Correlation of 68Ga Ventilation-Perfusion PET/CT with Pulmonary Function Test Indices for Assessing Lung Function.

PubMed

Le Roux, Pierre-Yves; Siva, Shankar; Steinfort, Daniel P; Callahan, Jason; Eu, Peter; Irving, Lou B; Hicks, Rodney J; Hofman, Michael S

2015-11-01

Pulmonary function tests (PFTs) are routinely used to assess lung function, but they do not provide information about regional pulmonary dysfunction. We aimed to assess correlation of quantitative ventilation-perfusion (V/Q) PET/CT with PFT indices. Thirty patients underwent V/Q PET/CT and PFT. Respiration-gated images were acquired after inhalation of (68)Ga-carbon nanoparticles and administration of (68)Ga-macroaggregated albumin. Functional volumes were calculated by dividing the volume of normal ventilated and perfused (%NVQ), unmatched and matched defects by the total lung volume. These functional volumes were correlated with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and diffusing capacity for carbon monoxide (DLCO). All functional volumes were significantly different in patients with chronic obstructive pulmonary disease (P < 0.05). FEV1/FVC and %NVQ had the highest correlation (r = 0.82). FEV1 was also best correlated with %NVQ (r = 0.64). DLCO was best correlated with the volume of unmatched defects (r = -0.55). Considering %NVQ only, a cutoff value of 90% correctly categorized 28 of 30 patients with or without significant pulmonary function impairment. Our study demonstrates strong correlations between V/Q PET/CT functional volumes and PFT parameters. Because V/Q PET/CT is able to assess regional lung function, these data support the feasibility of its use in radiation therapy and preoperative planning and assessing pulmonary dysfunction in a variety of respiratory diseases. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Quantitative 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.

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

Registration-based assessment of regional lung function via volumetric CT images of normal subjects vs. severe asthmatics

PubMed Central

Choi, Sanghun; Hoffman, Eric A.; Wenzel, Sally E.; Tawhai, Merryn H.; Yin, Youbing; Castro, Mario

2013-01-01

The purpose of this work was to explore the use of image registration-derived variables associated with computed tomographic (CT) imaging of the lung acquired at multiple volumes. As an evaluation of the utility of such an imaging approach, we explored two groups at the extremes of population ranging from normal subjects to severe asthmatics. A mass-preserving image registration technique was employed to match CT images at total lung capacity (TLC) and functional residual capacity (FRC) for assessment of regional air volume change and lung deformation between the two states. Fourteen normal subjects and thirty severe asthmatics were analyzed via image registration-derived metrics together with their pulmonary function test (PFT) and CT-based air-trapping. Relative to the normal group, the severely asthmatic group demonstrated reduced air volume change (consistent with air trapping) and more isotropic deformation in the basal lung regions while demonstrating increased air volume change associated with increased anisotropic deformation in the apical lung regions. These differences were found despite the fact that both PFT-derived TLC and FRC in the two groups were nearly 100% of predicted values. Data suggest that reduced basal-lung air volume change in severe asthmatics was compensated by increased apical-lung air volume change and that relative increase in apical-lung air volume change in severe asthmatics was accompanied by enhanced anisotropic deformation. These data suggest that CT-based deformation, assessed via inspiration vs. expiration scans, provides a tool for distinguishing differences in lung mechanics when applied to the extreme ends of a population range. PMID:23743399

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

PubMed

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

2016-02-01

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

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

X-Ray based Lung Function measurement-a sensitive technique to quantify lung function in allergic airway inflammation mouse models

NASA Astrophysics Data System (ADS)

Dullin, C.; Markus, M. A.; Larsson, E.; Tromba, G.; Hülsmann, S.; Alves, F.

2016-11-01

In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy.

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.

Effects of Body Mass Index on Lung Function Index of Chinese Population

NASA Astrophysics Data System (ADS)

Guo, Qiao; Ye, Jun; Yang, Jian; Zhu, Changan; Sheng, Lei; Zhang, Yongliang

2018-01-01

To study the effect of body mass index (BMI) on lung function indexes in Chinese population. A cross-sectional study was performed on 10, 592 participants. The linear relationship between lung function and BMI was evaluated by multivariate linear regression analysis, and the correlation between BMI and lung function was assessed by Pearson correlation analysis. Correlation analysis showed that BMI was positively related with the decreasing of forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and FEV1/FVC (P <0.05), the increasing of FVC% predicted value (FVC%pre) and FEV1% predicted value (FEV1%pre). These suggested that Chinese people can restrain the decline of lung function to prevent the occurrence and development of COPD by the control of BMI.

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

PubMed

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

2018-05-01

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

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.

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.

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

PubMed

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

2015-11-01

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

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

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.

Effect of Mindfulness Training on Asthma Quality of Life and Lung Function: A Randomized Controlled Trial

PubMed Central

Pbert, Lori; Madison, J. Mark; Druker, Susan; Olendzki, Nicholas; Magner, Robert; Reed, George; Carmody, James

2014-01-01

Background Improving asthma patients’ quality of life is an important clinical outcome. This study evaluated the efficacy of mindfulness-based stress reduction (MBSR) in improving quality of life and lung function in patients with asthma. Methods A randomized controlled trial compared an 8 week MBSR group-based program (n = 42) to an educational control program (n = 41) in adults with mild, moderate or severe persistent asthma recruited at a university hospital outpatient primary care and pulmonary care clinic. Primary outcomes were quality of life assessed by the Asthma Quality of Life Questionnaire (AQOL), and lung function assessed by change from baseline in two-week average morning peak expiratory flow (PEF). Secondary outcomes were asthma control assessed by 2007 NIH/NHLBI guidelines, and stress assessed by Perceived Stress Scale. Follow-up assessments were conducted at 10 weeks, 6 and 12 months. Results At 12 months MBSR resulted in clinically significant improvements in quality of life (intervention effect 0.55 (95% CI 0.21, 0.89, p=0.001)) and perceived stress (intervention effect −4.5 (95% CI −7.1, −1.9; p= 0.001)). No significant effect was found on lung function (morning PEF, PEF variability, and FEV1). At 12 months the percentage of patients in MBSR with well-controlled asthma showed a non-statistically significant increase (7.3% at baseline to 19.4%) compared to the control condition (7.5% and 7.9%, respectively) (p=0.30). Conclusions MBSR produced lasting clinically significant improvements in asthma-related quality of life and stress in patients with persistent asthma, even in the absence of improvements in lung function. PMID:22544892

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

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...

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

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.

High resolution multidetector CT aided tissue analysis and quantification of lung fibrosis

NASA Astrophysics Data System (ADS)

Zavaletta, Vanessa A.; Karwoski, Ronald A.; Bartholmai, Brian; Robb, Richard A.

2006-03-01

Idiopathic pulmonary fibrosis (IPF, also known as Idiopathic Usual Interstitial Pneumontis, pathologically) is a progressive diffuse lung disease which has a median survival rate of less than four years with a prevalence of 15-20/100,000 in the United States. Global function changes are measured by pulmonary function tests and the diagnosis and extent of pulmonary structural changes are typically assessed by acquiring two-dimensional high resolution CT (HRCT) images. The acquisition and analysis of volumetric high resolution Multi-Detector CT (MDCT) images with nearly isotropic pixels offers the potential to measure both lung function and structure. This paper presents a new approach to three dimensional lung image analysis and classification of normal and abnormal structures in lungs with IPF.

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.

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.

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

Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

PubMed

Morales, Eva; Garcia-Esteban, Raquel; de la Cruz, Oscar Asensio; Basterrechea, Mikel; Lertxundi, Aitana; de Dicastillo, Maria D Martinez López; Zabaleta, Carlos; Sunyer, Jordi

2015-01-01

Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed. Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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.

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.

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.

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

Mild Lung Restriction in Breast Cancer Patients After Hypofractionated and Conventional Radiation Therapy: A 3-Year Follow-Up

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

Verbanck, Sylvia, E-mail: sylvia.verbanck@uzbrussel.be; Hanon, Shane; Schuermans, Daniel

Purpose: To assess the effect of radiation therapy on lung function over the course of 3 years. Methods and Materials: Evolution of restrictive and obstructive lung function parameters was investigated in 108 breast cancer participants in a randomized, controlled trial comparing conventional radiation therapy (CR) and hypofractionated tomotherapy (TT) (age at inclusion ranging 32-81 years). Spirometry, plethysmography, and hemoglobin-corrected diffusing capacity were assessed at baseline and after 3 months and 1, 2, and 3 years. Natural aging was accounted for by considering all lung function parameters in terms of percent predicted values using the most recent reference values for women aged up to 80 years. Results:more » In the patients with negligible history of respiratory disease or smoking (n=77), the greatest rate of functional decline was observed during the initial 3 months, this acute decrease being more marked in the CR versus the TT arm. During the remainder of the 3-year follow-up period, values (in terms of percent predicted) were maintained (diffusing capacity) or continued to decline at a slower rate (forced vital capacity). However, the average decline of the restrictive lung function parameters over a 3-year period did not exceed 9% predicted in either the TT or the CR arm. Obstructive lung function parameters remained unaffected throughout. Including also the 31 patients with a history of respiratory disease or more than 10 pack-years showed a very similar restrictive pattern. Conclusions: In women with breast cancer, both conventional radiation therapy and hypofractionated tomotherapy induce small but consistent restrictive lung patterns over the course of a 3-year period, irrespective of baseline respiratory status or smoking history. The fastest rate of lung function decline generally occurred in the first 3 months.« less

Assessing Respiratory System Mechanical Function.

PubMed

Restrepo, Ruben D; Serrato, Diana M; Adasme, Rodrigo

2016-12-01

The main goals of assessing respiratory system mechanical function are to evaluate the lung function through a variety of methods and to detect early signs of abnormalities that could affect the patient's outcomes. In ventilated patients, it has become increasingly important to recognize whether respiratory function has improved or deteriorated, whether the ventilator settings match the patient's demand, and whether the selection of ventilator parameters follows a lung-protective strategy. Ventilator graphics, esophageal pressure, intra-abdominal pressure, and electric impedance tomography are some of the best-known monitoring tools to obtain measurements and adequately evaluate the respiratory system mechanical function. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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.

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.

Lung function in type 2 diabetes: the Normative Aging Study.

PubMed

Litonjua, Augusto A; Lazarus, Ross; Sparrow, David; Demolles, Debbie; Weiss, Scott T

2005-12-01

Cross-sectional studies have noted that subjects with diabetes have lower lung function than non-diabetic subjects. We conducted this analysis to determine whether diabetic subjects have different rates of lung function change compared with non-diabetic subjects. We conducted a nested case-control analysis in 352 men who developed diabetes and 352 non-diabetic subjects in a longitudinal observational study of aging in men. We assessed lung function among cases and controls at three time points: Time0, prior to meeting the definition of diabetes; Time1, the point when the definition of diabetes was met; and Time2, the most recent follow-up exam. Cases had lower forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) at all time points, even with adjustment for age, height, weight, and smoking. In multiple linear regression models adjusting for relevant covariates, there were no differences in rates of FEV1 or FVC change over time between cases and controls. Men who are predisposed to develop diabetes have decreased lung function many years prior to the diagnosis, compared with men who do not develop diabetes. This decrement in lung function remains after the development of diabetes. We postulate that mechanisms involved in the insulin resistant state contribute to the diminished lung function observed in our subjects.

Determination of right ventricular ejection fraction in children with cystic fibrosis

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

Piepsz, A.; Ham, H.R.; Millet, E.

1987-01-01

The radionuclide right ventricular ejection fraction (RVEF) determined by means of Krypton-81m represents a simple, noninvasive, and accurate procedure to quantify the right ventricular contractility. This procedure was applied to 25 young patients with cystic fibrosis. The RVEF tended to decrease with the progression of the lung disease, as assessed by the clinical S-K score, the degree of the defects on lung scintigraphy, the PaO/sub 2/, and the lung function tests. However, the decrease of RVEF in patients with marked lung function tests. However, the decrease of RVEF in patients with marked lung involvement was moderate, and terminal lung diseasemore » was sometimes associated with normal right heart contractility.« less

Congruence Between Pulmonary Function and Computed Tomography Imaging Assessment of Cystic Fibrosis Severity.

PubMed

Rybacka, Anna; Goździk-Spychalska, Joanna; Rybacki, Adam; Piorunek, Tomasz; Batura-Gabryel, Halina; Karmelita-Katulska, Katarzyna

2018-05-04

In cystic fibrosis, pulmonary function tests (PFTs) and computed tomography are used to assess lung function and structure, respectively. Although both techniques of assessment are congruent there are lingering doubts about which PFTs variables show the best congruence with computed tomography scoring. In this study we addressed the issue by reinvestigating the association between PFTs variables and the score of changes seen in computed tomography scans in patients with cystic fibrosis with and without pulmonary exacerbation. This retrospective study comprised 40 patients in whom PFTs and computed tomography were performed no longer than 3 weeks apart. Images (inspiratory: 0.625 mm slice thickness, 0.625 mm interval; expiratory: 1.250 mm slice thickness, 10 mm interval) were evaluated with the Bhalla scoring system. The most frequent structural abnormality found in scans were bronchiectases and peribronchial thickening. The strongest relationship was found between the Bhalla sore and forced expiratory volume in 1 s (FEV1). The Bhalla sore also was related to forced vital capacity (FVC), FEV1/FVC ratio, residual volume (RV), and RV/total lung capacity (TLC) ratio. We conclude that lung structural data obtained from the computed tomography examination are highly congruent to lung function data. Thus, computed tomography imaging may supersede functional assessment in cases of poor compliance with spirometry procedures in the lederly or children. Computed tomography also seems more sensitive than PFTs in the assessment of cystic fibrosis progression. Moreover, in early phases of cystic fibrosis, computed tomography, due to its excellent resolution, may be irreplaceable in monitoring pulmonary damage.

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.

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.

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.

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.

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.

[Oxidative stress, lung function and exposure to air pollutants in Mexican schoolchildren with and without asthma].

PubMed

Romero-Calderón, Ana Teresa; Moreno-Macías, Hortensia; Manrique-Moreno, Joel David Francisco; Riojas-Rodríguez, Horacio; Torres-Ramos, Yessica Dorín; Montoya-Estrada, Araceli; Hicks-Gómez, Juan José; Linares-Segovia, Benigno; Cárdenas, Beatriz; Bárcenas, Claudia; Barraza-Villarreal, Albino

2017-01-01

To assess the association between the air pollutants exposure on markers of oxidative stress and lung function in schoolchildren with and without asthma from Salamanca and Leon Guanajuato, Mexico. We realized determinations of oxidative stress biomarkers and lung function tests in 314 schoolchildren. Information of air pollutants (O3, SO2, CO, PM2.5 and PM10) were obtained from monitoring stations and multiple linear regression models were run to assess the association. An increase of 0.09 pmol in conjugated dienes was observed by exposure to PM10 lag 1 in asthmatics from Salamanca (p<0.05). The exposure to O3 during the same day increased the concentration of Lipohydroperoxides in 4.38 nmol in asthmatics of Salamanca, as well as in 2.31 nmol by exposure to PM10 lag 2 (p<0.05). The forced vital capacity decreased by 138 and 203 ml in children without asthma, respectively, due to exposure to carbon monoxide (p<0.05). Exposure to air pollutants increase oxidative stress and decreased lung function in schoolchildren, with and without asthma.

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

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

PubMed

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

2017-10-01

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

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.

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/.

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.

COPD management: role of symptom assessment in routine clinical practice

PubMed Central

van der Molen, Thys; Miravitlles, Marc; Kocks, Janwillem WH

2013-01-01

Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life. Despite this, COPD treatment and its management are mainly based on lung function assessments. There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives. Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD. Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice. In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. PMID:24143085

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.

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.

Extracellular matrix in lung development, homeostasis and disease

DOE PAGES

Zhou, Yong; Horowitz, Jeffrey C.; Naba, Alexandra; ...

2018-03-08

Here, the lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECMmore » in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.« less

Extracellular matrix in lung development, homeostasis and disease

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

Zhou, Yong; Horowitz, Jeffrey C.; Naba, Alexandra

Here, the lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECMmore » in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.« less

Extracellular matrix in lung development, homeostasis and disease

DOE PAGES

Zhou, Yong; Horowitz, Jeffrey C.; Naba, Alexandra; ...

2018-03-08

The lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this paper, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECM inmore » normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. Finally, we identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.« less

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.

Donor lung assessment using selective pulmonary vein gases.

PubMed

Costa, Joseph; Sreekanth, Sowmyashree; Kossar, Alex; Raza, Kashif; Lederer, David J; Robbins, Hilary; Shah, Lori; Sonett, Joshua R; Arcasoy, Selim; D'Ovidio, Frank

2016-11-01

Standard donor lung assessment relies on imaging, challenge gases and subjective interpretation of bronchoscopic findings, palpation and visual assessment. Central gases may not accurately represent true quality of the lungs. We report our experience using selective pulmonary vein gases to corroborate the subjective judgement. Starting, January 2012, donor lungs have been assessed by intraoperative bronchoscopy, palpation and visual judgement of lung collapse upon temporary disconnection from ventilator, central gases from the aorta and selective pulmonary vein gases. Partial pressure of oxygen (pO 2 ) <300 mmHg on FiO 2 of 1.0 was considered low. The results of the chest X-ray and last pO 2 in the intensive care unit were also collected. Post-transplant primary graft dysfunction and survival were monitored. To date, 259 consecutive brain-dead donors have been assessed and 157 transplants performed. Last pO 2 in the intensive care unit was poorly correlated with intraoperative central pO 2 (Spearman's rank correlation r s = 0.29). Right inferior pulmonary vein pO 2 was associated (Mann-Whitney, P < 0.001) with findings at bronchoscopy [clean: median pO 2 443 mmHg (25th-75th percentile range 349-512) and purulent: 264 mmHg (178-408)]; palpation [good: 463 mmHg (401-517) and poor: 264 mmHg (158-434)] and visual assessment of lung collapse [good lung collapse: 429 mmHg (320-501) and poor lung collapse: 205 mmHg (118-348)]. Left inferior pulmonary pO 2 was associated (P < 0.001) with findings at bronchoscopy [clean: 419 mmHg (371-504) and purulent: 254 mmHg (206-367)]; palpation [good: 444 mmHg (400-517) and poor 282 mmHg (211-419)] and visual assessment of lung collapse [good: 420 mmHg (349-496) and poor: 246 mmHg (129-330)]. At 72 h, pulmonary graft dysfunction 2 was in 21/157 (13%) and pulmonary graft dysfunction 3 in 17/157 (11%). Ninety-day and 1-year mortalities were 6/157 (4%) and 13/157 (8%), respectively. Selective pulmonary vein gases provide corroborative objective support to the findings at bronchoscopy, palpation and visual assessment. Central gases do not always reflect true function of the lungs, having high false-positive rate towards the individual lower lobe gas exchange. Objective measures of donor lung function may optimize donor surgeon assessment, allowing for low pulmonary graft dysfunction rates and low 90-day and 1-year mortality. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

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.

Feasibility of assessing [(18)F]FDG lung metabolism with late dynamic PET imaging.

PubMed

Laffon, Eric; de Clermont, Henri; Vernejoux, Jean-Marc; Jougon, Jacques; Marthan, Roger

2011-04-01

The aim of this work was to non-invasively establish the feasibility of assessing 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) lung metabolism with the use of a late dynamic positron emission tomograpy (PET) acquisition, i.e., beyond 2 h after injection. The present method has been probed in 11 patients without any respiratory disease, under fasting conditions, by assessing mean values of (18)F-FDG lung metabolism. A kinetic model analysis has been implemented on a simple calculation sheet. An arbitrary (population based) input function has been used in each individual, which was obtained from literature data. In the healthy lung, no (18)F-FDG release was found, and the mean values (±SD) of the (18)F-FDG uptake rate constant and of the fraction of the free tracer in blood and interstitial volume were: K = 0.0016 min(-1) (±0.0005), and F = 0.18 (±0.10), respectively. These results were in very close agreement with literature data that were obtained by both three-compartment model analysis and Patlak graphical analysis (gold standards), and that used an invasive blood sampling. Furthermore, K and the standard uptake value index have been compared. We conclude that assessing lung metabolism of (18)F-FDG in humans with the use of late dynamic PET imaging is feasible. The arbitrary input function of this non-invasive feasibility study could be replaced in further experiments by an input function obtained by arterial sampling. It is suggested that this method may prove useful to quantify (18)F-FDG lung metabolism under pathological conditions.

3D ECG- and respiratory-gated non-contrast-enhanced (CE) perfusion MRI for postoperative lung function prediction in non-small-cell lung cancer patients: A comparison with thin-section quantitative computed tomography, dynamic CE-perfusion MRI, and perfusion scan.

PubMed

Ohno, Yoshiharu; Seki, Shinichiro; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Takenaka, Daisuke; Kassai, Yoshimori; Yui, Masao; Sugimura, Kazuro

2015-08-01

To compare predictive capabilities of non-contrast-enhanced (CE)- and dynamic CE-perfusion MRIs, thin-section multidetector computed tomography (CT) (MDCT), and perfusion scan for postoperative lung function in non-small cell lung cancer (NSCLC) patients. Sixty consecutive pathologically diagnosed NSCLC patients were included and prospectively underwent thin-section MDCT, non-CE-, and dynamic CE-perfusion MRIs and perfusion scan, and had their pre- and postoperative forced expiratory volume in one second (FEV1 ) measured. Postoperative percent FEV1 (po%FEV1 ) was then predicted from the fractional lung volume determined on semiquantitatively assessed non-CE- and dynamic CE-perfusion MRIs, from the functional lung volumes determined on quantitative CT, from the number of segments observed on qualitative CT, and from uptakes detected on perfusion scans within total and resected lungs. Predicted po%FEV1 s were then correlated with actual po%FEV1 s, which were %FEV1 s measured postoperatively. The limits of agreement were also determined. All predicted po%FEV1 s showed significant correlation (0.73 ≤ r ≤ 0.93, P < 0.0001) and limits of agreement with actual po%FEV1 (non-CE-perfusion MRI: 0.3 ± 10.0%, dynamic CE-perfusion MRI: 1.0 ± 10.8%, perfusion scan: 2.2 ± 14.1%, quantitative CT: 1.2 ± 9.0%, qualitative CT: 1.5 ± 10.2%). Non-CE-perfusion MRI may be able to predict postoperative lung function more accurately than qualitatively assessed MDCT and perfusion scan. © 2014 Wiley Periodicals, Inc.

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

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.

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.

Five-year lung function observations and associations with a smoking ban among healthy miners at high altitude (4000 m).

PubMed

Vinnikov, Denis; Blanc, Paul D; Brimkulov, Nurlan; Redding-Jones, Rupert

2013-12-01

To assess the annual lung function decline associated with the reduction of secondhand smoke exposure in a high-altitude industrial workforce. We performed pulmonary function tests annually among 109 high-altitude gold-mine workers over 5 years of follow-up. The first 3 years included greater likelihood of exposure to secondhand smoke exposure before the initiation of extensive smoking restrictions that came into force in the last 2 years of observation. In repeated measures modeling, taking into account the time elapsed in relation to the smoking ban, there was a 115 ± 9 (standard error) mL per annum decline in lung function before the ban, but a 178 ± 20 (standard error) mL per annum increase afterward (P < 0.001, both slopes). Institution of a workplace smoking ban at high altitude may be beneficial in terms of lung function decline.

Functional mechanism of lung mosaic CT attenuation: assessment with deep-inspiration breath-hold perfusion SPECT-CT fusion imaging and non-breath-hold Technegas SPECT.

PubMed

Suga, K; Yasuhiko, K; Iwanaga, H; Tokuda, O; Matsunaga, N

2009-01-01

The functional mechanism of lung mosaic computed tomography attenuation (MCA) in pulmonary vascular disease (PVD) and obstructive airway disease (OAD) has not yet been fully clarified. To clarify the mechanism of MCA in these diseases by assessing the relationship between regional lung function and CT attenuation change at MCA sites with the use of automated deep-inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images and non-breath-hold Technegas SPECT. Subjects were 42 PVD patients (31 pulmonary thromboembolism, four primary/two secondary pulmonary hypertension, and five Takayasu arteritis), 12 OAD patients (five acute asthma, four obliterative bronchiolitis, and three bronchiectasis), and 12 normal controls, all of whom had MCA on DIBrH CT. The relationship between regional lung function and CT attenuation change at the lung slices with MCA was assessed using DIBrH perfusion SPECT-CT fusion images and non-breath-hold Technegas SPECT. The severity of perfusion defects with or without MCA was quantified by regions-of-interest analysis. On DIBrH CT and perfusion SPECT, in contrast to no noticeable CT attenuation abnormality and fairly uniform perfusion in controls, 60 MCA and 274 perfusion defects in PVD patients, and 18 MCA and 61 defects in OAD patients were identified, with a total of 77 ventilation defects on Technegas SPECT in all patients. SPECT-CT correlation showed that, throughout the 78 MCA sites of all patients, lung perfusion was persistently decreased at low CT attenuation and preserved at intervening high CT attenuation, while lung ventilation was poorly correlated with CT attenuation change. The radioactivity ratios of reduced perfusion and the intervening preserved perfusion at the 78 perfusion defects with MCA were significantly lower than those at the remaining 257 defects without MCA (P<0.0001). Although further validation is required, our results indicate that heterogeneous pulmonary arterial perfusion may be a dominant mechanism of MCA in PVD and OAD.

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

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.

Four SNPs and Systemic Level of FOXP3 in Smokers and Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Chu, Shuyuan; Zhong, Xiaoning; Zhang, Jianquan; Lai, Xiaoying; Xie, Jiajun; Li, Yu

2016-12-01

Forkhead box P3 (FOXP3) is the essential transcription factor for the function of regulatory T-cell (Treg). However, the gene mutation of FOXP3 in patients with chronic obstructive pulmonary disease (COPD) at different stages has not been reported. We aim to investigate four single nucleotide polymorphisms (SNPs) and the mRNA expression of FOXP3 in smokers with normal lung function and smokers with COPD at different stages. FOXP3 mRNA expression and SNPs in FOXP3 were assessed in nonsmokers with normal lung function (N), smokers with normal lung function (S), smokers with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 grade (COPD 1-2), and smokers with COPD in GOLD 3 or 4 grade (COPD 3-4). In peripheral blood sample, FOXP3 mRNA was assessed using real-time quantitative PCR and SNPs were analyzed by TaqMan PCR. FOXP3 mRNA level in peripheral blood sample was decreased when COPD was aggravated. The frequency of FOXP3 rs5902434 genotype del/del and allele del are lower in COPD 1-2 and COPD 3-4 than that in N or S. The rs5902434 genotype del/del and allele del were, respectively, associated with decreased risk of COPD and lung function decline. The rs5902434 genotypic distribution was correlated with FOXP3 mRNA level. In conclusion, both FOXP3 rs5902434 genotypes and alleles were differently distributed in COPD patients and smokers with normal lung function. The distribution of del/del genotype was associated with systemic expression of FOXP3 mRNA. More research is needed to explore the role of FOXP3 gene polymorphism in immunoinflammation of COPD.

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.

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

Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

PubMed Central

Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

2016-01-01

Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID:27683630

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.

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).

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.

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

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.

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.

Lung volumes: measurement, clinical use, and coding.

PubMed

Flesch, Judd D; Dine, C Jessica

2012-08-01

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

How best to capture the respiratory consequences of prematurity?

PubMed

Ciuffini, Francesca; Robertson, Colin F; Tingay, David G

2018-03-31

Chronic respiratory morbidity is a common complication of premature birth, generally defined by the presence of bronchopulmonary dysplasia, both clinically and in trials of respiratory therapies. However, recent data have highlighted that bronchopulmonary dysplasia does not correlate with chronic respiratory morbidity in older children born preterm. Longitudinally evaluating pulmonary morbidity from early life through to childhood provides a more rational method of defining the continuum of chronic respiratory morbidity of prematurity, and offers new insights into the efficacy of neonatal respiratory interventions. The changing nature of preterm lung disease suggests that a multimodal approach using dynamic lung function assessment will be needed to assess the efficacy of a neonatal respiratory therapy and predict the long-term respiratory consequences of premature birth. Our aim is to review the literature regarding the long-term respiratory outcomes of neonatal respiratory strategies, the difficulties of assessing dynamic lung function in infants, and potential new solutions. Copyright ©ERS 2018.

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

PubMed

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

2014-06-15

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

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

Improved biochemical preservation of lung slices during cold storage.

PubMed

Bull, D A; Connors, R C; Reid, B B; Albanil, A; Stringham, J C; Karwande, S V

2000-05-15

Development of lung preservation solutions typically requires whole-organ models which are animal and labor intensive. These models rely on physiologic rather than biochemical endpoints, making accurate comparison of the relative efficacy of individual solution components difficult. We hypothesized that lung slices could be used to assess preservation of biochemical function during cold storage. Whole rat lungs were precision cut into slices with a thickness of 500 microm and preserved at 4 degrees C in the following solutions: University of Wisconsin (UW), Euro-Collins (EC), low-potassium-dextran (LPD), Kyoto (K), normal saline (NS), or a novel lung preservation solution (NPS) developed using this model. Lung biochemical function was assessed by ATP content (etamol ATP/mg wet wt) and capacity for protein synthesis (cpm/mg protein) immediately following slicing (0 h) and at 6, 12, 18, and 24 h of cold storage. Six slices were assayed at each time point for each solution. The data were analyzed using analysis of variance and are presented as means +/- SD. ATP content was significantly higher in the lung slices stored in NPS compared with all other solutions at each time point (P < 0.0001). Protein synthesis was significantly higher in the lung slices stored in NPS compared with all other solutions at 6, 12, and 18 h of preservation (P < 0.05). This lung slice model allows the rapid and efficient screening of lung preservation solutions and their components using quantifiable biochemical endpoints. Using this model, we have developed a novel solution that improves the biochemical preservation of lung slices during cold storage. Copyright 2000 Academic Press.

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.

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.

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.

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

Children with chronic lung diseases have cognitive dysfunction as assessed by event-related potential (auditory P300) and Stanford-Binet IQ (SB-IV) test.

PubMed

Kamel, Terez Boshra; Abd Elmonaem, Mahmoud Tarek; Khalil, Lobna Hamed; Goda, Mona Hamdy; Sanyelbhaa, Hossam; Ramzy, Mourad Alfy

2016-10-01

Chronic lung disease (CLD) in children represents a heterogeneous group of many clinico-pathological entities with risk of adverse impact of chronic or intermittent hypoxia. So far, few researchers have investigated the cognitive function in these children, and the role of auditory P300 in the assessment of their cognitive function has not been investigated yet. This study was designed to assess the cognitive functions among schoolchildren with different chronic pulmonary diseases using both auditory P300 and Stanford-Binet test. This cross-sectional study included 40 school-aged children who were suffering from chronic chest troubles other than asthma and 30 healthy children of similar age, gender and socioeconomic state as a control group. All subjects were evaluated through clinical examination, radiological evaluation and spirometry. Audiological evaluation included (basic otological examination, pure-tone, speech audiometry and immittancemetry). Cognitive function was assessed by auditory P300 and psychological evaluation using Stanford-Binet test (4th edition). Children with chronic lung diseases had significantly lower anthropometric measures compared to healthy controls. They had statistically significant lower IQ scores and delayed P300 latencies denoting lower cognitive abilities. Cognitive dysfunction correlated to severity of disease. P300 latencies were prolonged among hypoxic patients. Cognitive deficits in children with different chronic lung diseases were best detected using both Stanford-Binet test and auditory P300. P300 is an easy objective tool. P300 is affected early with hypoxia and could alarm subtle cognitive dysfunction.

Influence of Central Obesity Assessed by Conicity Index on Lung Age in Young Adults.

PubMed

Shenoy, Usha; Jagadamba

2017-04-01

Central obesity is an emerging public health problem in young adults which compromises lung mechanics. Conicity Index (CI) is a simple anthropometric measure to assess central adiposity. The concept of lung age relates to a person's current lung function at which his/her lung function would be considered abnormal in relation to the present actual age. To determine the effect of central obesity by CI on lung age in young adults. A total of 319 young adults in the age group 18-25 years were recruited for this cross-sectional observational study. Written informed consent and Institutional Ethical Clearance (IEC) approval were obtained. Anthropometric parameters were measured and CI was calculated using the following formula: CI = Waist Circumference (WC) (m)/ [0.109 X√ {Bodyweight (kg)/ Height (m)}] where 0.109 is a constant. Spirometry was performed and all the lung volumes and capacities were obtained. There was a significant increase in mean values of CI in obese young adults compared to non obese (1.36±0.15 and 1.16±0.08, p<0.001). The effect of central obesity on lung age in young adults was compared using an independent t-test. Mean of lung age was significantly higher in centrally obese young adults compared to non obese 23.87±3.03 and 21.30±2.6, p<0.001) which was statistically significant. Lung age is significantly increased in centrally obese young adults compared to non obese. Hence, lung age can be used as a potential psychological tool to show an individual with central obesity that there is premature aging of their lungs.

Clonidine Reduces Norepinephrine and Improves Bone Marrow Function in a Rodent Model of Lung Contusion, Hemorrhagic Shock and Chronic Stress

PubMed Central

Alamo, Ines G.; Kannan, Kolenkode B.; Ramos, Harry; Loftus, Tyler J.; Efron, Philip A.; Mohr, Alicia M.

2016-01-01

Background Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Methods Male Sprague-Dawley rats underwent six days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75μg/kg) after the restraint stress. On post-injury day seven, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor (G-CSF), and peripheral blood mobilization of hematopoietic progenitor cells (HPC), as well as bone marrow cellularity and erythroid progenitor cell growth. Results The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress, significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1±0.6 vs. 10.8±0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased HPC mobilization and restored G-CSF levels. Conclusions After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. PMID:27742030

Variable versus conventional lung protective mechanical ventilation during open abdominal surgery: study protocol for a randomized controlled trial.

PubMed

Spieth, Peter M; Güldner, Andreas; Uhlig, Christopher; Bluth, Thomas; Kiss, Thomas; Schultz, Marcus J; Pelosi, Paolo; Koch, Thea; Gama de Abreu, Marcelo

2014-05-02

General anesthesia usually requires mechanical ventilation, which is traditionally accomplished with constant tidal volumes in volume- or pressure-controlled modes. Experimental studies suggest that the use of variable tidal volumes (variable ventilation) recruits lung tissue, improves pulmonary function and reduces systemic inflammatory response. However, it is currently not known whether patients undergoing open abdominal surgery might benefit from intraoperative variable ventilation. The PROtective VARiable ventilation trial ('PROVAR') is a single center, randomized controlled trial enrolling 50 patients who are planning for open abdominal surgery expected to last longer than 3 hours. PROVAR compares conventional (non-variable) lung protective ventilation (CV) with variable lung protective ventilation (VV) regarding pulmonary function and inflammatory response. The primary endpoint of the study is the forced vital capacity on the first postoperative day. Secondary endpoints include further lung function tests, plasma cytokine levels, spatial distribution of ventilation assessed by means of electrical impedance tomography and postoperative pulmonary complications. We hypothesize that VV improves lung function and reduces systemic inflammatory response compared to CV in patients receiving mechanical ventilation during general anesthesia for open abdominal surgery longer than 3 hours. PROVAR is the first randomized controlled trial aiming at intra- and postoperative effects of VV on lung function. This study may help to define the role of VV during general anesthesia requiring mechanical ventilation. Clinicaltrials.gov NCT01683578 (registered on September 3 3012).

Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis.

PubMed

Ramsey, Kathryn A; Ranganathan, Sarath; Park, Judy; Skoric, Billy; Adams, Anne-Marie; Simpson, Shannon J; Robins-Browne, Roy M; Franklin, Peter J; de Klerk, Nick H; Sly, Peter D; Stick, Steve M; Hall, Graham L

2014-11-15

Pulmonary inflammation, infection, and structural lung disease occur early in life in children with cystic fibrosis. We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung function in childhood. Lung function (forced expiratory volume in the first three-quarters of a second [FEV0.75], FVC) was assessed in individuals with cystic fibrosis diagnosed after newborn screening and healthy subjects during infancy (0-2 yr) and again at early school age (4-8 yr). Individuals with cystic fibrosis underwent annual bronchoalveolar lavage fluid examination, and chest computed tomography. We examined which clinical outcomes (pulmonary inflammation, infection, structural lung disease, respiratory hospitalizations, antibiotic prophylaxis) measured in the first 2 years of life were associated with reduced lung function in infants and young children with cystic fibrosis, using a mixed effects model. Children with cystic fibrosis (n = 56) had 8.3% (95% confidence interval [CI], -15.9 to -6.6; P = 0.04) lower FEV0.75 compared with healthy subjects (n = 18). Detection of proinflammatory bacterial pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus species, Streptococcus pneumoniae) in bronchoalveolar lavage fluid was associated with clinically significant reductions in FEV0.75 (ranging between 11.3 and 15.6%). The onset of lung disease in infancy, specifically the occurrence of lower respiratory tract infection, is associated with low lung function in young children with cystic fibrosis. Deficits in lung function measured in infancy persist into childhood, emphasizing the need for targeted therapeutic interventions in infancy to maximize functional outcomes later in life.

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.

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.

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.

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

PubMed

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

2008-06-01

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

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.

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.

Clinical review: Lung imaging in acute respiratory distress syndrome patients - an update

PubMed Central

2013-01-01

Over the past 30 years lung imaging has greatly contributed to the current understanding of the pathophysiology and the management of acute respiratory distress syndrome (ARDS). In the past few years, in addition to chest X-ray and lung computed tomography, newer functional lung imaging techniques, such as lung ultrasound, positron emission tomography, electrical impedance tomography and magnetic resonance, have been gaining a role as diagnostic tools to optimize lung assessment and ventilator management in ARDS patients. Here we provide an updated clinical review of lung imaging in ARDS over the past few years to offer an overview of the literature on the available imaging techniques from a clinical perspective. PMID:24238477

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

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India.

PubMed

Elango, Nithya; Kasi, Vallikkannu; Vembhu, Bhuvaneswari; Poornima, Jeyanthi Govindasamy

2013-09-11

We assessed indoor air quality in photocopier centers and investigated whether occupational exposure to emissions from photocopiers is associated with decline in lung function or changes in haematological parameters, oxidative stress and inflammatory status. Indoor air quality was monitored in five photocopier centers. Pulmonary function was assessed by spirometry in 81 photocopier operators (64 male and 17 female) and 43 healthy control (31 male and 12 female) subjects. Hematological status, serum thio-barbituric acid reactive substances (TBARS), total ferric reducing antioxidant capacity (FRAC), leukotriene B4 (LTB4), 8-isoprostane, C reactive protein (CRP), interleukin 8 (IL-8), clara cell protein (CC-16), intercellular adhesion molecule 1 (ICAM-1) and eosinophilic cationic protein (ECP) were analyzed. Relationships between cumulative exposure, lung function and inflammatory markers were assessed. PM10 and PM2.5 were above the permissible levels in all the photocopier centers, whereas the levels of carbon monoxide, nitrogen oxides, ozone, sulphur dioxide, lead, arsenic, nickel, ammonia, benzene and benzo(a)pyrene were within Indian ambient air quality standards. Lung function was similar in the photocopier operators and control subjects. Serum TBARS was significantly higher and FRAC was lower among photocopier operators when compared to healthy controls. Plasma IL-8, LTB4, ICAM-1 and ECP were significantly higher in the photocopier exposed group. Photocopiers emit high levels of particulate matter. Long term exposure to emissions from photocopiers was not associated with decreased lung function, but resulted in high oxidative stress and systemic inflammation leading to high risk of cardiovascular diseases.

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India

PubMed Central

2013-01-01

Background We assessed indoor air quality in photocopier centers and investigated whether occupational exposure to emissions from photocopiers is associated with decline in lung function or changes in haematological parameters, oxidative stress and inflammatory status. Methods Indoor air quality was monitored in five photocopier centers. Pulmonary function was assessed by spirometry in 81 photocopier operators (64 male and 17 female) and 43 healthy control (31 male and 12 female) subjects. Hematological status, serum thio-barbituric acid reactive substances (TBARS), total ferric reducing antioxidant capacity (FRAC), leukotriene B4 (LTB4), 8-isoprostane, C reactive protein (CRP), interleukin 8 (IL-8), clara cell protein (CC-16), intercellular adhesion molecule 1 (ICAM-1) and eosinophilic cationic protein (ECP) were analyzed. Relationships between cumulative exposure, lung function and inflammatory markers were assessed. Results PM10 and PM2.5 were above the permissible levels in all the photocopier centers, whereas the levels of carbon monoxide, nitrogen oxides, ozone, sulphur dioxide, lead, arsenic, nickel, ammonia, benzene and benzo(a)pyrene were within Indian ambient air quality standards. Lung function was similar in the photocopier operators and control subjects. Serum TBARS was significantly higher and FRAC was lower among photocopier operators when compared to healthy controls. Plasma IL-8, LTB4, ICAM-1 and ECP were significantly higher in the photocopier exposed group. Conclusions Photocopiers emit high levels of particulate matter. Long term exposure to emissions from photocopiers was not associated with decreased lung function, but resulted in high oxidative stress and systemic inflammation leading to high risk of cardiovascular diseases. PMID:24025094

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.

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.

Effect of gender specific anthropometric characteristics on lung function in young competitive triathletes from Malaysia.

PubMed

Johari, Hanapi M; Zainudin, Hakimi A; Knight, Victor F; Lumley, Steven A; Subramanium, Ananthan S; Caszo, Brinnell A; Gnanou, Justin V

2017-04-01

Anthropometric and lung function characteristics of triathletes are important for the implementation of individual specific training and recovery recommendations. However, limited data are available for these parameters in triathletes. Hence, the aim of this study was to characterize and examine the gender differences of lung function and anthropometry parameters in competitive triathletes from Malaysia. Body composition assessment and lung function tests were performed on sixteen competitive triathletes (nine male and seven female). The subject's body composition profile including muscle mass (kg), fat free mass (kg), and percent body fat was measured using a bio-impedance segmental body composition analyzer. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured by Quark PFT2 spirometer. The anthropometric measurements revealed that male triathletes were significantly taller than female triathletes and had significantly more protein and skeletal muscle mass. The female triathletes, however, had significantly higher percent body fat. Male triathletes had statistically significant higher FVC and FEV1 than female triathletes. Both the male and female triathletes showed a positive correlation between height, fat free mass and the lung function markers FVC and FEV1. This association was not seen with Body Mass Index (BMI) in female triathletes. The data from our study shows that anthropometric parameters are directly linked to lung function of a triathlete. We also found the relationship between BMI and lung function to be gender specific in triathletes and is dependent on the body protein and fat content. Hence, body composition characterization is essential and provides valuable information for developing individual specific training modules.

Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity.

PubMed

Botelho, Danielle J; Leo, Bey Fen; Massa, Christopher B; Sarkar, Srijata; Tetley, Terry D; Chung, Kian Fan; Chen, Shu; Ryan, Mary P; Porter, Alexandra E; Zhang, Junfeng; Schwander, Stephan K; Gow, Andrew J

2016-01-01

Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 μg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.

Menopause Is Associated with Accelerated Lung Function Decline.

PubMed

Triebner, Kai; Matulonga, Bobette; Johannessen, Ane; Suske, Sandra; Benediktsdóttir, Bryndís; Demoly, Pascal; Dharmage, Shyamali C; Franklin, Karl A; Garcia-Aymerich, Judith; Gullón Blanco, José Antonio; Heinrich, Joachim; Holm, Mathias; Jarvis, Debbie; Jõgi, Rain; Lindberg, Eva; Moratalla Rovira, Jesús Martínez; Muniozguren Agirre, Nerea; Pin, Isabelle; Probst-Hensch, Nicole; Puggini, Luca; Raherison, Chantal; Sánchez-Ramos, José Luis; Schlünssen, Vivi; Sunyer, Jordi; Svanes, Cecilie; Hustad, Steinar; Leynaert, Bénédicte; Gómez Real, Francisco

2017-04-15

Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. To study whether lung function decline, assessed by FVC and FEV 1 , is accelerated in women who undergo menopause. The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect. Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV 1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women. Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.

Static lung volumes in healthy subjects assessed by helium dilution during occlusion of one mainstem bronchus.

PubMed

Johansen, B; Bjørtuft, O; Boe, J

1993-04-01

Single lung function is usually assessed by radioisotopes or, more rarely, by bronchospirometry in which a double lumen catheter is used to separate ventilation of the two lungs. The latter is more precise but less comfortable. An alternative bronchoscopic method is described for determining the volume of a single lung. One mainstem bronchus was temporarily occluded with an inflatable balloon during fibreoptic bronchoscopy in 12 healthy volunteers aged 18-29 years. The functional residual capacities (FRC) of the right, left, and both lungs were measured in duplicate by closed circuit helium dilution. Supplementary vital capacity (VC) manoeuvres permitted calculation of single lung capacities (TLC) and residual volumes (RV). The standard deviation of a single determination of capacities of the right, left, and both lungs were: TLC, 80, 96, and 308 ml; VC, 56, 139, 171 ml; FRC, 131, 74, and 287 ml; RV, 112, 185, and 303 ml, respectively. The sum of the right and left unilateral TLC was not different from bilateral TLC (6.12 v 5.95 l) and the sum of the unilateral FRC was not different from the bilateral FRC (2.60 v 2.78 l). The sum of the unilateral VC was lower than bilateral VC (4.52 v 4.80 l), that of the unilateral RV was higher than bilateral RV (1.60 v 1.16 l). For all subdivisions of lung volume, the right lung was larger than the left. The most common complaint was substernal discomfort during complete exhalation. Oxygen saturation rarely fell below 90%. Temporary occlusion of a mainstem bronchus in normal subjects is safe, relatively simple, and allows fairly precise and accurate measurements of unilateral static lung volumes. Occlusion at TLC, however, probably prevents proper emptying of the non-occluded lung.

