenosine triphosphate production: time trends and relationship to postoperative infection.

PubMed

Takahashi, Mamoru; Ohsumi, Akihiro; Ohata, Keiji; Kondo, Takeshi; Motoyama, Hideki; Hijiya, Kyoko; Aoyama, Akihiro; Date, Hiroshi; Chen-Yoshikawa, Toyofumi F

2017-06-01

The ImmuKnow (IK) assay is a comprehensive immune function test that involves measuring adenosine triphosphate produced by the cluster of differentiation 4+ T lymphocytes in peripheral blood. The aim of this study was to analyze the time trends of IK values and assess the relationship between IK values and infections in lung transplants. We prospectively collected 178 blood samples from 22 deceased-donor lung transplant (DDLT) recipients and 17 living-donor lobar lung transplant (LDLLT) recipients. A surveillance IK assay was performed postoperatively, then after 1 week and 1, 3, 6, and 12 months. Time trends of IK values in stable recipients peaked 1 week after DDLT (477 ± 247 ATP ng/ml), and 1 month after LDLLT (433 ± 134 ng/ml), followed by a gradual decline over 1 year. The mean IK values in infections were significantly lower than those in the stable state (119 vs 312 ATP ng/ml, p = 0.0002). IK values increased sharply after lung transplantation and then decreased gradually over time in the first year, suggesting a natural history of immune function. IK values were also significantly reduced during infections. These results may provide new insights into the utility of immune monitoring after lung transplantation.

Plant Polyphenols as Chemopreventive Agents for Lung Cancer

PubMed Central

Amararathna, Madumani; Johnston, Michael R.; Rupasinghe, H. P. Vasantha

2016-01-01

Lung cancer may be prevented by a diet rich in fruits and vegetables as they are enriched with dietary antioxidant polyphenols, such as flavonoids, proanthocyanidins, lignans, stilbenes, and phenolic acids. Dietary polyphenols exert a wide range of beneficial biological functions beyond their antioxidative properties and are involved in regulation of cell survival pathways leading to anticarcinogenic and antimutagenic functions. There are sufficient evidence from in vitro, in vivo, and epidemiological studies to suggest that the dietary intervention of polyphenols in cancer prevention, including the chemopreventive ability of dietary polyphenols, act against lung carcinogens. Cohort and epidemiological studies in selected risk populations have evaluated clinical effects of polyphenols. Polyphenols have demonstrated three major actions: antioxidative activity, regulation of phase I and II enzymes, and regulation of cell survival pathways against lung carcinogenesis. They have also shown an inverse association of lung cancer occurrences among high risk populations who consumed considerable amounts of fruits and vegetables in their daily diet. In in vitro cell culture experimental models, polyphenols bind with electrophilic metabolites from carcinogens, inactivate cellular oxygen radicals, prevent membrane lipid peroxidation and DNA oxidative damage, and adduct formation. Further, polyphenols enhance the detoxifying enzymes such as the phase II enzymes, glutathione transferases and glucuronosyl transferases. PMID:27548149

ACID AIR AND AEROBIOLOGY RELATED TO THE MATURING HUMAN LUNG

EPA Science Inventory

The effect of 'acid air' on human health was studied by considering the effects of hygroscopicity upon aerosol deposition in the lung as a function of human subject age. Children are a critical sub-population to be incorporated into health effects analyses following ambient expos...

EFFECT OF ANTIOXIDANT SUPPLEMENTATION ON OZONE-INDUCED LUNG INJURY IN HUMAN SUBJECTS

EPA Science Inventory

Epidemiological, in vitro and animal studies suggest that dietary antioxidants can modulate the cellular and physiologic effects of ozone (O3) inhalation in humans. To determine whether antioxidants can influence human susceptibility to O3-induced changes in lung function and a...

Inhibition of the purinergic pathway prolongs mouse lung allograft survival.

PubMed

Liu, Kaifeng; Vergani, Andrea; Zhao, Picheng; Ben Nasr, Moufida; Wu, Xiao; Iken, Khadija; Jiang, Dawei; Su, Xiaofeng; Fotino, Carmen; Fiorina, Paolo; Visner, Gary A

2014-08-01

Lung transplantation has limited survival with current immunosuppression. ATP is released from activated T cells, which act as costimulatory molecules through binding to the purinergic receptor P2XR7. We investigated the role of blocking the ATP/purinergic pathway, primarily P2XR7, using its inhibitor oxidized ATP (oATP) in modulating rejection of mouse lung allografts. Mouse lung transplants were performed using mice with major histocompatibility complex mismatch, BALB/c to C57BL6. Recipients received suramin or oATP, and lung allografts were evaluated 15 to ≥ 60 days after transplantation. Recipients were also treated with oATP after the onset of moderate to severe rejection to determine its ability to rescue lung allografts. Outcomes measures included lung function, histology, thoracic imaging, and allo-immune responses. Blocking purinergic receptors with the nonselective inhibitor suramin or with the P2XR7-selective inhibitor oATP reduced acute rejection and prolonged lung allograft survival for ≥ 60 days with no progression in severity. There were fewer inflammatory cells within lung allografts, less rejection, and improved lung function, which was maintained over time. CD4 and CD8 T cells were reduced within lung allografts with impaired activation with prolonged impairment of CD8 responses. In vitro, oATP reduced CD8 activation of Th1 inflammatory cytokines IFN-γ and TNF-α and cytolytic machinery, granzyme B. Cotreatment with immunosuppressive agents, cyclosporine, rapamycin, or CTLA-4Ig resulted in no additive benefits, and oATP alone resulted in better outcomes than cyclosporine alone. This study illustrates a potential new pathway to target in hopes of prolonging survival of lung transplant recipients.