Quantitative Computerized Two-Point Correlation Analysis of Lung CT Scans Correlates With Pulmonary Function in Pulmonary Sarcoidosis

PubMed Central

Erdal, Barbaros Selnur; Yildiz, Vedat; King, Mark A.; Patterson, Andrew T.; Knopp, Michael V.; Clymer, Bradley D.

2012-01-01

Background: Chest CT scans are commonly used to clinically assess disease severity in patients presenting with pulmonary sarcoidosis. Despite their ability to reliably detect subtle changes in lung disease, the utility of chest CT scans for guiding therapy is limited by the fact that image interpretation by radiologists is qualitative and highly variable. We sought to create a computerized CT image analysis tool that would provide quantitative and clinically relevant information. Methods: We established that a two-point correlation analysis approach reduced the background signal attendant to normal lung structures, such as blood vessels, airways, and lymphatics while highlighting diseased tissue. This approach was applied to multiple lung fields to generate an overall lung texture score (LTS) representing the quantity of diseased lung parenchyma. Using deidentified lung CT scan and pulmonary function test (PFT) data from The Ohio State University Medical Center’s Information Warehouse, we analyzed 71 consecutive CT scans from patients with sarcoidosis for whom simultaneous matching PFTs were available to determine whether the LTS correlated with standard PFT results. Results: We found a high correlation between LTS and FVC, total lung capacity, and diffusing capacity of the lung for carbon monoxide (P < .0001 for all comparisons). Moreover, LTS was equivalent to PFTs for the detection of active lung disease. The image analysis protocol was conducted quickly (< 1 min per study) on a standard laptop computer connected to a publicly available National Institutes of Health ImageJ toolkit. Conclusions: The two-point image analysis tool is highly practical and appears to reliably assess lung disease severity. We predict that this tool will be useful for clinical and research applications. PMID:22628487

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

PubMed

Weitz, Charles A; Garruto, Ralph M

2015-12-01

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

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

NKG2D is Required for Regulation of Lung Pathology and Dendritic Cell Function Following RSV Infection.

PubMed

Liu, Huan; Osterburg, Andrew R; Flury, Jennifer; Huang, Shuo; McCormack, Francis X; Cormier, Stephania A; Borchers, Michael T

2018-03-15

Respiratory syncytial virus (RSV) is a common cause of respiratory tract infection in vulnerable populations. Natural killer (NK) cells and dendritic cells (DC) are important for the effector functions of both cell types following infection. Wild type and NKG2D deficient mice were infected with RSV. Lung pathology, was assessed by histology. DC function and phenotype was evaluated by ELISA and flow cytometry. The expression of NKG2D ligands on lung and lymph node DCs was measured by immunostaining and flow cytometry. Adoptive transfer experiments were performed to assess the importance of NKG2D dependent DC function in RSV infection. NKG2D deficient mice exhibited greater lung pathology, marked by the accumulation of DCs following RSV infection.  DCs isolated from NKG2D deficient mice had impaired responses towards TLR ligands. DCs expressed NKG2D ligands on their surface, which was further increased in NKG2D deficient mice and during RSV infection. Adoptive transfer of DCs isolated from WT mice into the airways of NKG2D deficient mice ameliorated the enhanced inflammation in NKG2D deficient mice after RSV infection. NKG2D-dependent interactions with DCs control the phenotype and function of DCs and play a critical role in pulmonary host defenses against RSV infection.

Native American Ancestry Affects the Risk for Gene Methylation in the Lungs of Hispanic Smokers from New Mexico

PubMed Central

Liu, Yushi; Thomas, Cynthia L.; Gauderman, W. James; Picchi, Maria A.; Bruse, Shannon E.; Zhang, Xiequn; Flores, Kristina G.; Van Den Berg, David; Stidley, Christine A.; Gilliland, Frank D.

2013-01-01

Rationale: Gene promoter methylation detected in sputum predicts lung cancer risk in smokers. Compared with non-Hispanic whites (NHW), Hispanics have a lower age-standardized incidence for lung cancer. Objectives: This study compared the methylation prevalence in sputum of NHWs with Hispanics using the Lovelace Smokers cohort (n = 1998) and evaluated the effect of Native American ancestry (NAA) and diet on biomarkers for lung cancer risk. Methods: Genetic ancestry was estimated using 48 ancestry markers. Diet was assessed by the Harvard University Dietary Assessment questionnaire. Methylation of 12 genes was measured in sputum using methylation-specific polymerase chain reaction. The association between NAA and risk for methylation was assessed using generalized estimating equations. The ethnic difference in the association between pack-years and risk for lung cancer was assessed in the New Mexico lung cancer study. Measurements and Main Results: Overall Hispanics had a significantly increased risk for methylation across the 12 genes analyzed (odds ratio, 1.18; P = 0.007). However, the risk was reduced by 32% (P = 0.032) in Hispanics with high versus low NAA. In the New Mexico lung cancer study, Hispanic non–small cell lung cancer cases have significantly lower pack-years than NHW counterparts (P = 0.007). Furthermore, compared with NHW smokers, Hispanic smokers had a more rapidly increasing risk for lung cancer as a function of pack-years (P = 0.058). Conclusions: NAA may be an important risk modifier for methylation in Hispanic smokers. Smoking intensity may have a greater impact on risk for lung cancer in Hispanics compared with NHWs. PMID:24032348

Development of a patient-specific model for calculation of pulmonary function

NASA Astrophysics Data System (ADS)

Zhong, Hualiang; Ding, Mingyue; Movsas, Benjamin; Chetty, Indrin J.

2011-06-01

The purpose of this paper is to develop a patient-specific finite element model (FEM) to calculate the pulmonary function of lung cancer patients for evaluation of radiation treatment. The lung model was created with an in-house developed FEM software with region-specific parameters derived from a four-dimensional CT (4DCT) image. The model was used first to calculate changes in air volume and elastic stress in the lung, and then to calculate regional compliance defined as the change in air volume corrected by its associated stress. The results have shown that the resultant compliance images can reveal the regional elastic property of lung tissue, and could be useful for radiation treatment planning and assessment.

Bridging the etiologic and prognostic outlooks in individualized assessment of absolute risk of an illness: application in lung cancer.

PubMed

Karp, Igor; Sylvestre, Marie-Pierre; Abrahamowicz, Michal; Leffondré, Karen; Siemiatycki, Jack

2016-11-01

Assessment of individual risk of illness is an important activity in preventive medicine. Development of risk-assessment models has heretofore relied predominantly on studies involving follow-up of cohort-type populations, while case-control studies have generally been considered unfit for this purpose. To present a method for individualized assessment of absolute risk of an illness (as illustrated by lung cancer) based on data from a 'non-nested' case-control study. We used data from a case-control study conducted in Montreal, Canada in 1996-2001. Individuals diagnosed with lung cancer (n = 920) and age- and sex-matched lung-cancer-free subjects (n = 1288) completed questionnaires documenting life-time cigarette-smoking history and occupational, medical, and family history. Unweighted and weighted logistic models were fitted. Model overfitting was assessed using bootstrap-based cross-validation and 'shrinkage.' The discriminating ability was assessed by the c-statistic, and the risk-stratifying performance was assessed by examination of the variability in risk estimates over hypothetical risk-profiles. In the logistic models, the logarithm of incidence-density of lung cancer was expressed as a function of age, sex, cigarette-smoking history, history of respiratory conditions and exposure to occupational carcinogens, and family history of lung cancer. The models entailed a minimal degree of overfitting ('shrinkage' factor: 0.97 for both unweighted and weighted models) and moderately high discriminating ability (c-statistic: 0.82 for the unweighted model and 0.66 for the weighted model). The method's risk-stratifying performance was quite high. The presented method allows for individualized assessment of risk of lung cancer and can be used for development of risk-assessment models for other illnesses.

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.

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.

When Is an Alveolar Type 2 Cell an Alveolar Type 2 Cell? A Conundrum for Lung Stem Cell Biology and Regenerative Medicine.

PubMed

Beers, Michael F; Moodley, Yuben

2017-07-01

Generating mature, differentiated, adult lung cells from pluripotent cells, such as induced pluripotent stem cells and embryonic stem cells, offers the hope of both generating disease-specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung-regenerative medicine, several groups have developed and reported on protocols using defined media, coculture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors. However, there remains significant controversy about the degree of differentiation of these cells compared with their primary counterparts, coupled with a lack of consistency or uniformity in assessing the resultant phenotypes. Given the inevitable, exponential expansion of these approaches and the probable, but yet-to-emerge second and higher generation techniques to create such assets, we were prompted to pose the question, what makes a lung epithelial cell a lung epithelial cell? More specifically for this Perspective, we also posed the question, what are the minimum features that constitute an alveolar type (AT) 2 epithelial cell? In addressing this, we summarize a body of work spanning nearly five decades, amassed by a series of "lung epithelial cell biology pioneers," which carefully describes well characterized molecular, functional, and morphological features critical for discriminately assessing an AT2 phenotype. Armed with this, we propose a series of core criteria to assist the field in confirming that cells obtained following a differentiation protocol are indeed mature and functional AT2 epithelial cells.

Cotton Dust Exposure and Resulting Respiratory Disorders Among Home-Based Garment Workers.

PubMed

Silpasuwan, Pimpan; Prayomyong, Somchit; Sujitrat, Dusit; Suwan-Ampai, Plernpit

2016-03-01

Cotton dust exposures and resulting respiratory disorders among Thai home-based garment workers in Bangkok were explored. Structured interviews focused on occupational health assessments of respiratory disorders; workflow process observations, lung function screening tests, and garment dust density assessments were used to gather data. Results revealed that garment workers in this study had worked in home-based tailoring an average of 14.88 years; 88.5% reported average health status, only 2.6% currently smoked cigarettes, and 8.6% had impaired lung function. The prevalence of respiratory disorders in this occupational group was 25%. Significant respiratory tract signs and symptoms were associated with lung function capacity (odds ratio [OR] = 52.15, 95% confidence interval [CI] = [6.49, 419.60]). Long work hours and few preventive behaviors were significantly associated with respiratory disorders (OR = 2.89 and OR = 10.183, respectively). Improving working conditions at home and minimizing fabric dust exposure among garment workers are recommended. © 2015 The Author(s).

Assessment of pulmonary structure-function relationships in young children and adolescents with cystic fibrosis by multivolume proton-MRI and CT.

PubMed

Pennati, Francesca; Roach, David J; Clancy, John P; Brody, Alan S; Fleck, Robert J; Aliverti, Andrea; Woods, Jason C

2018-02-19

Lung disease is the most frequent cause of morbidity and mortality in patients with cystic fibrosis (CF), and there is a shortage of sensitive biomarkers able to regionally monitor disease progression and to assess early responses to therapy. To determine the feasibility of noncontrast-enhanced multivolume MRI, which assesses intensity changes between expiratory and inspiratory breath-hold images, to detect and quantify regional ventilation abnormalities in CF lung disease, with a focus on the structure-function relationship. Retrospective. Twenty-nine subjects, including healthy young children (n = 9, 7-37 months), healthy adolescents (n = 4, 14-22 years), young children with CF lung disease (n = 10, 7-47 months), and adolescents with CF lung disease (n = 6, 8-18 years) were studied. 3D spoiled gradient-recalled sequence at 1.5T. Subjects were scanned during breath-hold at functional residual capacity (FRC) and total lung capacity (TLC) through noncontrast-enhanced MRI and CT. Expiratory-inspiratory differences in MR signal-intensity (Δ 1 H-MRI) and CT-density (ΔHU) were computed to estimate regional ventilation. MR and CT images were also evaluated using a CF-specific scoring system. Quadratic regression, Spearman's correlation, one-way analysis of variance (ANOVA). Δ 1 H-MRI maps were sensitive to ventilation heterogeneity related to gravity dependence in healthy lung and to ventilation impairment in CF lung disease. A high correlation was found between MRI and CT ventilation maps (R 2  = 0.79, P < 0.001). Globally, Δ 1 H-MRI and ΔHU decrease with increasing morphological score (respectively, R 2  = 0.56, P < 0.001 and R 2  = 0.31, P < 0.001). Locally, Δ 1 H-MRI was higher in healthy regions (median 15%) compared to regions with bronchiectasis, air trapping, consolidation, and to segments fed by airways with bronchial wall thickening (P < 0.001). Multivolume noncontrast-enhanced MRI, as a nonionizing imaging modality that can be used on nearly any MRI scanner without specialized equipment or gaseous tracers, may be particularly valuable in CF care, providing a new imaging biomarker to detect early alterations in regional lung structure-function. 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Production and Assessment of Decellularized Pig and Human Lung Scaffolds

PubMed Central

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

2013-01-01

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

Production and assessment of decellularized pig and human lung scaffolds.

PubMed

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

2013-09-01

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

Clonidine reduces norepinephrine and improves bone marrow function in a rodent model of lung contusion, hemorrhagic shock, and chronic stress.

PubMed

Alamo, Ines G; Kannan, Kolenkode B; Ramos, Harry; Loftus, Tyler J; Efron, Philip A; Mohr, Alicia M

2017-03-01

Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Male Sprague-Dawley rats underwent 6 days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75 μg/kg) after the restraint stress. On postinjury day 7, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor, and peripheral blood mobilization of hematopoietic progenitor cells, as well as bone marrow cellularity and erythroid progenitor cell growth. The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1 ± 0.6 vs 10.8 ± 0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased hematopoietic progenitor cells mobilization and restored granulocyte colony stimulating factor levels. After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Changes in lung volumes and gas trapping in patients with large hiatal hernia.

PubMed

Naoum, Christopher; Kritharides, Leonard; Ing, Alvin; Falk, Gregory L; Yiannikas, John

2017-03-01

Studies assessing hiatal hernia (HH)-related effects on lung volumes derived by body plethysmography are limited. We aimed to evaluate the effect of hernia size on lung volumes (including assessment by body plethysmography) and the relationship to functional capacity, as well as the impact of corrective surgery. Seventy-three patients (70 ± 10 years; 54 female) with large HH [mean ± standard deviation, intra-thoracic stomach (ITS) (%): 63 ± 20%; type III in 65/73] had respiratory function data (spirometry, 73/73; body plethysmography, 64/73; diffusing capacity, 71/73) and underwent HH surgery. Respiratory function was analysed in relation to hernia size (groups I, II and III: ≤50, 50%-75% and ≥75% ITS, respectively) and functional capacity. Post-operative changes were quantified in a subgroup. Total lung capacity (TLC) and vital capacity (VC) correlated inversely with hernia size (TLC: 97 ± 11%, 96 ± 13%, 88 ± 10% predicted in groups I, II and III, respectively, P = 0.01; VC: 110 ± 17%, 111 ± 14%, 98 ± 14% predicted, P = 0.02); however, mean values were normal and only 14% had abnormal lung volumes. Surgery increased TLC (93 ± 11% vs 97 ± 10% predicted) and VC (105 ± 15% vs 116 ± 18%), and decreased residual volume/total lung capacity (RV/TLC) ratio (39 ± 7% vs 37 ± 6%) (P < 0.01 for all). Respiratory changes were modest relative to the marked functional class improvement. Among parameters that improved following HH surgery, decreased TLC and forced expiratory volume in 1 s and increased RV/TLC ratio correlated with poorer functional class pre-operatively. Increasing HH size correlates with reduced TLC and VC. Surgery improves lung volumes and gas trapping; however, the changes are mild and within the normal range. © 2015 John Wiley & Sons Ltd.

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.

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.

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

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.

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

PubMed Central

Garruto, Ralph M.

2015-01-01

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

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

Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

PubMed

Ribeiro, A; Almeida, V I; Costola-de-Souza, C; Ferraz-de-Paula, V; Pinheiro, M L; Vitoretti, L B; Gimenes-Junior, J A; Akamine, A T; Crippa, J A; Tavares-de-Lima, W; Palermo-Neto, J

2015-02-01

We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.

Xenon-enhanced CT using subtraction CT: Basic and preliminary clinical studies for comparison of its efficacy with that of dual-energy CT and ventilation SPECT/CT to assess regional ventilation and pulmonary functional loss in smokers.

PubMed

Ohno, Yoshiharu; Yoshikawa, Takeshi; Takenaka, Daisuke; Fujisawa, Yasuko; Sugihara, Naoki; Kishida, Yuji; Seki, Shinichiro; Koyama, Hisanobu; Sugimura, Kazuro

2017-01-01

To prospectively and directly compare the capability for assessments of regional ventilation and pulmonary functional loss in smokers of xenon-ventilation CT obtained with the dual-energy CT (DE-CT) and subtraction CT (Sub-CT) MATERIALS AND METHODS: Twenty-three consecutive smokers (15 men and 8 women, mean age: 69.7±8.7years) underwent prospective unenhanced and xenon-enhanced CTs, the latter by Sub-CT and DE-CT methods, ventilation SPECT and pulmonary function tests. Sub-CT was generated from unenhanced and xenon-enhanced CT, and all co-registered SPECT/CT data were produced from SPECT and unenhanced CT data. For each method, regional ventilation was assessed by using a 11-point scoring system on a per-lobe basis. To determine the functional lung volume by each method, it was also calculated for individual sublets with a previously reported method. To determine inter-observer agreement for each method, ventilation defect assessment was evaluated by using the χ2 test with weighted kappa statistics. For evaluation of the efficacy of each method for pulmonary functional loss assessment, functional lung volume was correlated with%FEV 1 . Each inter-observer agreement was rated as substantial (Sub-CT: κ=0.69, p<0.0001; DE-CT: κ=0.64, p<0.0001; SPECT/CT: κ=0.64, p<0.0001). Functional lung volume for each method showed significant to good correlation with%FEV 1 (Sub-CT: r=0.72, p=0.0001; DE-CT: r=0.74, p<0.0001; SPECT/CT: r=0.66, p=0.0006). Xenon-enhanced CT obtained by Sub-CT can be considered at least as efficacious as that obtained by DE-CT and SPECT/CT for assessment of ventilation abnormality and pulmonary functional loss in smokers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

One year outcomes in patients with acute lung injury randomised to initial trophic or full enteral feeding: prospective follow-up of EDEN randomised trial.

PubMed

Needham, Dale M; Dinglas, Victor D; Bienvenu, O Joseph; Colantuoni, Elizabeth; Wozniak, Amy W; Rice, Todd W; Hopkins, Ramona O

2013-03-19

To evaluate the effect of initial low energy permissive underfeeding ("trophic feeding") versus full energy enteral feeding ("full feeding") on physical function and secondary outcomes in patients with acute lung injury. Prospective longitudinal follow-up evaluation of the NHLBI ARDS Clinical Trials Network's EDEN trial 41hospitals in the United States. 525 patients with acute lung injury. Randomised assignment to trophic or full feeding for up to six days; thereafter, all patients still receiving mechanical ventilation received full feeding. Blinded assessment of the age and sex adjusted physical function domain of the SF-36 instrument at 12 months after acute lung injury. Secondary outcome measures included survival; physical, psychological, and cognitive functioning; quality of life; and employment status at six and 12 months. After acute lung injury, patients had substantial physical, psychological, and cognitive impairments, reduced quality of life, and impaired return to work. Initial trophic versus full feeding did not affect mean SF-36 physical function at 12 months (55 (SD 33) v 55 (31), P=0.54), survival to 12 months (65% v 63%, P=0.63), or nearly all of the secondary outcomes. In survivors of acute lung injury, there was no difference in physical function, survival, or multiple secondary outcomes at 6 and 12 month follow-up after initial trophic or full enteral feeding. NCT No 00719446.

Method of lungs regional ventilation function assessment on the basis of continuous lung monitoring results using multi-angle electrical impedance tomography

NASA Astrophysics Data System (ADS)

Aleksanyan, Grayr; Shcherbakov, Ivan; Kucher, Artem; Sulyz, Andrew

2018-04-01

With continuous monitoring of the lungs using multi-angle electric impedance tomography method, a large array of images of impedance changes in the patient's chest cavity is accumulated. This article proposes a method for evaluating the regional ventilation function of lungs based on the results of continuous monitoring using the multi-angle electric impedance tomography method, which allows one image of the thoracic cavity to be formed on the basis of a large array of images of the impedance change in the patient's chest cavity. In the presence of pathologies in the lungs (neoplasms, fluid, pneumothorax, etc.) in these areas, air filling will be disrupted, which will be displayed on the generated image. When conducting continuous monitoring in several sections, a three-dimensional pattern of air filling of the thoracic cavity is possible.

Comparison of Acute Health Effects From Exposures to Diesel and Biodiesel Fuel Emissions

PubMed Central

Mehus, Aaron A.; Reed, Rustin J.; Lee, Vivien S. T.; Littau, Sally R.; Hu, Chengcheng; Lutz, Eric A.

2015-01-01

Objective: To investigate the comparative acute health effects associated with exposures to diesel and 75% biodiesel/25% diesel (B75) blend fuel emissions. Methods: We analyzed multiple health endpoints in 48 healthy adults before and after exposures to diesel and B75 emissions in an underground mine setting—lung function, lung and systemic inflammation, novel biomarkers of exposure, and oxidative stress were assessed. Results: B75 reduced respirable diesel particulate matter by 20%. Lung function declined significantly more after exposure to diesel emissions. Lung inflammatory cells along with sputum and plasma inflammatory mediators increased significantly to similar levels with both exposures. Urinary 8-hydroxydeoxyguanosine, a marker of oxidative stress, was not significantly changed after either exposure. Conclusions: Use of B75 lowered respirable diesel particulate matter exposure and some associated acute health effects, although lung and systemic inflammation were not reduced compared with diesel use. PMID:26147538

Comparison of Acute Health Effects From Exposures to Diesel and Biodiesel Fuel Emissions.

PubMed

Mehus, Aaron A; Reed, Rustin J; Lee, Vivien S T; Littau, Sally R; Hu, Chengcheng; Lutz, Eric A; Burgess, Jefferey L

2015-07-01

To investigate the comparative acute health effects associated with exposures to diesel and 75% biodiesel/25% diesel (B75) blend fuel emissions. We analyzed multiple health endpoints in 48 healthy adults before and after exposures to diesel and B75 emissions in an underground mine setting-lung function, lung and systemic inflammation, novel biomarkers of exposure, and oxidative stress were assessed. B75 reduced respirable diesel particulate matter by 20%. Lung function declined significantly more after exposure to diesel emissions. Lung inflammatory cells along with sputum and plasma inflammatory mediators increased significantly to similar levels with both exposures. Urinary 8-hydroxydeoxyguanosine, a marker of oxidative stress, was not significantly changed after either exposure. Use of B75 lowered respirable diesel particulate matter exposure and some associated acute health effects, although lung and systemic inflammation were not reduced compared with diesel use.

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.

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.

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

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

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.

Gender Differences in the Association of Individual and Contextual Exposures with Lung Function in a Rural Canadian Population.

PubMed

Janzen, Bonnie; Karunanayake, Chandima; Rennie, Donna; Pickett, William; Lawson, Joshua; Kirychuk, Shelley; Hagel, Louise; Senthilselvan, Ambikaipakan; Koehncke, Niels; Dosman, James; Pahwa, Punam

2017-02-01

To investigate the association of individual and contextual exposures with lung function by gender in rural-dwelling Canadians. A cross-sectional mail survey obtained completed questionnaires on exposures from 8263 individuals; a sub-sample of 1609 individuals (762 men, 847 women) additionally participated in clinical lung function testing. The three dependent variables were forced expired volume in one second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC ratio. Independent variables included smoking, waist circumference, body mass index, indoor household exposures (secondhand smoke, dampness, mold, musty odor), occupational exposures (grain dust, pesticides, livestock, farm residence), and socioeconomic status. The primary analysis was multiple linear regression, conducted separately for each outcome. The potential modifying influence of gender was tested in multivariable models using product terms between gender and each independent variable. High-risk waist circumference was related to reduced FVC and FEV 1 for both genders, but the effect was more pronounced in men. Greater pack-years smoking was associated with lower lung function values. Exposure to household smoke was related to reduced FEV 1 , and exposure to livestock, with increased FEV 1 . Lower income adequacy was associated with reduced FVC and FEV 1 . High-risk waist circumference was more strongly associated with reduced lung function in men than women. Longitudinal research combined with rigorous exposure assessment is needed to clarify how sex and gender interact to impact lung function in rural populations.

Exhaled breath condensate adenosine tracks lung function changes in cystic fibrosis

PubMed Central

Olsen, Bonnie M.; Lin, Feng-Chang; Fine, Jason; Boucher, Richard C.

2013-01-01

Measurement of exhaled breath condensate (EBC) biomarkers offers a noninvasive means to assess airway disease, but the ability of EBC biomarkers to track longitudinal changes in disease severity remains unproven. EBC was collected from pediatric patients with cystic fibrosis (CF) during regular clinic visits over 1 yr. EBC biomarkers urea, adenosine (Ado), and phenylalanine (Phe) were measured by mass spectrometry, and biomarker ratios were used to control for variable dilution of airway secretions. EBC biomarker ratios were assessed relative to lung function in longitudinal, multivariate models and compared with sputum inflammatory markers and quality of life assessment (CFQ-R). EBC was successfully analyzed from 51 subjects during 184 visits (3.6 ± 0.9 visits per subject). EBC Ado/urea ratio was reproducible in duplicate samples (r = 0.62, P < 0.01, n = 20) and correlated with sputum neutrophil elastase (β = 2.5, P < 0.05). EBC Ado/urea correlated with the percentage predicted of forced expiratory volume in 1 s in longitudinal, multivariate models (β = −2.9, P < 0.01); EBC Ado/Phe performed similarly (β = −2.1, P < 0.05). In contrast, IL-8 and elastase measured in spontaneously expectorated sputum (n = 57 samples from 25 subjects) and the CFQ-R respiratory scale (n = 90 tests from 47 subjects) were not significantly correlated with lung function. EBC was readily collected in a clinic setting from a wide range of subjects. EBC Ado tracked longitudinal changes in lung function in CF, with results similar to or better than established measures. PMID:23355385

Whole genome prediction and heritability of childhood asthma phenotypes.

PubMed

McGeachie, Michael J; Clemmer, George L; Croteau-Chonka, Damien C; Castaldi, Peter J; Cho, Michael H; Sordillo, Joanne E; Lasky-Su, Jessica A; Raby, Benjamin A; Tantisira, Kelan G; Weiss, Scott T

2016-12-01

While whole genome prediction (WGP) methods have recently demonstrated successes in the prediction of complex genetic diseases, they have not yet been applied to asthma and related phenotypes. Longitudinal patterns of lung function differ between asthmatics, but these phenotypes have not been assessed for heritability or predictive ability. Herein, we assess the heritability and genetic predictability of asthma-related phenotypes. We applied several WGP methods to a well-phenotyped cohort of 832 children with mild-to-moderate asthma from CAMP. We assessed narrow-sense heritability and predictability for airway hyperresponsiveness, serum immunoglobulin E, blood eosinophil count, pre- and post-bronchodilator forced expiratory volume in 1 sec (FEV 1 ), bronchodilator response, steroid responsiveness, and longitudinal patterns of lung function (normal growth, reduced growth, early decline, and their combinations). Prediction accuracy was evaluated using a training/testing set split of the cohort. We found that longitudinal lung function phenotypes demonstrated significant narrow-sense heritability (reduced growth, 95%; normal growth with early decline, 55%). These same phenotypes also showed significant polygenic prediction (areas under the curve [AUCs] 56% to 62%). Including additional demographic covariates in the models increased prediction 4-8%, with reduced growth increasing from 62% to 66% AUC. We found that prediction with a genomic relatedness matrix was improved by filtering available SNPs based on chromatin evidence, and this result extended across cohorts. Longitudinal reduced lung function growth displayed extremely high heritability. All phenotypes with significant heritability showed significant polygenic prediction. Using SNP-prioritization increased prediction across cohorts. WGP methods show promise in predicting asthma-related heritable traits.

The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure.

PubMed

Jones, Christina V; Alikhan, Maliha A; O'Reilly, Megan; Sozo, Foula; Williams, Timothy M; Harding, Richard; Jenkin, Graham; Ricardo, Sharon D

2014-09-06

Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration. Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 μg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry. Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an exacerbation of lung injury. The trophic functions of macrophages in lung development requires further elucidation in order to explore macrophage modulation as a strategy for promoting lung maturation.

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

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

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.

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.

Hydrostatic weighing at residual volume and functional residual capacity.

PubMed

Thomas, T R; Etheridge, G L

1980-07-01

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

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

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

PubMed

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

2018-01-01

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

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

PubMed Central

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

2018-01-01

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

Circadian molecular clock in lung pathophysiology

PubMed Central

Sundar, Isaac K.; Yao, Hongwei; Sellix, Michael T.

2015-01-01

Disrupted daily or circadian rhythms of lung function and inflammatory responses are common features of chronic airway diseases. At the molecular level these circadian rhythms depend on the activity of an autoregulatory feedback loop oscillator of clock gene transcription factors, including the BMAL1:CLOCK activator complex and the repressors PERIOD and CRYPTOCHROME. The key nuclear receptors and transcription factors REV-ERBα and RORα regulate Bmal1 expression and provide stability to the oscillator. Circadian clock dysfunction is implicated in both immune and inflammatory responses to environmental, inflammatory, and infectious agents. Molecular clock function is altered by exposomes, tobacco smoke, lipopolysaccharide, hyperoxia, allergens, bleomycin, as well as bacterial and viral infections. The deacetylase Sirtuin 1 (SIRT1) regulates the timing of the clock through acetylation of BMAL1 and PER2 and controls the clock-dependent functions, which can also be affected by environmental stressors. Environmental agents and redox modulation may alter the levels of REV-ERBα and RORα in lung tissue in association with a heightened DNA damage response, cellular senescence, and inflammation. A reciprocal relationship exists between the molecular clock and immune/inflammatory responses in the lungs. Molecular clock function in lung cells may be used as a biomarker of disease severity and exacerbations or for assessing the efficacy of chronotherapy for disease management. Here, we provide a comprehensive overview of clock-controlled cellular and molecular functions in the lungs and highlight the repercussions of clock disruption on the pathophysiology of chronic airway diseases and their exacerbations. Furthermore, we highlight the potential for the molecular clock as a novel chronopharmacological target for the management of lung pathophysiology. PMID:26361874

Lung densitometry: why, how and when

PubMed Central

Camiciottoli, Gianna; Diciotti, Stefano

2017-01-01

Lung densitometry assesses with computed tomography (CT) the X-ray attenuation of the pulmonary tissue which reflects both the degree of inflation and the structural lung abnormalities implying decreased attenuation, as in emphysema and cystic diseases, or increased attenuation, as in fibrosis. Five reasons justify replacement with lung densitometry of semi-quantitative visual scales used to measure extent and severity of diffuse lung diseases: (I) improved reproducibility; (II) complete vs. discrete assessment of the lung tissue; (III) shorter computation times; (IV) better correlation with pathology quantification of pulmonary emphysema; (V) better or equal correlation with pulmonary function tests (PFT). Commercially and open platform software are available for lung densitometry. It requires attention to technical and methodological issues including CT scanner calibration, radiation dose, and selection of thickness and filter to be applied to sections reconstructed from whole-lung CT acquisition. Critical is also the lung volume reached by the subject at scanning that can be measured in post-processing and represent valuable information per se. The measurements of lung density include mean and standard deviation, relative area (RA) at −970, −960 or −950 Hounsfield units (HU) and 1st and 15th percentile for emphysema in inspiratory scans, and RA at −856 HU for air trapping in expiratory scans. Kurtosis and skewness are used for evaluating pulmonary fibrosis in inspiratory scans. The main indication for lung densitometry is assessment of emphysema component in the single patient with chronic obstructive pulmonary diseases (COPD). Additional emerging applications include the evaluation of air trapping in COPD patients and in subjects at risk of emphysema and the staging in patients with lymphangioleiomyomatosis (LAM) and with pulmonary fibrosis. It has also been applied to assess prevalence of smoking-related emphysema and to monitor progression of smoking-related emphysema, alpha1 antitrypsin deficiency emphysema, and pulmonary fibrosis. Finally, it is recommended as end-point in pharmacological trials of emphysema and lung fibrosis. PMID:29221318

Long-term gas exchange characteristics as markers of deterioration in patients with cystic fibrosis

PubMed Central

2009-01-01

Background and Aim In patients with cystic fibrosis (CF) the architecture of the developing lungs and the ventilation of lung units are progressively affected, influencing intrapulmonary gas mixing and gas exchange. We examined the long-term course of blood gas measurements in relation to characteristics of lung function and the influence of different CFTR genotype upon this process. Methods Serial annual measurements of PaO2 and PaCO2 assessed in relation to lung function, providing functional residual capacity (FRCpleth), lung clearance index (LCI), trapped gas (VTG), airway resistance (sReff), and forced expiratory indices (FEV1, FEF50), were collected in 178 children (88 males; 90 females) with CF, over an age range of 5 to 18 years. Linear mixed model analysis and binary logistic regression analysis were used to define predominant lung function parameters influencing oxygenation and carbon dioxide elimination. Results PaO2 decreased linearly from age 5 to 18 years, and was mainly associated with FRCpleth, (p < 0.0001), FEV1 (p < 0.001), FEF50 (p < 0.002), and LCI (p < 0.002), indicating that oxygenation was associated with the degree of pulmonary hyperinflation, ventilation inhomogeneities and impeded airway function. PaCO2 showed a transitory phase of low PaCO2 values, mainly during the age range of 5 to 12 years. Both PaO2 and PaCO2 presented with different progression slopes within specific CFTR genotypes. Conclusion In the long-term evaluation of gas exchange characteristics, an association with different lung function patterns was found and was closely related to specific genotypes. Early examination of blood gases may reveal hypocarbia, presumably reflecting compensatory mechanisms to improve oxygenation. PMID:19909502

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

Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function

PubMed Central

Larcombe, Alexander N.; Foong, Rachel E.; Boylen, Catherine E.; Zosky, Graeme R.

2012-01-01

Please cite this paper as: Larcombe et al. (2012) Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12012. Background  Exposure to diesel exhaust particles (DEP) is thought to exacerbate many pre‐existing respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease, however, there is a paucity of data on whether DEP exacerbates illness due to respiratory viral infection. Objectives  To assess the physiological consequences of an acute DEP exposure during the peak of influenza‐induced illness. Methods  We exposed adult female BALB/c mice to 100 μg DEP (or control) 3·75 days after infection with 104·5 plaque forming units of influenza A/Mem71 (or control). Six hours, 24 hours and 7 days after DEP exposure we measured thoracic gas volume and lung function at functional residual capacity. Bronchoalveolar lavage fluid was taken for analyses of cellular inflammation and cytokines, and whole lungs were taken for measurement of viral titre. Results  Influenza infection resulted in significantly increased inflammation, cytokine influx and impairment to lung function. DEP exposure alone resulted in less inflammation and cytokine influx, and no impairment to lung function. Mice infected with influenza and exposed to DEP had higher viral titres and neutrophilia compared with infected mice, yet they did not have more impaired lung mechanics than mice infected with influenza alone. Conclusions  A single dose of DEP is not sufficient to physiologically exacerbate pre‐existing respiratory disease caused by influenza infection in mice. PMID:22994877

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.

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

Collateral Ventilation to Congenital Hyperlucent Lung Lesions Assessed on Xenon-Enhanced Dynamic Dual-Energy CT: an Initial Experience

PubMed Central

Yang, Dong Hyun; Kim, Namkug; Park, Seung Il; Kim, Dong Kwan; Kim, Ellen Ai-Rhan

2011-01-01

Objective We wanted to evaluate the resistance to collateral ventilation in congenital hyperlucent lung lesions and to correlate that with the anatomic findings on xenon-enhanced dynamic dual-energy CT. Materials and Methods Xenon-enhanced dynamic dual-energy CT was successfully and safely performed in eight children (median age: 5.5 years, 4 boys and 4 girls) with congenital hyperlucent lung lesions. Functional assessment of the lung lesions on the xenon map was done, including performing a time-xenon value curve analysis and assessing the amplitude of xenon enhancement (A) value, the rate of xenon enhancement (K) value and the time of arrival value. Based on the A value, the lung lesions were categorized into high or low (A value > 10 Hounsfield unit [HU]) resistance to collateral ventilation. In addition, the morphologic CT findings of the lung lesions, including cyst, mucocele and an accessory or incomplete fissure, were assessed on the weighted-average CT images. The xenon-enhanced CT radiation dose was estimated. Results Five of the eight lung lesions were categorized into the high resistance group and three lesions were categorized into the low resistance group. The A and K values in the normal lung were higher than those in the low resistance group. The time of arrival values were delayed in the low resistance group. Cysts were identified in five lesions, mucocele in four, accessory fissure in three and incomplete fissure in two. Either cyst or an accessory fissure was seen in four of the five lesions showing high resistance to collateral ventilation. The xenon-enhanced CT radiation dose was 2.3 ± 0.6 mSv. Conclusion Xenon-enhanced dynamic dual-energy CT can help visualize and quantitate various degrees of collateral ventilation to congenital hyperlucent lung lesions in addition to assessing the anatomic details of the lung. PMID:21228937

Collateral ventilation to congenital hyperlucent lung lesions assessed on xenon-enhanced dynamic dual-energy CT: an initial experience.

PubMed

Goo, Hyun Woo; Yang, Dong Hyun; Kim, Namkug; Park, Seung Il; Kim, Dong Kwan; Kim, Ellen Ai-Rhan

2011-01-01

We wanted to evaluate the resistance to collateral ventilation in congenital hyperlucent lung lesions and to correlate that with the anatomic findings on xenon-enhanced dynamic dual-energy CT. Xenon-enhanced dynamic dual-energy CT was successfully and safely performed in eight children (median age: 5.5 years, 4 boys and 4 girls) with congenital hyperlucent lung lesions. Functional assessment of the lung lesions on the xenon map was done, including performing a time-xenon value curve analysis and assessing the amplitude of xenon enhancement (A) value, the rate of xenon enhancement (K) value and the time of arrival value. Based on the A value, the lung lesions were categorized into high or low (A value > 10 Hounsfield unit [HU]) resistance to collateral ventilation. In addition, the morphologic CT findings of the lung lesions, including cyst, mucocele and an accessory or incomplete fissure, were assessed on the weighted-average CT images. The xenon-enhanced CT radiation dose was estimated. Five of the eight lung lesions were categorized into the high resistance group and three lesions were categorized into the low resistance group. The A and K values in the normal lung were higher than those in the low resistance group. The time of arrival values were delayed in the low resistance group. Cysts were identified in five lesions, mucocele in four, accessory fissure in three and incomplete fissure in two. Either cyst or an accessory fissure was seen in four of the five lesions showing high resistance to collateral ventilation. The xenon-enhanced CT radiation dose was 2.3 ± 0.6 mSv. Xenon-enhanced dynamic dual-energy CT can help visualize and quantitate various degrees of collateral ventilation to congenital hyperlucent lung lesions in addition to assessing the anatomic details of the lung.

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.

Health surveillance for occupational respiratory disease.

PubMed

Lewis, L; Fishwick, D

2013-07-01

Occupational lung diseases remain common, and health surveillance is one approach used to assist identification of early cases. To identify areas of good practice within respiratory health surveillance and to formulate recommendations for practice. Published literature was searched since 1990 using a semi-systematic methodology. A total of 561 documents were identified on Medline and Embase combined. Other search engines did not identify relevant documents that had not already been identified by these two main searches. Seventy-nine of these were assessed further and 36 documents were included for the full analysis. Respiratory health surveillance remains a disparate process, even within disease type. A standard validated questionnaire and associated guidance should be developed. Lung function testing was common and generally supported by the evidence. Cross-sectional interpretation of lung function in younger workers needs careful assessment in order to best identify early cases of disease. More informed interpretation of the forced expiratory volume in 1 s/forced vital capacity ratio, for example by using a lower limit of normal for each worker, and of longitudinal lung function information is advised. Immunological tests appear useful in small groups of workers exposed to common occupational allergens. Education, training and improved occupational health policies are likely to improve uptake of health surveillance, to ensure that those who fail health surveillance at any point are handled appropriately.

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

PubMed

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

2012-10-01

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

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.

Ultrasonographic assessment of the diaphragm in chronic obstructive pulmonary disease patients: relationships with pulmonary function and the influence of body composition - a pilot study.

PubMed

Smargiassi, Andrea; Inchingolo, Riccardo; Tagliaboschi, Linda; Di Marco Berardino, Alessandro; Valente, Salvatore; Corbo, Giuseppe Maria

2014-01-01

Skeletal muscle weakness with loss of fat-free mass (FFM) is one of the main systemic effects of chronic obstructive pulmonary disease (COPD). The diaphragm is also involved, leading to disadvantageous conditions and poor contractile capacities. We measured the thickness of the diaphragm (TD) by ultrasonography to evaluate the relationships between echographic measurements, parameters of respiratory function and body composition data. Thirty-two patients (23 males) underwent (1) pulmonary function tests, (2) echographic assessment of TD in the zone of apposition at various lung volumes, i.e. TD at residual volume (TDRV), TD at functional residual capacity (TDFRC) and TD at total lung capacity (TDTLC), and (3) bioelectrical body impedance analysis. The BMI and the BODE (BMI-Obstruction-Dyspnea-Exercise) index values were reported. TDRV, TDFRC and TDTLC measured 3.3, 3.6 and 6 mm, respectively, with good intraobserver reproducibility (0.97, 0.97 and 0.96, respectively). All the TDs were found to be related to FFM, with the relationship being greater for TDFRC (r(2) = 0.39 and p = 0.0002). With regard to lung volumes, inspiratory capacity (IC) was found to be closely related to TDTLC (r(2) = 0.42 and p = 0.0001). The difference between TDTLC and TDRV, as a thickening value (TDTLCRV), was closely related to FVC (r(2) = 0.34 and p = 0.0004) and to air-trapping indices (RV/TLC, FRC/TLC and IC/TLC): the degree of lung hyperinflation was greater and the TDTLCRV was less. Finally, we found a progressive reduction of both thicknesses and thickenings as the severity of IC/TLC increased, with a significant p value for the trend in both analyses (p = 0.02). Ultrasonographic assessment of the diaphragm could be a useful tool for studying disease progression in COPD patients, in terms of lung hyperinflation and the loss of FFM. © 2014 S. Karger AG, Basel.

DCD lung donation: donor criteria, procedural criteria, pulmonary graft function validation, and preservation.

PubMed

Erasmus, Michiel E; van Raemdonck, Dirk; Akhtar, Mohammed Zeeshan; Neyrinck, Arne; de Antonio, David Gomez; Varela, Andreas; Dark, John

2016-07-01

In an era where there is a shortage of lungs for transplantation is increased utilization of lungs from donation after circulatory death (DCD) donors. We review the reports of 11 controlled and 1 uncontrolled DCD programs focusing on donor criteria, procedural criteria, graft assessment, and preservation techniques including the use of ex vivo lung perfusion. We have formulated conclusions and recommendations for each of these areas, which were presented at the 6th International Conference on Organ Donation. A table of recommendations, the grade of recommendations, and references are provided. © 2015 Steunstichting ESOT.

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

The effect of donor treatment with hydrogen on lung allograft function in rats.

PubMed

Kawamura, Tomohiro; Huang, Chien-Sheng; Peng, Ximei; Masutani, Kosuke; Shigemura, Norihisa; Billiar, Timothy R; Okumura, Meinoshin; Toyoda, Yoshiya; Nakao, Atsunori

2011-08-01

Because inhaled hydrogen provides potent anti-inflammatory and antiapoptotic effects against acute lung injury, we hypothesized that treatment of organ donors with inhaled hydrogen during mechanical ventilation would decrease graft injury after lung transplantation. Orthotopic left lung transplants were performed using a fully allogeneic Lewis to Brown Norway rat model. The donors were exposed to mechanical ventilation with 98% oxygen plus 2% nitrogen or 2% hydrogen for 3 h prior to harvest, and the lung grafts underwent 4 h of cold storage in Perfadex (Vitrolife, Göteborg, Sweden). The graft function, histomorphologic changes, and inflammatory reactions were assessed. The combination of mechanical ventilation and prolonged cold ischemia resulted in marked deterioration of gas exchange when the donors were ventilated with 2% nitrogen/98% oxygen, which was accompanied by upregulation of proinflammatory cytokines and proapoptotic molecules. These lung injuries were attenuated significantly by ventilation with 2% hydrogen. Inhaled hydrogen induced heme oxygenase-1, an antioxidant enzyme, in the lung grafts prior to implantation, which might contribute to protective effects afforded by hydrogen. Preloaded hydrogen gas during ventilation prior to organ procurement protected lung grafts effectively from ischemia/reperfusion-induced injury in a rat lung transplantation model. Copyright © 2011 Mosby, Inc. 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.

The importance of phrenic nerve preservation and its effect on long-term postoperative lung function after pneumonectomy.

PubMed

Kocher, Gregor J; Poulson, Jannie Lysgaard; Blichfeldt-Eckhardt, Morten Rune; Elle, Bo; Schmid, Ralph A; Licht, Peter B

2016-04-01

The importance of phrenic nerve preservation during pneumonectomy remains controversial. We previously demonstrated that preservation of the phrenic nerve in the immediate postoperative period preserved lung function by 3-5% but little is known about its long-term effects. We, therefore, decided to investigate the effect of temporary ipsilateral cervical phrenic nerve block on dynamic lung volumes in mid- to long-term pneumonectomy patients. We investigated 14 patients after a median of 9 years post pneumonectomy (range: 1-15 years). Lung function testing (spirometry) and fluoroscopic and/or sonographic assessment of diaphragmatic motion on the pneumonectomy side were performed before and after ultrasonographic-guided ipsilateral cervical phrenic nerve block by infiltration with lidocaine. Ipsilateral phrenic nerve block was successfully achieved in 12 patients (86%). In the remaining 2 patients, diaphragmatic motion was already paradoxical before the nerve block. We found no significant difference on dynamic lung function values (FEV1 'before' 1.39 ± 0.44 vs FEV1 'after' 1.38 ± 0.40; P = 0.81). Induction of a temporary diaphragmatic palsy did not significantly influence dynamic lung volumes in mid- to long-term pneumonectomy patients, suggesting that preservation of the phrenic nerve is of greater importance in the immediate postoperative period after pneumonectomy. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

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

PubMed Central

Cortés-Telles, Arturo

2016-01-01

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

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.

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

PubMed

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

1993-01-01

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

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.

Dietary Nutrient Intake, Ethnicity, and Epigenetic Silencing of Lung Cancer Genes Detected in Sputum in New Mexican Smokers.

PubMed

Leng, Shuguang; Picchi, Maria A; Kang, Huining; Wu, Guodong; Filipczak, Piotr T; Juri, Daniel E; Zhang, Xiequn; Gauderman, W James; Gilliland, Frank D; Belinsky, Steven A

2018-02-01

Lung cancer gene methylation detected in sputum assesses field cancerization and predicts lung cancer incidence. Hispanic smokers have higher lung cancer susceptibility compared with non-Hispanic whites (NHW). We aimed to identify novel dietary nutrients affecting lung cancer gene methylation and determine the degree of ethnic disparity in methylation explained by diet. Dietary intakes of 139 nutrients were assessed using a validated Harvard food frequency questionnaire in 327 Hispanics and 1,502 NHWs from the Lovelace Smokers Cohort. Promoter methylation of 12 lung cancer genes was assessed in sputum DNA. A global association was identified between dietary intake and gene methylation ( P permutation = 0.003). Seventeen nutrient measurements were identified with magnitude of association with methylation greater than that seen for folate. A stepwise approach identified B12, manganese, sodium, and saturated fat as the minimally correlated set of nutrients whose optimal intakes could reduce the methylation by 36% ( P permutation < 0.001). Six protective nutrients included vitamin D, B12, manganese, magnesium, niacin, and folate. Approximately 42% of ethnic disparity in methylation was explained by insufficient intake of protective nutrients in Hispanics compared with NHWs. Functional validation of protective nutrients showed an enhanced DNA repair capacity toward double-strand DNA breaks, a mechanistic biomarker strongly linked to acquisition of lung cancer gene methylation in smokers. Dietary intake is a major modifiable factor for preventing promoter methylation of lung cancer genes in smokers' lungs. Complex dietary supplements could be developed on the basis of these protective nutrients for lung cancer chemoprevention in smokers. Hispanic smokers may benefit the most from this complex for reducing their lung cancer susceptibility. Cancer Prev Res; 11(2); 93-102. ©2017 AACR . ©2017 American Association for Cancer Research.

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

Participation restrictions in ambulatory amyotrophic lateral sclerosis patients: Physical and psychological factors.

PubMed

Van Groenestijn, Annerieke C; Schröder, Carin D; Kruitwagen-Van Reenen, Esther T; Van Den Berg, Leonard H; Visser-Meily, Johanna M A

2017-11-01

The aim of this study was to assess the prevalence of participation restrictions in ambulatory patients with amyotrophic lateral sclerosis (ALS) and to identify physical and psychological contributory factors. In this cross-sectional study, self-reported participation restrictions of 72 ambulatory ALS patients were assessed using the social health status dimension (SIPSOC) of the Sickness Impact Profile (SIP-68). Associations between SIPSOC and physical functioning, psychological factors, and demographic factors were analyzed using hierarchical regression analyses. Ninety-two percent of the patients reported participation restrictions; 54.9% could be explained by physical functioning; psychological factors accounted for 8.1% of the variance. Lung capacity, functional mobility, fatigue, and helplessness were independently associated with participation restrictions. Ambulatory ALS patients have participation restrictions, which may be influenced if early ALS care is directed toward lung capacity, functional mobility, fatigue, and feelings of helplessness. Muscle Nerve 56: 912-918, 2017. © 2017 Wiley Periodicals, Inc.

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.

CPAP of 4 cm H(2)O Has no short-term benefit at term in infants with BPD.

PubMed

Sandberg, Kenneth L; Hjalmarson, Ola

2012-01-01

Lung development and function is compromised at term in infants with bronchopulmonary dysplasia (BPD), characterized by reduced functional residual capacity (FRC) and impaired gas-mixing efficiency in distal airways. To determine whether continuous positive airway pressure (CPAP) improves FRC, ventilation, distal airway function, and gas exchange in spontaneously breathing infants with BPD. Twenty-one infants with BPD (median birth weight 0.72 kg (range 0.50-1.27) and median gestational age 26 weeks (range 23-28)) were studied before and after CPAP of 4 cm H(2)O was applied by a facemask system. A multiple-breath nitrogen washout method was used to assess FRC, ventilation, and gas-mixing efficiency. Moment analysis and lung clearance index was calculated from the nitrogen-decay curve for assessment of gas-mixing efficiency. Transcutaneous (Tc) PO(2)/PCO(2) was monitored during stable infant conditions before each washout test. When CPAP was raised from 0 to 4 cm H(2)O, FRC increased significantly together with a significant increase in moment ratios (M(1)/M(0) and M(2)/M(0)). Tc PO(2) decreased significantly and the breathing pattern changed, with significantly reduced respiratory rate, minute ventilation, and alveolar ventilation. There was also an increase in tidal volume and dead space. CPAP of 4 cm H(2)O applied with a facemask at term to infants with BPD did not improve ventilation, gas-mixing efficiency in distal airways, or oxygenation despite an increase in FRC. We speculate that instead of promoting recruitment of unventilated lung volumes, increasing the end-expiratory pressure in infants with BPD may lead to an overexpansion of already ventilated parts of the lung, causing further compromise of lung function. Copyright © 2012 S. Karger AG, Basel.

HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

PubMed

Brune, Kieran A; Ferreira, Fernanda; Mandke, Pooja; Chau, Eric; Aggarwal, Neil R; D'Alessio, Franco R; Lambert, Allison A; Kirk, Gregory; Blankson, Joel; Drummond, M Bradley; Tsibris, Athe M; Sidhaye, Venkataramana K

2016-01-01

Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD). We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE) cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI) to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1) and activated extracellular signal-regulated kinase (ERK). We demonstrate that HIV can enter airway epithelial cells and alter their function by impairing cell-cell adhesion and increasing the expression of inflammatory mediators. These observed changes may contribute local inflammation, which can lead to lung function decline and increased susceptibility to COPD in HIV 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).

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.

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.

The measurement of lung volumes using body plethysmography and helium dilution methods in COPD patients: a correlation and diagnosis analysis.

PubMed

Tang, Yongjiang; Zhang, Mingke; Feng, Yulin; Liang, Binmiao

2016-11-23

Chronic obstructive pulmonary disease (COPD) is a chronic airway disease characterized by persistent airflow limitation. Moreover, lung hyperinflation evaluated by lung volumes is also the key pathophysiologic process during COPD progression. Nevertheless, there is still no preferred method to evaluate lung volumes. For this study, we recruited 170 patients with stable COPD to assess lung volumes stratified by airflow limitation severity. Lung volumes including residual volume (RV) and total lung capacity (TLC) were determined by both body plethysmography and helium dilution methods. The discrepancies between these two methods were recorded as ΔRV%pred, ΔTLC%pred, and ΔRV/TLC. We found that ΔRV%pred, ΔTLC%pred, and ΔRV/TLC increased significantly with the severity of COPD. The differences of lung capacity between these two methods were negatively correlated with FEV 1 %pred, and diffusing capacity for carbon monoxide (D L CO%pred). Moreover, the receiver operating characteristic (ROC) for ΔTLC%pred to distinguish severe COPD from non-severe COPD had an area under curve (AUC) of 0.886. The differences of lung volume parameters measured by body plethysmography and helium dilution methods were associated with airflow limitation and can effectively differentiate COPD severity, which may be a supportive method to assess the lung function of stable COPD patients.

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

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

Assessment of Lung Function in Asthma and COPD using Hyperpolarized 129Xe Chemical Shift Saturation Recovery Spectroscopy and Dissolved-Phase MR Imaging

PubMed Central

Qing, Kun; Mugler, John P.; Altes, Talissa A.; Jiang, Yun; Mata, Jaime F.; Miller, G. Wilson; Ruset, Iulian C.; Hersman, F. William; Ruppert, Kai

2014-01-01

Magnetic-resonance spectroscopy and imaging using hyperpolarized xenon-129 show great potential for evaluation of the most important function of the human lung -- gas exchange. In particular, Chemical Shift Saturation Recovery (CSSR) xenon-129 spectroscopy provides important physiological information for the lung as a whole by characterizing the dynamic process of gas exchange, while dissolved-phase xenon-129 imaging captures the time-averaged regional distribution of gas uptake by lung tissue and blood. Herein, we present recent advances in assessing lung function using CSSR spectroscopy and dissolved-phase imaging in a total of 45 subjects (23 healthy, 13 chronic obstructive pulmonary disease (COPD) and 9 asthma). From CSSR acquisitions, the COPD subjects showed red blood cell to tissue/plasma (RBC-to-TP) ratios below the average for the healthy subjects (p<0.001), but significantly higher septal wall thicknesses, as compared with the healthy subjects (p<0.005); the RBC-to-TP ratios for the asthmatics fell outside 2 standard deviations (either higher or lower) from the mean of the healthy subjects although there was no statistically significant difference for the average ratio of the study group as a whole. Similarly, from the 3D DP imaging acquisitions, we found all the ratios (TP-to-GP, RBC-to-GP, RBC-to-TP) measured in the COPD subjects were lower than those from the healthy subjects (p<0.05 for all ratios), while these ratios in the asthmatics differed considerably between subjects. Despite having been performed at different lung inflation levels, the RBC-to-TP ratios measured by CSSR and 3D DP imaging were fairly consistent with each other, with a mean difference of 0.037 (ratios from 3D DP imaging larger). In ten subjects the RBC-to-GP ratios obtained from the 3D DP imaging acquisitions were also highly correlated with their DLCO/Va ratios measured by pulmonary function testing (R=0.91). PMID:25146558

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

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

Vitamin E isoform γ-tocotrienol protects against emphysema in cigarette smoke-induced COPD.

PubMed

Peh, Hong Yong; Tan, W S Daniel; Chan, Tze Khee; Pow, Chen Wei; Foster, Paul S; Wong, W S Fred

2017-09-01

Inflammation and oxidative stress contribute to emphysema in COPD. Although corticosteroids are the standard of care for COPD, they do not reduce oxidative stress, and a subset of patients is steroid-resistant. Vitamin E isoform γ-tocotrienol possesses both anti-inflammatory and anti-oxidative properties that may protect against emphysema. We aimed to establish the therapeutic potential of γ-tocotrienol in cigarette smoke-induced COPD models in comparison with prednisolone. BALB/c mice were exposed to cigarette smoke for 2 weeks or 2 months. γ-Tocotrienol and prednisolone were given orally. Bronchoalveolar lavage (BAL) fluid and lung tissues were assessed for inflammation, oxidative damage, and regulation of transcription factor activities. Emphysema and lung function were also evaluated. γ-Tocotrienol dose-dependently reduced cigarette smoke-induced BAL fluid neutrophil counts and levels of cytokines, chemokines and oxidative damage biomarkers, and pulmonary pro-inflammatory and pro-oxidant gene expression, but restored lung endogenous antioxidant activities. γ-Tocotrienol acted by inhibiting nuclear translocation of STAT3 and NF-κB, and up-regulating Nrf2 activation in the lungs. In mice exposed to 2-month cigarette smoke, γ-tocotrienol ameliorated bronchial epithelium thickening and destruction of alveolar sacs in lungs, and improved lung functions. In comparison with prednisolone, γ-tocotrienol demonstrated better anti-oxidative efficacy, and protection against emphysema and lung function in COPD. We revealed for the first time the anti-inflammatory and antioxidant efficacies of γ-tocotrienol in cigarette smoke-induced COPD models. In addition, γ-tocotrienol was able to attenuate emphysematous lesions and improve lung function in COPD. γ-Tocotrienol may have therapeutic potential for the treatment of COPD. Copyright © 2017 Elsevier Inc. All rights reserved.

Applicability of avidin protein coated mesoporous silica nanoparticles as drug carriers in the lung

NASA Astrophysics Data System (ADS)

van Rijt, S. H.; Bölükbas, D. A.; Argyo, C.; Wipplinger, K.; Naureen, M.; Datz, S.; Eickelberg, O.; Meiners, S.; Bein, T.; Schmid, O.; Stoeger, T.

2016-04-01

Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties and are thus considered as promising candidates for next generation nano-medicines. In particular, inhalation into the lungs represents a direct, non-invasive delivery route for treating lung disease. To assess MSN biocompatibility in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as well as aminated (uncoated) MSNs, after direct application into the lungs of mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and inflammatory responses to MSNs within one week after instillation. We show that amine-functionalized (MSN-NH2) particles are not taken up by lung epithelial cells, but induced a prolonged inflammatory response in the lung and macrophage cell death. In contrast, MSN-AVI co-localized with alveolar epithelial type 1 and type 2 cells in the lung in the absence of sustained inflammatory responses or cell death, and showed preferential epithelial cell uptake in in vitro co-cultures. Further, MSN-AVI particles demonstrated uniform particle distribution in mouse lungs and slow clearance rates. Thus, we provide evidence that avidin functionalized MSNs (MSN-AVI) have the potential to serve as versatile biocompatible drug carriers for lung-specific drug delivery.Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties and are thus considered as promising candidates for next generation nano-medicines. In particular, inhalation into the lungs represents a direct, non-invasive delivery route for treating lung disease. To assess MSN biocompatibility in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as well as aminated (uncoated) MSNs, after direct application into the lungs of mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and inflammatory responses to MSNs within one week after instillation. We show that amine-functionalized (MSN-NH2) particles are not taken up by lung epithelial cells, but induced a prolonged inflammatory response in the lung and macrophage cell death. In contrast, MSN-AVI co-localized with alveolar epithelial type 1 and type 2 cells in the lung in the absence of sustained inflammatory responses or cell death, and showed preferential epithelial cell uptake in in vitro co-cultures. Further, MSN-AVI particles demonstrated uniform particle distribution in mouse lungs and slow clearance rates. Thus, we provide evidence that avidin functionalized MSNs (MSN-AVI) have the potential to serve as versatile biocompatible drug carriers for lung-specific drug delivery. Electronic supplementary information (ESI) available: Synthesis of MSN particles. Characterisation of MSN particles (Fig. S1 and S2), DLS measurements of MSNs over time, lymphocyte and PMN cell count after MSN exposure (Fig. S3). Toxicity in BAL cytospins controls, phalloidin staining on BAL cytospins of MSN-NH2 exposed mice (Fig. S4), nanoparticle distribution in lung cryo-slices of Balb/c mice exposed to 100 μg MSNs (Fig. S5). Balb/c mice cryo-slices exposed to MSN-AVI for 1 or 7 days, co-stained with alveolar epithelial cell type 1 marker or with alveolar epithelial cell type 2 marker (Fig. S6), DiD selective labeling in a co-culture set-up (Fig. S7). See DOI: 10.1039/c5nr04119h

Assessment of regional ventilation and deformation using 4D-CT imaging for healthy human lungs during tidal breathing

PubMed Central

Jahani, Nariman; Choi, Jiwoong; Iyer, Krishna; Hoffman, Eric A.

2015-01-01

This study aims to assess regional ventilation, nonlinearity, and hysteresis of human lungs during dynamic breathing via image registration of four-dimensional computed tomography (4D-CT) scans. Six healthy adult humans were studied by spiral multidetector-row CT during controlled tidal breathing as well as during total lung capacity and functional residual capacity breath holds. Static images were utilized to contrast static vs. dynamic (deep vs. tidal) breathing. A rolling-seal piston system was employed to maintain consistent tidal breathing during 4D-CT spiral image acquisition, providing required between-breath consistency for physiologically meaningful reconstructed respiratory motion. Registration-derived variables including local air volume and anisotropic deformation index (ADI, an indicator of preferential deformation in response to local force) were employed to assess regional ventilation and lung deformation. Lobar distributions of air volume change during tidal breathing were correlated with those of deep breathing (R2 ≈ 0.84). Small discrepancies between tidal and deep breathing were shown to be likely due to different distributions of air volume change in the left and the right lungs. We also demonstrated an asymmetric characteristic of flow rate between inhalation and exhalation. With ADI, we were able to quantify nonlinearity and hysteresis of lung deformation that can only be captured in dynamic images. Nonlinearity quantified by ADI is greater during inhalation, and it is stronger in the lower lobes (P < 0.05). Lung hysteresis estimated by the difference of ADI between inhalation and exhalation is more significant in the right lungs than that in the left lungs. PMID:26316512

Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth.

PubMed

Alphonse, Rajesh S; Vadivel, Arul; Fung, Moses; Shelley, William Chris; Critser, Paul John; Ionescu, Lavinia; O'Reilly, Megan; Ohls, Robin K; McConaghy, Suzanne; Eaton, Farah; Zhong, Shumei; Yoder, Merv; Thébaud, Bernard

2014-05-27

Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth. Human fetal and neonatal rat lungs contain ECFCs with robust proliferative potential, secondary colony formation on replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In contrast, human fetal lung ECFCs exposed to hyperoxia in vitro and neonatal rat ECFCs isolated from hyperoxic alveolar growth-arrested rat lungs mimicking bronchopulmonary dysplasia proliferated less, showed decreased clonogenic capacity, and formed fewer capillary-like networks. Intrajugular administration of human cord blood-derived ECFCs after established arrested alveolar growth restored lung function, alveolar and lung vascular growth, and attenuated pulmonary hypertension. Lung ECFC colony- and capillary-like network-forming capabilities were also restored. Low ECFC engraftment and the protective effect of cell-free ECFC-derived conditioned media suggest a paracrine effect. Long-term (10 months) assessment of ECFC therapy showed no adverse effects with persistent improvement in lung structure, exercise capacity, and pulmonary hypertension. Impaired ECFC function may contribute to arrested alveolar growth. Cord blood-derived ECFC therapy may offer new therapeutic options for lung diseases characterized by alveolar damage. © 2014 American Heart Association, Inc.

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.

Hydrogen coadministration slows the development of COPD-like lung disease in a cigarette smoke-induced rat model.

PubMed

Liu, Xiaoyu; Ma, Cuiqing; Wang, Xiaoyu; Wang, Wenjing; Li, Zhu; Wang, Xiansheng; Wang, Pengyu; Sun, Wuzhuang; Xue, Baojian

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a progressive pulmonary disease caused by harmful gases or particles. Recent studies have shown that 2% hydrogen or hydrogen water is effective in the treatment and prevention of a variety of diseases. This study investigated the beneficial effects and the possible mechanisms of different hydrogen concentrations on COPD. A rat COPD model was established through smoke exposure methods, and inhalation of different concentrations of hydrogen was used as the intervention. The daily condition of rats and the weight changes were observed; lung function and right ventricular hypertrophy index were assessed. Also, white blood cells were assessed in bronchoalveolar lavage fluid. Pathologic changes in the lung tissue were analyzed using light microscopy and electron microscopy; cardiovascular structure and pulmonary arterial pressure changes in rats were observed using ultrasonography. Tumor necrosis factor alpha, interleukin (IL)-6, IL-17, IL-23, matrix metalloproteinase-12, tissue inhibitor of metalloproteinase-1, caspase-3, caspase-8 protein, and mRNA levels in the lung tissue were determined using immunohistochemistry, Western blot, and real-time polymerase chain reaction. The results showed that hydrogen inhalation significantly reduced the number of inflammatory cells in the bronchoalveolar lavage fluid, and the mRNA and protein expression levels of tumor necrosis factor alpha, IL-6, IL-17, IL-23, matrix metalloproteinase-12, caspase-3, and caspase-8, but increased the tissue inhibitor of metalloproteinase-1 expression. Furthermore, hydrogen inhalation ameliorated lung pathology, lung function, and cardiovascular function and reduced the right ventricular hypertrophy index. Inhalation of 22% and 41.6% hydrogen showed better outcome than inhalation of 2% hydrogen. These results suggest that hydrogen inhalation slows the development of COPD-like lung disease in a cigarette smoke-induced rat model. Higher concentrations of hydrogen may represent a more effective way for the rat model.

Hydrogen coadministration slows the development of COPD-like lung disease in a cigarette smoke-induced rat model

PubMed Central

Liu, Xiaoyu; Ma, Cuiqing; Wang, Xiaoyu; Wang, Wenjing; Li, Zhu; Wang, Xiansheng; Wang, Pengyu; Sun, Wuzhuang; Xue, Baojian

2017-01-01

Background Chronic obstructive pulmonary disease (COPD) is a progressive pulmonary disease caused by harmful gases or particles. Recent studies have shown that 2% hydrogen or hydrogen water is effective in the treatment and prevention of a variety of diseases. This study investigated the beneficial effects and the possible mechanisms of different hydrogen concentrations on COPD. Methods A rat COPD model was established through smoke exposure methods, and inhalation of different concentrations of hydrogen was used as the intervention. The daily condition of rats and the weight changes were observed; lung function and right ventricular hypertrophy index were assessed. Also, white blood cells were assessed in bronchoalveolar lavage fluid. Pathologic changes in the lung tissue were analyzed using light microscopy and electron microscopy; cardiovascular structure and pulmonary arterial pressure changes in rats were observed using ultrasonography. Tumor necrosis factor alpha, interleukin (IL)-6, IL-17, IL-23, matrix metalloproteinase-12, tissue inhibitor of metalloproteinase-1, caspase-3, caspase-8 protein, and mRNA levels in the lung tissue were determined using immunohistochemistry, Western blot, and real-time polymerase chain reaction. Results The results showed that hydrogen inhalation significantly reduced the number of inflammatory cells in the bronchoalveolar lavage fluid, and the mRNA and protein expression levels of tumor necrosis factor alpha, IL-6, IL-17, IL-23, matrix metalloproteinase-12, caspase-3, and caspase-8, but increased the tissue inhibitor of metalloproteinase-1 expression. Furthermore, hydrogen inhalation ameliorated lung pathology, lung function, and cardiovascular function and reduced the right ventricular hypertrophy index. Inhalation of 22% and 41.6% hydrogen showed better outcome than inhalation of 2% hydrogen. Conclusion These results suggest that hydrogen inhalation slows the development of COPD-like lung disease in a cigarette smoke-induced rat model. Higher concentrations of hydrogen may represent a more effective way for the rat model. PMID:28496315

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

PubMed Central

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

2015-01-01

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

Six-minute walk test as a determinant of the functional capacity of children and adolescents with cystic fibrosis: A systematic review.

PubMed

Andrade Lima, Cibelle; Dornelas de Andrade, Armèle; Campos, Shirley Lima; Brandão, Daniella Cunha; Mourato, Ianny Pereira; Britto, Murilo Carlos Amorim de

2018-04-01

Cystic Fibrosis (CF) is a multisystem disorder. The involvement of the respiratory system is frequent and culminates in dyspnea and exercise intolerance. Functional capacity is an important diagnostic tool, because it reflects the cardiorespiratory status, quality of life and prognosis. This systematic review aims to assess the reproducibility and validity of the six minute walk test (6MWT) to reflect the functional capacity of children and adolescents with cystic fibrosis, and also the correlation between 6MWT and lung function. Searches for articles were performed in eight databases using MeSH/DeCS keywords. A total of 695 articles were found and, after verifying all eligibility criteria, six articles were included for analysis and scoring regarding the methodological quality according to the QUADAS scale (Quality Assessment of Diagnostic Accuracy Studies). All articles had good methodology (QUADAS between 9 and 11 points). The 6MWT is not correlated with lung function. There is a strong indication that the 6MWT is a reproducible test to assess the functional capacity of children and adolescents with CF. The validity assessment could not be reached because the studies included in this systematic review did not use adequate statistical tools to carry out such an evaluation. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Effect of omega-3 fatty acids supplementation during pregnancy on lung function in preschoolers: a clinical trial.

PubMed

Gutiérrez-Delgado, R I; Barraza-Villarreal, A; Escamilla-Núñez, C; Hernández-Cadena, L; Garcia-Feregrino, R; Shackleton, C; Ramakrishnan, U; Sly, P D; Romieu, I

2018-04-04

Prenatal omega-3 fatty acids improve alveolarization, diminish inflammation, and improve pulmonary growth, but it is unclear whether these outcomes translate into improved postnatal lung function. We assessed the effect of prenatal supplementation with docosahexaenoic acid (DHA) on offspring lung function through 60 months of age. We included a cohort of 772 Mexican preschoolers whose mothers participated in a clinical trial (NCT00646360) of supplementation with DHA or a placebo from week 18-22 of gestation through delivery. The children were followed after birth and anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. The effect of DHA was tested using a longitudinal mixed effect models. Overall, mean (Standard Deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during follow up period were 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and -5.2 (1.6), -4.8 (1.7), -4.6 (1.6), respectively. There were no significant differences in pulmonary function by treatment group. DHA did not affect the average lung function or the trajectories through 60 months. Prenatal DHA supplementation did not influence pulmonary function in this cohort of Mexican preschoolers.

Local and Systemic Inflammation May Mediate Diesel Engine Exhaust-Induced Lung Function Impairment in a Chinese Occupational Cohort.

PubMed

Wang, Haitao; Duan, Huawei; Meng, Tao; Yang, Mo; Cui, Lianhua; Bin, Ping; Dai, Yufei; Niu, Yong; Shen, Meili; Zhang, Liping; Zheng, Yuxin; Leng, Shuguang

2018-04-01

Diesel exhaust (DE) as the major source of vehicle-emitted particle matter in ambient air impairs lung function. The objectives were to assess the contribution of local (eg, the fraction of exhaled nitric oxide [FeNO] and serum Club cell secretory protein [CC16]) and systemic (eg, serum C-reaction protein [CRP] and interleukin-6 [IL-6]) inflammation to DE-induced lung function impairment using a unique cohort of diesel engine testers (DETs, n = 137) and non-DETs (n = 127), made up of current and noncurrent smokers. Urinary metabolites, FeNO, serum markers, and spirometry were assessed. A 19% reduction in CC16 and a 94% increase in CRP were identified in DETs compared with non-DETs (all p values <10-4), which were further corroborated by showing a dose-response relationship with internal dose for DE exposure (all p values <.04) and a time-course relationship with DE exposure history (all p values <.005). Mediation analysis showed that 43% of the difference in FEV1 between DETs and non-DETs can be explained by circulating CC16 and CRP (permuted p < .001). An inverse dose-dependent relationship between FeNO and internal dose for cigarette smoke was identified (p = .0003). A range of 95% lower bounds of benchmark dose of 1.0261-1.4513 μg phenanthrols/g creatinine in urine as an internal dose was recommended for regulatory risk assessment. Local and systemic inflammation may be key processes that contribute to the subsequent development of obstructive lung disease in DE-exposed populations.

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

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.

Is incentive spirometry effective following thoracic surgery?

PubMed

Agostini, Paula; Calvert, Rachel; Subramanian, Hariharan; Naidu, Babu

2008-04-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether incentive spirometry is a useful intervention for patients after thoracic surgery. Altogether 255 papers were found using the reported search, of which seven represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that incentive spirometry is a relatively good measure of lung function and may be used to assess respiratory recovery in the days after thoracic surgery. Physiotherapy either with or without incentive spirometry reduces the incidence of postoperative complications and improves lung function but there is currently no evidence that incentive spirometry in itself could either replace or significantly augment the work of the physiotherapists. Clinicians should be aware that while incentive spirometry can provide an assessment of lung recovery, well-organised and regular physiotherapy remains the most effective mechanism to augment their patient's recovery and avoid postoperative complications.

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

Noncalcified Lung Nodules: Volumetric Assessment with Thoracic CT

PubMed Central

Gavrielides, Marios A.; Kinnard, Lisa M.; Myers, Kyle J.; Petrick, Nicholas

2009-01-01

Lung nodule volumetry is used for nodule diagnosis, as well as for monitoring tumor response to therapy. Volume measurement precision and accuracy depend on a number of factors, including image-acquisition and reconstruction parameters, nodule characteristics, and the performance of algorithms for nodule segmentation and volume estimation. The purpose of this article is to provide a review of published studies relevant to the computed tomographic (CT) volumetric analysis of lung nodules. A number of underexamined areas of research regarding volumetric accuracy are identified, including the measurement of nonsolid nodules, the effects of pitch and section overlap, and the effect of respiratory motion. The need for public databases of phantom scans, as well as of clinical data, is discussed. The review points to the need for continued research to examine volumetric accuracy as a function of a multitude of interrelated variables involved in the assessment of lung nodules. Understanding and quantifying the sources of volumetric measurement error in the assessment of lung nodules with CT would be a first step toward the development of methods to minimize that error through system improvements and to correctly account for any remaining error. © RSNA, 2009 PMID:19332844

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.

Ultrasound assessment of diaphragmatic function in patients with amyotrophic lateral sclerosis.

PubMed

Fantini, Riccardo; Mandrioli, Jessica; Zona, Stefano; Antenora, Federico; Iattoni, Andrea; Monelli, Marco; Fini, Nicola; Tonelli, Roberto; Clini, Enrico; Marchioni, Alessandro

2016-07-01

Evaluation of diaphragm function in Amyotrophic Lateral Sclerosis (ALS) is critical in determining when to commence non-invasive mechanical ventilation (NIV). Currently, forced vital capacity (FVC) and sniff nasal inspiratory pressure (SNIP) are volitional measures for this evaluation, but require collaboration and are poorly specific. The primary aim of this study was to assess whether diaphragmatic thickness measured by ultrasound (US) correlates with lung function impairment in ALS patients. The secondary aim was then to compare US diaphragm thickness index (ΔTdi) with a new parameter (ΔTmax index). 41 patients with ALS and 30 healthy subjects were enrolled in the study. All subjects underwent spirometry, SNIP and diaphragm US evaluation, while arterial blood gases were measured in some patients only. US assessed diaphragm thickness (Tdi) at tidal volume (Vt) or total lung capacity (TLC), and their ratio (ΔTmax) were recorded. Changes (Δ) in Tdi indices during tidal volume (ΔTdiVt) and maximal inspiration (ΔTdiTLC) were also assessed. ΔTdiTLC (p <0.001) and ΔTmax (p = 0.007), but not ΔTdiVt, differed between patients and controls. Significant correlation (p < 0.05) was found between ΔTdiTLC, ΔTmax and FVC. The ROC curve analysis for comparison of individual testing showed better accuracy with Δtmax than with ΔtdiTLC for FVC (AUC 0.76 and 0.27) and SNIP (AUC 0.71 and 0.25). Diaphragm thickness assessed by ultrasound significantly correlates with global respiratory alterations in patients with ALS. ΔTmax represents a new US index of early diaphragmatic dysfunction, better related with the routinely performed lung function tests. © 2016 Asian Pacific Society of Respirology.

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.

Violence exposure, a chronic psychosocial stressor, and childhood lung function

PubMed Central

Suglia, Shakira Franco; Ryan, Louise; Laden, Francine; Dockery, Douglas; Wright, Rosalind J

2011-01-01

Background Chronic psychosocial stressors, including violence, have been linked to neuropsychological and behavioral development in children as well as physiologic alterations that may lead to broader health effects. Methods We examined the relationship between violence and childhood lung function in a prospective birth cohort of 313 urban children 6 and 7 years of age. Mothers reported on their child’s lifetime exposure to community violence (ETV) and interparental conflict in the home [Conflict Tactics Scale (CTS)] within one year of the lung function assessment. Results In linear regression analyses, adjusting for maternal education, child’s age, race, birthweight, tobacco smoke exposure, and medical history, girls in the highest CTS verbal aggression tertile had a 5.5% (95% CI: −9.6, −1.5) decrease in percent predicted FEV1 and a 5.4% (95% CI: −9.7, −1.1) decrease in FVC compared to girls in the lowest tertile. The CTS verbal aggression subscale was associated with lung function among boys in the same direction, albeit this was not statistically significant. Boys in the highest ETV tertile had a 3.4% (95% CI: −8.0, 1.1) lower FEV1 and 5.3% lower (95% CI: −10.2, −0.4) FVC compared to boys in the lowest tertile. The ETV score was not a significant predictor of girl’s lung function. Conclusions Interparental conflict, specifically verbal aggression, and exposure to community violence were associated with decreased childhood lung function independent of socioeconomic status, tobacco smoke exposure, birthweight and respiratory illness history. Gender differences were noted based on the type of violence exposure which may warrant further exploration. PMID:18158365

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.

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

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 Feiji decoction for soothing the liver combined with psychotherapy on quality of life in primary lung cancer patients].

PubMed

Yao, Yilin

2012-01-01

Primary lung cancer is one of the most common malignant tumors. It causes great pain and mood disorders to patients, and significantly reduces their quality of life. The aim of the current study is to evaluate the effect of Feiji Decoction for soothing the liver combined with psychotherapy on quality of life (QoL) and physical status of patients with primary lung cancer. A total of 118 patients with primary non-small cell lung cancer were randomly divided into two groups. The 57 patients in the combined therapy group were treated with Feiji Decoction for soothing the liver and psychotherapy combined with chemotherapy, whereas the 61 patients in the control group were treated with chemotherapy only. Both groups were observed for the two treatment courses. The European Organization for Research and Treatment of Cancer QoL Questionnaire LC-43 (EORTC QLQ-LC43) was used to assess the QoL of every patient in both groups before and after treatment scales. At the same time, physical status was assessed using the Karnofsky performance status (KPS) and East Cooperative Oncology Group performance status (ECOG). The scores of physiology function, role function, emotion function, cognize function, society function, and general health in the therapy group were higher than that of the control group. The therapy group also showed better QoL results than the contol group. Significant differences were observed between the two groups (P<0.01). Meanwhile, the scores of fatigue, vomit, pain, polypnea, insomnia, anorexia, constipation, and specific manifestation of lung cancer in the therapy group were obviously lower than that of the control group; more patients were observed to be relieved. Significant differences between the two groups were observed (P<0.01). The KPS and ECOG scores of the patients were observed to have improved and stabilized in the therapy group than that of the control group; the differences were statistically significant (P<0.01). Feiji Decoction for soothing the liver combined with psychotherapy can alleviate the clinical symptoms, elevate the physical status, and improve the QOL of patients with primary lung cancer. Thus, this therapy has a good clinical therapeutic effect.

Influence of radiological emphysema on lung function test in idiopathic pulmonary fibrosis.

PubMed

Bodlet, Aline; Maury, Gisèle; Jamart, Jacques; Dahlqvist, Caroline

2013-11-01

Idiopathic pulmonary fibrosis (IPF) is one of the most frequent interstitial lung disease. Emphysema can be associated with IPF as described in the «Combined pulmonary fibrosis and emphysema» syndrome. The primary endpoint of this retrospective cohort study was to evaluate the impact of the association of IPF and emphysema on lung function tests parameters (FVC, TLC, FEV1, FEV1/FVC and DLCO). The secondary endpoint was to assess the impact of the associated radiological emphysema on lung function parameters used in the du Bois prognostic score recently developed by Ron du Bois et al. We retrospectively reviewed the medical files of 98 patients with lung fibrosis who were followed in our University Hospital with access to pharmacological studies and lung transplantation from 1981 to 2011. Fifty six patients were considered for analysis. The collected data included gender, age, smoking history and respiratory hospitalizations. We also analysed their pulmonary functional parameters along with radiological characteristics, in particular the presence of emphysema which was assessed on thoracic high resolution CT scan. The du Bois score was retrospectively calculated from these data. TLC and FVC at diagnosis were significantly higher in the IPF-E group compared to the IPF group (respectively 86.6 ± 17.2% pv versus 72.0 ± 15.0% pv; p: 0.004 and 86.8 ± 18.4% pv versus 72.6 ± 20.6% pv; p: 0.020). The [Formula: see text] used in the calculation of the du Bois prognostic score was significantly higher in the IPF-E group. By cons, [Formula: see text] was not statistically different between the two groups. Radiological emphysema associated with IPF had an impact on pulmonary function tests. Despite this difference, the du Bois score was not statistically different between these two groups. Nevertheless, after one year of follow up, the patients with emphysema were in a subclass with a lower mortality rate than those without emphysema. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2013-01-01

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

Non-small cell lung cancer therapy in the elderly.

PubMed

Gridelli, Cesare; Rossi, Antonio; Maione, Paolo; Schettino, Clorinda; Bareschino, Maria Anna; Palazzolo, Giovanni; Zeppa, Rosario; Ambrosio, Rita; Barbato, Valentina; Sacco, Paola Claudia

2011-05-01

To date, lung cancer is still the leading cause of cancer-related mortality worldwide, with the majority of lung cancers arising in the elderly. As a consequence, we can expect an increase in the number of older lung cancer patients considered suitable for chemotherapy in the near future. Elderly patients often have comorbid conditions and progressive physiologic reduction of organ function, which can make the selection of proper treatment daunting. Some patients will be able to tolerate chemotherapy as well as their younger counterparts, whereas others will experience severe toxicity and require treatment modifications. Thus, a major issue is effectively selecting patients suitable for standard or attenuated therapy. A comprehensive geriatric assessment performed at baseline is a useful tool that can help select the best treatment regimen to be administered to elderly patients. Until now, few trials have specifically focused on elderly patients affected by non-small cell lung cancer (NSCLC), particularly those with advanced disease; prospective elderly-specific studies in early stages are still lacking. High priority should be given to evaluating the role of new targeted therapies. Unfortunately, to date, clinical trials that include functional status and comorbidity as part of the geriatric assessment are rare. Future trials, specifically in the elderly population, should include these kinds of evaluations. The most recent therapies for the treatment of elderly patients with NSCLC will be discussed here.

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

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

Huang, Q; Zhang, M; Chen, T

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

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.

Clinical value of Pro-GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC-CIK biological therapy.

PubMed

He, Lijie; Wang, Jing; Chang, Dandan; Lv, Dandan; Li, Haina; Zhang, Heping

2018-02-01

The present study investigated the aptness of assessing the levels of progastrin-releasing peptide (Pro-GRP) in addition to the T lymphocyte subpopulation in lung cancer patients prior to and after therapy for determining immune function. A total of 45 patients with lung cancer were recruited and stratified in to a non-small cell lung cancer (NSCLC) and an SCLC group. Prior to and after treatment by combined biological therapy comprising chemotherapy or chemoradiotherapy followed by three cycles of retransformation of autologous dendritic cells-cytokine-induced killer cells (DC-CIK), the peripheral blood was assessed for populations of CD3 + , CD4 + , CD8 + and regulatory T cells (Treg) by flow cytometry, and for the levels of pro-GRP, carcinoembryonic antigen, neuron-specific enolase and Cyfra 21-1. The results revealed that in NSCLC patients, CD8 + T lymphocytes and Treg populations were decreased, and that CD3 + and CD4 + T lymphocytes as well as the CD4 + /CD8 + ratio were increased after therapy; in SCLC patients, CD3 + , CD4 + and CD8 + T lymphocytes were increased, while Treg cells were decreased after treatment compared with those at baseline. In each group, Pro-GRP was decreased compared with that prior to treatment, and in the SCLC group only, an obvious negative correlation was identified between Pro-GRP and the T lymphocyte subpopulation. Furthermore, a significant correlation between Pro-GRP and Tregs was identified in each group. In conclusion, the present study revealed that the immune function of the patients was improved after biological therapy. The results suggested a significant correlation between Pro-GRP and the T lymphocyte subpopulation in SCLC patients. Detection of Pro-GRP may assist the early clinical diagnosis of SCLC and may also be used to assess the immune regulatory function of patients along with the T lymphocyte subpopulation. Biological therapy with retransformed autologous DC-CIK was indicated to enhance the specific elimination of tumor cells and improve the immune surveillance function in cancer patients, and also restrained the immune evasion of the tumor, leading to decreased Pro-GRP levels.

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.

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.

Cthrc1 lowers pulmonary collagen associated with bleomycin-induced fibrosis and protects lung function.

PubMed

Binks, Andrew P; Beyer, Megyn; Miller, Ryan; LeClair, Renee J

2017-03-01

Idiopathic pulmonary fibrosis (IPF) involves collagen deposition that results in a progressive decline in lung function. This process involves activation of Smad2/3 by transforming growth factor (TGF)- β and Wnt signaling pathways. Collagen Triple Helix Repeat-Containing-1 (Cthrc1) protein inhibits Smad2/3 activation. To test the hypothesis that Cthrc1 limits collagen deposition and the decline of lung function, Cthrc1 knockout (Cthrc1 -/- ) and wild-type mice (WT) received intratracheal injections of 2.5 U/kg bleomycin or saline. Lungs were harvested after 14 days and Bronchoalveolar lavage (BAL) TGF- β , IL1- β , hydroxyproline and lung compliance were assessed. TGF- β was significantly higher in Cthrc1 -/- compared to WT (53.45 ± 6.15 ng/mL vs. 34.48 ± 11.05) after saline injection. Bleomycin injection increased TGF- β in both Cthrc1 -/- (66.37 ± 8.54 ng/mL) and WT (63.64 ± 8.09 ng/mL). Hydroxyproline was significantly higher in Cthrc1 -/- compared to WT after bleomycin-injection (2.676 ± 0.527  μ g/mg vs. 1.889 ± 0.520, P  = 0.028). Immunohistochemistry of Cthrc1 -/- lung sections showed intracellular localization and activation of β -catenin Y654 in areas of tissue remodeling that was not evident in WT Lung compliance was significantly reduced by bleomycin in Cthrc1 -/- but there was no effect in WT animals. These data suggest Cthrc1 reduces fibrotic tissue formation in bleomycin-induced lung fibrosis and the effect is potent enough to limit the decline in lung function. We conclude that Cthrc1 plays a protective role, limiting collagen deposition and could form the basis of a novel therapy for pulmonary fibrosis. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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.

Decrease in pulmonary function and oxygenation after lung resection

PubMed Central

Westerdahl, Elisabeth; Langer, Daniel; Souza, Domingos S.R.; Andreasen, Jan Jesper

2018-01-01

Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure) and 6-min walk test (6MWT) were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years). Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity −0.6±0.6 L and forced expiratory volume in 1 s −0.43±0.4 L; both p<0.0001), 6MWT (−37.6±74.8 m; p<0.0001) and oxygenation (−2.9±4.7 units; p<0.001), while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001), whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength. PMID:29362707

Decrease in pulmonary function and oxygenation after lung resection.

PubMed

Brocki, Barbara Cristina; Westerdahl, Elisabeth; Langer, Daniel; Souza, Domingos S R; Andreasen, Jan Jesper

2018-01-01

Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure) and 6-min walk test (6MWT) were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years). Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity -0.6±0.6 L and forced expiratory volume in 1 s -0.43±0.4 L; both p<0.0001), 6MWT (-37.6±74.8 m; p<0.0001) and oxygenation (-2.9±4.7 units; p<0.001), while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001), whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength.

Strategies for safe donor expansion: donor management, donations after cardiac death, ex-vivo lung perfusion.

PubMed

Cypel, Marcelo; Keshavjee, Shaf

2013-10-01

The number of patients listed for lung transplantation largely exceeds the number of available transplantable organs because of both a shortage of organ donors and a low utilization rate of lungs from those donors. Two major innovations in recent years include the use of lungs from donations after cardiac death (DCD) and the use of ex-vivo lung perfusion (EVLP) to assess and improve injured donor lungs. DCD lung transplants now account for about 20% of lung transplants in many centres and outcomes after transplantation have been excellent with this source of donation. Clinical experience using EVLP has shown the method to be well tolerated and allow for reassessment and improvement in function from high-risk donor lungs. When these lungs were transplanted, low rates of primary graft dysfunction were achieved and long-term survival was comparable with standard transplantation. Preclinical studies have shown a great potential of EVLP as a platform for the delivery of novel therapies to repair injured donor lungs. A significant increase on the number of available lungs for transplantation is expected in the coming years with the wider use of DCD lungs and with organ-specific ex-vivo treatment strategies.

Lung tumor segmentation in PET images using graph cuts.

PubMed

Ballangan, Cherry; Wang, Xiuying; Fulham, Michael; Eberl, Stefan; Feng, David Dagan

2013-03-01

The aim of segmentation of tumor regions in positron emission tomography (PET) is to provide more accurate measurements of tumor size and extension into adjacent structures, than is possible with visual assessment alone and hence improve patient management decisions. We propose a segmentation energy function for the graph cuts technique to improve lung tumor segmentation with PET. Our segmentation energy is based on an analysis of the tumor voxels in PET images combined with a standardized uptake value (SUV) cost function and a monotonic downhill SUV feature. The monotonic downhill feature avoids segmentation leakage into surrounding tissues with similar or higher PET tracer uptake than the tumor and the SUV cost function improves the boundary definition and also addresses situations where the lung tumor is heterogeneous. We evaluated the method in 42 clinical PET volumes from patients with non-small cell lung cancer (NSCLC). Our method improves segmentation and performs better than region growing approaches, the watershed technique, fuzzy-c-means, region-based active contour and tumor customized downhill. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Ventilation/Perfusion Positron Emission Tomography—Based Assessment of Radiation Injury to Lung

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

Siva, Shankar, E-mail: shankar.siva@petermac.org; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville; Hardcastle, Nicholas

2015-10-01

Purpose: To investigate {sup 68}Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). Methods and Materials: In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation andmore » perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). Results: A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r{sup 2}=0.99, P<.01), with ventilation strongly negatively linear (r{sup 2}=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. Conclusions: Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT.« less

Predictors of microbial agents in dust and respiratory health in the Ecrhs.

PubMed

Tischer, Christina; Zock, Jan-Paul; Valkonen, Maria; Doekes, Gert; Guerra, Stefano; Heederik, Dick; Jarvis, Deborah; Norbäck, Dan; Olivieri, Mario; Sunyer, Jordi; Svanes, Cecilie; Täubel, Martin; Thiering, Elisabeth; Verlato, Giuseppe; Hyvärinen, Anne; Heinrich, Joachim

2015-05-02

Dampness and mould exposure have been repeatedly associated with respiratory health. However, less is known about the specific agents provoking or arresting health effects in adult populations. We aimed to assess predictors of microbial agents in mattress dust throughout Europe and to investigate associations between microbial exposures, home characteristics and respiratory health. Seven different fungal and bacterial parameters were assessed in mattress dust from 956 adult ECRHS II participants in addition to interview based home characteristics. Associations between microbial parameters and the asthma score and lung function were examined using mixed negative binomial regression and linear mixed models, respectively. Indoor dampness and pet keeping were significant predictors for higher microbial agent concentrations in mattress dust. Current mould and condensation in the bedroom were significantly associated with lung function decline and current mould at home was positively associated with the asthma score. Higher concentrations of muramic acid were associated with higher mean ratios of the asthma score (aMR 1.37, 95%CI 1.17-1.61). There was no evidence for any association between fungal and bacterial components and lung function. Indoor dampness was associated with microbial levels in mattress dust which in turn was positively associated with asthma symptoms.

Co-registered perfusion SPECT/CT: utility for prediction of improved postoperative outcome in lung volume reduction surgery candidates.

PubMed

Takenaka, Daisuke; Ohno, Yoshiharu; Koyama, Hisanobu; Nogami, Munenobu; Onishi, Yumiko; Matsumoto, Keiko; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Sugimura, Kazuro

2010-06-01

To directly compare the capabilities of perfusion scan, SPECT, co-registered SPECT/CT, and quantitatively and qualitatively assessed MDCT (i.e. quantitative CT and qualitative CT) for predicting postoperative clinical outcome for lung volume reduction surgery (LVRS) candidates. Twenty-five consecutive candidates (19 men and six women, age range: 42-72 years) for LVRS underwent preoperative CT and perfusion scan with SPECT. Clinical outcome of LVRS for all subjects was also assessed by determining the difference between pre- and postoperative forced expiratory volume in 1s (FEV(1)) and 6-min walking distance (6MWD). All SPECT examinations were performed on a SPECT scanner, and co-registered to thin-section CT by using commercially available software. On planar imaging, SPECT and SPECT/CT, upper versus lower zone or lobe ratios (U/Ls) were calculated from regional uptakes between upper and lower lung fields in the operated lung. On quantitatively assessed CT, U/L for all subjects was assessed from regional functional lung volumes. On qualitatively assessed CT, planar imaging, SPECT and co-registered SPECT/CT, U/Ls were assessed with a 4-point visual scoring system. To compare capabilities of predicting clinical outcome, each U/L was statistically correlated with the corresponding clinical outcome. Significantly fair or moderate correlations were observed between quantitatively and qualitatively assessed U/Ls obtained with all four methods and clinical outcomes (-0.60

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

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.

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.

Electrical impedance tomography

PubMed Central

Lobo, Beatriz; Hermosa, Cecilia; Abella, Ana

2018-01-01

Continuous assessment of respiratory status is one of the cornerstones of modern intensive care unit (ICU) monitoring systems. Electrical impedance tomography (EIT), although with some constraints, may play the lead as a new diagnostic and guiding tool for an adequate optimization of mechanical ventilation in critically ill patients. EIT may assist in defining mechanical ventilation settings, assess distribution of tidal volume and of end-expiratory lung volume (EELV) and contribute to titrate positive end-expiratory pressure (PEEP)/tidal volume combinations. It may also quantify gains (recruitment) and losses (overdistention or derecruitment), granting a more realistic evaluation of different ventilator modes or recruitment maneuvers, and helping in the identification of responders and non-responders to such maneuvers. Moreover, EIT also contributes to the management of life-threatening lung diseases such as pneumothorax, and aids in guiding fluid management in the critical care setting. Lastly, assessment of cardiac function and lung perfusion through electrical impedance is on the way. PMID:29430443

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.

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.

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.

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.

Effects of allergen and trigger factor avoidance advice in primary care on asthma control: a randomized-controlled trial.

PubMed

Bobb, C; Ritz, T; Rowlands, G; Griffiths, C

2010-01-01

Allergy contributes significantly to asthma exacerbation, yet avoidance of triggers, in particular allergens, is rarely addressed in detail in regular asthma review in primary care. To determine whether structured, individually tailored allergen and trigger avoidance advice, given as part of a primary care asthma review, improves lung function and asthma control. In a randomized-controlled trial 214 adults with asthma in six general practices were either offered usual care during a primary care asthma review or usual care with additional allergen and trigger identification (by skin prick testing and structured allergy assessment) and avoidance advice according to a standardized protocol by trained practice nurses. Main outcome measures were lung function, asthma control, asthma self-efficacy. Both intervention groups were equivalent in demographic and asthma-related variables at baseline. At 3-6-month follow-up, patients receiving the allergen and trigger avoidance review showed significant improvements in lung function (assessed by blinded research nurses) compared with those receiving usual care. Significantly more patients in the intervention group than in the control group showed improvements in forced expiratory volume in 1 s > or =15%. No significant differences were found in self-report measures of asthma control. Asthma-specific self-efficacy improved in both groups but did not differ between groups. Allergen and trigger identification and avoidance advice, given as part of a structured asthma review delivered in primary care by nurses results in clinically important improvements in lung function but not self-report of asthma control. ISRCTN45684820.

Proton MRI as a noninvasive tool to assess elastase-induced lung damage in spontaneously breathing rats.

PubMed

Quintana, Harry Karmouty; Cannet, Catherine; Zurbruegg, Stefan; Blé, François-Xavier; Fozard, John R; Page, Clive P; Beckmann, Nicolau

2006-12-01

Elastase-induced changes in lung morphology and function were detected in spontaneously breathing rats using conventional proton MRI at 4.7 T. A single dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline) was administered intratracheally (i.t.) to male Brown Norway (BN) rats. MRI fluid signals were detected in the lungs 24 hr after administration of elastase and resolved within 2 weeks. These results correlated with perivascular edema and cellular infiltration observed histologically. Reductions in MRI signal intensity of the lung parenchyma, and increases in lung volume were detected as early as 2 weeks following elastase administration and remained uniform throughout the study, which lasted 8 weeks. Observations were consistent with air trapping resulting from emphysema detected histologically. In a separate experiment, animals were treated daily intraperitoneally (i.p.) with all-trans-retinoic acid (ATRA; 500 microg/kg body weight) or its vehicle (triglyceride oil) starting on day 21 after elastase administration and continuing for 12 days. Under these conditions, ATRA did not elicit a reversal of elastase-induced lung damage as measured by MRI and histology. The present approach complements other validated applications of proton MRI in experimental lung research as a method for assessing drugs in rat models of respiratory diseases.

Glycine ameliorates lung reperfusion injury after cold preservation in an ex vivo rat lung model.

PubMed

Omasa, Mitsugu; Fukuse, Tatsuo; Toyokuni, Shinya; Mizutani, Yoichi; Yoshida, Hiroshi; Ikeyama, Kazuyuki; Hasegawa, Seiki; Wada, Hiromi

2003-03-15

The role of glycine has not been investigated in lung ischemia-reperfusion injury after cold preservation. Furthermore, the role of apoptosis after reperfusion following cold preservation has not been fully understood. Lewis rats were divided into three groups (n=6 each). In the GLY(-) and GLY(+) groups, isolated lungs were preserved for 15 hr at 4 degrees C after a pulmonary artery (PA) flush using our previously developed preservation solution (ET-K; extracellular-type trehalose containing Kyoto), with or without the addition of glycine (5 mM). In the Fresh group, isolated lungs were reperfused immediately after a PA flush with ET-K. They were reperfused for 60 min with an ex vivo perfusion model. Pulmonary function, oxidative stress, apoptosis, and tumor necrosis factor (TNF)-alpha expression were assessed after reperfusion. Shunt fraction and peak inspiratory pressure after reperfusion in the GLY(-) group were significantly higher than those in the GLY(+) and Fresh groups. Oxidative damage and apoptosis in the alveolar epithelial cells of the GLY(-) group, assessed by immunohistochemical staining and quantification of 8-hydroxy-2'-deoxyguanosine and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method, were significantly higher than those of the GLY(+) and Fresh groups. There were correlations among shunt fraction, oxidative damage, and apoptosis. There was no expression of TNF-alpha messenger RNA in all groups evaluated by the reverse transcription-polymerase chain reaction. Glycine attenuates ischemia/reperfusion injury after cold preservation by reducing oxidative damage and suppressing apoptosis independent of TNF-alpha in this model. The suppression of apoptosis might ameliorate lung function after reperfusion.

Fibrocytes Regulate Wilms’ Tumor 1-Positive Cell Accumulation in Severe Fibrotic Lung Disease

PubMed Central

Sontake, Vishwaraj; Shanmukhappa, Shiva K.; DiPasquale, Betsy A.; Reddy, Geereddy B.; Medvedovic, Mario; Hardie, William D.; White, Eric S.; Madala, Satish K.

2015-01-01

Collagen-producing myofibroblast transdifferentiation is considered a crucial determinant in the formation of scar tissue in the lungs of patients with idiopathic pulmonary fibrosis (IPF). Multiple resident pulmonary cell types and bone marrow-derived fibrocytes have been implicated as contributors to fibrotic lesions due to the transdifferentiation potential of these cells into myofibroblasts. In this study, we assessed the expression of Wilms’ tumor 1 (WT1), a known marker of mesothelial cells, in various cell types in normal and fibrotic lungs. We demonstrate that WT1 is expressed by both mesothelial and mesenchymal cells in IPF lungs, but has limited or no expression in normal human lungs. We also demonstrate that WT1-positive cells accumulate in fibrotic lung lesions, using two different mouse models of pulmonary fibrosis and WT1 promoter-driven fluorescent reporter mice. Reconstitution of bone-marrow cells into a transforming growth factor-α transgenic-mouse model demonstrated that fibrocytes do not transform into WT1-positive mesenchymal cells, but do augment accumulation of WT1-positive cells in severe fibrotic lung disease. Importantly, the number of WT1-positive cells in fibrotic lesions were correlated with severity of lung disease as assessed by changes in lung function, histology, and hydroxyproline levels in mice. Finally, inhibition of WT1 expression was sufficient to attenuate collagen and other extracellular-matrix gene production by mesenchymal cells from both murine and human fibrotic lungs. Thus, the results of this study demonstrate a novel association between fibrocyte-driven WT1-positive cell accumulation and severe fibrotic lung disease. PMID:26371248

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.

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.

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.

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.

[FEDERAL CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS, PREVENTION AND TREATMENT OF PNEUMOCONIOSIS].

PubMed

Artemoval, L V; Baskova, N V; Burmistrova, T B; Buryakinal, E A; Buhtiyarov, I V; Bushmanov, A Yu; Vasilyeva, O S; Vlasov, V G; Gorblyansky, Y Y; Zhabina, S A; Zaharinskaya, O N; Ismerov, N F; Kovalevsky, E V; Kuznetsova, G V; Kuzmina, L P; Kunyaeva, T A; Logvinenko, I I; Lutsenko, L A; Mazitova, N N; Obukhova, T Yu; Odintseva, O V; Orlova, G P; Panacheva, L A; Piktushanskaya, I N; Plyukhin, A E; Poteryaeva, E L; Pravilo, S M; Razumov, V V; Roslaya, N A; Roslyi, O F; Rushkevich, O P; Semenihin, V A; Serebryakov, P V; Smirnova, E L; Sorkina, N S; Tsidil'kovskaya, E S; Chasovskikh, E V; Shpagina, L A

2016-01-01

The purpose of development of this clinical practice guidelines was to provide evidence-based protocols that help the practitioner and the patient make the right decision for the health assessment, treatment and prevention of pneumoconiosis. Pneumoconiosis is the interstitial lung disease of occupational origin caused by prolonged inhalation of inorganic dust, characterized by chronic diffuse aseptic inflammation in lung tissue with the development of pulmonary fibrosis. Currently, thereare no treatment that provide a cure pulmonary fibrosis and changes in the dynamics of decline in lung function. Regular, individually tailored treatment should be directed to the pathogenic mechanisms and some clinical symptoms of pneumoconiosis, as well as the prevention of complications. To enhance the effect of pharmacotherapy is recommended to use non-drug therapies that enhance the functionality of the respiratory system.

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

PubMed

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

2017-01-01

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

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.

Developing Physiologic Models for Emergency Medical Procedures Under Microgravity

NASA Technical Reports Server (NTRS)

Parker, Nigel; O'Quinn, Veronica

2012-01-01

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

Developing Physiologic Models for Emergency Medical Procedures Under Microgravity

NASA Technical Reports Server (NTRS)

Parker, Nigel; OQuinn, Veronica

2012-01-01

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

Functional analysis of Discoidin domain receptor 2 mutation and expression in squamous cell lung cancer.

PubMed

Kobayashi-Watanabe, Naomi; Sato, Akemi; Watanabe, Tatsuro; Abe, Tomonori; Nakashima, Chiho; Sueoka, Eisaburo; Kimura, Shinya; Sueoka-Aragane, Naoko

2017-08-01

Discoidin domain receptor (DDR) 2 mutations have recently been reported to be candidate targets of molecular therapy in lung squamous cell carcinoma (SQCC). However, the status of DDR2 expression and mutations, as well as their precise roles in lung SQCC, have not been clarified. We here report DDR2 mutation and expression status in clinical samples and its role of lung SQCC. We investigated DDR2 expression and mutation status in 44 human clinical samples and 7 cell lines. Biological functions of DDR2 were assessed by in vitro cell invasion assay and animal model experiments. Endogenous DDR2 protein expression levels were high in one cell line, PC-1, and immunohistochemistry of lung cancer tissue array showed high levels of DDR2 protein in 29% of lung SQCC patients. A mutation (T681I) identified in lung SQCC and the cell line EBC-1 was detected among 44 primary lung SQCC samples and 7 lung SQCC cell lines. Although Forced expression of DDR2 and its mutant (T681I) led to induce SQCC cell invasion in vitro, only wild type DDR2 enhanced lung metastasis in an animal model. We also found that ectopic expression of DDR2 induced MMP-1 mRNA expression accompanied by phosphorylation of c-Jun after treatment with its ligand, collagen type I, but DDR2 with the T681I mutation did not, suggesting that T681I mutation is an inactivating mutation. Overexpression of DDR2 might contribute to tumor progression in lung SQCC. The overexpression of DDR2 could be potential molecular target of lung SQCC. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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

PubMed

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

2014-03-01

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

Non-invasive interventions for improving well-being and quality of life in patients with lung cancer.

PubMed

Solà, I; Thompson, E; Subirana, M; López, C; Pascual, A

2004-10-18

Lung cancer is one of the leading causes of death globally. Despite advances in treatment, outlook for the majority of patients remains grim and most face a pessimistic outlook accompanied by sometimes devastating effects on emotional and psychological health. Although chemotherapy is accepted as an effective treatment for advanced lung cancer, the high prevalence of treatment-related side effects as well the symptoms of disease progression highlight the need for high quality palliative and supportive care to minimise symptom distress and to promote quality of life. To assess the effectiveness of non-invasive interventions delivered by healthcare professionals in improving symptoms, psychological functioning and quality of life in patients with lung cancer. The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2003), MEDLINE (1966-March 2003), EMBASE (1974-March 2003), CINAHL (1982-September 2002), CancerLit (1975-October 2002), PsycINFO (1873-March 2003), reference lists of relevant articles and contact with authors. Randomised or quasi-randomised clinical trials assessing the effects of non-invasive interventions in improving well-being and quality of life in patients diagnosed with lung cancer. Two reviewers independently assessed relevant studies for inclusion. Data extraction and quality assessment of relevant studies was performed by one reviewer and checked by a second reviewer. Nine trials were included and categorised into six groups. Two trials of a nursing intervention to manage breathlessness showed benefit on symptom experience, performance status and emotional functioning. Three trials assessed structured nursing programmes and found positive effects on delay in clinical deterioration, dependency and symptom distress, and improvements in emotional functioning and satisfaction with care. One trial assessing counselling showed benefit on some emotional components of the illness but findings were not conclusive. One trial assessing an exercise programme, found a beneficial effect on self-empowerment. One trial of nutritional interventions found positive effects for increasing energy intake, but no improvement in quality of life. One trial of reflexology showed some positive, but short-lasting effects on anxiety. Nurse follow-up programmes and a nurse intervention to manage breathlessness may produce beneficial effects. Psychotherapeutic study indicates that counselling may help patients cope more effectively with emotional symptoms, but the evidence is not conclusive. Findings from the included studies reinforce the necessity for increased training and education of healthcare professionals giving in these interventions. More research, of higher methodological quality is needed in this area to explore possible underlying explanatory mechanisms.

Impact of lung disease on respiratory impedance in young children with cystic fibrosis.

PubMed

Ramsey, Kathryn A; Ranganathan, Sarath C; Gangell, Catherine L; Turkovic, Lidija; Park, Judy; Skoric, Billy; Stick, Stephen M; Sly, Peter D; Hall, Graham L

2015-12-01

This study aimed to evaluate the ability of the forced oscillation technique (FOT) to detect underlying lung disease in preschool children with cystic fibrosis (CF) diagnosed following newborn screening.184 children (aged 3-6 years) with CF underwent lung function testing on 422 occasions using the FOT to assess respiratory resistance and reactance at the time of their annual bronchoalveolar lavage collection and chest computed tomography scan. We examined associations between FOT outcomes and the presence and progression of respiratory inflammation, infection and structural lung disease.Children with CF who had pronounced respiratory disease, including free neutrophil elastase activity, infection with pro-inflammatory pathogens and structural lung abnormalities had similar FOT outcomes to those children without detectable lung disease. In addition, the progression of lung disease over 1 year was not associated with worsening FOT outcomes.We conclude that the forced oscillation technique is relatively insensitive to detect underlying lung disease in preschool children with CF. However, FOT may still be of value in improving our understanding of the physiological changes associated with early CF lung disease. Copyright ©ERS 2015.

Assessing exposure risk for dust storm events-associated lung function decrement in asthmatics and implications for control

NASA Astrophysics Data System (ADS)

Hsieh, Nan-Hung; Liao, Chung-Min

2013-04-01

Asian dust storms (ADS) events are seasonally-based meteorological phenomena that exacerbate chronic respiratory diseases. The purpose of this study was to assess human health risk from airborne dust exposure during ADS events in Taiwan. A probabilistic risk assessment framework was developed based on exposure and experimental data to quantify ADS events induced lung function decrement. The study reanalyzed experimental data from aerosol challenge in asthmatic individuals to construct the dose-response relationship between inhaled dust aerosol dose and decreasing percentage of forced expiratory volume in 1 s (%FEV1). An empirical lung deposition model was used to predict deposition fraction for size specific dust aerosols in pulmonary regions. The toxicokinetic and toxicodynamic models were used to simulate dust aerosols binding kinetics in lung airway in that %FEV1 change was also predicted. The mask respirators were applied to control the inhaled dose under dust aerosols exposure. Our results found that only 2% probability the mild ADS events were likely to cause %FEV1 decrement higher than 5%. There were 50% probability of decreasing %FEV1 exceeding 16.9, 18.9, and 7.1% in north, center, and south Taiwan under severe ADS events, respectively. Our result implicates that the use of activated carbon of mask respirators has the best efficacy for reducing inhaled dust aerosol dose, by which the %FEV1 decrement can be reduced up to less than 1%.

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.

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

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

Chen, Jing; Mo, Yiqun; Schlueter, Connie F.

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-inducedmore » neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.« less

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.

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

Characterizing functional lung heterogeneity in COPD using reference equations for CT scan-measured lobar volumes.

PubMed

Come, Carolyn E; Diaz, Alejandro A; Curran-Everett, Douglas; Muralidhar, Nivedita; Hersh, Craig P; Zach, Jordan A; Schroeder, Joyce; Lynch, David A; Celli, Bartolome; Washko, George R

2013-06-01

CT scanning is increasingly used to characterize COPD. Although it is possible to obtain CT scan-measured lung lobe volumes, normal ranges remain unknown. Using COPDGene data, we developed reference equations for lobar volumes at maximal inflation (total lung capacity [TLC]) and relaxed exhalation (approximating functional residual capacity [FRC]). Linear regression was used to develop race-specific (non-Hispanic white [NHW], African American) reference equations for lobar volumes. Covariates included height and sex. Models were developed in a derivation cohort of 469 subjects with normal pulmonary function and validated in 546 similar subjects. These cohorts were combined to produce final prediction equations, which were applied to 2,191 subjects with old GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage II to IV COPD. In the derivation cohort, women had smaller lobar volumes than men. Height positively correlated with lobar volumes. Adjusting for height, NHWs had larger total lung and lobar volumes at TLC than African Americans; at FRC, NHWs only had larger lower lobes. Age and weight had no effect on lobar volumes at TLC but had small effects at FRC. In subjects with COPD at TLC, upper lobes exceeded 100% of predicted values in GOLD II disease; lower lobes were only inflated to this degree in subjects with GOLD IV disease. At FRC, gas trapping was severe irrespective of disease severity and appeared uniform across the lobes. Reference equations for lobar volumes may be useful in assessing regional lung dysfunction and how it changes in response to pharmacologic therapies and surgical or endoscopic lung volume reduction.

Thyroid function in lung cancer

PubMed Central

Ratcliffe, J G; Stack, B H R; Burt, R W; Ratcliffe, W A; Spilg, W G S; Cuthbert, J; Kennedy, R S

1978-01-01

Thyroid function was assessed at the time of initial diagnosis in 204 patients with lung cancer and compared with that of age and sex-matched patients with non-malignant lung disease. Abnormalities in thyroid function were found in 67 patients (33%). The most prevalent abnormality was a low T3 concentration; this was not associated with other clinical or biochemical evidence of hypothyroidism, but the short-term prognosis of these patients was worse than that of matched patients with lung cancer having normal T3 concentrations. Primary hypothyroidism occurred in three patients, low T4 concentrations and free thyroxine index (FTI) with normal thyrotrophin (TSH) concentrations in four patients, and moderately raised TSH with normal thyroid hormone concentrations in six patients; nine patients had a raised FTI with or without raised T4 concentration as the sole abnormality. Overall, the pattern of thyroid hormone metabolism in lung cancer was a tendency towards reduced T3 concentrations with significantly increased T4/T3 ratios and modestly increased 3,3′,5′-triiodothyronine (rT3) concentrations. The altered T4/T3 ratio was particularly noticeable in patients with anaplastic tumours of small (“oat cell”) and large cell types, but was not apparently related to detectable extrathoracic metastases. These data suggest that thyroid hormone metabolism is altered in patients with lung cancer by decreased 5′-monodeiodination of T4. The resulting low T3 concentrations and altered T4/T3 ratio may be partly responsible for the reduced ratio of androsterone to aetiocholanolone observed in lung cancer, which is known to be a poor prognostic sign. PMID:620266

Correlation between the signal-to-noise ratio improvement factor (KSNR) and clinical image quality for chest imaging with a computed radiography system

NASA Astrophysics Data System (ADS)

Moore, C. S.; Wood, T. J.; Saunderson, J. R.; Beavis, A. W.

2015-12-01

This work assessed the appropriateness of the signal-to-noise ratio improvement factor (KSNR) as a metric for the optimisation of computed radiography (CR) of the chest. The results of a previous study in which four experienced image evaluators graded computer simulated chest images using a visual grading analysis scoring (VGAS) scheme to quantify the benefit of using an anti-scatter grid were used for the clinical image quality measurement (number of simulated patients  =  80). The KSNR was used to calculate the improvement in physical image quality measured in a physical chest phantom. KSNR correlation with VGAS was assessed as a function of chest region (lung, spine and diaphragm/retrodiaphragm), and as a function of x-ray tube voltage in a given chest region. The correlation of the latter was determined by the Pearson correlation coefficient. VGAS and KSNR image quality metrics demonstrated no correlation in the lung region but did show correlation in the spine and diaphragm/retrodiaphragmatic regions. However, there was no correlation as a function of tube voltage in any region; a Pearson correlation coefficient (R) of  -0.93 (p  =  0.015) was found for lung, a coefficient (R) of  -0.95 (p  =  0.46) was found for spine, and a coefficient (R) of  -0.85 (p  =  0.015) was found for diaphragm. All demonstrate strong negative correlations indicating conflicting results, i.e. KSNR increases with tube voltage but VGAS decreases. Medical physicists should use the KSNR metric with caution when assessing any potential improvement in clinical chest image quality when introducing an anti-scatter grid for CR imaging, especially in the lung region. This metric may also be a limited descriptor of clinical chest image quality as a function of tube voltage when a grid is used routinely.

Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples

PubMed Central

Dullin, Christian; dal Monego, Simeone; Larsson, Emanuel; Mohammadi, Sara; Krenkel, Martin; Garrovo, Chiara; Biffi, Stefania; Lorenzon, Andrea; Markus, Andrea; Napp, Joanna; Salditt, Tim; Accardo, Agostino; Alves, Frauke; Tromba, Giuliana

2015-01-01

Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites. PMID:25537601

Lung structure and function similarities between primary ciliary dyskinesia and mild cystic fibrosis: a pilot study.

PubMed

Maglione, Marco; Montella, Silvia; Mollica, Carmine; Carnovale, Vincenzo; Iacotucci, Paola; De Gregorio, Fabiola; Tosco, Antonella; Cervasio, Mariarosaria; Raia, Valeria; Santamaria, Francesca

2017-04-12

Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are increasingly compared. There are no chest magnetic resonance imaging (MRI) comparative studies of PCD and CF. We assessed clinical, functional, microbiological and MRI findings in PCD and mild CF patients in order to evaluate different expression of lung disease. Twenty PCD (15.1 years) and 20 CF subjects with mild respiratory impairment (16 years, 70% with pancreatic insufficiency) underwent MRI, spirometry, and sputum cultures when clinically stable. MRI was scored using the modified Helbich system. PCD was diagnosed later than CF (9.9 versus 0.6 years, p = 0.03), despite earlier symptoms (0.1 versus 0.6 years, p = 0.02). In the year preceding the study, patients from both groups underwent two systemic antibiotic courses (p = 0.48). MRI total scores were 11.6 ± 0.7 and 9.1 ± 1 in PCD and CF, respectively. FEV 1 and FVC Z-scores were -1.75 (range, -4.6-0.7) and -0.6 (-3.9-1.8) in PCD, and -0.9 (range, -5.4-2.3) and -0.3 (-3.4-2.5) in CF, respectively. No difference was found between lung function or structure, despite a higher MRI subscore of collapse/consolidation in PCD versus CF (1.6 ± 0.1 and 0.6 ± 0.2, p < 0.001). These findings were confirmed after data-control for diagnostic delay. Pseudomonas aeruginosa and Staphylococcus aureus were more frequent in CF than in PCD (p = 0.05 and p = 0.003, respectively). MRI is a valuable radiation-free tool for comparative PCD and CF lung disease assessment. Patients with PCD may exhibit similar MRI and lung function changes as CF subjects with mild pulmonary disease. Delay in PCD diagnosis is unlikely the only determinant of similarities.

Electromyographic assessment of muscle activity between genders during unilateral weight-bearing tasks using adjusted distances.

PubMed

Bouillon, Lucinda E; Wilhelm, Jacqueline; Eisel, Patricia; Wiesner, Jessica; Rachow, Megan; Hatteberg, Lindsay

2012-12-01

Researchers have observed differences in muscle activity patterns between males and females during functional exercises. The research methods employed have used various step heights and lunge distances to assess functional exercise making gender comparisons difficult. The purpose of this study was to examine core and lower extremity muscle activity between genders during single-limb exercises using adjusted distances and step heights based on a percentage of the participant's height. Twenty men and 20 women who were recreationally active and healthy participated in the study. Two-dimensional video and surface electromyography (SEMG) were used to assess performance during three exercise maneuvers (step down, forward lunge, and side-step lunge). Eight muscles were assessed using SEMG (rectus abdominus, external oblique, erector spinae, rectus femoris, tensor fascia latae, gluteus medius, gluteus maximus, biceps femoris). Maximal voluntary isometric contractions (MVIC) were used for each muscle and expressed as %MVIC to normalize SEMG to account for body mass differences. Exercises were randomized and distances were normalized to the participant's lower limb length. Descriptive statistics, mixed-model ANOVA, and ICCs with 95% confidence intervals were calculated. Males were taller, heavier, and had longer leg length when compared to the females. No differences in %MVIC activity were found between genders by task across the eight muscles. For both males and females, the step down task resulted in higher %MVIC for gluteus maximus compared to lunge, (p=0.002). Step down exercise produced higher %MVIC for gluteus medius than lunge (p=0.002) and side step (p=0.006). ICC(3,3) ranged from moderate to high (0.74 to 0.97) for the three tasks. Muscle activation among the eight muscles was similar between females and males during the lunge, side-step, and step down tasks, with distances adjusted to leg length. Both males and females elicited higher muscle activity for gluteus maximus and gluteus medius as compared to the trunk, hip flexors, or hamstring muscles. However these values were well below the recruitment levels necessary for strengthening in both genders. 4.

ELECTROMYOGRAPHIC ASSESSMENT OF MUSCLE ACTIVITY BETWEEN GENDERS DURING UNILATERAL WEIGHT‐BEARING TASKS USING ADJUSTED DISTANCES

PubMed Central

Wilhelm, Jacqueline; Eisel, Patricia; Wiesner, Jessica; Rachow, Megan; Hatteberg, Lindsay

2012-01-01

Purpose/Background: Researchers have observed differences in muscle activity patterns between males and females during functional exercises. The research methods employed have used various step heights and lunge distances to assess functional exercise making gender comparisons difficult. The purpose of this study was to examine core and lower extremity muscle activity between genders during single‐limb exercises using adjusted distances and step heights based on a percentage of the participant's height. Methods: Twenty men and 20 women who were recreationally active and healthy participated in the study. Two‐dimensional video and surface electromyography (SEMG) were used to assess performance during three exercise maneuvers (step down, forward lunge, and side‐step lunge). Eight muscles were assessed using SEMG (rectus abdominus, external oblique, erector spinae, rectus femoris, tensor fascia latae, gluteus medius, gluteus maximus, biceps femoris). Maximal voluntary isometric contractions (MVIC) were used for each muscle and expressed as %MVIC to normalize SEMG to account for body mass differences. Exercises were randomized and distances were normalized to the participant's lower limb length. Descriptive statistics, mixed‐model ANOVA, and ICCs with 95% confidence intervals were calculated. Results: Males were taller, heavier, and had longer leg length when compared to the females. No differences in %MVIC activity were found between genders by task across the eight muscles. For both males and females, the step down task resulted in higher %MVIC for gluteus maximus compared to lunge, (p=0.002). Step down exercise produced higher %MVIC for gluteus medius than lunge (p=0.002) and side step (p=0.006). ICC3,3 ranged from moderate to high (0.74 to 0.97) for the three tasks. Conclusions: Muscle activation among the eight muscles was similar between females and males during the lunge, side‐step, and step down tasks, with distances adjusted to leg length. Both males and females elicited higher muscle activity for gluteus maximus and gluteus medius as compared to the trunk, hip flexors, or hamstring muscles. However these values were well below the recruitment levels necessary for strengthening in both genders. Level of evidence: 4 PMID:23316423

Quantitative in vivo assessment of lung microstructure at the alveolar level with hyperpolarized 3He diffusion MRI

NASA Astrophysics Data System (ADS)

Yablonskiy, Dmitriy A.; Sukstanskii, Alexander L.; Leawoods, Jason C.; Gierada, David S.; Bretthorst, G. Larry; Lefrak, Stephen S.; Cooper, Joel D.; Conradi, Mark S.

2002-03-01

The study of lung emphysema dates back to the beginning of the 17th century. Nevertheless, a number of important questions remain unanswered because a quantitative localized characterization of emphysema requires knowledge of lung structure at the alveolar level in the intact living lung. This information is not available from traditional imaging modalities and pulmonary function tests. Herein, we report the first in vivo measurements of lung geometrical parameters at the alveolar level obtained with 3He diffusion MRI in healthy human subjects and patients with severe emphysema. We also provide the first experimental data demonstrating that 3He gas diffusivity in the acinus of human lung is highly anisotropic. A theory of anisotropic diffusion is presented. Our results clearly demonstrate substantial differences between healthy and emphysematous lung at the acinar level and may provide new insights into emphysema progression. The technique offers promise as a clinical tool for early diagnosis of emphysema.

Air Trapping on Chest CT Is Associated with Worse Ventilation Distribution in Infants with Cystic Fibrosis Diagnosed following Newborn Screening

PubMed Central

Hall, Graham L.; Logie, Karla M.; Parsons, Faith; Schulzke, Sven M.; Nolan, Gary; Murray, Conor; Ranganathan, Sarath; Robinson, Phil; Sly, Peter D.; Stick, Stephen M.

2011-01-01

Background In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF. Methods Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M1/M0 and M2/M0, respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping. Results Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M2/M0 but not LCI or M1/M0. There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes. Conclusion These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF. PMID:21886842

Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive utility of precision cut lung slices.

PubMed

Kim, Yong Ho; Tong, Haiyan; Daniels, Mary; Boykin, Elizabeth; Krantz, Q Todd; McGee, John; Hays, Michael; Kovalcik, Kasey; Dye, Janice A; Gilmour, M Ian

2014-06-16

Emissions from a large peat fire in North Carolina in 2008 were associated with increased hospital admissions for asthma and the rate of heart failure in the exposed population. Peat fires often produce larger amounts of smoke and last longer than forest fires, however few studies have reported on their toxicity. Moreover, reliable alternatives to traditional animal toxicity testing are needed to reduce the number of animals required for hazard identification and risk assessments. Size-fractionated particulate matter (PM; ultrafine, fine, and coarse) were obtained from the peat fire while smoldering (ENCF-1) or when nearly extinguished (ENCF-4). Extracted samples were analyzed for chemical constituents and endotoxin content. Female CD-1 mice were exposed via oropharyngeal aspiration to 100 μg/mouse, and assessed for relative changes in lung and systemic markers of injury and inflammation. At 24 h post-exposure, hearts were removed for ex vivo functional assessments and ischemic challenge. Lastly, 8 mm diameter lung slices from CD-1 mice were exposed (11 μg) ± co-treatment of PM with polymyxin B (PMB), an endotoxin-binding compound. On an equi-mass basis, coarse ENCF-1 PM had the highest endotoxin content and elicited the greatest pro-inflammatory responses in the mice including: increases in bronchoalveolar lavage fluid protein, cytokines (IL-6, TNF-α, and MIP-2), neutrophils and intracellular reactive oxygen species (ROS) production. Exposure to fine or ultrafine particles from either period failed to elicit significant lung or systemic effects. In contrast, mice exposed to ENCF-1 ultrafine PM developed significantly decreased cardiac function and greater post-ischemia-associated myocardial infarction. Finally, similar exposures to mouse lung slices induced comparable patterns of cytokine production; and these responses were significantly attenuated by PMB. The findings suggest that exposure to coarse PM collected during a peat fire causes greater lung inflammation in association with endotoxin and ROS, whereas the ultrafine PM preferentially affected cardiac responses. In addition, lung tissue slices were shown to be a predictive, alternative assay to assess pro-inflammatory effects of PM of differing size and composition. Importantly, these toxicological findings were consistent with the cardiopulmonary health effects noted in epidemiologic reports from exposed populations.

Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive utility of precision cut lung slices

PubMed Central

2014-01-01

Background Emissions from a large peat fire in North Carolina in 2008 were associated with increased hospital admissions for asthma and the rate of heart failure in the exposed population. Peat fires often produce larger amounts of smoke and last longer than forest fires, however few studies have reported on their toxicity. Moreover, reliable alternatives to traditional animal toxicity testing are needed to reduce the number of animals required for hazard identification and risk assessments. Methods Size-fractionated particulate matter (PM; ultrafine, fine, and coarse) were obtained from the peat fire while smoldering (ENCF-1) or when nearly extinguished (ENCF-4). Extracted samples were analyzed for chemical constituents and endotoxin content. Female CD-1 mice were exposed via oropharyngeal aspiration to 100 μg/mouse, and assessed for relative changes in lung and systemic markers of injury and inflammation. At 24 h post-exposure, hearts were removed for ex vivo functional assessments and ischemic challenge. Lastly, 8 mm diameter lung slices from CD-1 mice were exposed (11 μg) ± co-treatment of PM with polymyxin B (PMB), an endotoxin-binding compound. Results On an equi-mass basis, coarse ENCF-1 PM had the highest endotoxin content and elicited the greatest pro-inflammatory responses in the mice including: increases in bronchoalveolar lavage fluid protein, cytokines (IL-6, TNF-α, and MIP-2), neutrophils and intracellular reactive oxygen species (ROS) production. Exposure to fine or ultrafine particles from either period failed to elicit significant lung or systemic effects. In contrast, mice exposed to ENCF-1 ultrafine PM developed significantly decreased cardiac function and greater post-ischemia-associated myocardial infarction. Finally, similar exposures to mouse lung slices induced comparable patterns of cytokine production; and these responses were significantly attenuated by PMB. Conclusions The findings suggest that exposure to coarse PM collected during a peat fire causes greater lung inflammation in association with endotoxin and ROS, whereas the ultrafine PM preferentially affected cardiac responses. In addition, lung tissue slices were shown to be a predictive, alternative assay to assess pro-inflammatory effects of PM of differing size and composition. Importantly, these toxicological findings were consistent with the cardiopulmonary health effects noted in epidemiologic reports from exposed populations. PMID:24934158

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.

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.

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

PubMed Central

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

1994-01-01

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

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.

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.

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.

Insulin resistance, metabolic syndrome, and lung function in US adolescents with and without asthma.

PubMed

Forno, Erick; Han, Yueh-Ying; Muzumdar, Radhika H; Celedón, Juan C

2015-08-01

Obesity increases both the risk of asthma and asthma severity and is a well-known risk factor for insulin resistance and the metabolic syndrome (MS) in children and adolescents. We aimed to examine the association among obesity, insulin sensitivity, MS, and lung function in US adolescents with and without asthma. We performed a cross-sectional study of 1429 adolescents aged 12 to 17 years in the 2007-2010 National Health and Nutrition Examination Survey. Adjusted regression was used to assess the relationships among obesity, insulin sensitivity/resistance, MS, and lung function in children with and without asthma. Insulin resistance was negatively associated with FEV1 and forced vital capacity (FVC) in adolescents with and without asthma, whereas MS was associated with lower FEV1/FVC ratios, with a more pronounced decrease found among asthmatic patients; these associations were driven by overweight/obese adolescents. Higher body mass index was associated with a decrease in FEV1/FVC ratios among adolescents with insulin resistance. Compared with healthy participants, adolescents with MS had an approximately 2% decrease in FEV1/FVC ratios, adolescents with asthma had an approximately 6% decrease, and those with MS and asthma had approximately 10% decreased FEV1/FVC ratios (P < .05). Insulin resistance and MS are associated with worsened lung function in overweight/obese adolescents. Asthma and MS synergistically decrease lung function, as do obesity and insulin resistance. These factors might contribute to the pathogenesis of asthma severity in obese patients and warrant further investigation. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

Global DNA hypomethylation has no impact on lung function or serum inflammatory and fibrosis cytokines in asbestos-exposed population.

PubMed

Yu, Min; Lou, Jianlin; Xia, Hailing; Zhang, Min; Zhang, Yixiao; Chen, Junqiang; Zhang, Xing; Ying, Shibo; Zhu, Lijin; Liu, Lihong; Jia, Guang

2017-04-01

To examine the effect of asbestos exposure on global DNA methylation and determine whether lung function and inflammatory and fibrosis biomarkers are correlated with the methylation state. A total of 26 healthy subjects without asbestos exposure (Group 1), 47 healthy subjects with exposure (Group 2), and 52 subjects with benign asbestos-related disorders (ARDs) (Group 3) participated in this cross-sectional study. Blood global 5-methylcytosine (5mC) and serum TNF-α, collagen IV, CCL5 and CC16 concentrations were analyzed using enzyme-linked immunosorbent assay-like assays. Spirometric maneuvers were performed to assess lung function. Decreased 5mC levels were observed in Groups 2 and 3 compared to Group 1, irrespective of lung function (p < 0.01). There was no significant change in 5mC between Groups 2 and 3. Overall, 5mC was negatively correlated with CCL5 and collagen IV (p < 0.05), but no significant inverse relationship was found between 5mC and CCL5 or collagen IV in each group. Additionally, both 5mC and CC16 were inversely associated with FEV1/FVC% (p = 0.001, adjusted R 2  = 0.145) for non-smokers, and consistently significant inverse relationships were found between CC16 and FEV1/FVC%, independent of asbestos exposure. Asbestos exposure causes global DNA hypomethylation. DNA hypomethylation has no influence on serum biomarkers and lung function in asbestos-exposed population with or without pleural and pulmonary parenchymal abnormalities.

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.

Influence of pulmonary emphysema on COPD assessment test-oriented categorization in GOLD document.

PubMed

Suzuki, Toshio; Tada, Yuji; Kawata, Naoko; Ikari, Jun; Kasahara, Yasunori; Sakurai, Yoriko; Iesato, Ken; Nishimura, Rintaro; West, James; Tatsumi, Koichiro

2015-01-01

The COPD assessment test (CAT) score is a key component of the multifactorial assessment of COPD in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines of 2014. Nevertheless, little is known regarding the differences among COPD categories in terms of clinical parameters such as pulmonary function or radiological findings. Thus, our aims in this study were to evaluate the associations between CAT scores and pulmonary clinical parameters, and to investigate factors that could discriminate between a "less symptomatic group" (categories A and C) and a "more symptomatic group" (categories B and D) among stable COPD patients. We enrolled 200 outpatients at Chiba University Hospital. Study subjects were assessed by CAT, pulmonary function testing, and multidetector computed tomography (MDCT). We assessed possible correlations between these indices. CAT scores were negatively correlated with percentage of the forced expiratory volume in 1 second predicted value (FEV1 %predicted) and percentage of the diffusing capacity for carbon monoxide per liter of lung volume predicted value (DLCO/VA [%predicted]) results and positively correlated with low attenuation volume percentage (LAV%) and residual volume to total lung capacity ratios (RV/TLC). In the "more symptomatic group" (category B or D), the mean DLCO/VA (%predicted) was significantly lower and the mean LAV% and RV/TLC was significantly higher than those in the "less symptomatic group" (category A or C), respectively. Interestingly, those in category B had higher mean LAV% compared to those in category C. CAT scores were significantly correlated with pulmonary function parameters and emphysematous changes on MDCT. The new GOLD classification system would be a step toward a phenotypic approach, especially taking into account the degree of emphysema and hyperinflation.

Lung Function in Pregnancy in Langerhans Cell Histiocytosis.

PubMed

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

2018-01-01

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

Brain Functional Connectivity in Small Cell Lung Cancer Population after Chemotherapy Treatment: an ICA fMRI Study

NASA Astrophysics Data System (ADS)

Bromis, K.; Kakkos, I.; Gkiatis, K.; Karanasiou, I. S.; Matsopoulos, G. K.

2017-11-01

Previous neurocognitive assessments in Small Cell Lung Cancer (SCLC) population, highlight the presence of neurocognitive impairments (mainly in attention processing and executive functioning) in this type of cancer. The majority of these studies, associate these deficits with the Prophylactic Cranial Irradiation (PCI) that patients undergo in order to avoid brain metastasis. However, there is not much evidence exploring cognitive impairments induced by chemotherapy in SCLC patients. For this reason, we aimed to investigate the underlying processes that may potentially affect cognition by examining brain functional connectivity in nineteen SCLC patients after chemotherapy treatment, while additionally including fourteen healthy participants as control group. Independent Component Analysis (ICA) is a functional connectivity measure aiming to unravel the temporal correlation between brain regions, which are called brain networks. We focused on two brain networks related to the aforementioned cognitive functions, the Default Mode Network (DMN) and the Task-Positive Network (TPN). Permutation tests were performed between the two groups to assess the differences and control for familywise errors in the statistical parametric maps. ICA analysis showed functional connectivity disruptions within both of the investigated networks. These results, propose a detrimental effect of chemotherapy on brain functioning in the SCLC population.

Assessing breathing motion by shape matching of lung and diaphragm surfaces

NASA Astrophysics Data System (ADS)

Urschler, Martin; Bischof, Horst

2005-04-01

Studying complex thorax breating motion is an important research topic for accurate fusion of functional and anatomical data, radiotherapy planning or reduction of breathing motion artifacts. We investigate segmented CT lung, airway and diaphragm surfaces at several different breathing states between Functional Residual and Total Lung Capacity. In general, it is hard to robustly derive corresponding shape features like curvature maxima from lung and diaphragm surfaces since diaphragm and rib cage muscles tend to deform the elastic lung tissue such that e.g. ridges might disappear. A novel registration method based on the shape context approach for shape matching is presented where we extend shape context to 3D surfaces. The shape context approach was reported as a promising method for matching 2D shapes without relying on extracted shape features. We use the point correspondences for a non-rigid thin-plate-spline registration to get deformation fields that describe the movement of lung and diaphragm. Our validation consists of experiments on phantom and real sheep thorax data sets. Phantom experiments make use of shapes that are manipulated with known transformations that simulate breathing behaviour. Real thorax data experiments use a data set showing lungs and diaphragm at 5 distinct breathing states, where we compare subsets of the data sets and qualitatively and quantitatively asses the registration performance by using manually identified corresponding landmarks.

Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

PubMed Central

Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W.

2013-01-01

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. PMID:23800689

Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide.

PubMed

Chen, Jing; Mo, Yiqun; Schlueter, Connie F; Hoyle, Gary W

2013-10-15

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. © 2013.

Lung transplantation in children. Specific aspects.

PubMed

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

2013-12-01

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

OZONE-INDUCED RESPIRATORY SYMPTOMS: EXPOSURE-RESPONSE MODELS AND ASSOCIATION WITH LUNG FUNCTION

EPA Science Inventory

Ozone-induced respiratory symptoms are known to be functions of concentration, minute ventilation, and duration of exposure. The purposes of this study were to identify an exposure-response model for symptoms, to determine whether response was related to age, and to assess the re...

Sensitivity of newly defined impulse oscillometry indices in preschool children.

PubMed

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

2017-05-01

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

Respiratory health and lung function in Chinese restaurant kitchen workers.

PubMed

Wong, Tze Wai; Wong, Andromeda H S; Lee, Frank S C; Qiu, Hong

2011-10-01

To measure air pollutant concentrations in Chinese restaurant kitchens using different stove types and assess their influence on workers' respiratory health. 393 kitchen workers from 53 Chinese restaurants were surveyed over 16 months: 115 workers from 21 restaurants using only electric stoves and 278 workers from 32 restaurants using only gas stoves. Workers were interviewed about their respiratory symptoms and had their lung function tested. Concentrations of nitric oxide (NO), nitrogen dioxide (NO(2)), carbon monoxide (CO), carbon dioxide (CO(2)), methane (CH(4)), non-methane hydrocarbons (NMHC), total volatile organic compounds (TVOC) and fine particulate matter (PM(2.5)) were measured using portable monitors and air-bag sampling. Temperature and noise levels were assessed. Median concentrations of NO, NO(2) and CO were 7.4, 1.5 and 1.6 times higher in gas-fuelled kitchens than in electric ones and average concentrations of PM(2.5) and TVOC were 81% and 78% higher, respectively. Differences were smaller for CH(4) and NMHC. Electricity-run kitchens were 4.5°C cooler and 9 dBA less noisy than gas-fuelled ones. Workers using electric cookers had significantly better lung function than their gas-using counterparts and their mean FEV(1) and FVC values were 5.4% and 3.8% higher, respectively, after adjustment for confounders. Wheeze, phlegm, cough and sore throat were more prevalent in workers using gas. The adjusted OR for having phlegm regularly was significantly higher. The poorer lung function and higher prevalence of respiratory symptoms among workers in gas-fuelled kitchens compared to those in electricity-powered kitchens may be associated with exposure to higher concentrations of toxic air pollutants generated during gas cooking.

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.

Association of the relative change in weight and body mass index with lung function in teenagers and adults with cystic fibrosis: Influence of gender and diabetes.

PubMed

Cano Megías, Marta; Guisado Vasco, Pablo; González Albarrán, Olga; Lamas Ferreiro, Adelaida; Máiz Carro, Luis

2015-11-01

Nutritional status is a prognostic factor in cystic fibrosis. Prevention of nutritional impairment and weigh loss are major clinical objectives because they are associated with worsening of lung function and increased mortality. To identify a potential relationship of clinical nutrition parameters, and their relative changes, with lung function (FEV1%) in a cohort of adolescent and adult patients with CF. A retrospective analysis of 64 patients older than 14years. Weight, height, BMI, and lung function data were collected at a period of disease stability, both in the year of the first abnormal oral glucose tolerance test (OGTT) and in the previous year. Relative changes in weight and BMI, and their relationship with FEV1%, were determined by linear regression and ANOVA tests; influence of gender and diabetes was also assessed. Mean age of the series (28 females and 36 males) was 26.8years. Normal glucose tolerance (NGT) was found in 26.7%, while 18.3% had diabetes without impaired fasting glucose (CFRD without FPG). Mean BMI was 20.32, with a mean weight of 53.53kg; 32.8% had BMI<18.5, and only 4.7% were overweight. Overall, a positive relative change in weight (≥6%) was associated with an increase in FEV1% (9.31%), as compared to those with a greater weight loss (at least 2%), who had a 12.09% fall in FEV1. Patients with CFRD without FPG had poorer lung function if they had a negative relative change in weight by at least 2% as compared to NGT. In patients with CF, a relative weight gain is positively associated to FEV1%, while a relative weight loss of at least 2% has a significant negative impact on lung function. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

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

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.

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

PubMed

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

1994-04-01

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

Progression of structural lung disease on CT scans in children with cystic fibrosis related diabetes.

PubMed

Widger, John; Ranganathan, Sarath; Robinson, Philip J

2013-05-01

Diabetes has a deleterious effect on clinical status in children with Cystic Fibrosis (CF). We hypothesized that children with CF Related Diabetes (CFRD) or Impaired Glucose Tolerance (IGT) would have more rapidly progressive lung disease based on chest computed tomography (CT) than those with normal glucose tolerance (NGT). In a retrospective study we compared lung structure changes over time, as assessed by CT, in 34 CF children with CFRD, IGT or NGT. We then compared CT findings with changes in lung function. Percentage forced expiratory volume in 1s (%FEV1) remained stable over time with a mean (±SD) yearly change of -0.5% (±3.9), -0.4% (±2.3) and -0.85% (±2.8) (p=0.92) for the CFRD, IGT and NGT groups respectively. However, there was a mean (95%CI) increase in % CT score of 3.86%/year (1.77-5.95%), 1.59%/year (0.6-2.58%) and 1.09%/year (0.07-2.11%) (p=0.023). In patients with CFRD, there was a more rapid progression of structural lung disease, compared to those who had NGT that was not reflected by change in lung function. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

[Lung is also involved in juvenile dermatomyositis].

PubMed

Pouessel, G; Thumerelle, C; Nève, V; Santangelo, T; Flammarion, S; Pruvot, I; Tillie-Leblond, I; Deschildre, A

2014-07-01

Juvenile dermatomyositis is the leading cause of chronic idiopathic inflammatory myopathy of auto-immune origin in children. Lung involvement in inflammatory myopathies is well described in adults, involving mostly interstitial lung disease, aspiration pneumonia and alveolar hypoventilation. We propose to describe its specificities in children. Pulmonary involvement may be asymptomatic and therefore must be systematically screened for. In case of clinical or functional respiratory abnormality, a chest computed tomographic (CT) scan is necessary. In children, a decrease of respiratory muscle strength seems common and should be systematically and specifically searched for by non-invasive and reproducible tests (sniff test). Interstitial lung disease usually associates restrictive functional defect, impairment of carbon monoxide diffusion and interstitial lung disease on CT scan. As in adults, the first-line treatment of juvenile dermatomyositis is based on corticosteroids. Corticosteroid resistant forms require corticosteroid bolus or adjuvant immunosuppressive drugs (methotrexate or cyclosporine). There is no consensus in pediatrics for the treatment of diffuse interstitial lung disease. Complications of treatment, including prolonged steroid therapy, are frequent and therefore a careful assessment of the treatments risk-benefit ratio is necessary, especially in growing children. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Lung transplant recipients holding companion animals: impact on physical health and quality of life.

PubMed

Irani, S; Mahler, C; Goetzmann, L; Russi, E W; Boehler, A

2006-02-01

Since lung transplant recipients are susceptible to infections and inhaled pollution, many centers warn against pets. However, data supporting this recommendation are lacking. Our program is less restrictive regarding pets. This study, for the first time, investigates the association of pets with physiological and psychological parameters in these patients. A questionnaire concerning pets was sent to 104 lung transplant recipients. Lung function tests, levels of exhaled nitric oxide (FE(NO)), need for antibiotic treatments and hospitalizations, creatinine clearance, body mass index (BMI) and demographic data were assessed. Additionally, the questionnaire of life satisfaction (FLZ), a question on summarized life satisfaction (LS), the life orientation test (LOT), the hospital anxiety depression scale (HADS) and the social support questionnaire (F-SozU) were assessed. Response rate was 86%. Fifty-two percent defined themselves as pet owners, whereas 48% did not. The two groups did not differ in demographic or physiological data. Significant differences in FLZ (79/65, p = 0.04), in LS (4.3/3.9, p = 0.01), LOT (32/29, p = 0.006) and F-SozU (4.5/4.2, p = 0.04) were found in favor of pet owners. In lung transplant recipients keeping pets the frequency of somatic complications is not higher compared to lung transplant recipients without pets. After lung transplantation, pets are associated with a better quality of life.

A Multimedia Self-management Intervention to Prepare Cancer Patients and Family Caregivers for Lung Surgery and Postoperative Recovery.

PubMed

Sun, Virginia; Raz, Dan J; Ruel, Nora; Chang, Walter; Erhunmwunsee, Loretta; Reckamp, Karen; Tiep, Brian; Ferrell, Betty; McCorkle, Ruth; Kim, Jae Y

2017-05-01

The purpose of this study was to evaluate the feasibility and acceptability of a multimedia self-management (MSM) intervention to prepare patients and family caregivers for lung surgery. This is a quasi-experimental, 2-group, sequential enrollment pilot study of a 4-session multimedia intervention (audio/visual + print) to enhance self-management and quality of life (QOL) for patients and family caregivers. The intervention, Preparing for Lung Surgery, begins before surgery, and continues through hospitalization and discharge, with 2 telephone support sessions after discharge. Outcomes were assessed before surgery (preintervention), at discharge, and 2 to 4 weeks postdischarge (postintervention). Patient outcomes were assessed using the Functional Assessment of Cancer Therapy-General (QOL), MD Anderson Symptom Inventory and Functional Assessment of Cancer Therapy-Pulmonary Symptom Index (symptoms), self-efficacy, surgery-related knowledge, and patient activation. Family caregiver outcomes included City of Hope-QOL-Family (QOL), Caregiver Burden Scale, and knowledge. Paired t tests were used for exploratory evaluations of score changes from pre- to postintervention. Sixty participants (38 patients, 22 family caregivers) enrolled in the study (70% accrual). Postintervention scores were significantly improved for patients' emotional QOL (P = .001). Trends for improvements were observed for patient self-efficacy, surgery-related knowledge, and activation. Family caregivers' surgery-related knowledge was significantly improved (P = .02). Overall, participants were highly satisfied with the acceptability/usability of the intervention (3.6-3.7 of 4.0). A standardized MSM intervention was feasible and acceptable in supporting readiness and preparedness for lung surgery and postoperative recovery. A larger randomized trial is needed to verify the impact of the MSM intervention on patient/family caregiver outcomes and health care resource use. Copyright © 2017 Elsevier Inc. All rights reserved.

Heavy metals found in the breathing zone, toenails and lung function of welders working in an air-conditioned welding workplace.

PubMed

Hariri, Azian; Mohamad Noor, Noraishah; Paiman, Nuur Azreen; Ahmad Zaidi, Ahmad Mujahid; Zainal Bakri, Siti Farhana

2017-09-22

Welding operations are rarely conducted in an air-conditioned room. However, a company would set its welding operations in an air-conditioned room to maintain the humidity level needed to reduce hydrogen cracks in the specimen being welded. This study intended to assess the exposure to metal elements in the welders' breathing zone and toenail samples. Heavy metal concentration was analysed using inductively coupled plasma mass spectrometry. The lung function test was also conducted and analysed using statistical approaches. Chromium and manganese concentrations in the breathing zone exceeded the permissible exposure limit stipulated by Malaysian regulations. A similar trend was obtained in the concentration of heavy metals in the breathing zone air sampling and in the welders' toenails. Although there was no statistically significant decrease in the lung function of welders, it is suggested that exposure control through engineering and administrative approaches should be considered for workplace safety and health improvement.

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.

Clinical outcomes in cystic fibrosis patients with Trichosporon respiratory infection.

PubMed

Esther, Charles R; Plongla, Rongpong; Kerr, Alan; Lin, Feng-Chang; Gilligan, Peter

2016-09-01

Relationships between clinical outcomes and novel respiratory pathogens such as Trichosporon are not well understood. Respiratory cultures from CF patients were screened for novel pathogens Trichosporon and Chryseobacterium as well as other pathogens over 28months. Relationships between microbiologic and clinical data were assessed using univariate and multivariate methods. Of 4934 respiratory cultures from 474 CF patients, 37 cultures from 10 patients were Trichosporon positive. Patients with positive Trichosproron cultures had a greater decline in FEV1 over time (-3.9%/year vs. -1.3%/year, p<0.05), whereas Chryseobacterium did not influence lung function. These findings were confirmed in multivariate analyses that included age, gender, and other common pathogens as confounders. Treatment of Trichosporon infected patients was associated with improved lung function. Trichosporon can be recovered from a small but clinically meaningful fraction of CF patients. The presence of Trichosporon, but not Chryseobacterium, is associated with greater declines in lung function. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

PubMed

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

2014-09-01

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

WE-AB-202-03: Quantifying Ventilation Change Due to Radiation Therapy Using 4DCT Jacobian Calculations

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

Patton, T; Du, K; Bayouth, J

Purpose: Four-dimensional computed tomography (4DCT) and image registration can be used to determine regional lung ventilation changes after radiation therapy (RT). This study aimed to determine if lung ventilation change following radiation therapy was affected by the pre-RT ventilation of the lung. Methods: 13 subjects had three 4DCT scans: two repeat scans acquired before RT and one three months after RT. Regional ventilation was computed using Jacobian determinant calculations on the registered 4DCT images. The post-RT ventilation map was divided by the pre-RT ventilation map to get a voxel-by-voxel Jacobian ratio map depicting ventilation change over the course of RT.more » Jacobian ratio change was compared over the range of delivered doses. The first pre-RT ventilation image was divided by the second to establish a control for Jacobian ratio change without radiation delivered. The functional change between scans was assessed using histograms of the Jacobian ratios. Results: There were significantly (p < 0.05) more voxels that had a large decrease in Jacobian ratio in the post-RT divided by pre-RT map (15.6%) than the control (13.2%). There were also significantly (p < .01) more voxels that had a large increase in Jacobian ratio (16.2%) when compared to control (13.3%). Lung regions with low function (<10% expansion by Jacobian) showed a slight linear reduction in expansion (0.2%/10 Gy delivered), while high function regions (>10% expansion) showed a greater response (1.2% reduction/10 Gy). Contiguous high function regions > 1 liter occurred in 11 of 13 subjects. Conclusion: There is a significant change in regional ventilation following a course of radiation therapy. The change in Jacobian following RT is dependent both on the delivered dose and the initial ventilation of the lung tissue: high functioning lung has greater ventilation loss for equivalent radiation doses. Substantial regions of high function lung tissue are prevalent. Research support from NIH grants CA166119 and CA166703, a gift from Roger Koch, and a Pilot Grant from University of Iowa Carver College of Medicine.« less

PUREAIR protocol: randomized controlled trial of intensive pulmonary rehabilitation versus standard care in patients undergoing surgical resection for lung cancer.

PubMed

Fugazzaro, Stefania; Costi, Stefania; Mainini, Carlotta; Kopliku, Besa; Rapicetta, Cristian; Piro, Roberto; Bardelli, Roberta; Rebelo, Patricia Filipa Sobral; Galeone, Carla; Sgarbi, Giorgio; Lococo, Filippo; Paci, Massimiliano; Ricchetti, Tommaso; Cavuto, Silvio; Merlo, Domenico Franco; Tenconi, Sara

2017-07-31

Non-small cell lung cancer is the most common type of lung cancer. Surgery is proven to be the most effective treatment in early stages, despite its potential impact on quality of life. Pulmonary rehabilitation, either before or after surgery, is associated with reduced morbidity related symptoms and improved exercise capacity, lung function and quality of life. We describe the study protocol for the open-label randomized controlled trial we are conducting on patients affected by primary lung cancer (stages I-II) eligible for surgical treatment. The control group receives standard care consisting in one educational session before surgery and early inpatient postoperative physiotherapy. The treatment group receives, in addition to standard care, intensive rehabilitation involving 14 preoperative sessions (6 outpatient and 8 home-based) and 39 postoperative sessions (15 outpatient and 24 home-based) with aerobic, resistance and respiratory training, as well as scar massage and group bodyweight exercise training. Assessments are performed at baseline, the day before surgery and one month and six months after surgery. The main outcome is the long-term exercise capacity measured with the Six-Minute Walk Test; short-term exercise capacity, lung function, postoperative morbidity, length of hospital stay, quality of life (Short Form 12), mood disturbances (Hospital Anxiety and Depression Scale) and pain (Numeric Rating Scale) are also recorded and analysed. Patient compliance and treatment-related side effects are also collected. Statistical analyses will be performed according to the intention-to-treat approach. T-test for independent samples will be used for continuous variables after assessment of normality of distribution. Chi-square test will be used for categorical variables. Expecting a 10% dropout rate, assuming α of 5% and power of 80%, we planned to enrol 140 patients to demonstrate a statistically significant difference of 25 m at Six-Minute Walk Test. Pulmonary Resection and Intensive Rehabilitation study (PuReAIR) will contribute significantly in investigating the effects of perioperative rehabilitation on exercise capacity, symptoms, lung function and long-term outcomes in surgically treated lung cancer patients. This study protocol will facilitate interpretation of future results and wide application of evidence-based practice. ClinicalTrials.gov Registry n. NCT02405273 [31.03.2015].

Sub-Volumetric Classification and Visualization of Emphysema Using a Multi-Threshold Method and Neural Network

NASA Astrophysics Data System (ADS)

Tan, Kok Liang; Tanaka, Toshiyuki; Nakamura, Hidetoshi; Shirahata, Toru; Sugiura, Hiroaki

Chronic Obstructive Pulmonary Disease is a disease in which the airways and tiny air sacs (alveoli) inside the lung are partially obstructed or destroyed. Emphysema is what occurs as more and more of the walls between air sacs get destroyed. The goal of this paper is to produce a more practical emphysema-quantification algorithm that has higher correlation with the parameters of pulmonary function tests compared to classical methods. The use of the threshold range from approximately -900 Hounsfield Unit to -990 Hounsfield Unit for extracting emphysema from CT has been reported in many papers. From our experiments, we realize that a threshold which is optimal for a particular CT data set might not be optimal for other CT data sets due to the subtle radiographic variations in the CT images. Consequently, we propose a multi-threshold method that utilizes ten thresholds between and including -900 Hounsfield Unit and -990 Hounsfield Unit for identifying the different potential emphysematous regions in the lung. Subsequently, we divide the lung into eight sub-volumes. From each sub-volume, we calculate the ratio of the voxels with the intensity below a certain threshold. The respective ratios of the voxels below the ten thresholds are employed as the features for classifying the sub-volumes into four emphysema severity classes. Neural network is used as the classifier. The neural network is trained using 80 training sub-volumes. The performance of the classifier is assessed by classifying 248 test sub-volumes of the lung obtained from 31 subjects. Actual diagnoses of the sub-volumes are hand-annotated and consensus-classified by radiologists. The four-class classification accuracy of the proposed method is 89.82%. The sub-volumetric classification results produced in this study encompass not only the information of emphysema severity but also the distribution of emphysema severity from the top to the bottom of the lung. We hypothesize that besides emphysema severity, the distribution of emphysema severity in the lung also plays an important role in the assessment of the overall functionality of the lung. We confirm our hypothesis by showing that the proposed sub-volumetric classification results correlate with the parameters of pulmonary function tests better than classical methods. We also visualize emphysema using a technique called the transparent lung model.

Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline: Five-Year Follow-up in Adult Smokers From the COPDGene Study.

PubMed

Hayden, Lystra P; Hardin, Megan E; Qiu, Weiliang; Lynch, David A; Strand, Matthew J; van Beek, Edwin J; Crapo, James D; Silverman, Edwin K; Hersh, Craig P

2018-02-01

Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV 1 and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions. Subjects returning for 5-year follow-up were assessed. Childhood pneumonia was defined by self-reported pneumonia at < 16 years. Childhood asthma was defined as self-reported asthma diagnosed by a health professional at < 16 years. ACO was defined as subjects with COPD who self-reported asthma diagnosed by a health-professional at ≤ 40 years. Smokers with and those without these early-life respiratory diseases were compared on measures of disease progression. Follow-up data from 4,915 subjects were examined, including 407 subjects who had childhood pneumonia, 323 subjects who had childhood asthma, and 242 subjects with ACO. History of childhood asthma or ACO was associated with an increased exacerbation frequency (childhood asthma, P < .001; ACO, P = .006) and odds of severe exacerbations (childhood asthma, OR, 1.41; ACO, OR, 1.42). History of childhood pneumonia was associated with increased exacerbations in subjects with COPD (absolute difference [β], 0.17; P = .04). None of these early-life respiratory diseases were associated with an increased rate of lung function decline or progression on CT scans. Subjects who had early-life asthma are at increased risk of developing COPD and of having more active disease with more frequent and severe respiratory exacerbations without an increased rate of lung function decline over a 5-year period. ClinicalTrials.gov; No. NCT00608764; https://clinicaltrials.gov. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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

Accuracy and Utility of Deformable Image Registration in {sup 68}Ga 4D PET/CT Assessment of Pulmonary Perfusion Changes During and After Lung Radiation Therapy

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

Hardcastle, Nicholas, E-mail: nick.hardcastle@gmail.com; Centre for Medical Radiation Physics, University of Wollongong, Wollongong; Hofman, Michael S.

2015-09-01

Purpose: Measuring changes in lung perfusion resulting from radiation therapy dose requires registration of the functional imaging to the radiation therapy treatment planning scan. This study investigates registration accuracy and utility for positron emission tomography (PET)/computed tomography (CT) perfusion imaging in radiation therapy for non–small cell lung cancer. Methods: {sup 68}Ga 4-dimensional PET/CT ventilation-perfusion imaging was performed before, during, and after radiation therapy for 5 patients. Rigid registration and deformable image registration (DIR) using B-splines and Demons algorithms was performed with the CT data to obtain a deformation map between the functional images and planning CT. Contour propagation accuracy andmore » correspondence of anatomic features were used to assess registration accuracy. Wilcoxon signed-rank test was used to determine statistical significance. Changes in lung perfusion resulting from radiation therapy dose were calculated for each registration method for each patient and averaged over all patients. Results: With B-splines/Demons DIR, median distance to agreement between lung contours reduced modestly by 0.9/1.1 mm, 1.3/1.6 mm, and 1.3/1.6 mm for pretreatment, midtreatment, and posttreatment (P<.01 for all), and median Dice score between lung contours improved by 0.04/0.04, 0.05/0.05, and 0.05/0.05 for pretreatment, midtreatment, and posttreatment (P<.001 for all). Distance between anatomic features reduced with DIR by median 2.5 mm and 2.8 for pretreatment and midtreatment time points, respectively (P=.001) and 1.4 mm for posttreatment (P>.2). Poorer posttreatment results were likely caused by posttreatment pneumonitis and tumor regression. Up to 80% standardized uptake value loss in perfusion scans was observed. There was limited change in the loss in lung perfusion between registration methods; however, Demons resulted in larger interpatient variation compared with rigid and B-splines registration. Conclusions: DIR accuracy in the data sets studied was variable depending on anatomic changes resulting from radiation therapy; caution must be exercised when using DIR in regions of low contrast or radiation pneumonitis. Lung perfusion reduces with increasing radiation therapy dose; however, DIR did not translate into significant changes in dose–response assessment.« less

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

PubMed Central

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

2014-01-01

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

Correlation between the international consensus definition of the Cancer Anorexia-Cachexia Syndrome (CACS) and patient-centered outcomes in advanced non-small cell lung cancer.

PubMed

LeBlanc, Thomas W; Nipp, Ryan D; Rushing, Christel N; Samsa, Greg P; Locke, Susan C; Kamal, Arif H; Cella, David F; Abernethy, Amy P

2015-04-01

The cancer anorexia-cachexia syndrome (CACS) is common in patients with advanced solid tumors and is associated with adverse outcomes including poor quality of life (QOL), impaired functioning, and shortened survival. To apply the recently posed weight-based international consensus CACS definition to a population of patients with advanced non-small cell lung cancer (NSCLC) and explore its impact on patient-reported outcomes. Ninety-nine patients participated in up to four study visits over a six-month period. Longitudinal assessments included measures of physical function, QOL, and other clinical variables such as weight and survival. Patients meeting the consensus CACS criteria at Visit 1 had a significantly shorter median survival (239.5 vs. 446 days; hazard ratio, 2.06, P < 0.05). Physical function was worse in the CACS group (mean Karnofsky Performance Status score 68 vs. 77, Eastern Cooperative Oncology Group Performance Status score 1.8 vs. 1.3, P < 0.05 for both), as was QOL (Functional Assessment of Cancer Therapy-General [FACT-G] Lung Cancer subscale of 17.2 vs. 19.9, Anorexia/Cachexia subscale of 31.4 vs. 37.9, P < 0.05 for both). Differences in the FACT-G and the Functional Assessment of Chronic Illness Therapy-Fatigue subscale approached but did not reach statistical significance. Longitudinally, all measures of physical function and QOL worsened regardless of CACS status, but the rate of decline was more rapid in the CACS group. The weight-based component of the recently proposed international consensus CACS definition is useful in identifying patients with advanced NSCLC who are likely to have significantly inferior survival and who will develop more precipitous declines in physical function and QOL. This definition may be useful for clinical screening purposes and identify patients with high palliative care needs. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Effect of ivacaftor in patients with advanced cystic fibrosis and a G551D-CFTR mutation: Safety and efficacy in an expanded access program in the United States.

PubMed

Taylor-Cousar, Jennifer; Niknian, Minoo; Gilmartin, Geoffrey; Pilewski, Joseph M

2016-01-01

Ivacaftor is the first therapeutic agent approved for the treatment of cystic fibrosis (CF) that targets the underlying molecular defect. Patients with severe lung disease were excluded from the randomized Phase 3 trials. This open-label study was designed to provide ivacaftor to patients in critical medical need prior to commercial product availability. CF patients aged ≥6 years with a G551D-CFTR mutation and FEV1 ≤ 40% predicted or listed for lung transplant received ivacaftor 150 mg every 12 h. The primary endpoint was safety as determined by adverse events. Secondary endpoints included assessment of lung function and weight. The rate of serious adverse events was consistent with disease severity. At 24 weeks of treatment with ivacaftor, there was a mean absolute increase in percent predicted FEV1 of 5.5 percentage points and a 3.3 kg mean absolute increase in weight from baseline. In patients with severe lung disease, ivacaftor was well tolerated and was associated with improved lung function and weight gain. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Functional MUC4 suppress epithelial-mesenchymal transition in lung adenocarcinoma metastasis.

PubMed

Gao, Liuwei; Liu, Jun; Zhang, Bin; Zhang, Hua; Wang, Daowei; Zhang, Tiemei; Liu, Yang; Wang, Changli

2014-02-01

The mucin MUC4 is a high molecular weight membrane-bound transmembrane glycoprotein that is frequently detected in invasive and metastatic cancer. The overexpression of MUC4 is associated with increased risks for several types of cancer. However, the functional role of MUC4 is poorly understood in lung adenocarcinoma. Using antisense-MUC4-RNA transfected adenocarcinoma cells, we discovered that the loss of MUC4 expression results in epithelial-mesenchymal transition (EMT). We found morphological alterations and the repression of the epithelial marker E-cadherin in transfected cells. Additionally, the loss of MUC4 caused the upregulation of the mesenchymal marker vimentin compared to control cells. Using a MUC4-knockdown versus control LTEP xenograft mice model (129/sv mice), we also found that EMT happened in lung tissues of MUC4-knockdown-LTEP xenograft mice. Moreover, antisense-MUC4-RNA transfected cells had a significantly increased cellular migration ability in vitro. The loss of MUC4 also occurred in lung adenocarcinoma patients with lymph node metastases. We further investigated MUC4 and found that it plays a critical role in regulating EMT by modulating β-catenin. Taken together, our study reveals a novel role for MUC4 in suppressing EMT and suggests that the assessment of MUC4 may function as a prognostic biomarker and could be a potential therapeutic target for lung adenocarcinoma metastasis.

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.

Non-contrast-enhanced perfusion and ventilation assessment of the human lung by means of fourier decomposition in proton MRI.

PubMed

Bauman, Grzegorz; Puderbach, Michael; Deimling, Michael; Jellus, Vladimir; Chefd'hotel, Christophe; Dinkel, Julien; Hintze, Christian; Kauczor, Hans-Ulrich; Schad, Lothar R

2009-09-01

Assessment of regional lung perfusion and ventilation has significant clinical value for the diagnosis and follow-up of pulmonary diseases. In this work a new method of non-contrast-enhanced functional lung MRI (not dependent on intravenous or inhalative contrast agents) is proposed. A two-dimensional (2D) true fast imaging with steady precession (TrueFISP) pulse sequence (TR/TE = 1.9 ms/0.8 ms, acquisition time [TA] = 112 ms/image) was implemented on a 1.5T whole-body MR scanner. The imaging protocol comprised sets of 198 lung images acquired with an imaging rate of 3.33 images/s in coronal and sagittal view. No electrocardiogram (ECG) or respiratory triggering was used. A nonrigid image registration algorithm was applied to compensate for respiratory motion. Rapid data acquisition allowed observing intensity changes in corresponding lung areas with respect to the cardiac and respiratory frequencies. After a Fourier analysis along the time domain, two spectral lines corresponding to both frequencies were used to calculate the perfusion- and ventilation-weighted images. The described method was applied in preliminary studies on volunteers and patients showing clinical relevance to obtain non-contrast-enhanced perfusion and ventilation data.

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

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.

Spirometry and volumetric capnography in lung function assessment of obese and normal-weight individuals without asthma.

PubMed

Ferreira, Mariana S; Mendes, Roberto T; Marson, Fernando A L; Zambon, Mariana P; Antonio, Maria A R G M; Paschoal, Ilma A; Toro, Adyléia A D C; Severino, Silvana D; Ribeiro, Maria A G O; Ribeiro, José D

To analyze and compare lung function of obese and healthy, normal-weight children and adolescents, without asthma, through spirometry and volumetric capnography. Cross-sectional study including 77 subjects (38 obese) aged 5-17 years. All subjects underwent spirometry and volumetric capnography. The evaluations were repeated in obese subjects after the use of a bronchodilator. At the spirometry assessment, obese individuals, when compared with the control group, showed lower values of forced expiratory volume in the first second by forced vital capacity (FEV 1 /FVC) and expiratory flows at 75% and between 25 and 75% of the FVC (p<0.05). Volumetric capnography showed that obese individuals had a higher volume of produced carbon dioxide and alveolar tidal volume (p<0.05). Additionally, the associations between dead space volume and tidal volume, as well as phase-3 slope normalized by tidal volume, were lower in healthy subjects (p<0.05). These data suggest that obesity does not alter ventilation homogeneity, but flow homogeneity. After subdividing the groups by age, a greater difference in lung function was observed in obese and healthy individuals aged >11 years (p<0.05). Even without the diagnosis of asthma by clinical criteria and without response to bronchodilator use, obese individuals showed lower FEV 1 /FVC values and forced expiratory flow, indicating the presence of an obstructive process. Volumetric capnography showed that obese individuals had higher alveolar tidal volume, with no alterations in ventilation homogeneity, suggesting flow alterations, without affecting lung volumes. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Automated CT Scan Scores of Bronchiectasis and Air Trapping in Cystic Fibrosis

PubMed Central

Swiercz, Waldemar; Heltshe, Sonya L.; Anthony, Margaret M.; Szefler, Paul; Klein, Rebecca; Strain, John; Brody, Alan S.; Sagel, Scott D.

2014-01-01

Background: Computer analysis of high-resolution CT (HRCT) scans may improve the assessment of structural lung injury in children with cystic fibrosis (CF). The goal of this cross-sectional pilot study was to validate automated, observer-independent image analysis software to establish objective, simple criteria for bronchiectasis and air trapping. Methods: HRCT scans of the chest were performed in 35 children with CF and compared with scans from 12 disease control subjects. Automated image analysis software was developed to count visible airways on inspiratory images and to measure a low attenuation density (LAD) index on expiratory images. Among the children with CF, relationships among automated measures, Brody HRCT scanning scores, lung function, and sputum markers of inflammation were assessed. Results: The number of total, central, and peripheral airways on inspiratory images and LAD (%) on expiratory images were significantly higher in children with CF compared with control subjects. Among subjects with CF, peripheral airway counts correlated strongly with Brody bronchiectasis scores by two raters (r = 0.86, P < .0001; r = 0.91, P < .0001), correlated negatively with lung function, and were positively associated with sputum free neutrophil elastase activity. LAD (%) correlated with Brody air trapping scores (r = 0.83, P < .0001; r = 0.69, P < .0001) but did not correlate with lung function or sputum inflammatory markers. Conclusions: Quantitative airway counts and LAD (%) on HRCT scans appear to be useful surrogates for bronchiectasis and air trapping in children with CF. Our automated methodology provides objective quantitative measures of bronchiectasis and air trapping that may serve as end points in CF clinical trials. PMID:24114359

Early bronchiectasis in cystic fibrosis detected by surveillance CT.

PubMed

Pillarisetti, Naveen; Linnane, Barry; Ranganathan, Sarath

2010-08-01

There is emerging evidence that cystic fibrosis lung disease begins early in infancy. Newborn screening allows early detection and surveillance of pulmonary disease and the possibility of early intervention in this life-shortening condition. We report two children with cystic fibrosis who underwent a comprehensive assessment from diagnosis that included measurement of lung function, limited-slice high-resolution CT and BAL performed annually. Early aggressive surveillance enabled significant lung disease and bronchiectasis to be detected during the first few years of life and led to a change in management, highlighting a clinical role for CT scanning during the preschool years in children with cystic fibrosis.

Imaging Lung Clearance of Radiolabeled Tumor Cells to Study Mice with Normal, Activated or Depleted Natural Killer (NK) Cells

NASA Astrophysics Data System (ADS)

Kulkarni, P. V.; Bennett, M.; Constantinescu, A.; Arora, V.; Viguet, M.; Antich, P.; Parkey, R. W.; Mathews, D.; Mason, R. P.; Oz, O. K.

2003-08-01

Lung clearance of 51CR and 125I iododeoxyuridine (IUDR) labeled cancer cells assess NK cell activity. It is desirable to develop noninvasive imaging technique to assess NK activity in mice. We labeled target YAC-1 tumor cells with 125I, 111In, 99mTc, or 67Ga and injected I.V. into three groups of BALB/c mice. Animals were treated with medium (group I), 300mg/kg cyclophosmamide (CY) to kill NK cell (group II), or anti-LY49C/1) (ab')2 mAb to augment NK function (group III). Lungs were removed 15 min or 2 h later for tissue counting. Control and treated mice were imaged every 5 min with a scintillating camera for 1 h after 15 min of infusion of the 111In labeled cells. Lung clearance increased after 15 min (lodging: 60-80%) and (2 h retention: 3-7%). Similar results were obtained with all the isotopes studied. Images distinguished the control and treated mice for lung activity. Cells labeled with 111In, 99mTc or 67Ga are cleared similar to those labeled with 51Cr or 125I. NK cell destruction of tumor cells may be assessed by noninvasive imaging method either by SPECT (99mTc, 111In, 67Ga) or by PET (68Ga).

Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease.

PubMed

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

2011-10-01

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

Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats

PubMed Central

Zeidler-Erdely, Patti C.; Meighan, Terence G.; Erdely, Aaron; Fedan, Jeffrey S.; Thompson, Janet A.; Bilgesu, Suzan; Waugh, Stacey; Anderson, Stacey; Marshall, Nikki B.; Afshari, Aliakbar; McKinney, Walter; Frazer, David G.; Antonini, James M.

2015-01-01

Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m3 to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (RL) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline RL was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased RL and result in endothelial dysfunction, but otherwise had minor effects on the lung. PMID:25140454

Impact of TG4010 Vaccine on Health-Related Quality of Life in Advanced Non-Small-Cell Lung Cancer: Results of a Phase IIB Clinical Trial

PubMed Central

Rotonda, Christine; Anota, Amélie; Mercier, Mariette; Bastien, Bérangère; Lacoste, Gisèle; Limacher, Jean-Marc; Quoix, Elisabeth; Bonnetain, Franck

2015-01-01

Background This study describes the effect of TG4010 vaccine on Health related Quality of Life (HRQOL) in patients with stage IIIb and IV non–small-cell lung cancer (NSCLC). Methods 148 patients with advanced NSCLC expressing MUC1 were randomly assigned to receive TG4010 plus chemotherapy or chemotherapy alone. HRQOL was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) at baseline and every 6 weeks until disease progression. Time until definitive deterioration (TUDD) of the four well-being dimensions of the FACT-L physical (PWB), functional (FWB), emotional (EWB) and social well-being (SWB) and the Lung Cancer Subscale (LCS) domains were analyzed for a 5-point minimal clinically important difference. Results No difference of TUDD of HRQOL has been found between treatment arms. No prognostic factors have been found to have a significant impact on the TUDD of PWB, SWB and LCS domains. The gender, the performance status and the smoking habits seemed to be associated with a shorter TUDD of EWB domain. The smokers and the former smokers seemed to present a shorter TUDD of FWB domain. Conclusion This study suggests that adding therapeutic vaccination with TG4010 to standard chemotherapy in patients with advanced NSCLC is associated with a similar evolution in HRQOL compared to chemotherapy alone. PMID:26207902

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.

Differential diagnosis of granulomatous lung disease: clues and pitfalls: Number 4 in the Series "Pathology for the clinician" Edited by Peter Dorfmüller and Alberto Cavazza.

PubMed

Ohshimo, Shinichiro; Guzman, Josune; Costabel, Ulrich; Bonella, Francesco

2017-09-30

Granulomatous lung diseases are a heterogeneous group of disorders that have a wide spectrum of pathologies with variable clinical manifestations and outcomes. Precise clinical evaluation, laboratory testing, pulmonary function testing, radiological imaging including high-resolution computed tomography and often histopathological assessment contribute to make a confident diagnosis of granulomatous lung diseases. Differential diagnosis is challenging, and includes both infectious (mycobacteria and fungi) and noninfectious lung diseases (sarcoidosis, necrotising sarcoid granulomatosis, hypersensitivity pneumonitis, hot tub lung, berylliosis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, rheumatoid nodules, talc granulomatosis, Langerhans cell histiocytosis and bronchocentric granulomatosis). Bronchoalveolar lavage, endobronchial ultrasound-guided transbronchial needle aspiration, transbronchial cryobiopsy, positron emission tomography and genetic evaluation are potential candidates to improve the diagnostic accuracy for granulomatous lung diseases. As granuloma alone is a nonspecific histopathological finding, the multidisciplinary approach is important for a confident diagnosis. Copyright ©ERS 2017.

Function of the Dräger Oxylog ventilator at high altitude.

PubMed

Thomas, G; Brimacombe, J

1994-06-01

We have assessed the performance of the Dräger Oxylog ventilator at high altitude using a decompression chamber and a lung simulator set to mimic the normal and non-compliant lung. In the normal lung, tidal volume increased by 28% at 2040 metres and by 106% at 9120 metres. A lesser change, but in the opposite direction, occurred in respiratory rate. The net effect was a linear increase in minute volume with altitude. At 2040 and 9144 metres minute volume increased by 13% and by 45%, and rate decreased by 10% and 30% respectively. In the abnormal lung stimulation, similar, but slightly less marked, changes occurred in all variables. These changes are of sufficient magnitude to require frequent observation of tidal volume and respiratory rate during aircraft ascent and descent.

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

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.

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

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

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2016-01-01

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

[Effect of verapamil and nitroglycerin on transplanted lung function in canines].

PubMed

Jiang, Zhibin; Hu, Ping; Liu, Jianxin; Wang, Dianjun; Jin, Longyu; Hong, Chao

2014-08-01

To investigate the protective effect of combined administration of verapamil and nitroglycerin on the function of canine transplanted lungs. Twenty orthotopic left lung transplantations were performed in 40 canines, which were randomly divided into 4 groups. In group I (control), the donor lungs were perfused and preserved with LPD solution, while group II with LPD solution plus verapamil 0.1 g/L, group III with LPD solution plus nitroglycerin 0.1g/L, and group IV with LPD solution plus verapamil 0.1 g/L and nitroglycerin 0.1 g/L. Hemodynamics and graft gas exchange were assessed 0, 2 and 4 h after the operation. The lung grafts were harvested to measure the wet/dry weight ratio, malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity. Compared with group I, II and III, the mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), partial pressure of oxygen in arterial blood (PaO₂), dynamic compliance (Cdyn) and alveolar-arterial oxygen tension volume [P(A- a)O₂] in group IV were improved significantly (P<0.05). No significant difference in the partial pressure of carbondioxide (PaCO₂) and peak inspiratory pressure (PIP) was observed in the 4 groups (P>0.05). In group IV, the wet/dry weight ratio and MDA contents were lower than those in the other 3 groups, and the SOD activity was significantly higher than that of the other 3 groups (P<0.05). Verapamil and nitroglycerin in LPD solution can protect the respiratory function of canine lung grafts by attenuating pulmonary edema and oxidative stress.

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.

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.

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.

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

PubMed

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

2010-12-27

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

The role of hyperpolarized 129xenon in MR imaging of pulmonary function

PubMed Central

Ebner, Lukas; Kammerman, Jeff; Driehuys, Bastiaan; Schiebler, Mark L.; Cadman, Robert V.; Fain, Sean B.

2016-01-01

In the last two decades, functional imaging of the lungs using hyperpolarized noble gases has entered the clinical stage. Both helium (3 He) and xenon (129Xe) gas have been thoroughly investigated for their ability to assess both the global and regional patterns of lung ventilation. With advances in polarizer technology and the current transition towards the widely available 129Xe gas, this method is ready for translation to the clinic. Currently, hyperpolarized (HP) noble gas lung MRI is limited to selected academic institutions; yet, the promising results from initial clinical trials have drawn the attention of the pulmonary medicine community. HP 129Xe MRI provides not only 3-dimensional ventilation imaging, but also unique capabilities for probing regional lung physiology. In this review article, we aim to (1) provide a brief overview of current ventilation MR imaging techniques, (2) emphasize the role of HP 129Xe MRI within the array of different imaging strategies, (3) discuss the unique imaging possibilities with HP 129Xe MRI, and (4) propose clinical applications. PMID:27707585

Unilateral empyema impacts the assessment of regional lung ventilation by electrical impedance tomography.

PubMed

Bläser, D; Pulletz, S; Becher, T; Schädler, D; Elke, G; Weiler, N; Frerichs, I

2014-06-01

Several studies have shown the ability of electrical impedance tomography (EIT) to assess regional ventilation distribution in human lungs. Fluid accumulation in the pleural space as in empyema, typically occurring on one chest side, may influence the distribution of ventilation and the corresponding EIT findings. The aim of our study was to examine this effect on the assessment of regional ventilation by EIT. Six patients suffering from unilateral empyema and intubated with a double-lumen endotracheal tube were studied. EIT data were acquired during volume-controlled ventilation with bilateral (tidal volume (V(T)): 800 ml) and unilateral ventilation (V(T): 400 ml) of the right and left lungs. Mean tidal amplitudes of the EIT signal were calculated in all image pixels. The sums of these values, expressed as relative impedance change (rel. ΔZ), were then determined in whole images and functionally defined regions-of-interest (ROI). The sums of rel. ΔZ calculated during the two cases of one-lung ventilation either on the affected or unaffected side were significantly smaller than during bilateral ventilation. However, in contrast to previous findings in patients with no pleural pathology, very low values of rel. ΔZ were found when the lung on the affected side was ventilated. ROI-based analysis rendered higher values than the whole-image analysis in this case, nonetheless, the values were significantly smaller than when the unaffected side was ventilated in spite of identical VT. In conclusion, our results indicate that the presence of empyema may affect the quantitative evaluation of regional lung ventilation by EIT.

[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).

[MRI methods for pulmonary ventilation and perfusion imaging].

PubMed

Sommer, G; Bauman, G

2016-02-01

Separate assessment of respiratory mechanics, gas exchange and pulmonary circulation is essential for the diagnosis and therapy of pulmonary diseases. Due to the global character of the information obtained clinical lung function tests are often not sufficiently specific in the differential diagnosis or have a limited sensitivity in the detection of early pathological changes. The standard procedures of pulmonary imaging are computed tomography (CT) for depiction of the morphology as well as perfusion/ventilation scintigraphy and single photon emission computed tomography (SPECT) for functional assessment. Magnetic resonance imaging (MRI) with hyperpolarized gases, O2-enhanced MRI, MRI with fluorinated gases and Fourier decomposition MRI (FD-MRI) are available for assessment of pulmonary ventilation. For assessment of pulmonary perfusion dynamic contrast-enhanced MRI (DCE-MRI), arterial spin labeling (ASL) and FD-MRI can be used. Imaging provides a more precise insight into the pathophysiology of pulmonary function on a regional level. The advantages of MRI are a lack of ionizing radiation, which allows a protective acquisition of dynamic data as well as the high number of available contrasts and therefore accessible lung function parameters. Sufficient clinical data exist only for certain applications of DCE-MRI. For the other techniques, only feasibility studies and case series of different sizes are available. The clinical applicability of hyperpolarized gases is limited for technical reasons. The clinical application of the techniques described, except for DCE-MRI, should be restricted to scientific studies.

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

PubMed

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

2015-06-01

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

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

PubMed

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

2017-03-23

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

Magnetomotive optical coherence elastography for relating lung structure and function in cystic fibrosis

NASA Astrophysics Data System (ADS)

Chhetri, Raghav K.; Carpenter, Jerome; Superfine, Richard; Randell, Scott H.; Oldenburg, Amy L.

2010-02-01

Cystic fibrosis (CF) is a genetic defect in the cystic fibrosis transmembrane conductance regulator protein and is the most common life-limiting genetic condition affecting the Caucasian population. It is an autosomal recessive, monogenic inherited disorder characterized by failure of airway host defense against bacterial infection, which results in bronchiectasis, the breakdown of airway wall extracellular matrix (ECM). In this study, we show that the in vitro models consisting of human tracheo-bronchial-epithelial (hBE) cells grown on porous supports with embedded magnetic nanoparticles (MNPs) at an air-liquid interface are suitable for long term, non-invasive assessment of ECM remodeling using magnetomotive optical coherence elastography (MMOCE). The morphology of ex vivo CF and normal lung tissues using OCT and correlative study with histology is also examined. We also demonstrate a quantitative measure of normal and CF airway elasticity using MMOCE. The improved understanding of pathologic changes in CF lung structure and function and the novel method of longitudinal in vitro ECM assessment demonstrated in this study may lead to new in vivo imaging and elastography methods to monitor disease progression and treatment in cystic fibrosis.

Evaluation of respiratory system mechanics in mice using the forced oscillation technique.

PubMed

McGovern, Toby K; Robichaud, Annette; Fereydoonzad, Liah; Schuessler, Thomas F; Martin, James G

2013-05-15

The forced oscillation technique (FOT) is a powerful, integrative and translational tool permitting the experimental assessment of lung function in mice in a comprehensive, detailed, precise and reproducible manner. It provides measurements of respiratory system mechanics through the analysis of pressure and volume signals acquired in reaction to predefined, small amplitude, oscillatory airflow waveforms, which are typically applied at the subject's airway opening. The present protocol details the steps required to adequately execute forced oscillation measurements in mice using a computer-controlled piston ventilator (flexiVent; SCIREQ Inc, Montreal, Qc, Canada). The description is divided into four parts: preparatory steps, mechanical ventilation, lung function measurements, and data analysis. It also includes details of how to assess airway responsiveness to inhaled methacholine in anesthetized mice, a common application of this technique which also extends to other outcomes and various lung pathologies. Measurements obtained in naïve mice as well as from an oxidative-stress driven model of airway damage are presented to illustrate how this tool can contribute to a better characterization and understanding of studied physiological changes or disease models as well as to applications in new research areas.

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

PubMed Central

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

2015-01-01

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

Deposition in the distal parts of the bovine respiratory tract: assessment of equipment suitable for drug inhalation.

PubMed

Genicot, B; Votion, D; Munsters, K; Close, R; Lindsey, J K; Lekeux, P

1996-03-30

The efficiency of equipment suitable for the inhalation of drugs by calves was assessed in six animals which inhaled radioisotopically labelled particles while suffering from reversible diffuse bronchoconstriction induced experimentally with 5-hydroxytryptamine and while they were breathing normally. Respiratory rates and data from pulmonary function tests and scintiscans were recorded during both investigations. After the first investigation, a mean (se) wash-out period of 9.8 (3.2) days was allowed. Under diffuse bronchoconstriction, the respiratory rate, the oscillatory resistance and the compliance of the respiratory system reached 282.1 (22.0), 161.1 (10.8) and 68.8 (2.7) per cent of their respective baseline values. When the calves were breathing normally these parameters did not change over time. The ratios (Cp/Ct) of the counts of gamma-disintegrations in the peripheral part (Cp) of the lungs and in the total lung area (Ct) were not significantly different when comparing the results from the two investigations. The ratios of Cp/Ct in the left lungs did not differ significantly from those in the right lungs.

Medical waste tissues - breathing life back into respiratory research.

PubMed

BéruBé, Kelly A

2013-12-01

With the advent of biobanks to store human lung cells and tissues from patient donations and from the procurement of medical waste tissues, it is now possible to integrate (both spatially and temporally) cells into anatomically-correct and physiologically-functional tissues. Modern inhalation toxicology relies on human data on exposure and adverse effects, to determine the most appropriate risk assessments and mitigations for beneficial respiratory health. A point in case is the recapitulation of airway tissue, such as the bronchial epithelium, to investigate the impact of air pollution on human respiratory health. The bronchi are the first point of contact for inhaled substances that bypass defences in the upper respiratory tract. Animal models have been used to resolve such inhalation toxicology hazards. However, the access to medical waste tissues has enabled the Lung Particle Research Group to tissue-engineer the Micro-Lung (TM) and Metabo-Lung(TM) cell culture models, as alternatives to animals in basic research and in the safety testing of aerosolised consumer goods. The former model favours investigations focused on lung injury and repair mechanisms, and the latter model provides the element of metabolism, through the co-culturing of lung and liver (hepatocyte) cells. These innovations represent examples of the animal-free alternatives advocated by the 21st century toxicology paradigm, whereby human-derived cell/tissue data will lead to more-accurate and more-reliable public health risk assessments and therapeutic mitigations (e.g. exposure to ambient air pollutants and adverse drug reactions) for lung disease. 2013 FRAME.

Prolonged use of wind or brass instruments does not alter lung function in musicians.

PubMed

Fuhrmann, Anita G; Franklin, Peter J; Hall, Graham L

2011-05-01

Respiratory function impacts on musical expression for wind/brass (W/B) musicians. Investigation of musicians' respiratory health to date has rarely progressed further than assessments of flow limitation through spirometry. This study aimed to compare W/B musicians' respiratory function to a non-wind/brass (NW/B) group with a comprehensive respiratory function assessment. Non-smoking, non-asthmatic participants aged 18-60 years completed a respiratory health questionnaire followed by spirometry, static lung volumes, respiratory mechanics, using forced oscillations, gas transfer and airway responsiveness (AR). Measurements were compared between participant groups using T-tests and linear regression modelling. Data from 102 participants (55 W/B musicians and 47 NW/B subjects) were included in the analysis. There were no differences between the two groups for any spirometry or lung volume outcomes, with the exception of RV/TLC which was decreased among W/B musicians (p=0.03). Measures of gas transfer and AR were similar between participant groups. Resistance at 6 Hz, measured by forced oscillation, was increased among W/B musicians compared to NW/B musicians (p=0.02) but reactance at 6 Hz was similar between the groups (p=0.10). The results suggest that W/B musicians' do not have altered respiratory function when compared to a non-musical control group. However, increased R(rs6) may indicate inflammatory, remodelling or other pathophysiological processes associated with W/B playing. Although the difference between groups was small it warrants further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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

2014-01-01

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

An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK.

PubMed

Fisher, Andrew; Andreasson, Anders; Chrysos, Alexandros; Lally, Joanne; Mamasoula, Chrysovalanto; Exley, Catherine; Wilkinson, Jennifer; Qian, Jessica; Watson, Gillian; Lewington, Oli; Chadwick, Thomas; McColl, Elaine; Pearce, Mark; Mann, Kay; McMeekin, Nicola; Vale, Luke; Tsui, Steven; Yonan, Nizar; Simon, Andre; Marczin, Nandor; Mascaro, Jorge; Dark, John

2016-11-01

Many patients awaiting lung transplantation die before a donor organ becomes available. Ex vivo lung perfusion (EVLP) allows initially unusable donor lungs to be assessed and reconditioned for clinical use. The objective of the Donor Ex Vivo Lung Perfusion in UK lung transplantation study was to evaluate the clinical effectiveness and cost-effectiveness of EVLP in increasing UK lung transplant activity. A multicentre, unblinded, non-randomised, non-inferiority observational study to compare transplant outcomes between EVLP-assessed and standard donor lungs. Multicentre study involving all five UK officially designated NHS adult lung transplant centres. Patients aged ≥ 18 years with advanced lung disease accepted onto the lung transplant waiting list. The study intervention was EVLP assessment of donor lungs before determining suitability for transplantation. The primary outcome measure was survival during the first 12 months following lung transplantation. Secondary outcome measures were patient-centred outcomes that are influenced by the effectiveness of lung transplantation and that contribute to the health-care costs. Lungs from 53 donors unsuitable for standard transplant were assessed with EVLP, of which 18 (34%) were subsequently transplanted. A total of 184 participants received standard donor lungs. Owing to the early closure of the study, a non-inferiority analysis was not conducted. The Kaplan-Meier estimate of survival at 12 months was 0.67 [95% confidence interval (CI) 0.40 to 0.83] for the EVLP arm and 0.80 (95% CI 0.74 to 0.85) for the standard arm. The hazard ratio for overall 12-month survival in the EVLP arm relative to the standard arm was 1.96 (95% CI 0.83 to 4.67). Patients in the EVLP arm required ventilation for a longer period and stayed longer in an intensive therapy unit (ITU) than patients in the standard arm, but duration of overall hospital stay was similar in both groups. There was a higher rate of very early grade 3 primary graft dysfunction (PGD) in the EVLP arm, but rates of PGD did not differ between groups after 72 hours. The requirement for extracorporeal membrane oxygenation (ECMO) support was higher in the EVLP arm (7/18, 38.8%) than in the standard arm (6/184, 3.2%). There were no major differences in rates of chest radiograph abnormalities, infection, lung function or rejection by 12 months. The cost of EVLP transplants is approximately £35,000 higher than the cost of standard transplants, as a result of the cost of the EVLP procedure, and the increased ECMO use and ITU stay. Predictors of cost were quality of life on joining the waiting list, type of transplant and number of lungs transplanted. An exploratory model comparing a NHS lung transplant service that includes EVLP and standard lung transplants with one including only standard lung transplants resulted in an incremental cost-effectiveness ratio of £73,000. Interviews showed that patients had a good understanding of the need for, and the processes of, EVLP. If EVLP can increase the number of usable donor lungs and reduce waiting, it is likely to be acceptable to those waiting for lung transplantation. Study limitations include small numbers in the EVLP arm, limiting analysis to descriptive statistics and the EVLP protocol change during the study. Overall, one-third of donor lungs subjected to EVLP were deemed suitable for transplant. Estimated survival over 12 months was lower than in the standard group, but the data were also consistent with no difference in survival between groups. Patients receiving these additional transplants experience a higher rate of early graft injury and need for unplanned ECMO support, at increased cost. The small number of participants in the EVLP arm because of early study termination limits the robustness of these conclusions. The reason for the increased PGD rates, high ECMO requirement and possible differences in lung injury between EVLP protocols needs evaluation. Current Controlled Trials ISRCTN44922411. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 20, No. 85. See the NIHR Journals Library website for further project information.

Overall and peripheral lung function assessment by spirometry and forced oscillation technique in relation to asthma diagnosis and control.

PubMed

Heijkenskjöld Rentzhog, C; Janson, C; Berglund, L; Borres, M P; Nordvall, L; Alving, K; Malinovschi, A

2017-12-01

Classic spirometry is effort dependent and of limited value in assessing small airways. Peripheral airway involvement, and relation to poor control, in asthma, has been highlighted recently. Forced oscillation technique (FOT) offers an effort-independent assessment of overall and peripheral lung mechanics. We studied the association between lung function variables, obtained either by spirometry or multifrequency (5, 11 and 19 Hz) FOT, and asthma diagnosis and control. Spirometry measures, resistance at 5 (R5) and 19 Hz (R19), reactance at 5 Hz (X5), resonant frequency (f res ), resistance difference between 5-19 Hz (R5-R19) and Asthma Control Test scores were determined in 234 asthmatic and 60 healthy subjects (aged 13-39 years). We used standardized lung function variables in logistic regression analyses, unadjusted and adjusted for age, height, gender and weight. Lower FEV 1 /FVC (OR [95% CI] 0.47 [0.32, 0.69]) and FEF 50 (0.62 [0.46, 0.85]) per standard deviation increase, and higher R5 (3.31 [1.95, 5.62]) and R19 (2.54 [1.65, 3.91]) were associated with asthma diagnosis. Independent predictive effects of FEV 1 /FVC and R5 or R19, respectively, were found for asthma diagnosis. Lower FEV 1 /FVC and altered peripheral FOT measures (X5, f res and R5-R19) were associated with uncontrolled asthma (P-values < .05). Resistance FOT measures were equally informative as spirometry, related to asthma diagnosis, and, furthermore, offered additive information to FEV 1 /FVC, supporting a complementary role for FOT. Asthma control was related to FOT measures of peripheral airways, suggesting a potential use in identifying such involvement. Further studies are needed to determine a clinical value and relevant reference values in children, for the multifrequency FOT measurements. © 2017 John Wiley & Sons Ltd.

TU-G-BRA-01: Assessing Radiation-Induced Reductions in Regional Lung Perfusion Following Stereotactic Radiotherapy for Lung Cancer

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

McGurk, R; Green, R; Lawrence, M

2015-06-15

Purpose: The dose-dependent nature of radiation therapy (RT)-induced lung injury following hypo-fractionated stereotactic RT is unclear. We herein report preliminary results of a prospective study assessing the magnitude of RT-induced reductions in regional lung perfusion following hypo-fractionated stereotactic RT. Methods: Four patients undergoing hypo-fractionated stereotactic lung RT (SBRT: 12 Gy x 4 fractions or 10 Gy x 5 fractions) had a pre-treatment SPECT (single-photon emission computed tomography) perfusion scan providing a 3D map of regional lung perfusion. Scans were repeated 3–6 months post-treatment. Pre- and post SPECT scans were registered to the planning CT scan (and hence the 3D dosemore » data). Changes in regional perfusion (counts per cc on the pre-post scans) were computed in regions of the lung exposed to different doses of radiation (in 5 Gy intervals), thus defining a dose-response function. SPECT scans were internally normalized to the regions receiving <5 Gy. Results: At 3 months post-RT, the changes in perfusion are highly variable. At 6 months, there is a consistent dose-dependent reduction in regional perfusion. The average percent decline in regional perfusion was 10% at 15–20 Gy, 20% at 20–25 Gy, and 30% at 25–30 Gy representing a relatively linear dose response with an approximate 2% reduction per Gray for doses in excess of 10 Gy. There was a subtle increase in perfusion in the lung receiving <10 Gy. Conclusion: Hypo-fractionated stereotactic RT appears to cause a dose-dependent reduction in regional lung perfusion. There appears to be a threshold effect with no apparent perfusion loss at doses <10 Gy, though this might be in part due to the normalization technique used. Additional data is needed from a larger number of patients to better assess this issue. This sort of data can be used to assist optimizing RT treatment plans that minimize the risk of lung injury. Partly supported by the NIH (CA69579) and the Lance Armstrong Foundation.« less

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

PubMed

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

2018-04-01

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

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

PubMed

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

2000-12-01

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

The role of interleukin-1β as a predictive biomarker and potential therapeutic target during clinical ex vivo lung perfusion.

PubMed

Andreasson, Anders S I; Borthwick, Lee A; Gillespie, Colin; Jiwa, Kasim; Scott, Jonathan; Henderson, Paul; Mayes, Jonny; Romano, Rosalba; Roman, Marius; Ali, Simi; Fildes, James E; Marczin, Nandor; Dark, John H; Fisher, Andrew J

2017-09-01

Extended criteria donor lungs deemed unsuitable for immediate transplantation can be reconditioned using ex vivo lung perfusion (EVLP). Objective identification of which donor lungs can be successfully reconditioned and will function well post-operatively has not been established. This study assessed the predictive value of markers of inflammation and tissue injury in donor lungs undergoing EVLP as part of the DEVELOP-UK study. Longitudinal samples of perfusate, bronchoalveolar lavage, and tissue from 42 human donor lungs undergoing clinical EVLP assessments were analyzed for markers of inflammation and tissue injury. Levels were compared according to EVLP success and post-transplant outcomes. Neutrophil adhesion to human pulmonary microvascular endothelial cells (HPMECs) conditioned with perfusates from EVLP assessments was investigated on a microfluidic platform. The most effective markers to differentiate between in-hospital survival and non-survival post-transplant were perfusate interleukin (IL)-1β (area under the curve = 1.00, p = 0.002) and tumor necrosis factor-α (area under the curve = 0.95, p = 0.006) after 30 minutes of EVLP. IL-1β levels in perfusate correlated with upregulation of intracellular adhesion molecule-1 in donor lung vasculature (R 2 = 0.68, p < 0.001) and to a lesser degree upregulation of intracellular adhesion molecule-1 (R 2 = 0.30, p = 0.001) and E-selectin (R 2 = 0.29, p = 0.001) in conditioned HPMECs and neutrophil adhesion to conditioned HPMECs (R 2 = 0.33, p < 0.001). Neutralization of IL-1β in perfusate effectively inhibited neutrophil adhesion to conditioned HPMECs (91% reduction, p = 0.002). Donor lungs develop a detectable and discriminatory pro-inflammatory signature in perfusate during EVLP. Blocking the IL-1β pathway during EVLP may reduce endothelial activation and subsequent neutrophil adhesion on reperfusion; this requires further investigation in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

Initiating transitional care for adolescents with cystic fibrosis at the age of 12 is both feasible and promising.

PubMed

Skov, M; Teilmann, G; Damgaard, I N; Nielsen, K G; Hertz, P G; Holgersen, M G; Presfeldt, M; Dalager, A M S; Brask, M; Boisen, K A

2018-05-05

Adolescence is a vulnerable period in cystic fibrosis, associated with declining lung function. This study described, implemented and evaluated a transition programme for adolescents. We conducted a single centre, non-randomised and non-controlled prospective programme at the cystic fibrosis centre at Copenhagen University Hospital Rigshospitalet from 2010-2011, assessing patients aged 12 to 18 at baseline and after 12 months. Changes implemented included staff training on communication, a more youth friendly feel to the outpatient clinic, the introduction of youth consultations partly alone with the adolescent, and a parents' evening focusing on cystic fibrosis in adolescence. Lung function and body mass index (BMI) were measured monthly and adolescents were assessed for their readiness for transition and quality of life at baseline and 12 months. We found that 40 (98%) of the eligible patients participated and youth consultations were successfully implemented with no dropouts. The readiness checklist score increased significantly over the one-year study period, indicating increased readiness for transfer and self-care. Overall quality of life, lung function and BMI remained stable during the study period. A well structured transition programme for cystic fibrosis patients as young as 12 years of age proved to be both feasible and sustainable. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A home-based exercise program to improve function, fatigue, and sleep quality in patients with Stage IV lung and colorectal cancer: a randomized controlled trial.

PubMed

Cheville, Andrea L; Kollasch, Jenny; Vandenberg, Justin; Shen, Tiffany; Grothey, Axel; Gamble, Gail; Basford, Jeffrey R

2013-05-01

Exercise benefits patients with cancer, but studies of home-based approaches, particularly among those with Stage IV disease, remain small and exploratory. To conduct an adequately powered trial of a home-based exercise intervention that can be facilely integrated into established delivery and reimbursement structures. Sixty-six adults with Stage IV lung or colorectal cancer were randomized, in an eight-week trial, to usual care or incremental walking and home-based strength training. The exercising participants were instructed during a single physiotherapy visit and subsequently exercised four days or more per week; training and step-count goals were advanced during bimonthly telephone calls. The primary outcome measure was mobility assessed with the Ambulatory Post Acute Care Basic Mobility Short Form. Secondary outcomes included ratings of pain and sleep quality as well as the ability to perform daily activities (Ambulatory Post Acute Care Daily Activities Short Form), quality of life (Functional Assessment of Cancer Therapy-General), and fatigue (Functional Assessment of Cancer Therapy-Fatigue). Three participants dropped out and seven died (five in the intervention and two in the control group, P=0.28). At Week 8, the intervention group reported improved mobility (P=0.01), fatigue (P=0.02), and sleep quality (P=0.05) compared with the usual care group, but did not differ on the other measures. A home-based exercise program seems capable of improving the mobility, fatigue, and sleep quality of patients with Stage IV lung and colorectal cancer. Copyright © 2013. Published by Elsevier Inc.

The influence of inspiratory muscle training combined with the Pilates method on lung function in elderly women: A randomized controlled trial.

PubMed

Alvarenga, Guilherme Medeiros de; Charkovski, Simone Arando; Santos, Larissa Kelin Dos; Silva, Mayara Alves Barbosa da; Tomaz, Guilherme Oliveira; Gamba, Humberto Remigio

2018-01-01

Aging is progressive, and its effects on the respiratory system include changes in the composition of the connective tissues of the lung that influence thoracic and lung compliance. The Powerbreathe® K5 is a device used for inspiratory muscle training with resistance adapted to the level of the inspiratory muscles to be trained. The Pilates method promotes muscle rebalancing exercises that emphasize the powerhouse. The aim of this study was to evaluate the influence of inspiratory muscle training combined with the Pilates method on lung function in elderly women. The participants were aged sixty years or older, were active women with no recent fractures, and were not gait device users. They were randomly divided into a Pilates with inspiratory training group (n=11), a Pilates group (n=11) and a control group (n=9). Spirometry, manovacuometry, a six-minute walk test, an abdominal curl-up test, and pulmonary variables were assessed before and after twenty intervention sessions. The intervention led to an increase in maximal inspiratory muscle strength and pressure and power pulmonary variables (p<0.0001), maximal expiratory muscle strength (p<0.0014), six-minute walk test performance (p<0.01), and abdominal curl-up test performance (p<0.00001). The control group showed no differences in the analyzed variables (p>0.05). The results of this study suggest inspiratory muscle training associated with the Pilates method provides an improvement in the lung function and physical conditioning of elderly patients.

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.

Aberrant microRNA-137 promoter methylation is associated with lymph node metastasis and poor clinical outcomes in non-small cell lung cancer

PubMed Central

Min, Lingfeng; Wang, Fang; Hu, Suwei; Chen, Yong; Yang, Junjun; Liang, Sudong; Xu, Xingxiang

2018-01-01

MicroRNA-137 (miR-137) functions as a tumor suppressor and is silenced by aberrant promoter methylation. Previous studies have demonstrated that miR-137 is downregulated in lung cancer. The purpose of the present study was to investigate miR-137 promoter methylation and to assess its prognostic value in non-small cell lung cancer (NSCLC). The expression of miR-137 was analyzed inhuman lung cancer A549 and H1299 cells and normal bronchial epithelial BEAS-2B cells, 10 paired formalin-fixed paraffin-embedded lung cancer and normal tissue samples, and 56 archived paraffin-embedded lung cancer tissues. Quantitative methylation-specific polymerase chain reaction analysis was used to assess the miR-137 methylation status. The associations between miR-137 promoter methylation and the clinicopathological features and prognosis of patients with NSCLC (n=56) were analyzed using analysis of variance. miR-137 was markedly downregulated in lung cancer cells and lung cancer tissue specimens compared with expression in BEAS-2B cells and matched adjacent normal lung tissues. A significant negative correlation between miR-137 expression and miR-137 promoter methylation was observed in human lung cancer tissues (r=−0.343; P=0.01). Smoking, lymph node metastasis and advanced clinical stage were associated with significantly lower expression of miR-137 in variance analysis. High levels of miR-137 promoter methylation were associated with a significantly poorer disease-free survival rate (P=0.034), but were not associated with overall survival, in Kaplan-Meier analysis and univariate analysis. In conclusion, the results of the present study indicated that miR-137 is downregulated and that its promoter is aberrantly methylated in lung cancer, and that high levels of miR-137 promoter methylation may have prognostic value for poor disease-free survival. PMID:29740491

MRI of the lung: state of the art.

PubMed

Wielpütz, Mark; Kauczor, Hans-Ulrich

2012-01-01

Magnetic resonance imaging (MRI) of the lung is technically challenging due to the low proton density and fast signal decay of the lung parenchyma itself. Additional challenges consist of tissue loss, hyperinflation, and hypoxic hypoperfusion, e.g., in emphysema, a so-called "minus-pathology". However, pathological changes resulting in an increase of tissue ("plus-pathology"), such as atelectases, nodules, infiltrates, mucus, or pleural effusion, are easily depicted with high diagnostic accuracy. Although MRI is inferior or at best equal to multi-detector computed tomography (MDCT) for the detection of subtle morphological features, MRI now offers an increasing spectrum of functional imaging techniques such as perfusion assessment and measurement of ventilation and respiratory mechanics that are superior to what is possible with MDCT. Without putting patients at risk with ionizing radiation, repeated examinations allow for the evaluation of the course of lung disease and monitoring of the therapeutic response through quantitative imaging, providing a level of functional detail that cannot be obtained by any other single imaging modality. As such, MRI will likely be used for clinical applications beyond morphological imaging for many lung diseases. In this article, we review the technical aspects and protocol suggestions for chest MRI and discuss the role of MRI in the evaluation of nodules and masses, airway disease, respiratory mechanics, ventilation, perfusion and hemodynamics, and pulmonary vasculature.

Submaximal Exercise Capacity in Juvenile Dermatomyositis after Longterm Disease: The Contribution of Muscle, Lung, and Heart Involvement.

PubMed

Berntsen, Kristin Schjander; Tollisen, Anita; Schwartz, Thomas; Kirkhus, Eva; Aaløkken, Trond Mogens; Lund, May Brit; Flatø, Berit; Sjaastad, Ivar; Sanner, Helga

2017-06-01

To compare submaximal exercise capacity in patients with juvenile dermatomyositis (JDM) with controls, and analyze contributions of muscle, heart, and lung impairment in patients. Fifty-nine patients with JDM, with a mean 16.9 years after symptom onset, and 59 sex- and age-matched controls completed a 6-min walk test (6MWT) and a timed up and go (TUG) test. Muscle function, disease activity/damage, and health-related quality of life (HRQOL) were assessed by validated tools; heart function by echocardiography and electrocardiography; and lung function by spirometry, DLCO, and body plethysmography. A thoracic high-resolution computed tomography (HRCT) scan and magnetic resonance imaging of the thighs were completed in patients. The 6MWT distance (6MWD) was 592 ± 81 m in patients versus 649 ± 79 m in controls (p < 0.001), and 563 ± 75 m in active versus 622 ± 76 m in inactive JDM (p = 0.004). The TUG time was 13.1 ± 2.1 s in patients versus 12.3 ± 2.0 s in controls (p = 0.034), and 13.7 ± 2.2 s in active versus 12.5 ± 1.8 s in inactive JDM (p = 0.028). No statistically significant difference was found between inactive JDM and controls in either test. In patients, the Childhood Myositis Assessment Score influenced the 6MWD and TUG time the most, followed by a low DLCO and HRCT pathology in the 6MWT and forced vital capacity in the TUG test. Medical Outcomes Study Short Form-36 physical component summary correlated strongly with both tests. Submaximal exercise capacity was reduced in patients with JDM, particularly those with active disease. This reduction was associated with muscle and lung dysfunction and poorer HRQOL.

The effect of nabilone on appetite, nutritional status, and quality of life in lung cancer patients: a randomized, double-blind clinical trial.

PubMed

Turcott, Jenny G; Del Rocío Guillen Núñez, María; Flores-Estrada, Diana; Oñate-Ocaña, Luis F; Zatarain-Barrón, Zyanya Lucia; Barrón, Feliciano; Arrieta, Oscar

2018-03-17

Over one half of the patients diagnosed with advanced lung cancer experience anorexia. In addition to its high incidence, cancer-induced anorexia promotes the development of the anorexia-cachexia syndrome, which is related to poor clinical outcomes. Recently, drugs derived from cannabinoids, such as Nabilone, have been recognized for their appetite improvement properties; however, clinical trials to support their use in cancer patients are necessary. This is a randomized, double-blind, placebo-controlled clinical trial to assess the effect of Nabilone vs. placebo on the appetite, nutritional status, and quality of life in patients diagnosed with advanced Non-small cell lung cancer (NSCLC) (NCT02802540). A total of 65 patients from the outpatient clinic at the National Institute of Cancer (INCan) were assessed for eligibility and 47 were randomized to receive Nabilone (0.5 mg/2 weeks followed by 1.0 mg/6 weeks) or placebo. After 8 weeks of treatment, patients who received Nabilone increased their caloric intake (342-kcal) and had a significantly higher intake of carbohydrates (64 g) compared to patients receiving placebo (p = 0.040). Quality of life also showed significant improvements in patients in the experimental arm of the trial, particularly in role functioning (p = 0.030), emotional functioning (p = 0.018), social functioning (p = 0.036), pain (p = 0.06), and insomnia (p = 0.020). No significant change in these scales was seen in the control group. Nabilone is an adequate and safe therapeutic option to aid in the treatment of patients diagnosed with anorexia. Larger trials are necessary in order to draw robust conclusions in regard to its efficacy in lung cancer patients.

Clinical Rating of Movement-Pattern Quality in Patients With Femoroacetabular Impingement Syndrome: A Methodological Study.

PubMed

Casartelli, Nicola C; Maffiuletti, Nicola A; Brunner, Romana; Büchi, Marcel; Sutter, Reto; Pfirrmann, Christian W; Naal, Florian D; Leunig, Michael; Bizzini, Mario

2018-04-01

Study Design Cross-sectional study. Objectives To evaluate intrarater and interrater agreement among physical therapists with different clinical experience in performing a visual rating of movement-pattern quality of patients with femoroacetabular impingement (FAI) syndrome using a semi-quantitative scale. Background Visual rating of movement patterns in patients with FAI syndrome is of interest, because poor control of dynamic hip motion is frequently noted. Methods A video camera was used to record the performance of 34 patients with FAI syndrome performing single-limb standing, squat, frontal lunge, hop lunge, bridge, and plank. Visual rating of movement, as recorded on video, was performed by a highly experienced, a moderately experienced, and a novice physical therapist on 2 occasions using a semi-quantitative scale. Hip abductor strength was assessed using dynamometry, and hip pain and function were assessed with a patient-reported questionnaire. Intrarater and interrater agreement among physical therapists was evaluated using Gwet's agreement coefficient 1. Construct validity was evaluated as the association between physical therapists' rating and patients' hip abductor strength, pain, and function. Results Good intrarater and interrater agreement was observed in the highly experienced and moderately experienced physical therapists when rating single-limb standing, bridge, and plank. Poor to moderate intrarater and interrater agreement was found when they rated squat, frontal lunge, and hop lunge. Poor performers, as rated by the highly experienced physical therapist only, demonstrated lower hip abductor strength (P<.05), and similar hip pain and hip function compared to those of good performers. Conclusion Movement-pattern quality of patients with FAI syndrome should be rated by a highly experienced physical therapist. J Orthop Sports Phys Ther 2018;48(4):260-269. doi:10.2519/jospt.2018.7840.

Effects of periodontal treatment on exacerbation frequency and lung function in patients with chronic periodontitis: study protocol of a 1-year randomized controlled trial.

PubMed

Romero, Sergio dos Santos; Pinto, Erika Horácio; Longo, Priscila Larcher; Dal Corso, Simone; Lanza, Fernanda Cordoba; Stelmach, Rafael; Rached, Samia Zahi; Lino-Dos-Santos-Franco, Adriana; Mayer, Marcia Pinto Alves; Bussadori, Sandra Kalil; Fernandes, Kristianne Porta Santos; Mesquita-Ferrari, Raquel Agnelli; Horliana, Anna Carolina Ratto Tempestini

2017-01-23

Chronic obstructive pulmonary disease (COPD) has been associated with periodontal disease (PD), and periodontal treatment (PT) has been connected to reduction of lung disease exacerbations. Bronchiectasis has many clinical similarities with COPD but, although it is also a chronic lung disease, to date it has not been studied with relation to PD. The aim of this study is to evaluate whether PT associated with photodynamic therapy (PDT) reduces the number of exacerbations, improves pulmonary function, periodontal clinical parameters and quality of life after 1 year of periodontal treatment follow-up. Bronchiectasis patients will undergo medical anamnesis and periodontal examination. Participants with periodontitis will be divided into two groups and PT will be performed as G1 control group (n = 32) - OHO (oral hygiene orientation) + supragingival treatment + simulation of using photodynamic therapy (PDT); G2 experimental (n = 32) - scaling and root planing + PDT + OHO. Lung function will be assessed both at baseline and after 1 year by spirometry, exacerbation history will be analyzed through clinical records monitoring. Three instruments for quality of life assessment will also be applied - Saint George's Respiratory Questionnaire and Impact Profile Analysis Oral health (OHIP-14). It is expected that periodontal treatment can improve the analyzed parameters after 1 year. Although only one study evaluates exacerbation in COPD after 1 year of PT, bronchiectasis has not been studied in the dentistry field to date. NCT02514226. Version #1. This study protocol receives grant from FAPESP (São Paulo Research Foundation) #2015/20535-1. First received: July 22, 2015, 1 st version. This protocol has been approved by the Research Ethics Committee of Nove de Julho University.

Refining Low Physical Activity Measurement Improves Frailty Assessment in Advanced Lung Disease and Survivors of Critical Illness.

PubMed

Baldwin, Matthew R; Singer, Jonathan P; Huang, Debbie; Sell, Jessica; Gonzalez, Wendy C; Pollack, Lauren R; Maurer, Mathew S; D'Ovidio, Frank F; Bacchetta, Matthew; Sonett, Joshua R; Arcasoy, Selim M; Shah, Lori; Robbins, Hilary; Hays, Steven R; Kukreja, Jasleen; Greenland, John R; Shah, Rupal J; Leard, Lorriana; Morrell, Matthew; Gries, Cynthia; Katz, Patricia P; Christie, Jason D; Diamond, Joshua M; Lederer, David J

2017-08-01

The frail phenotype has gained popularity as a clinically relevant measure in adults with advanced lung disease and in critical illness survivors. Because respiratory disease and chronic illness can greatly limit physical activity, the measurement of participation in traditional leisure time activities as a frailty component may lead to substantial misclassification of frailty in pulmonary and critical care patients. To test and validate substituting the Duke Activity Status Index (DASI), a simple 12-item questionnaire, for the Minnesota Leisure Time Physical Activity (MLTA) questionnaire, a detailed questionnaire covering 18 leisure time activities, as the measure of low activity in the Fried frailty phenotype (FFP) instrument. In separate multicenter prospective cohort studies of adults with advanced lung disease who were candidates for lung transplant and older survivors of acute respiratory failure, we assessed the FFP using either the MLTA or the DASI. For both the DASI and MLTA, we evaluated content validity by testing floor effects and construct validity through comparisons with conceptually related factors. We tested the predictive validity of substituting the DASI for the MLTA in the FFP assessment using Cox models to estimate associations between the FFP and delisting/death before transplant in those with advanced lung disease and 6-month mortality in older intensive care unit (ICU) survivors. Among 618 adults with advanced lung disease and 130 older ICU survivors, the MLTA had a substantially greater floor effect than the DASI (42% vs. 1%, and 49% vs. 12%, respectively). The DASI correlated more strongly with strength and function measures than did the MLTA in both cohorts. In models adjusting for age, sex, comorbidities, and illness severity, substitution of the DASI for the MLTA led to stronger associations of the FFP with delisting/death in lung transplant candidates (FFP-MLTA hazard ratio [HR], 1.42; 95% confidence interval [CI], 0.55-3.65; FFP-DASI HR, 2.99; 95% CI, 1.03-8.65) and with mortality in older ICU survivors (FFP-MLTA HR, 2.68; 95% CI, 0.62-11.6; FFP-DASI HR, 5.71; 95% CI, 1.34-24.3). The DASI improves the construct and predictive validity of frailty assessment in adults with advanced lung disease or recent critical illness. This simple questionnaire should replace the more complex MLTA in assessing the frailty phenotype in these populations.

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

PubMed

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

2016-02-01

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

Reproducibility of Lobar Perfusion and Ventilation Quantification Using SPECT/CT Segmentation Software in Lung Cancer Patients.

PubMed

Provost, Karine; Leblond, Antoine; Gauthier-Lemire, Annie; Filion, Édith; Bahig, Houda; Lord, Martin

2017-09-01

Planar perfusion scintigraphy with 99m Tc-labeled macroaggregated albumin is often used for pretherapy quantification of regional lung perfusion in lung cancer patients, particularly those with poor respiratory function. However, subdividing lung parenchyma into rectangular regions of interest, as done on planar images, is a poor reflection of true lobar anatomy. New tridimensional methods using SPECT and SPECT/CT have been introduced, including semiautomatic lung segmentation software. The present study evaluated inter- and intraobserver agreement on quantification using SPECT/CT software and compared the results for regional lung contribution obtained with SPECT/CT and planar scintigraphy. Methods: Thirty lung cancer patients underwent ventilation-perfusion scintigraphy with 99m Tc-macroaggregated albumin and 99m Tc-Technegas. The regional lung contribution to perfusion and ventilation was measured on both planar scintigraphy and SPECT/CT using semiautomatic lung segmentation software by 2 observers. Interobserver and intraobserver agreement for the SPECT/CT software was assessed using the intraclass correlation coefficient, Bland-Altman plots, and absolute differences in measurements. Measurements from planar and tridimensional methods were compared using the paired-sample t test and mean absolute differences. Results: Intraclass correlation coefficients were in the excellent range (above 0.9) for both interobserver and intraobserver agreement using the SPECT/CT software. Bland-Altman analyses showed very narrow limits of agreement. Absolute differences were below 2.0% in 96% of both interobserver and intraobserver measurements. There was a statistically significant difference between planar and SPECT/CT methods ( P < 0.001) for quantification of perfusion and ventilation for all right lung lobes, with a maximal mean absolute difference of 20.7% for the right middle lobe. There was no statistically significant difference in quantification of perfusion and ventilation for the left lung lobes using either method; however, absolute differences reached 12.0%. The total right and left lung contributions were similar for the two methods, with a mean difference of 1.2% for perfusion and 2.0% for ventilation. Conclusion: Quantification of regional lung perfusion and ventilation using SPECT/CT-based lung segmentation software is highly reproducible. This tridimensional method yields statistically significant differences in measurements for right lung lobes when compared with planar scintigraphy. We recommend that SPECT/CT-based quantification be used for all lung cancer patients undergoing pretherapy evaluation of regional lung function. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Characterization of the seven-day course of pulmonary response following unilateral lung acid injury in rats.

PubMed

Setzer, Florian; Schmidt, Barbara; Hueter, Lars; Schwarzkopf, Konrad; Sänger, Jörg; Schreiber, Torsten

2018-01-01

Aspiration of gastric acid is an important cause of acute lung injury. The time course of the pulmonary response to such an insult beyond the initial 48 hours is incompletely characterized. The purpose of this study was to comprehensively describe the pulmonary effects of focal lung acid injury over a seven day period in both directly injured and not directly injured lung tissue. Male Wistar rats underwent left-endobronchial instillation with hydrochloric acid and were sacrificed at 4, 24, 48, 96 or 168 h after the insult. Healthy non-injured animals served as controls. We assessed inflammatory cell counts and cytokine levels in right and left lung lavage fluid and blood, arterial oxygen tension, alterations in lung histology, lung wet-to-dry weight ratio and differential lung perfusion. Lung acid instillation induced an early strong inflammatory response in the directly affected lung, peaking at 4-24 hours, with only partial resolution after 7 days. A less severe response with complete resolution after 4 days was seen in the opposite lung. Alveolar cytokine levels, with exception of IL-6, only partially reflected the localization of lung injury and the time course of the functional and histologic alterations. Alveolar leucocyte subpopulations exhibited different time courses in the acid injured lung with persistent elevation of alveolar lymphocytes and macrophages. After acid instillation there was an early transient decrease in arterial oxygen tension and lung perfusion was preferentially distributed to the non-injured lung. These findings provide a basis for further research in the field of lung acid injury and for studies exploring effects of mechanical ventilation on injured lungs. Incomplete recovery in the directly injured lung 7 days after acid instillation suggests that increased vulnerability and susceptibility to further noxious stimuli are still present at that time.

Indirect measurement of lung density and air volume from electrical impedance tomography (EIT) data.

PubMed

Nebuya, Satoru; Mills, Gary H; Milnes, Peter; Brown, Brian H

2011-12-01

This paper describes a method for estimating lung density, air volume and changes in fluid content from a non-invasive measurement of the electrical resistivity of the lungs. Resistivity in Ω m was found by fitting measured electrical impedance tomography (EIT) data to a finite difference model of the thorax. Lung density was determined by comparing the resistivity of the lungs, measured at a relatively high frequency, with values predicted from a published model of lung structure. Lung air volume can then be calculated if total lung weight is also known. Temporal changes in lung fluid content will produce proportional changes in lung density. The method was implemented on EIT data, collected using eight electrodes placed in a single plane around the thorax, from 46 adult male subjects and 36 adult female subjects. Mean lung densities (±SD) of 246 ± 67 and 239 ± 64 kg m(-3), respectively, were obtained. In seven adult male subjects estimates of 1.68 ± 0.30, 3.42 ± 0.49 and 4.40 ± 0.53 l in residual volume, functional residual capacity and vital capacity, respectively, were obtained. Sources of error are discussed. It is concluded that absolute differences in lung density of about 30% and changes over time of less than 30% should be detected using the current technology in normal subjects. These changes would result from approximately 300 ml increase in lung fluid. The method proposed could be used for non-invasive monitoring of total lung air and fluid content in normal subjects but needs to be assessed in patients with lung disease.

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.

Prospective external convergence evaluation of two different quality-of-life instruments in lung resection patients.

PubMed

Pompili, Cecilia; Brunelli, Alessandro; Xiumé, Francesco; Refai, Majed; Salati, Michele; Socci, Laura; Di Nunzio, Luca; Sabbatini, Armando

2011-07-01

The interpretation of studies on quality of life (QoL) after lung surgery is often difficult owing to the use of multiple instruments with inconsistent scales and metrics. Although a more standardized approach would be desirable, the most appropriate instrument to be used in this setting is still largely undefined. The aim of the study was to assess the respective ability of two validated QoL instruments (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/L13 and Short Form (36) Health Survey (SF-36)) to detect perioperative changes in QoL of patients submitted to pulmonary resection for non-small-cell lung cancer (NSCLC). A prospective study on 33 consecutive patients (May 2009-December 2009) was submitted to pulmonary resection. All patients completed both EORTC QLQ-C30 with lung module 13 and SF-36 pre- and postoperatively (3 months). Preoperative changes of all SF-36 and EORTC scales were assessed by using the Cohen's effect-size method. External convergence between different instruments (SF-36 vs EORTC) was assessed by measuring the correlation of scales evaluating the same concepts (physical, psychosocial, and emotional). The correlation coefficients between standardized perioperative changes (effect sizes) of objective functional parameters (forced expiratory volume in 1s (FEV1) and diffusion lung capacity for carbon monoxide (DLCO)) and SF-36 or EORTC scales were also investigated. A poor correlation (r < 0.5) was detected between most of the scales of the two instruments measuring the same QoL concepts, indicating that they may be complementary in investigating different aspects of QoL. Only the SF-36 and EORTC social functioning scales and the SF-36 mental health and EORTC emotional functioning scales had a correlation coefficient >0.5. In general, EORTC was more sensitive in detecting physical or emotional declines but was more conservative in detecting improvements. Both SF-36 and EORTC showed poor correlations (r < 0.5) between perioperative changes in QoL and FEV1 or DLCO, confirming that objective parameters cannot be surrogates to the subjective perception of QoL. In particular, there was a poor correlation between perceived changes in dyspnea and objective changes in FEV1 or DLCO. EORTC behaved similarly to SF-36 in assessing perioperative changes in generic QoL scales, but, with the use of its lung module, provided a more detailed evaluation of specific symptoms. For this reason, EORTC should be regarded as the instrument of choice for measuring QoL in the thoracic surgery setting. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Respiratory symptoms and lung functional impairments associated with occupational exposure to asphalt fumes.

PubMed

Neghab, M; Zare Derisi, F; Hassanzadeh, J

2015-04-01

Controversy exists as to the potential of asphalt fumes to induce respiratory symptoms and lung functional impairments. To examine the respiratory effects, if any, of occupational inhalation exposure to asphalt fumes. In this cross-sectional study, 74 asphalt workers and 110 unexposed employees were investigated. The prevalence of respiratory symptoms among subjects was investigated by a standard questionnaire. Additionally, the parameters of pulmonary function were measured both, prior to exposure and at the end of work-shift. Furthermore, to assess the extent to which workers were exposed to asphalt fumes, total particulate and the benzene-soluble fraction were measured in different worksites. The mean levels of exposure to total particulate and benzene-soluble fraction in asphalt fumes were estimated to be 0.9 (SD 0.2) and 0.3 (SD 0.1) mg/m^3, respectively. Mean values of FEV1, both prior to the exposure (89.58% [SD 18.69%] predicted value) and at the end of shift (85.38% [SD 19.4%]), were significantly (p<0.05) smaller than those of the comparison subjects (93.88% [SD 13.93%]). Similarly, pre-shift (87.05 [SD 8.57]) and postexposure (89.95 [SD 6.85]) FEV1/FVC ratio were both significantly (p<0.01) lower than those of the unexposed employees (107.56 [SD 9.64]). Moreover, the prevalence of respiratory symptoms such as cough and wheezing in exposed employees were 41% and 42%, respectively. The corresponding values for comparison subjects were 10.0% and 3.6%, respectively (p<0.001). The pattern of changes in parameters of lung function in asphalt workers was consistent with that of chronic obstructive lung disease. Significant decrements in the parameters of pulmonary function as well as, a significant increase in the prevalence of respiratory symptoms in asphalt paving workers compared to their unexposed counterparts provided evidence in favor of a significant association between exposure to asphalt fumes and lung function impairments.

Children with Chronic Lung Disease: Facilitating Smoking Cessation for their Caregivers.

PubMed

Bacewicz, Aleksandra; Wang, Wei; Ashouri, Judy; ElMallah, Mai K

2015-06-01

Through a QI project at a tertiary referral pediatric pulmonary center, our objective was to establish a methodical approach to identify and engage smoking parents of children with chronic lung disease in a smoking cessation program. We hypothesized that smoking caregivers of children with chronic lung disease would be more motivated to enroll in a smoking cessation program when referred from tertiary pediatric pulmonary center. We assessed smoking habits and interest in quitting of parents with surveys. Parents ready to quit within 30 days were referred to the Florida Quitline from clinic. Pulmonary function tests, exacerbations, hospitalizations and need for prednisone or antibiotics were obtained from the patient charts and surveys. Follow-up two to 6 months later assessed the quit rate and child's clinical well-being and lung function. A standard mechanism to identify caregivers who smoked was established by engaging our medical assistants through a prompt in our EMR system. Out of those caregivers who were identified as smokers and accompanied their children to clinic, 52% were interested in a referral to the Florida Quitline. Out of those, only 12% successfully completed the program and ceased to smoke. The Florida Quitline was unable to reach the majority of parents who were referred to them. The majority of those referred to the Ouitline were not successfully contacted or enrolled in the program. The current procedure for referring and enrolling individuals to the Quitline is not effective for our population, but compares to the national average.

Is sweat chloride predictive of severity of cystic fibrosis lung disease assessed by chest computed tomography?

PubMed

Caudri, Daan; Zitter, David; Bronsveld, Inez; Tiddens, Harm

2017-09-01

Cystic Fibrosis (CF) lung disease is characterized by a marked heterogeneity. Sweat chloride-level is a functional marker of the CF Transmembrane Regulator (CFTR) protein and could be an important predictor of later disease severity. In this retrospective analysis children from the Rotterdam CF clinic with available sweat chloride level at diagnosis and at least one routine spirometry-controlled volumetric chest CT scan in follow-up were included. CT scans were scored using the CF-CT scoring system (% of maximum). Associations between sweat chloride-levels and CF-CT scores were calculated using linear regression models, adjusting for age at sweat test and age at follow-up. Because structural lung damage develops over the course of many years, effect modification by the age at follow-up CT-scan was tested for by age-stratification. In 59 children (30 male) sweat chloride was measured at diagnosis (median age 0.5 years, range 0-13) and later chest CT performed (median age 14 years, range 6-18). Sweat chloride was associated with significantly higher CT-CT total score, bronchiectasis score, and mucus plugging score. Stratification for age at follow-up in tertiles showed this association remained only in the oldest age group (range 15-18 years). In that subgroup associations were found with all but one of the CF-CT subscores, as well as with all tested lung functions parameters. Sweat chloride-level is a significant predictor of CF lung disease severity as determined by chest CT and lung function. This association could only be demonstrated in children with follow-up to age 15 years and above. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2018-04-25

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

Fourier decomposition pulmonary MRI using a variable flip angle balanced steady-state free precession technique.

PubMed

Corteville, D M R; Kjïrstad, Å; Henzler, T; Zöllner, F G; Schad, L R

2015-05-01

Fourier decomposition (FD) is a noninvasive method for assessing ventilation and perfusion-related information in the lungs. However, the technique has a low signal-to-noise ratio (SNR) in the lung parenchyma. We present an approach to increase the SNR in both morphological and functional images. The data used to create functional FD images are usually acquired using a standard balanced steady-state free precession (bSSFP) sequence. In the standard sequence, the possible range of the flip angle is restricted due to specific absorption rate (SAR) limitations. Thus, using a variable flip angle approach as an optimization is possible. This was validated using measurements from a phantom and six healthy volunteers. The SNR in both the morphological and functional FD images was increased by 32%, while the SAR restrictions were kept unchanged. Furthermore, due to the higher SNR, the effective resolution of the functional images was increased visibly. The variable flip angle approach did not introduce any new transient artifacts, and blurring artifacts were minimized. Both a gain in SNR and an effective resolution gain in functional lung images can be obtained using the FD method in conjunction with a variable flip angle optimized bSSFP sequence. © 2014 Wiley Periodicals, Inc.

Lung volumes, ventricular function and pulmonary arterial flow in children operated on for left-sided congenital diaphragmatic hernia: long-term results.

PubMed

Abolmaali, Nasreddin; Koch, Arne; Götzelt, Knut; Hahn, Gabriele; Fitze, Guido; Vogelberg, Christian

2010-07-01

To compare MRI-based functional pulmonary and cardiac measurements in the long-term follow-up of children operated on for left-sided congenital diaphragmatic hernia (CDH) with age- and body size-matched healthy controls. Twelve children who received immediate postnatal surgery for closure of isolated left-sided CDH were included and received basic medical examinations, pulmonary function testing and echocardiography. MRI included measurement of lung volume, ventricular function assessment and velocity-encoded imaging of the pulmonary arteries and was compared with the data for 12 healthy children matched for age and body size. While patients' clinical test results were not suspicious, comparison between the MRI data for patients and those for healthy controls revealed significant differences. In patients, the volumes of the left lungs were increased and the tidal volume was larger on the right side. While the stroke volumes of both ventricles were reduced, heart rate and ejection fraction were increased. Flow, acceleration time and cross-sectional area of the left pulmonary artery were reduced. Functional MRI detected pulmonary and cardiac findings in the late follow-up of CDH children which may be missed by standard clinical methods and might be relevant for decisions regarding late outcome and treatment.

Predictors of deterioration of lung function in Polish children with cystic fibrosis.

PubMed

Olszowiec-Chlebna, Małgorzata; Koniarek-Maniecka, Agnieszka; Stelmach, Włodzimierz; Smejda, Katarzyna; Jerzyńska, Joanna; Majak, Paweł; Białas, Monika; Stelmach, Iwona

2016-04-01

Severity of lung disease varies in patients with the same CFTR genotype. It suggests that other factors affect the severity of cystic fibrosis (CF). The aim of the study was to identify risk factors that determine lung function decline in Polish cystic fibrosis children. The follow-up time was no less than 5 years of respiratory status observation based on the forced expiratory volume in 1 s value (FEV1). The socio-economic data, perinatal interview, presence of meconium ileus (MI), time of CF diagnosis, initiation of tobramycin inhalation solution (TIS), pancreatic function, sensitization to Aspergillus fumigatus, presence of impaired glucose tolerance (IGT) or diabetes mellitus, chronic bacterial colonization and number of exacerbations and hospitalizations were assessed. The mean age of 61 included children was 13.3 ±7.6 years. Delta F508 homozygosity was detected in 45.9%, 44.3% were delta F508 heterozygous, and 9.8% had other genotypes. FEV1 decline was observed among 20% of patients; the rest of the patients presented stable values of FEV1 during at least 5 years of observation. The most significant predictors related to the decline of FEV1 were presentation of MI (p = 0.0344), IGT (p = 0.0227), number of exacerbations (p = 0.0288), and early Pseudomonas aeruginosa (PA) chronic colonization (p = 0.0165) followed by late TIS initiation after the first detection of PA (p=0.0071). Neither time of diagnosis nor type of CFTR mutation was statistically significant as a predictor of lung deterioration. The presence of MI, IGT, chronic PA colonization, and number of exacerbations are risk factors for lung function deterioration.

Impact of hydrogel nanoparticle size and functionalization on in vivo behavior for lung imaging and therapeutics

PubMed Central

Liu, Yongjian; Ibricevic-Richardson, Aida; Cohen, Joel A.; Cohen, Jessica L.; Gunsten, Sean P.; Fréchet, Jean M. J.; Walter, Michael J.; Welch, Michael J.; Brody, Steven L.

2009-01-01

Polymer chemistry offers the possibility of synthesizing multifunctional nanoparticles which incorporate moieties that enhance diagnostic and therapeutic targeting of cargo delivery to the lung. However, since rules for predicting particle behavior following modification are not well defined, it is essential that probes for tracking fate in vivo are also included. Accordingly, we designed polyacrylamide-based hydrogel particles of differing sizes, functionalized with a nona-arginine cell-penetrating peptide (Arg9), and labeled with imaging components to assess lung retention and cellular uptake after intratracheal administration. Radiolabeled microparticles (1–5 µm diameter) and nanoparticles (20–40 nm diameter) without and with Arg9 showed diffuse airspace distribution by positron emission tomography imaging. Biodistribution studies revealed that particle clearance and extrapulmonary distribution was, in part, size dependent. Microparticles were rapidly cleared by mucociliary routes but unexpectedly, also through the circulation. In contrast, nanoparticles had prolonged lung retention enhanced by Arg9 and were significantly restricted to the lung. For all particle types, uptake was predominant in alveolar macrophages, and, to a lesser extent, lung epithelial cells. In general, particles did not induce local inflammatory responses, with the exception of microparticles bearing Arg9. Whereas microparticles may be advantageous for short-term applications, nano-sized particles constitute an efficient high-retention and non-inflammatory vehicle for the delivery of diagnostic imaging agents and therapeutics to lung airspaces and alveolar macrophages that can be enhanced by Arg9. Importantly, our results show that minor particle modifications may significantly impact in vivo behavior within the complex environments of the lung, underscoring the need for animal modeling. PMID:19852512

Anti-sFlt-1 Therapy Preserves Lung Alveolar and Vascular Growth in Antenatal Models of Bronchopulmonary Dysplasia.

PubMed

Wallace, Bradley; Peisl, Amelie; Seedorf, Gregory; Nowlin, Taylor; Kim, Christina; Bosco, Jennifer; Kenniston, Jon; Keefe, Dennis; Abman, Steven H

2018-03-15

Pregnancies complicated by antenatal stress, including preeclampsia (PE) and chorioamnionitis (CA), increase the risk for bronchopulmonary dysplasia (BPD) in preterm infants, but biologic mechanisms linking prenatal factors with BPD are uncertain. Levels of sFlt-1 (soluble fms-like tyrosine kinase 1), an endogenous antagonist to VEGF (vascular endothelial growth factor), are increased in amniotic fluid and maternal blood in PE and associated with CA. Because impaired VEGF signaling has been implicated in the pathogenesis of BPD, we hypothesized that fetal exposure to sFlt-1 decreases lung growth and causes abnormal lung structure and pulmonary hypertension during infancy. To test this hypothesis, we studied the effects of anti-sFlt-1 monoclonal antibody (mAb) treatment on lung growth in two established antenatal models of BPD that mimic PE and CA induced by intraamniotic (i.a.) injections of sFlt-1 or endotoxin, respectively. In experimental PE, mAb was administered by three different approaches, including antenatal treatment by either i.a. instillation or maternal uterine artery infusion, or by postnatal intraperitoneal injections. With each strategy, mAb therapy improved infant lung structure as assessed by radial alveolar count, vessel density, right ventricular hypertrophy, and lung function. As found in the PE model, the adverse lung effects of i.a. endotoxin were also reduced by antenatal or postnatal mAb therapy. We conclude that treatment with anti-sFlt-1 mAb preserves lung structure and function and prevents right ventricular hypertrophy in two rat models of BPD of antenatal stress and speculate that early mAb therapy may provide a novel strategy for the prevention of BPD.

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

PubMed Central

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

2013-01-01

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

Vitamin D deficiency causes airway hyperresponsiveness, increases airway smooth muscle mass, and reduces TGF‐β expression in the lungs of female BALB/c mice

PubMed Central

Foong, Rachel E.; Shaw, Nicole C.; Berry, Luke J.; Hart, Prue H.; Gorman, Shelley; Zosky, Graeme R.

2014-01-01

Abstract Vitamin D deficiency is associated with disease severity in asthma. We tested whether there is a causal association between vitamin D deficiency, airway smooth muscle (ASM) mass, and the development of airway hyperresponsiveness (AHR). A physiologically relevant mouse model of vitamin D deficiency was developed by raising BALB/c mice on vitamin D‐deficient or ‐replete diets. AHR was assessed by measuring lung function responses to increasing doses of inhaled methacholine. Five‐micron sections from formalin‐fixed lungs were used for ASM measurement and assessment of lung structure using stereological methods. Transforming growth factor (TGF)‐β levels were measured in bronchoalveolar lavage fluid (BALF). Lungs were dissected from embryonic day (E) 17.5 vitamin D‐deficient and ‐replete fetal mice for quantification of ASM density and relative gene expression of TGF‐β signaling pathway molecules. Eight‐week‐old adult vitamin D‐deficient female mice had significantly increased airway resistance and ASM in the large airways compared with controls. Vitamin D‐deficient female mice had a smaller lung volume, volume of parenchyma, and alveolar septa. Both vitamin D‐deficient male and female mice had reduced TGF‐β levels in BALF. Vitamin D deficiency did not have an effect on ASM density in E17.5 mice, however, expression of TGF‐β1 and TGF‐β receptor I was downregulated in vitamin D‐deficient female fetal mice. Decreased expression of TGF‐β1 and TGF‐β receptor I during early lung development in vitamin D‐deficient mice may contribute to airway remodeling and AHR in vitamin D‐deficient adult female mice. This study provides a link between vitamin D deficiency and respiratory symptoms in chronic lung disease. PMID:24760528

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

PubMed

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

2012-06-01

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

Ex vivo rehabilitation of non-heart-beating donor lungs in preclinical porcine model: delayed perfusion results in superior lung function.

PubMed

Mulloy, Daniel P; Stone, Matthew L; Crosby, Ivan K; Lapar, Damien J; Sharma, Ashish K; Webb, David V; Lau, Christine L; Laubach, Victor E; Kron, Irving L

2012-11-01

Ex vivo lung perfusion (EVLP) is a promising modality for the evaluation and treatment of marginal donor lungs. The optimal timing of EVLP initiation and the potential for rehabilitation of donor lungs with extended warm ischemic times is unknown. The present study compared the efficacy of different treatment strategies for uncontrolled non-heart-beating donor lungs. Mature swine underwent hypoxic arrest, followed by 60 minutes of no-touch warm ischemia. The lungs were harvested and flushed with 4°C Perfadex. Three groups (n = 5/group) were stratified according to the preservation method: cold static preservation (CSP; 4 hours of 4°C storage), immediate EVLP (I-EVLP: 4 hours EVLP at 37°C), and delayed EVLP (D-EVLP; 4 hours of CSP followed by 4 hours of EVLP). The EVLP groups were perfused with Steen solution supplemented with heparin, methylprednisolone, cefazolin, and an adenosine 2A receptor agonist. The lungs then underwent allotransplantation and 4 hours of recipient reperfusion before allograft assessment for resultant ischemia-reperfusion injury. The donor blood oxygenation (partial pressure of oxygen/fraction of inspired oxygen ratio) before death was not different between the groups. The oxygenation after transplantation was significantly greater in the D-EVLP group than in the I-EVLP or CSP groups. The mean airway pressure, pulmonary artery pressure, and expression of interleukin-8, interleukin-1β, and tumor necrosis factor-α were all significantly reduced in the D-EVLP group. Post-transplant oxygenation exceeded the acceptable clinical levels only in the D-EVLP group. Uncontrolled non-heart-beating donor lungs with extended warm ischemia can be reconditioned for successful transplantation. The combination of CSP and EVLP in the D-EVLP group was necessary to obtain optimal post-transplant function. This finding, if confirmed clinically, will allow expanded use of nonheart-beating donor lungs. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

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.

SU-D-202-01: Functional Lung Avoidance and Response-Adaptive Escalation (FLARE) RT: Feasibility of a Precision Radiation Oncology Strategy

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

Bowen, S; Lee, E; Miyaoka, R

Purpose: NSCLC patient RT is planned without consideration of spatial heterogeneity in lung function or tumor response, which may have contributed to failed uniform dose escalation in a randomized trial. The feasibility of functional lung avoidance and response-adaptive escalation (FLARE) RT to reduce dose to [{sup 99m}Tc]MAA-SPECT/CT perfused lung while redistributing 74Gy within [{sup 18}F]FDG-PET/CT biological target volumes was assessed. Methods: Eight Stage IIB–IIIB NSCLC patients underwent FDG-PET/CT and MAA-SPECT/CT treatment planning scans. Perfused lung objectives were derived from scatter/collimator/attenuation-corrected MAA-SPECT uptake relative to ITV-subtracted lung to maintain <20Gy mean lung dose (MLD). Prescriptions included 60Gy to PTV and concomitantmore » boost of 74Gy mean to biological target volumes (BTV=GTV+PET margin) scaled to each BTV voxel by relative FDG-PET SUV. Dose-painting-by-numbers prescriptions were integrated into commercial TPS via previously reported ROI discretization. Dose constraints for lung, heart, cord, and esophagus were defined. FLARE RT plans were optimized with VMAT, proton pencil beam scanning (PBS) with 3%-3mm robust optimization, and combination PBS (avoidance) plus VMAT (escalation). Dosimetric differences were evaluated by Friedman non-parametric paired test with multiple sampling correction. Results: PTV and normal tissue objectives were not violated in 24 FLARE RT plans. Population median of mean BTV dose was 73.7Gy (68.5–75.5Gy), mean FDG-PET peak dose was 89.7Gy (73.5–103Gy), MLD was 12.3Gy (7.5–19.6Gy), and perfused MLD was 4.8Gy (0.9–12.1Gy). VMAT achieved higher dose to the FDG-PET peak subvolume (p=0.01), while PBS delivered lower dose to lung (p<0.001). Voxelwise linear correlation between BTV dose and FDG-PET uptake was higher for VMAT (R=0.93) and PBS+VMAT (R=0.94) compared to PBS alone (R=0.89). Conclusion: FLARE RT is feasible with VMAT and PBS. A combination of PBS for functional lung avoidance and VMAT for FDG-PET dose escalation balances target/normal tissue objective tradeoffs. These results support future testing of FLARE RT safety and efficacy within a precision radiation oncology trial. This work was supported by a Research Scholar grant from the Radiological Society of North American Research & Education Foundation.« less

Oscillation mechanics of the respiratory system.

PubMed

Bates, Jason H T; Irvin, Charles G; Farré, Ramon; Hantos, Zoltán

2011-07-01

The mechanical impedance of the respiratory system defines the pressure profile required to drive a unit of oscillatory flow into the lungs. Impedance is a function of oscillation frequency, and is measured using the forced oscillation technique. Digital signal processing methods, most notably the Fourier transform, are used to calculate impedance from measured oscillatory pressures and flows. Impedance is a complex function of frequency, having both real and imaginary parts that vary with frequency in ways that can be used empirically to distinguish normal lung function from a variety of different pathologies. The most useful diagnostic information is gained when anatomically based mathematical models are fit to measurements of impedance. The simplest such model consists of a single flow-resistive conduit connecting to a single elastic compartment. Models of greater complexity may have two or more compartments, and provide more accurate fits to impedance measurements over a variety of different frequency ranges. The model that currently enjoys the widest application in studies of animal models of lung disease consists of a single airway serving an alveolar compartment comprising tissue with a constant-phase impedance. This model has been shown to fit very accurately to a wide range of impedance data, yet contains only four free parameters, and as such is highly parsimonious. The measurement of impedance in human patients is also now rapidly gaining acceptance, and promises to provide a more comprehensible assessment of lung function than parameters derived from conventional spirometry. © 2011 American Physiological Society.

Low-grade systemic inflammation: a partial mediator of the relationship between diabetes and lung function.

PubMed

Giovannelli, Jonathan; Trouiller, Philippe; Hulo, Sébastien; Chérot-Kornobis, Natalie; Ciuchete, Alina; Edmé, Jean-Louis; Matran, Régis; Amouyel, Philippe; Meirhaeghe, Aline; Dauchet, Luc

2018-01-01

An association has been consistently found between diabetes mellitus and decreased lung function. We evaluated to what extent low-grade inflammation (as measured by the level of high-sensitivity C-reactive protein [hs-CRP]) could explain this relationship. A sample of 1878 middle-aged adults from the cross-sectional Enquête Littoral Souffle Air Biologie Environnement survey without self-reported pulmonary and atherosclerosis disease was included. A mediation analysis was performed to assess and quantify the hs-CRP level as a mediator of the relationship between diabetes and lung function. Diabetes was associated with higher hs-CRP level (+22.9%, 95% confidence interval = [5.1, 43.6]). The hs-CRP (>4 vs. ≤1 mg/L) was associated with lower percentage predicted values for the forced expiratory volume in the first second (FEV1) (-4% [-6.1, -1.9]) and forced vital capacity (FVC) (-4.4% [-6.5, -2.3]). Diabetes was associated with FEV1 (-3.5% [-5.8, -1.3]) and FVC (-3.6% [-5.9, -1.3]). The proportion of the effect that is mediated by hs-CRP was 12% [2.4, 37] and 13% [3.7, 39.4] for FEV1 and FVC, respectively. Our results suggest that low-grade systemic inflammation could only explain a small part of the relationship between diabetes and lung function. Copyright © 2017 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

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

Prevalence of respiratory symptoms and disorders among rice mill workers in India.

PubMed

Ghosh, Tirthankar; Gangopadhyay, Somnath; Das, Banibrata

2014-05-01

Lung function tests have become an integral part of assessment of pulmonary disease. Diseases of the respiratory system induced by occupational dusts are influenced by the duration of exposure. The aim of the study is to investigate the impairment of lung function and prevalence of respiratory symptoms among the rice mill workers. A total of 120 rice mill workers from three districts of Karnataka were included in this study. Fifty urban dwellers from the same socio-economic level were selected as controls. The study included clinical examination, assessment of respiratory symptoms, pulmonary function test, measurement of peak expiratory flow rate, absolute eosinophil count, ESR estimation, total IgE estimation and radiographic test. The present study has shown that the rice mill workers complained of several types of respiratory disorders like phlegm (40.8 %), dyspnea (44.2 %), chest tightness (26.7 %), cough (21.7 %), and nose irritation (27.5 %). Rice mill workers exposed to dust presented significantly (p < 0.05) lower levels of FVC (3.44 ± 0.11), FEV1 (2.73 ± 0.15) and PEFR (304.95 ± 28.79) than the controls. The rice mill workers are having significantly higher absolute eosinophil counts, total IgE and ESR than control groups. The hematological findings suggest that the harmful effects may be linked to both non-specific irritation and allergic responses to rice husk dust among rice mill workers. Dust exposure in the working environment affects the lung function values and increased the respiratory symptoms among the rice mill workers.

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

[Chronic pulmonary diseases: point of view of partners and their assessments with regard to the effects of lung sports].

PubMed

Nell, C; Kehr, K; Hildebrandt, O; Sohrabi, K; Cassel, W; Greulich, T; Koehler, K-I; Koehler, U

2011-12-01

Chronic diseases of the respiratory organs have, besides restrictions of lung function, also physical, mental and social consequences. The chronic disease impacts negatively not only the patient's own quality of life but also that of his/her partner and/or relative. As treatment modalities, besides drug therapy, above all outpatient rehabilitation measures have proved to be effective. In this pilot study we sought answers to three questions: (i) How is the quality of life of the patient's partner and/or relative influenced by the disease? How does the partner/relative assess the effect of the disease on the chronically ill patient? How does the partner/relative assess the effect of lung sports on the chronically ill patient? A specially conceived questionnaire was given to the partners/relatives of 25 patients with chronic pulmonary diseases. The patients, 23 with chronic obstructive pulmonary disease and 2 with pulmonary fibrosis, have been participating in lung sports once a week for more than three years. The average age of the patients was 67 years. The patients' illness also negatively influenced the quality of life of the partner to a considerable extent. The impact of the patients' pulmonary disease on the healthy partner was assessed as being rather moderate. Restrictions of social life were essentially influenced by the amount of assistance required by the pulmonary patient. The therapeutic effects of lung sports on the well-being of the patient were aways considered to be positive by the respective partner/relatives. A chronic pulmonary illness also has a negative influence on the partner/relative's quality of life. The necessity for extensive assistance in daily life is accompanied by a considerable negative impact on the partner's quality of life. According to the opinion of the partner/relative, lung sports have positive effects in all of the chronically ill patient's fields of life. © Georg Thieme Verlag KG Stuttgart · New York.

Volumetric dynamic oxygen-enhanced MRI (OE-MRI): comparison with CT Brody score and lung function in cystic fibrosis patients.

PubMed

Martini, K; Gygax, C M; Benden, C; Morgan, A R; Parker, G J M; Frauenfelder, T

2018-04-13

To demonstrate, in patients with cystic fibrosis (CF), the correlation between three-dimensional dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) measurements and computed tomography Brody score (CF-CT) and lung function testing (LFT). Twenty-one patients (median age, 25 years; female, n = 8) with a range of CF lung disease and five healthy volunteers (median age, 31 years; female, n = 2) underwent OE-MRI performed on a 1.5-T MRI scanner. Coronal volumes were acquired while patients alternately breathed room air and 100% oxygen. Pre-oxygen T 1 was measured. Dynamic series of T 1 -weighted volumes were then obtained while breathing oxygen. T 1 -parameter maps were generated and the following OE-MRI parameters were measured: oxygen uptake (ΔPO 2max ), wash-in time and wash-out time. High-resolution CT and LFT were performed. The relationship between CF-CT, LFT and OE-MRI parameters were evaluated using Pearson correlation for the whole lung and regionally. Mean CF-CT was 24.1±17.1. Mean ΔPO 2max and mean wash-in as well as skewness of wash-out showed significant correlation with CF-CT (ΔPO 2max : r = -0.741, p < 0.001; mean wash-in: r = 0.501, p = 0.017; skewness of wash-out: r = 0.597, p = 0.001). There was significant correlation for the whole lung and regionally between LFT parameters and OE-MR (ΔPO 2max : r = 0.718, p < 0.001; wash-in: r = -0.576, p = 0.003; wash-out skewness: r = -0.552, p = 0.004). Functional lung imaging using OE-MRI has the capability to assess the severity of CF lung disease and shows a significant correlation with LFT and CF-CT. • Oxygen-enhanced MRI might play a future role in evaluation and follow-up of cystic fibrosis. • Heterogeneity of parameter maps reflects localised functional impairment in cystic fibrosis. • Avoidance of cumulative radiation burden in CF is feasible using OE-MRI.

Short and long-term effects of supervised versus unsupervised exercise training on health-related quality of life and functional outcomes following lung cancer surgery - a randomized controlled trial.

PubMed

Brocki, Barbara Cristina; Andreasen, Jane; Nielsen, Lene Rodkjaer; Nekrasas, Vytautas; Gorst-Rasmussen, Anders; Westerdahl, Elisabeth

2014-01-01

Surgical resection enhances long-term survival after lung cancer, but survivors face functional deficits and report on poor quality of life long time after surgery. This study evaluated short and long-term effects of supervised group exercise training on health-related quality of life and physical performance in patients, who were radically operated for lung cancer. A randomized, assessor-blinded, controlled trial was performed on 78 patients undergoing lung cancer surgery. The intervention group (IG, n=41) participated in supervised out-patient exercise training sessions, one hour once a week for ten weeks. The sessions were based on aerobic exercises with target intensity of 60-80% of work capacity, resistance training and dyspnoea management. The control group (CG, n=37) received one individual instruction in exercise training. Measurements consisted of: health-related quality of life (SF36), six minute walk test (6MWT) and lung function (spirometry), assessed three weeks after surgery and after four and twelve months. Both groups were comparable at baseline on demographic characteristic and outcome values. We found a statistically significant effect after four months in the bodily pain domain of SF36, with an estimated mean difference (EMD) of 15.3 (95% CI:4 to 26.6, p=0.01) and a trend in favour of the intervention for role physical functioning (EMD 12.04, 95% CI: -1 to 25.1, p=0.07) and physical component summary (EMD 3.76, 95% CI:-0.1 to 7.6, p=0.06). At 12 months, the tendency was reversed, with the CG presenting overall slightly better measures. We found no effect of the intervention on 6MWT or lung volumes at any time-point. Supervised compared to unsupervised exercise training resulted in no improvement in health-related quality of life, except for the bodily pain domain, four months after lung cancer surgery. No effects of the intervention were found for any outcome after one year. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Computational modeling of the obstructive lung diseases asthma and COPD

PubMed Central

2014-01-01

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow limitation and pose a huge burden to society. These obstructive lung diseases impact the lung physiology across multiple biological scales. Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways. These changes are propagated upwards to the organ level again and vice versa. In order to understand the pathophysiology behind these diseases we need to integrate and understand changes occurring across these scales and this is the driving force for multiscale computational modeling. There is an urgent need for improved diagnosis and assessment of obstructive lung diseases. Standard clinical measures are based on global function tests which ignore the highly heterogeneous regional changes that are characteristic of obstructive lung disease pathophysiology. Advances in scanning technology such as hyperpolarized gas MRI has led to new regional measurements of ventilation, perfusion and gas diffusion in the lungs, while new image processing techniques allow these measures to be combined with information from structural imaging such as Computed Tomography (CT). However, it is not yet known how to derive clinical measures for obstructive diseases from this wealth of new data. Computational modeling offers a powerful approach for investigating this relationship between imaging measurements and disease severity, and understanding the effects of different disease subtypes, which is key to developing improved diagnostic methods. Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone. Computational models offer a complementary method to unravel the structure-function relationships occurring within a multiscale, multiphysics system such as this. Here we review the current state-of-the-art in techniques developed for pulmonary image analysis, development of structural models of the respiratory system and predictions of function within these models. We discuss application of modeling techniques to obstructive lung diseases, namely asthma and emphysema and the use of models to predict response to therapy. Finally we introduce a large European project, AirPROM that is developing multiscale models to investigate structure-function relationships in asthma and COPD. PMID:25471125

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

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

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

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

Budget impact of everolimus for the treatment of progressive, well-differentiated, non-functional neuroendocrine tumors of gastrointestinal or lung origin that are advanced or metastatic.

PubMed

Rose, Darya B; Nellesen, Dave; Neary, Maureen P; Cai, Beilei

2017-04-01

Advanced neuroendocrine tumors (NETs) are a rare malignancy with considerable need for effective therapies. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2016 for treatment of adults with progressive, well-differentiated, non-functional NETs of gastrointestinal (GI) or lung origin that are unresectable, locally advanced, or metastatic. To assess the 3-year budget impact for a typical US health plan following availability of everolimus for treatment of GI and lung NETs. Methods An economic model was developed that considered two perspectives: an entire health plan and a pharmacy budget. The total budget impact included costs of drug therapies, administration, hospitalizations, physician visits, monitoring, and adverse events (AEs). The pharmacy model only considered drug costs. In a US health plan with 1 million members, the model estimated 66 patients with well-differentiated, non-functional, and advanced or metastatic GI NETs and 20 with lung NETs undergoing treatment each year. Total budget impact in the first through third year after FDA approval ranged from $0.0568-$0.1443 per member per month (PMPM) for GI NETs and from $0.0181-$0.0355 PMPM for lung NETs. The total budget impact was lower than the pharmacy budget impact because it included cost offsets from administration and AE management for everolimus compared with alternative therapies (e.g. chemotherapies). Because GI and lung NETs are rare diseases with limited published data, several assumptions were made that may influence interpretation of results. The budget impact for everolimus was minimal in this rare disease area with a high unmet need, largely due to low disease prevalence. These results should be considered in the context of significant clinical benefits potentially provided by everolimus, including significantly longer progression-free survival (PFS) for advanced GI and lung NET patients.

Relationship between birth weight, maternal smoking during pregnancy and childhood and adolescent lung function: A path analysis.

PubMed

Balte, Pallavi; Karmaus, Wilfried; Roberts, Graham; Kurukulaaratchy, Ramesh; Mitchell, Frances; Arshad, Hasan

2016-12-01

Low birth weight and gestational maternal smoking have been linked with reduced lung function in children in many cross sectional studies. However, these associations have not yet been assessed with repeated measurements of lung function. Our aim was to investigate the effects of birth weight, gestational age, and gestational maternal smoking on lung function in children at age 10 and 18 years. In the Isle of Wight birth cohort spirometry was performed at age 10 and 18 years. Information on birth weight and gestational age were obtained from hospital records. Mothers were asked about smoking during pregnancy. We employed linear mixed models to estimate the effect of these risk factors on repeated measurements of lung function. We considered maternal asthma, sex, neonatal intensive care unit admission, height, socio-economic status, personal smoking in participants at age 18, body mass index and environmental tobacco smoke exposure as potential confounders. Finally, we used path analysis to determine links between birth weight, gestational age and gestational maternal smoking on lung function at age 10 and 18 years. Linear mixed models showed that with every 1 kg increase in birth weight, Forced expiratory volume in one second (FEV 1 ) increased by 42.6 ± 17.2 mL and Forced expiratory flow between 25% and 75% (FEF 25-75 ) of Forced vital capacity (FVC) increased by 95.5 ± 41.2 mL at age 18 years after adjusting for potential confounders. Path analysis suggested that birth weight had positive direct effects on FEV 1 and FEF 25-75 and positive indirect effect on FVC at 10 years which were carried forward to 18 years. Additionally, results also suggested a positive association between gestational age and FEV 1 , FVC and FEF 25-75  at ages 10 and 18 years and an inverse association between gestational smoke exposure and FEV 1 /FVC ratio and FEF 25-75  at age 18 years. Higher birth weight and gestational age were associated with higher FEV 1 , FVC and FEF 25-75 and maternal smoking during pregnancy was associated with reduced FEV 1 /FVC ratio and FEF 25-75 . The use of path analysis can improve our understanding of underlying "causal" pathways among different prenatal and childhood factors that affect lung function in both pre-adolescent and adolescent periods. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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

PubMed

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

2017-09-01

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

Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats.

PubMed

Zeidler-Erdely, Patti C; Meighan, Terence G; Erdely, Aaron; Fedan, Jeffrey S; Thompson, Janet A; Bilgesu, Suzan; Waugh, Stacey; Anderson, Stacey; Marshall, Nikki B; Afshari, Aliakbar; McKinney, Walter; Frazer, David G; Antonini, James M

2014-10-01

Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m³ to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (R(L)) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline R(L) was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased R(L) and result in endothelial dysfunction, but otherwise had minor effects on the lung.

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

PubMed

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

2010-06-01

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

[Pulmonary rehabilitation after total laryngectomy using a heat and moisture exchanger (HME)].

PubMed

Lorenz, K J; Maier, H

2009-08-01

A complete removal of the larynx has profound consequences for a patient. Since laryngectomy involves the separation of the upper airway from the lower airway, it not only implies a loss of the voice organ but also leads to chronic lung problems such as increased coughing, mucus production and expectoration. In addition, laryngectomees complain of fatigue, sleeping problems, a reduced sense of smell and taste, and a loss of social contact. A heat and moisture exchanger (HME) cassette can replace a function of the upper airway which consists in conditioning inspired air. It can improve pulmonary symptoms in three ways. 1. An HME cassette heats and moisturises inhaled air and thus creates nearly physiological conditions in the region of the deep airway. 2. The use of an HME cassette leads to an increase in breathing resistance, thereby reducing dynamic airway compression and improving lung ventilation. 3. An HME cassette acts as a filter and removes larger particles from incoming air. This review examines the current understanding of lung physiology after laryngectomy and assesses the effects of HME cassettes on the conditioning of respiratory air, lung function and psychosocial problems. Georg Thieme Verlag KG Stuttgart, New York.

Lungs in Heart Failure

PubMed Central

Apostolo, Anna; Giusti, Giuliano; Gargiulo, Paola; Bussotti, Maurizio; Agostoni, Piergiuseppe

2012-01-01

Lung function abnormalities both at rest and during exercise are frequently observed in patients with chronic heart failure, also in the absence of respiratory disease. Alterations of respiratory mechanics and of gas exchange capacity are strictly related to heart failure. Severe heart failure patients often show a restrictive respiratory pattern, secondary to heart enlargement and increased lung fluids, and impairment of alveolar-capillary gas diffusion, mainly due to an increased resistance to molecular diffusion across the alveolar capillary membrane. Reduced gas diffusion contributes to exercise intolerance and to a worse prognosis. Cardiopulmonary exercise test is considered the “gold standard” when studying the cardiovascular, pulmonary, and metabolic adaptations to exercise in cardiac patients. During exercise, hyperventilation and consequent reduction of ventilation efficiency are often observed in heart failure patients, resulting in an increased slope of ventilation/carbon dioxide (VE/VCO2) relationship. Ventilatory efficiency is as strong prognostic and an important stratification marker. This paper describes the pulmonary abnormalities at rest and during exercise in the patients with heart failure, highlighting the principal diagnostic tools for evaluation of lungs function, the possible pharmacological interventions, and the parameters that could be useful in prognostic assessment of heart failure patients. PMID:23365739

Effects of symptom clusters and depression on the quality of life in patients with advanced lung cancer.

PubMed

Choi, S; Ryu, E

2018-01-01

People with advanced lung cancer experience later symptoms after treatment that is related to poorer psychosocial and quality of life (QOL) outcomes. The purpose of this study was to identify the effect of symptom clusters and depression on the QOL of patients with advanced lung cancer. A sample of 178 patients with advanced lung cancer at the National Cancer Center in Korea completed a demographic questionnaire, the M.D. Anderson Symptom Inventory-Lung Cancer, the Center for Epidemiological Studies Depression Scale, and the Functional Assessment of Cancer Therapy-General scale. The most frequently experienced symptom was fatigue, anguish was the most severe symptom-associated distress, and 28.9% of participants were clinically depressed. Factor analysis was used to identify symptom clusters based on the severity of patients' symptom experiences. Three symptom clusters were identified: treatment-associated, lung cancer and psychological symptom clusters. The regression model found a significant negative impact on QOL for depression and lung cancer symptom cluster. Age as the control variable was found to be significant impact on QOL. Therefore, psychological screening and appropriate intervention is an essential part of advanced cancer care. Both pharmacological and non-pharmacological approaches for alleviating depression may help to improve the QOL of lung cancer patients. © 2016 John Wiley & Sons Ltd.

Lung parenchymal analysis on dynamic MRI in thoracic insufficiency syndrome to assess changes following surgical intervention

NASA Astrophysics Data System (ADS)

Jagadale, Basavaraj N.; Udupa, Jayaram K.; Tong, Yubing; Wu, Caiyun; McDonough, Joseph; Torigian, Drew A.; Campbell, Robert M.

2018-02-01

General surgeons, orthopedists, and pulmonologists individually treat patients with thoracic insufficiency syndrome (TIS). The benefits of growth-sparing procedures such as Vertical Expandable Prosthetic Titanium Rib (VEPTR)insertionfor treating patients with TIS have been demonstrated. However, at present there is no objective assessment metricto examine different thoracic structural components individually as to their roles in the syndrome, in contributing to dynamics and function, and in influencing treatment outcome. Using thoracic dynamic MRI (dMRI), we have been developing a methodology to overcome this problem. In this paper, we extend this methodology from our previous structural analysis approaches to examining lung tissue properties. We process the T2-weighted dMRI images through a series of steps involving 4D image construction of the acquired dMRI images, intensity non-uniformity correction and standardization of the 4D image, lung segmentation, and estimation of the parameters describing lung tissue intensity distributions in the 4D image. Based on pre- and post-operative dMRI data sets from 25 TIS patients (predominantly neuromuscular and congenital conditions), we demonstrate how lung tissue can be characterized by the estimated distribution parameters. Our results show that standardized T2-weighted image intensity values decrease from the pre- to post-operative condition, likely reflecting improved lung aeration post-operatively. In both pre- and post-operative conditions, the intensity values decrease also from end-expiration to end-inspiration, supporting the basic premise of our results.

Variable mechanical ventilation

PubMed Central

Fontela, Paula Caitano; Prestes, Renata Bernardy; Forgiarini Jr., Luiz Alberto; Friedman, Gilberto

2017-01-01

Objective To review the literature on the use of variable mechanical ventilation and the main outcomes of this technique. Methods Search, selection, and analysis of all original articles on variable ventilation, without restriction on the period of publication and language, available in the electronic databases LILACS, MEDLINE®, and PubMed, by searching the terms "variable ventilation" OR "noisy ventilation" OR "biologically variable ventilation". Results A total of 36 studies were selected. Of these, 24 were original studies, including 21 experimental studies and three clinical studies. Conclusion Several experimental studies reported the beneficial effects of distinct variable ventilation strategies on lung function using different models of lung injury and healthy lungs. Variable ventilation seems to be a viable strategy for improving gas exchange and respiratory mechanics and preventing lung injury associated with mechanical ventilation. However, further clinical studies are necessary to assess the potential of variable ventilation strategies for the clinical improvement of patients undergoing mechanical ventilation. PMID:28444076

Consecutive Food and Respiratory Allergies Amplify Systemic and Gut but Not Lung Outcomes in Mice.

PubMed

Bouchaud, Gregory; Gourbeyre, Paxcal; Bihouée, Tiphaine; Aubert, Phillippe; Lair, David; Cheminant, Marie-Aude; Denery-Papini, Sandra; Neunlist, Michel; Magnan, Antoine; Bodinier, Marie

2015-07-22

Epidemiological data suggest a link between food allergies and the subsequent development of asthma. Although this progression may result from the additional effects of exposure to multiple allergens, whether both allergies amplify each other's effects remains unknown. This study investigated whether oral exposure to food allergens influences the outcomes of subsequent respiratory exposure to an asthma-inducing allergen. Mice were sensitized and orally challenged with wheat (FA) and then exposed to house dust mite (HDM) extract (RA). Immunoglobulin (Ig), histamine, and cytokine levels were assayed by ELISA. Intestinal and lung physiology was assessed. Ig levels, histamine release, and cytokine secretion were higher after exposure to both allergens than after separate exposure to each. Intestinal permeability was higher, although airway hyper-responsiveness and lung inflammation remained unchanged. Exposure to food and respiratory allergens amplifies systemic and gut allergy-related immune responses without any additional effect on lung function and inflammation.

Isolation and Characterization of Human Lung Lymphatic Endothelial Cells

PubMed Central

Lorusso, Bruno; Falco, Angela; Madeddu, Denise; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Gervasi, Andrea; Rinaldi, Laura; Lagrasta, Costanza; Maselli, Davide; Gnetti, Letizia; Silini, Enrico M.; Quaini, Eugenio; Ampollini, Luca; Carbognani, Paolo; Quaini, Federico

2015-01-01

Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy. PMID:26137493

Optical medical imaging: from glass to man

NASA Astrophysics Data System (ADS)

Bradley, Mark

2016-11-01

A formidable challenge in modern respiratory healthcare is the accurate and timely diagnosis of lung infection and inflammation. The EPSRC Interdisciplinary Research Collaboration (IRC) `Proteus' seeks to address this challenge by developing an optical fibre based healthcare technology platform that combines physiological sensing with multiplexed optical molecular imaging. This technology will enable in situ measurements deep in the human lung allowing the assessment of tissue function and characterization of the unique signatures of pulmonary disease and is illustrated here with our in-man application of Optical Imaging SmartProbes and our first device Versicolour.

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

Why does the lung hyperinflate?

PubMed

Ferguson, Gary T

2006-04-01

Patients with chronic obstructive pulmonary disease (COPD) often have some degree of hyperinflation of the lungs. Hyperinflated lungs can produce significant detrimental effects on breathing, as highlighted by improvements in patient symptoms after lung volume reduction surgery. Measures of lung volumes correlate better with impairment of patient functional capabilities than do measures of airflow. Understanding the mechanisms by which hyperinflation occurs in COPD provides better insight into how treatments can improve patients' health. Both static and dynamic processes can contribute to lung hyperinflation in COPD. Static hyperinflation is caused by a decrease in elasticity of the lung due to emphysema. The lungs exert less recoil pressure to counter the recoil pressure of the chest wall, resulting in an equilibrium of recoil forces at a higher resting volume than normal. Dynamic hyperinflation is more common and can occur independent of or in addition to static hyperinflation. It results from air being trapped within the lungs after each breath due to a disequilibrium between the volumes inhaled and exhaled. The ability to fully exhale depends on the degree of airflow limitation and the time available for exhalation. These can both vary, causing greater hyperinflation during exacerbations or increased respiratory demand, such as during exercise. Reversibility of dynamic hyperinflation offers the possibility for intervention. Use of bronchodilators with prolonged durations of action, such as tiotropium, can sustain significant reductions in lung inflation similar in effect to lung volume reduction surgery. How efficacy of bronchodilators is assessed may, therefore, need to be reevaluated.

Tuberculosis associates with both airflow obstruction and low lung function: BOLD results.

PubMed

Amaral, André F S; Coton, Sonia; Kato, Bernet; Tan, Wan C; Studnicka, Michael; Janson, Christer; Gislason, Thorarinn; Mannino, David; Bateman, Eric D; Buist, Sonia; Burney, Peter G J

2015-10-01

In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. The objective of the present study was to assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults.The study was performed in adults, aged 40 years and above, who took part in the multicentre, cross-sectional, general population-based Burden of Obstructive Lung Disease study, and had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high- and low/middle-income countries, according to gross national income.A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio 2.51, 95% CI 1.83-3.42) and spirometric restriction (adjusted odds ratio 2.13, 95% CI 1.42-3.19).A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common. Copyright ©ERS 2015.

Tuberculosis associates with both airflow obstruction and low lung function: BOLD results

PubMed Central

Amaral, André F. S.; Coton, Sonia; Kato, Bernet; Tan, Wan C.; Studnicka, Michael; Janson, Christer; Gislason, Thorarinn; Mannino, David; Bateman, Eric D.; Buist, Sonia; Burney, Peter G. J.

2015-01-01

Background In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. Objective To assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults. Methods The study was performed in adults, aged 40 and above, who took part in the multicentre cross-sectional, general population-based, Burden of Obstructive Lung Disease study, had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high and low/middle income countries, according to gross national income. Results A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio = 2.51, 95% confidence interval 1.83-3.42) and spirometric restriction (adjusted odds ratio = 2.13, 95% confidence interval 1.42-3.19). Conclusion A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common. PMID:26113680

HSP90 Inhibition Suppresses Lipopolysaccharide-Induced Lung Inflammation In Vivo

PubMed Central

Lilja, Andrew; Weeden, Clare E.; McArthur, Kate; Nguyen, Thao; Donald, Alastair; Wong, Zi Xin; Dousha, Lovisa; Bozinovski, Steve; Vlahos, Ross; Burns, Christopher J.; Asselin-Labat, Marie-Liesse; Anderson, Gary P.

2015-01-01

Inflammation is an important component of cancer diathesis and treatment-refractory inflammation is a feature of many chronic degenerative lung diseases. HSP90 is a 90kDa protein which functions as an ATP-dependent molecular chaperone that regulates the signalling conformation and expression of multiple protein client proteins especially oncogenic mediators. HSP90 inhibitors are in clinical development as cancer therapies but the myeleosuppressive and neutropenic effect of first generation geldanamycin-class inhibitors has confounded studies on the effects on HSP90 inhibitors on inflammation. To address this we assessed the ability of Ganetespib, a non-geldanamycin HSP90 blocker, to suppress lipopolysaccharide (LPS)-induced cellular infiltrates, proteases and inflammatory mediator and transcriptional profiles. Ganetespib (10–100mg/kg, i.v.) did not directly cause myelosuppression, as assessed by video micrography and basal blood cell count, but it strongly and dose-dependently suppressed LPS-induced neutrophil mobilization into blood and neutrophil- and mononuclear cell-rich steroid-refractory lung inflammation. Ganetespib also suppressed B cell and NK cell accumulation, inflammatory cytokine and chemokine induction and MMP9 levels. These data identify non-myelosuppresssive HSP90 inhibitors as potential therapies for inflammatory diseases refractory to conventional therapy, in particular those of the lung. PMID:25615645

Effects of Behavioral Activation on the Quality of Life and Emotional State of Lung Cancer and Breast Cancer Patients During Chemotherapy Treatment.

PubMed

Fernández-Rodríguez, Concepción; Villoria-Fernández, Erica; Fernández-García, Paula; González-Fernández, Sonia; Pérez-Álvarez, Marino

2017-12-01

Research suggests that the progressive abandonment of activities in cancer patients are related to depression and worse quality of life. Behavioral activation (BA) encourages subjects to activate their sources of reinforcement and modify the avoidance responses. This study assesses the effectiveness of BA in improving quality of life and preventing emotional disorders during chemotherapy treatment. One sample of lung cancer patients and another of breast cancer patients were randomized into a BA experimental group (E.G. lung/4sess . n = 50; E.G. breast/6sess . n = 33) and a control group (C.G. lung/4sess . n = 40; C.G. breast/6sess. n = 35), respectively. In each session and in follow-ups (3/6/9 months), all participants completed different assessment scales. The results converge to show the effectiveness of BA, encouraging cancer patients to maintain rewarding activities which can activate their sources of day-to-day reinforcement and modify their experience avoidance patterns. BA appears to be a practical intervention which may improve social and role functioning and the emotional state of cancer patients during chemotherapy treatment.

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

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

PubMed

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

2002-01-01

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

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

PubMed Central

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

2002-01-01

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

Effect of reducing indoor air pollution on women's respiratory symptoms and lung function: the RESPIRE Randomized Trial, Guatemala.

PubMed

Smith-Sivertsen, Tone; Díaz, Esperanza; Pope, Dan; Lie, Rolv T; Díaz, Anaite; McCracken, John; Bakke, Per; Arana, Byron; Smith, Kirk R; Bruce, Nigel

2009-07-15

Exposure to household wood smoke from cooking is a risk factor for chronic obstructive lung disease among women in developing countries. The Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) is a randomized intervention trial evaluating the respiratory health effects of reducing indoor air pollution from open cooking fires. A total of 504 rural Mayan women in highland Guatemala aged 15-50 years, all using traditional indoor open fires, were randomized to either receive a chimney woodstove (plancha) or continue using the open fire. Assessments of chronic respiratory symptoms and lung function and individual measurements of carbon monoxide exposure were performed at baseline and every 6 months up to 18 months. Use of a plancha significantly reduced carbon monoxide exposure by 61.6%. For all respiratory symptoms, reductions in risk were observed in the plancha group during follow-up; the reduction was statistically significant for wheeze (relative risk = 0.42, 95% confidence interval: 0.25, 0.70). The number of respiratory symptoms reported by the women at each follow-up point was also significantly reduced by the plancha (odds ratio = 0.7, 95% confidence interval: 0.50, 0.97). However, no significant effects on lung function were found after 12-18 months. Reducing indoor air pollution from household biomass burning may relieve symptoms consistent with chronic respiratory tract irritation.

The influence of inspiratory muscle training combined with the Pilates method on lung function in elderly women: A randomized controlled trial

PubMed Central

de Alvarenga, Guilherme Medeiros; Charkovski, Simone Arando; dos Santos, Larissa Kelin; da Silva, Mayara Alves Barbosa; Tomaz, Guilherme Oliveira; Gamba, Humberto Remigio

2018-01-01

OBJECTIVE: Aging is progressive, and its effects on the respiratory system include changes in the composition of the connective tissues of the lung that influence thoracic and lung compliance. The Powerbreathe® K5 is a device used for inspiratory muscle training with resistance adapted to the level of the inspiratory muscles to be trained. The Pilates method promotes muscle rebalancing exercises that emphasize the powerhouse. The aim of this study was to evaluate the influence of inspiratory muscle training combined with the Pilates method on lung function in elderly women. METHODS: The participants were aged sixty years or older, were active women with no recent fractures, and were not gait device users. They were randomly divided into a Pilates with inspiratory training group (n=11), a Pilates group (n=11) and a control group (n=9). Spirometry, manovacuometry, a six-minute walk test, an abdominal curl-up test, and pulmonary variables were assessed before and after twenty intervention sessions. RESULTS: The intervention led to an increase in maximal inspiratory muscle strength and pressure and power pulmonary variables (p<0.0001), maximal expiratory muscle strength (p<0.0014), six-minute walk test performance (p<0.01), and abdominal curl-up test performance (p<0.00001). The control group showed no differences in the analyzed variables (p>0.05). CONCLUSION: The results of this study suggest inspiratory muscle training associated with the Pilates method provides an improvement in the lung function and physical conditioning of elderly patients. PMID:29924184

Lung diffusion capacity in children with respiratory symptoms and untreated GERD.

PubMed

Mirić, Mirjana; Turkalj, Mirjana; Nogalo, Boro; Erceg, Damir; Perica, Marija; Plavec, Davor

2014-05-12

Gastroesophageal reflux disease (GERD) is associated with many respiratory disorders, among which, chronic cough, laryngitis, and asthma are among the most common. We investigated lung function, including gas diffusion capacity, in children with poor asthma control or chronic laryngitis with untreated GERD. A total of 71 children, aged 6-17 years, with chronic respiratory and other symptoms suggestive for GERD, were enrolled and divided into 2 groups: chronic laryngitis and asthma. Participants underwent 24-hour pH monitoring and lung function assessment, measurement of single-breath diffusing capacity of the lung for carbon monoxide (DLCO), and fraction of exhaled nitric oxide (FENO) measurement. 24-hour pH monitoring was positive for GERD in 92.1% of preselected children with asthma and 90.1% of children with chronic recurrent laryngitis. All flows (PEF, MEF75, MEF50, and MEF25) were significantly lower in the asthma group, while FENO and DLCO were significantly lower in the laryngitis group. A significant inverse relationship was found between DLCO and all reflux indexes in the laryngitis group. Each unit change of Johnson-DeMeester score and Boix-Ochoa score increased the odds for significantly lower DLCO in laryngitis patients by 3.9% and 5.5%, respectively. In children with uncontrolled asthma and chronic laryngitis, the regurgitation of gastric contents due to GERD contributes to poor asthma control and aggravation of chronic laryngitis. Despite having normal lung function, the gas diffusion capacity should be controlled in patients with GERD and chronic laryngitis, and it might be the very first abnormality in distal airways.

Rapid 3D in vivo 1H human lung respiratory imaging at 1.5 T using ultra-fast balanced steady-state free precession.

PubMed

Pusterla, Orso; Bauman, Grzegorz; Wielpütz, Mark O; Nyilas, Sylvia; Latzin, Philipp; Heussel, Claus P; Bieri, Oliver

2017-09-01

To introduce a reproducible, nonenhanced 1H MRI method for rapid in vivo functional assessment of the whole lung at 1.5 Tesla (T). At different respiratory volumes, the pulmonary signal of ultra-fast steady-state free precession (ufSSFP) follows an adapted sponge model, characterized by a respiratory index α. From the model, α reflects local ventilation-related information, is virtually independent from the lung density and thus from the inspiratory phase and breathing amplitude. Respiratory α-mapping is evaluated for healthy volunteers and patients with obstructive lung disease from a set of five consecutive 3D ultra-fast steady-state free precession (ufSSFP) scans performed in breath-hold and at different inspiratory volumes. For the patients, α-maps were compared with CT, dynamic contrast-enhanced MRI (DCE-MRI), and Fourier decomposition (FD). In healthy volunteers, respiratory α-maps showed good reproducibility and were homogeneous on iso-gravitational planes, but showed a gravity-dependent respiratory gradient. In patients with obstructive pulmonary disease, the functional impairment observed in respiratory α-maps was associated with emphysematous regions present on CT images, perfusion defects observable on DCE-MRI, and impairments visualized on FD ventilation and perfusion maps. Respiratory α-mapping derived from multivolumetric ufSSFP provides insights into functional lung impairment and may serve as a reproducible and normative measure for clinical studies. Magn Reson Med 78:1059-1069, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Biologic lung volume reduction in advanced upper lobe emphysema: phase 2 results.

PubMed

Criner, Gerard J; Pinto-Plata, Victor; Strange, Charlie; Dransfield, Mark; Gotfried, Mark; Leeds, William; McLennan, Geoffrey; Refaely, Yael; Tewari, Sanjiv; Krasna, Mark; Celli, Bartolome

2009-05-01

Biologic lung volume reduction (BioLVR) is a new endobronchial treatment for advanced emphysema that reduces lung volume through tissue remodeling. Assess the safety and therapeutic dose of BioLVR hydrogel in upper lobe predominant emphysema. Open-labeled, multicenter phase 2 dose-ranging studies were performed with BioLVR hydrogel administered to eight subsegmental sites (four in each upper lobe) involving: (1) low-dose treatment (n = 28) with 10 ml per site (LD); and (2) high-dose treatment (n = 22) with 20 ml per site (HD). Safety was assessed by the incidence of serious medical complications. Efficacy was assessed by change from baseline in pulmonary function tests, dyspnea score, 6-minute walk distance, and health-related quality of life. After treatment there were no deaths and four serious treatment-related complications. A reduction in residual volume to TLC ratio at 12 weeks (primary efficacy outcome) was achieved with both LD (-6.4 +/- 9.3%; P = 0.002) and HD (-5.5 +/- 9.4%; P = 0.028) treatments. Improvements in pulmonary function in HD (6 mo: DeltaFEV(1) = +15.6%; P = 0.002; DeltaFVC = +9.1%; P = 0.034) were greater than in LD patients (6 mo: DeltaFEV(1) = +6.7%; P = 0.021; DeltaFVC = +5.1%; P = 0.139). LD- and HD-treated groups both demonstrated improved symptom scores and health-related quality of life. BioLVR improves physiology and functional outcomes up to 6 months with an acceptable safety profile in upper lobe predominant emphysema. Overall improvement was greater and responses more durable with 20 ml per site than 10 ml per site dosing. Clinical trial registered with www.clinicaltrials.gov (NCT 00435253 and NCT 00515164).

Omalizumab Effectiveness by Biomarker Status in Patients with Asthma: Evidence From PROSPERO, A Prospective Real-World Study.

PubMed

Casale, Thomas B; Luskin, Allan T; Busse, William; Zeiger, Robert S; Trzaskoma, Benjamin; Yang, Ming; Griffin, Noelle M; Chipps, Bradley E

2018-05-22

Omalizumab has demonstrated efficacy in clinical trials of patients with asthma, but real-world data are needed. To assess outcomes after omalizumab initiation in patients with asthma in a real-world setting. Patients aged 12 years and older with allergic asthma who were candidates for omalizumab on the basis of physician-assessed need were enrolled in a US-based, prospective, single-arm, 48-week multicenter study, the Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab. Monthly assessments included exacerbations, health care utilization, asthma control test (ACT), and adverse events. At baseline, 6 months, and end of study, biomarkers (blood eosinophils and fractional exhaled nitric oxide) were collected and spirometry performed. Of 806 enrollees, 801 (99.4%) received omalizumab and 622 (77.2%) completed the study. The exacerbation rate significantly improved from a mean of 3.00 ± 3.28 in the 12 months before baseline to 0.78 ± 1.37 through month 12 (P < .001) and was similar in adults and adolescents; there was a reduction of 81.9% in the percentage of patients with 1 or more hospitalizations. Lung function remained generally unchanged. A mean improvement of 4.4 ± 4.9 in ACT scores was observed. Eighty-seven percent of patients were responders on the basis of clinical improvement in exacerbations, lung function, or ACT scores. Baseline biomarker status was associated with ACT scores and lung function improvement, but the magnitude of this improvement was not clinically relevant. No new safety signals emerged. Omalizumab initiation in patients with asthma resulted in improved exacerbation rates, reduced hospitalizations, and improved ACT scores compared with pretreatment values, regardless of biomarker status. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Cystic fibrosis gene modifier SLC26A9 modulates airway response to CFTR-directed therapeutics.

PubMed

Strug, Lisa J; Gonska, Tanja; He, Gengming; Keenan, Katherine; Ip, Wan; Boëlle, Pierre-Yves; Lin, Fan; Panjwani, Naim; Gong, Jiafen; Li, Weili; Soave, David; Xiao, Bowei; Tullis, Elizabeth; Rabin, Harvey; Parkins, Michael D; Price, April; Zuberbuhler, Peter C; Corvol, Harriet; Ratjen, Felix; Sun, Lei; Bear, Christine E; Rommens, Johanna M

2016-10-15

Cystic fibrosis is realizing the promise of personalized medicine. Recent advances in drug development that target the causal CFTR directly result in lung function improvement, but variability in response is demanding better prediction of outcomes to improve management decisions. The genetic modifier SLC26A9 contributes to disease severity in the CF pancreas and intestine at birth and here we assess its relationship with disease severity and therapeutic response in the airways. SLC26A9 association with lung disease was assessed in individuals from the Canadian and French CF Gene Modifier consortia with CFTR-gating mutations and in those homozygous for the common Phe508del mutation. Variability in response to a CFTR-directed therapy attributed to SLC26A9 genotype was assessed in Canadian patients with gating mutations. A primary airway model system determined if SLC26A9 shows modification of Phe508del CFTR function upon treatment with a CFTR corrector. In those with gating mutations that retain cell surface-localized CFTR we show that SLC26A9 modifies lung function while this is not the case in individuals homozygous for Phe508del where cell surface expression is lacking. Treatment response to ivacaftor, which aims to improve CFTR-channel opening probability in patients with gating mutations, shows substantial variability in response, 28% of which can be explained by rs7512462 in SLC26A9 (P = 0.0006). When homozygous Phe508del primary bronchial cells are treated to restore surface CFTR, SLC26A9 likewise modifies treatment response (P = 0.02). Our findings indicate that SLC26A9 airway modification requires CFTR at the cell surface, and that a common variant in SLC26A9 may predict response to CFTR-directed therapeutics.

Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome

PubMed Central

Feng, Xiaomei; Maze, Mervyn; Koch, Lauren G.; Britton, Steven L.; Hellman, Judith

2015-01-01

Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses. PMID:25978669

Cognitive function in chronic obstructive pulmonary disease: relationship to global initiative for chronic obstructive lung disease 2011 categories.

PubMed

Tulek, Baykal; Atalay, Nart Bedin; Yildirim, Gulfem; Kanat, Fikret; Süerdem, Mecit

2014-08-01

Recently, comorbidities such as impaired cognitive function have been attracting more focus when considering the management of chronic obstructive pulmonary disease (COPD). Here we investigated the relationship between cognitive function and the categories given in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in 2011. Specifically, after controlling for non-COPD covariates, we assessed the clinical features that may be predictive of cognitive impairment in patients with COPD. We recruited 119 stable patients with mild to very severe COPD. We administered a broad array of standardized neuropsychological tests that assessed cognitive functions in the domains of attention, memory, psychomotor coordination and language. Cognitive scores were significantly different between patients falling within GOLD 2011 categories. Scores were lower in patients with high future risk compared with low future risk. In parallel, there were significant differences in cognitive function between COPD patient subgroups when patients were grouped according to the forced expiratory volume in 1 s, exacerbation history and C-reactive protein levels. After controlling for non-COPD predictors, only exacerbation history remained a significant predictor of cognitive scores. The number of exacerbation events in a year may be used as a predictor of cognitive impairment in patients with COPD. © 2014 Asian Pacific Society of Respirology.

Childhood-Onset Asthma in Smokers. Association between CT Measures of Airway Size, Lung Function, and Chronic Airflow Obstruction

PubMed Central

Hardin, Megan E.; Come, Carolyn E.; San José Estépar, Raúl; Ross, James C.; Kurugol, Sila; Okajima, Yuka; Han, MeiLan K.; Kim, Victor; Ramsdell, Joe; Silverman, Edwin K.; Crapo, James D.; Lynch, David A.; Make, Barry; Barr, R. Graham; Hersh, Craig P.; Washko, George R.

2014-01-01

Rationale and Objectives: Asthma is associated with chronic airflow obstruction. Our goal was to assess the association of computed tomographic measures of airway wall volume and lumen volume with the FEV1 and chronic airflow obstruction in smokers with childhood-onset asthma. Methods: We analyzed clinical, lung function, and volumetric computed tomographic airway volume data from 7,266 smokers, including 590 with childhood-onset asthma. Small wall volume and small lumen volume of segmental airways were defined as measures 1 SD below the mean. We assessed the association between small wall volume, small lumen volume, FEV1, and chronic airflow obstruction (post-bronchodilator FEV1/FVC ratio < 0.7) using linear and logistic models. Measurements and Main Results: Compared with subjects without childhood-onset asthma, those with childhood-onset asthma had smaller wall volume and lumen volume (P < 0.0001) of segmental airways. Among subjects with childhood-onset asthma, those with the smallest wall volume and lumen volume had the lowest FEV1 and greatest odds of chronic airflow obstruction. A similar tendency was seen in those without childhood-onset asthma. When comparing these two groups, both small wall volume and small lumen volume were more strongly associated with FEV1 and chronic airflow obstruction among subjects with childhood-asthma in multivariate models. Conclusion: In smokers with childhood-onset asthma, smaller airways are associated with reduced lung function and chronic airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT00608764). PMID:25296268

Longitudinal assessment of spirometry in the World Trade Center medical monitoring program.

PubMed

Skloot, Gwen S; Schechter, Clyde B; Herbert, Robin; Moline, Jacqueline M; Levin, Stephen M; Crowley, Laura E; Luft, Benjamin J; Udasin, Iris G; Enright, Paul L

2009-02-01

Multiple studies have demonstrated an initial high prevalence of spirometric abnormalities following World Trade Center (WTC) disaster exposure. We assessed prevalence of spirometric abnormalities and changes in spirometry between baseline and first follow-up evaluation in participants in the WTC Worker and Volunteer Medical Monitoring Program. We also determined the predictors of spirometric change between the two examinations. Prebronchodilator and postbronchodilator spirometry, demographics, occupational history, smoking status, and respiratory symptoms and exposure onset were obtained at both examinations (about 3 years apart). At the second examination, 24.1% of individuals had abnormal spirometry findings. The predominant defect was a low FVC without obstruction (16.1%). Between examinations, the majority of individuals did not have a greater-than-expected decline in lung function. The mean declines in prebronchodilator FEV(1) and FVC were 13 mL/yr and 2 mL/yr, respectively (postbronchodilator results were similar and not reported). Significant predictors of greater average decline between examinations were lack of bronchodilator responsiveness at examination 1 and weight gain [corrected]. Elevated rates of spirometric abnormalities were present at both examinations, with reduced FVC most common. Although the majority had a normal decline in lung function, lack of bronchodilator response at examination 1 and weight gain were significantly associated with greater-than-normal lung function declines [corrected]. Due to the presence of spirometric abnormalities > 5 years after the disaster in many exposed individuals, longer-term monitoring of WTC responders is essential.

Childhood-onset asthma in smokers. association between CT measures of airway size, lung function, and chronic airflow obstruction.

PubMed

Diaz, Alejandro A; Hardin, Megan E; Come, Carolyn E; San José Estépar, Raúl; Ross, James C; Kurugol, Sila; Okajima, Yuka; Han, MeiLan K; Kim, Victor; Ramsdell, Joe; Silverman, Edwin K; Crapo, James D; Lynch, David A; Make, Barry; Barr, R Graham; Hersh, Craig P; Washko, George R

2014-11-01

Asthma is associated with chronic airflow obstruction. Our goal was to assess the association of computed tomographic measures of airway wall volume and lumen volume with the FEV1 and chronic airflow obstruction in smokers with childhood-onset asthma. We analyzed clinical, lung function, and volumetric computed tomographic airway volume data from 7,266 smokers, including 590 with childhood-onset asthma. Small wall volume and small lumen volume of segmental airways were defined as measures 1 SD below the mean. We assessed the association between small wall volume, small lumen volume, FEV1, and chronic airflow obstruction (post-bronchodilator FEV1/FVC ratio < 0.7) using linear and logistic models. Compared with subjects without childhood-onset asthma, those with childhood-onset asthma had smaller wall volume and lumen volume (P < 0.0001) of segmental airways. Among subjects with childhood-onset asthma, those with the smallest wall volume and lumen volume had the lowest FEV1 and greatest odds of chronic airflow obstruction. A similar tendency was seen in those without childhood-onset asthma. When comparing these two groups, both small wall volume and small lumen volume were more strongly associated with FEV1 and chronic airflow obstruction among subjects with childhood-asthma in multivariate models. In smokers with childhood-onset asthma, smaller airways are associated with reduced lung function and chronic airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Reduction of physical activity in daily life and its determinants in smokers without airflow obstruction.

PubMed

Furlanetto, Karina Couto; Mantoani, Leandro Cruz; Bisca, Gianna; Morita, Andrea Akemi; Zabatiero, Juliana; Proença, Mahara; Kovelis, Demétria; Pitta, Fabio

2014-04-01

In smokers without airflow obstruction, detailed, objective and controlled quantification of the level of physical inactivity in daily life has never been performed. This study aimed to objectively assess the level of physical activity in daily life in adult smokers without airflow obstruction in comparison with matched non-smokers, and to investigate the determinants for daily physical activity in smokers. Sixty smokers (aged 50 (39-54) years) and 50 non-smokers (aged 48 (40-53) years) matched for gender, age, anthropometric characteristics, educational level, employment status and seasons of the year assessment period were cross-sectionally assessed regarding their daily physical activity with a step counter, besides assessment of lung function, functional exercise capacity, quality of life, anxiety, depression, self-reported comorbidities carbon monoxide level, nicotine dependence and smoking habits. When compared with non-smokers, smokers walked less in daily life (7923 ± 3558 vs 9553 ± 3637 steps/day, respectively), presented worse lung function, functional exercise capacity, quality of life, anxiety and depression. Multiple regression analyses identified functional exercise capacity, Borg fatigue, self-reported motivation/physical activity behaviour and cardiac disease as significant determinants of number of steps/day in smokers (partial r(2)  = 0.10, 0.12, 0.16 and 0.05; b = 15, -997, 1207 and -2330 steps/day, respectively; overall fit of the model R(2)  = 0.38; P < 0.001). Adult smokers without airflow obstruction presented reduced level of daily physical activity. Functional exercise capacity, extended fatigue sensation, aspects of motivation/physical activity behaviour and self-reported cardiac disease are significant determinants of physical activity in daily life in smokers. © 2014 The Authors. Respirology © 2014 Asian Pacific Society of Respirology.

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.

Receptor for advanced glycation end-products and World Trade Center particulate induced lung function loss: A case-cohort study and murine model of acute particulate exposure

PubMed Central

Haider, Syed H.; Crowley, George; Lee, Audrey; Ebrahim, Minah; Zhang, Liqun; Chen, Lung-Chi; Gordon, Terry; Liu, Mengling; Prezant, David J.; Schmidt, Ann Marie

2017-01-01

World Trade Center-particulate matter(WTC-PM) exposure and metabolic-risk are associated with WTC-Lung Injury(WTC-LI). The receptor for advanced glycation end-products (RAGE) is most highly expressed in the lung, mediates metabolic risk, and single-nucleotide polymorphisms at the AGER-locus predict forced expiratory volume(FEV). Our objectives were to test the hypotheses that RAGE is a biomarker of WTC-LI in the FDNY-cohort and that loss of RAGE in a murine model would protect against acute PM-induced lung disease. We know from previous work that early intense exposure at the time of the WTC collapse was most predictive of WTC-LI therefore we utilized a murine model of intense acute PM-exposure to determine if loss of RAGE is protective and to identify signaling/cytokine intermediates. This study builds on a continuing effort to identify serum biomarkers that predict the development of WTC-LI. A case-cohort design was used to analyze a focused cohort of male never-smokers with normal pre-9/11 lung function. Odds of developing WTC-LI increased by 1.2, 1.8 and 1.0 in firefighters with soluble RAGE (sRAGE)≥97pg/mL, CRP≥2.4mg/L, and MMP-9≤397ng/mL, respectively, assessed in a multivariate logistic regression model (ROCAUC of 0.72). Wild type(WT) and RAGE-deficient(Ager-/-) mice were exposed to PM or PBS-control by oropharyngeal aspiration. Lung function, airway hyperreactivity, bronchoalveolar lavage, histology, transcription factors and plasma/BAL cytokines were quantified. WT-PM mice had decreased FEV and compliance, and increased airway resistance and methacholine reactivity after 24-hours. Decreased IFN-γ and increased LPA were observed in WT-PM mice; similar findings have been reported for firefighters who eventually develop WTC-LI. In the murine model, lack of RAGE was protective from loss of lung function and airway hyperreactivity and was associated with modulation of MAP kinases. We conclude that in a multivariate adjusted model increased sRAGE is associated with WTC-LI. In our murine model, absence of RAGE mitigated acute deleterious effects of PM and may be a biologically plausible mediator of PM-related lung disease. PMID:28926576

Diagnostic management of chronic obstructive pulmonary disease.

PubMed

Broekhuizen, B D L; Sachs, A P E; Hoes, A W; Verheij, T J M; Moons, K G M

2012-01-01

Detection of early chronic obstructive pulmonary disease (COPD) in patients presenting with respiratory symptoms is recommended; however, diagnosing COPD is difficult because a single gold standard is not available. The aim of this article is to review and interpret the existing evidence, theories and consensus on the individual parts of the diagnostic work-up for COPD. Relevant articles are discussed under the subheadings: history taking, physical examination, spirometry and additional lung function assessment. Wheezing, cough, phlegm and breathlessness on exertion are suggestive signs for COPD. The diagnostic value of the physical examination is limited, except for auscultated pulmonary wheezing or reduced breath sounds, increasing the probability of COPD. Spirometric airflow obstruction after bronchodilation, defined as a lowered ratio of the forced volume in one second to the forced vital capacity (FEV1/FVC ratio), is a prerequisite, but can only confirm COPD in combination with suggestive symptoms. Different thresholds are being recommended to define low FEV1/FVC, including a fixed threshold, and one varying with gender and age; however, the way physicians interpret these thresholds in their assessment is not well known. Body plethysmography allows a more complete assessment of pulmonary function, providing results on the total lung capacity and the residual volume and is indicated when conventional spirometry results are inconclusive. Chest radiography has no diagnostic value for COPD but is useful to exclude alternative diagnoses such as heart failure or lung cancer. Extensive history taking is of key importance in diagnosing COPD.

Drillers and mill operators in an open-pit gold mine are at risk for impaired lung function.

PubMed

Vinnikov, Denis

2016-01-01

Occupational studies of associations of exposures with impaired lung function in mining settings are built on exposure assessment and far less often on workplace approach, so the aim of this study was to identify vulnerable occupational groups for early lung function reduction in a cohort of healthy young miners. Data from annual screening lung function tests in gold mining company in Kyrgyzstan were linked to occupations. We compared per cent predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC between occupational groups and tested selected occupations in multivariate regression adjusted for smoking and work duration for the following outcomes: FEV1 < 80 %, FEV1/FVC < 70 % and both. 1550 tests of permanent workers of 41 occupations (mean age 40.5 ± 9.2 years, 29.8 % never smokers) were included in the analysis. The mean overall VC was 103.0 ± 12.9 %; FVC 109.1 ± 13.0 % and FEV1 100.2 ± 25.9 %. Drillers and smoking food handlers had the lowest FEV1%. In non-smokers, the lowest FEV1 was in drillers (94.9 ± 11.3 % compared to 115.2 ± 17.7 % in engineers). Drillers (adjusted odds ratio (OR) 1.53 (95 % confidence interval (CI) 1.11-2.09)) and mill operators (OR 2.01 (1.13-3.57)) were at greater risk of obstructive ventilation pattern (FEV1/FVC < 70 %). Drilling and mill operations are the highest risk jobs in an open-pit mine for reduced lung function. Occupational medical clinic at site should follow-up workers in these occupations with depth and strongly recommend smoking cessation.

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.

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

Personalized Risk Assessment in Never, Light, and Heavy Smokers in a prospective cohort in Taiwan.

PubMed

Wu, Xifeng; Wen, Chi Pang; Ye, Yuanqing; Tsai, MinKwang; Wen, Christopher; Roth, Jack A; Pu, Xia; Chow, Wong-Ho; Huff, Chad; Cunningham, Sonia; Huang, Maosheng; Wu, Shuanbei; Tsao, Chwen Keng; Gu, Jian; Lippman, Scott M

2016-11-02

The objective of this study was to develop markedly improved risk prediction models for lung cancer using a prospective cohort of 395,875 participants in Taiwan. Discriminatory accuracy was measured by generation of receiver operator curves and estimation of area under the curve (AUC). In multivariate Cox regression analysis, age, gender, smoking pack-years, family history of lung cancer, personal cancer history, BMI, lung function test, and serum biomarkers such as carcinoembryonic antigen (CEA), bilirubin, alpha fetoprotein (AFP), and c-reactive protein (CRP) were identified and included in an integrative risk prediction model. The AUC in overall population was 0.851 (95% CI = 0.840-0.862), with never smokers 0.806 (95% CI = 0.790-0.819), light smokers 0.847 (95% CI = 0.824-0.871), and heavy smokers 0.732 (95% CI = 0.708-0.752). By integrating risk factors such as family history of lung cancer, CEA and AFP for light smokers, and lung function test (Maximum Mid-Expiratory Flow, MMEF 25-75% ), AFP and CEA for never smokers, light and never smokers with cancer risks as high as those within heavy smokers could be identified. The risk model for heavy smokers can allow us to stratify heavy smokers into subgroups with distinct risks, which, if applied to low-dose computed tomography (LDCT) screening, may greatly reduce false positives.

Effects of marijuana smoking on the lung.

PubMed

Tashkin, Donald P

2013-06-01

Regular smoking of marijuana by itself causes visible and microscopic injury to the large airways that is consistently associated with an increased likelihood of symptoms of chronic bronchitis that subside after cessation of use. On the other hand, habitual use of marijuana alone does not appear to lead to significant abnormalities in lung function when assessed either cross-sectionally or longitudinally, except for possible increases in lung volumes and modest increases in airway resistance of unclear clinical significance. Therefore, no clear link to chronic obstructive pulmonary disease has been established. Although marijuana smoke contains a number of carcinogens and cocarcinogens, findings from a limited number of well-designed epidemiological studies do not suggest an increased risk for the development of either lung or upper airway cancer from light or moderate use, although evidence is mixed concerning possible carcinogenic risks of heavy, long-term use. Although regular marijuana smoking leads to bronchial epithelial ciliary loss and impairs the microbicidal function of alveolar macrophages, evidence is inconclusive regarding possible associated risks for lower respiratory tract infection. Several case reports have implicated marijuana smoking as an etiologic factor in pneumothorax/pneumomediastinum and bullous lung disease, although evidence of a possible causal link from epidemiologic studies is lacking. In summary, the accumulated weight of evidence implies far lower risks for pulmonary complications of even regular heavy use of marijuana compared with the grave pulmonary consequences of tobacco.

Normative Functional Performance Values in High School Athletes: The Functional Pre-Participation Evaluation Project.

PubMed

Onate, James A; Starkel, Cambrie; Clifton, Daniel R; Best, Thomas M; Borchers, James; Chaudhari, Ajit; Comstock, R Dawn; Cortes, Nelson; Grooms, Dustin R; Hertel, Jay; Hewett, Timothy E; Miller, Meghan Maume; Pan, Xueliang; Schussler, Eric; Van Lunen, Bonnie L

2018-01-01

  The fourth edition of the Preparticipation Physical Evaluation recommends functional testing for the musculoskeletal portion of the examination; however, normative data across sex and grade level are limited. Establishing normative data can provide clinicians reference points with which to compare their patients, potentially aiding in the development of future injury-risk assessments and injury-mitigation programs.   To establish normative functional performance and limb-symmetry data for high school-aged male and female athletes in the United States.   Cross-sectional study.   Athletic training facilities and gymnasiums across the United States.   A total of 3951 male and female athletes who participated on high school-sponsored basketball, football, lacrosse, or soccer teams enrolled in this nationwide study.   Functional performance testing consisted of 3 evaluations. Ankle-joint range of motion, balance, and lower extremity muscular power and landing control were assessed via the weight-bearing ankle-dorsiflexion-lunge, single-legged anterior-reach, and anterior single-legged hop-for-distance (SLHOP) tests, respectively. We used 2-way analyses of variance and χ 2 analyses to examine the effects of sex and grade level on ankle-dorsiflexion-lunge, single-legged anterior-reach, and SLHOP test performance and symmetry.   The SLHOP performance differed between sexes (males = 187.8% ± 33.1% of limb length, females = 157.5% ± 27.8% of limb length; t = 30.3, P < .001). A Cohen d value of 0.97 indicated a large effect of sex on SLHOP performance. We observed differences for SLHOP and ankle-dorsiflexion-lunge performance among grade levels, but these differences were not clinically meaningful.   We demonstrated differences in normative data for lower extremity functional performance during preparticipation physical evaluations across sex and grade levels. The results of this study will allow clinicians to compare sex- and grade-specific functional performances and implement approaches for preventing musculoskeletal injuries in high school-aged athletes.

TU-A-12A-02: Novel Lung Ventilation Imaging with Single Energy CT After Single Inhalation of Xenon: Comparison with SPECT Ventilation Images

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

Negahdar, M; Yamamoto, T; Shultz, D

Purpose: We propose a novel lung functional imaging method to determine the spatial distribution of xenon (Xe) gas in a single inhalation as a measure of regional ventilation. We compare Xe-CT ventilation to single-photon emission CT (SPECT) ventilation, which is the current clinical reference. Regional lung ventilation information may be useful for the diagnosis and monitoring of pulmonary diseases such as COPD, radiotherapy planning, and assessing the progression of toxicity after radiation therapy. Methods: In an IRB-approved clinical study, Xe-CT and SPECT ventilation scans were acquired for three patients including one patient with severe emphysema and two lung cancer patientsmore » treated with radiotherapy. For Xe- CT, we acquired two breath-hold single energy CT images of the entire lung with inspiration of 100% O2 and a mixture of 70% Xe and 30% O2, respectively. A video biofeedback system was used to achieve reproducible breath-holds. We used deformable image registration to align the breathhold images with each other to accurately subtract them, producing a map of the distribution of Xe as a surrogate of lung ventilation. We divided each lung into twelve parts and correlated the Hounsfield unit (HU) enhancement at each part with the SPECT ventilation count of the corresponding part of the lung. Results: The mean of the Pearson linear correlation coefficient values between the Xe-CT and ventilation SPECT count for all three patients were 0.62 (p<0.01). The Xe-CT image had a higher resolution than SPECT, and did not show central airway deposition artifacts that were present in the SPECT image. Conclusion: We developed a rapid, safe, clinically practical, and potentially widely accessible method for regional lung functional imaging. We demonstrated strong correlations between the Xe-CT ventilation image and SPECT ventilation image as the clinical reference. This ongoing study will investigate more patients to confirm this finding.« less

Ex vivo expansion of alveolar macrophages with Mycobacterium tuberculosis from the resected lungs of patients with pulmonary tuberculosis

PubMed Central

Petrunina, Ekaterina; Umpeleva, Tatiana; Karskanova, Svetlana; Bayborodin, Sergey; Vakhrusheva, Diana; Kravchenko, Marionella; Skornyakov, Sergey

2018-01-01

Tuberculosis (TB), with the Mycobacterium tuberculosis (Mtb) as the causative agent, remains to be a serious world health problem. Traditional methods used for the study of Mtb in the lungs of TB patients do not provide information about the number and functional status of Mtb, especially if Mtb are located in alveolar macrophages. We have developed a technique to produce ex vivo cultures of cells from different parts of lung tissues surgically removed from patients with pulmonary TB and compared data on the number of cells with Mtb inferred by the proposed technique to the results of bacteriological and histological analyses used for examination of the resected lungs. The ex vivo cultures of cells obtained from the resected lungs of all patients were largely composed of CD14-positive alveolar macrophages, foamy or not, with or without Mtb. Lymphocytes, fibroblasts, neutrophils, and multinucleate Langhans giant cells were also observed. We found alveolar macrophages with Mtb in the ex vivo cultures of cells from the resected lungs of even those TB patients, whose sputum smears and lung tissues did not contain acid-fast Mtb or reveal growing Mtb colonies on dense medium. The detection of alveolar macrophages with Mtb in ex vivo culture as soon as 16–18 h after isolation of cells from the resected lungs of all TB patients suggests that the technique proposed for assessing the level of infection in alveolar macrophages of TB patients has higher sensitivity than do prolonged bacteriological or pathomorphological methods. The proposed technique allowed us to rapidly (in two days after surgery) determine the level of infection with Mtb in the cells of the resected lungs of TB patients and, by the presence or absence of Mtb colonies, including those with cording morphology, the functional status of the TB agent at the time of surgery. PMID:29401466

Lung lavage with oxygenated perfluorochemical liquid in acute lung injury.

PubMed

Richman, P S; Wolfson, M R; Shaffer, T H

1993-05-01

To investigate the effects of lung lavage with oxygenated liquid perfluorochemical on gas exchange, lung mechanics, and cardiac function in animals with acute lung injury. Prospective, randomized, controlled trial. Animal laboratory. Eight adult cats (2 to 4 kg, random sex). Two insults were combined to cause lung injury: oleic acid infusion and saline whole-lung wash. Animals were assigned to either the control or treatment group which consisted of a perfluorochemical liquid (Rimar 101) lavage. Perfluorochemical liquid lavage was performed three times at hourly intervals after lung injury. Three other cats with identical injury but no perfluorochemical liquid lavage served as control animals. All cats were ventilated with an FIO2 of 0.95 and positive end-expiratory pressure of 2 cm H2O continuously. Arterial blood gas tensions and pH, dynamic pulmonary compliance were measured at 15-min intervals. Cardiac index was assessed hourly, and lung fluid was collected after each of the three perfluorochemical liquid lavages. Arterial oxygen tension and pulmonary compliance deteriorated abruptly after lung injury in all cats, and improved significantly (p < .001, two-way analysis of variance) 15 mins after perfluorochemical liquid lavage. These parameters gradually returned to their baseline over 60 mins. Arterial blood pressure and cardiac index decreased after injury in all cats, and were not significantly changed after perfluorochemical liquid lavage. Hemorrhagic fluid was recovered from distal airways by perfluorochemical liquid lavage, despite prior suctioning of the airway. Perfluorochemical liquid lavage removes pulmonary edema fluid and improves gas exchange and the mechanical properties of the lung, after acute severe lung injury.

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

PubMed

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

1993-01-01

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

Estimation of Lung Ventilation

NASA Astrophysics Data System (ADS)

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

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

Functional Analysis of Somatic Mutations in Lung Cancer

DTIC Science & Technology

2015-10-01

antibody cetuximab [11]. Finally, we have developed novel single cell sequencing approaches to uncover EGFR mutational variants in glioblastoma and their...assessed which mutations are epistatic to EGFR or capable of initiating xenograft tumor formation in vivo. Using eVIP, we identified 69% of mutations...analyzed as impactful whereas 31% appear functionally neutral. A subset of the impactful mutations induce xenograft tumor formation in mice and/or

Association between lung function in school children and exposure to three transition metals from an e-waste recycling area.

PubMed

Zheng, Guina; Xu, Xijin; Li, Bin; Wu, Kusheng; Yekeen, Taofeek Akangbe; Huo, Xia

2013-01-01

The informal processing of electronic waste or e-waste contributes to the release of high concentrations of transition metals into the ambient air. The damage caused by chromium, nickel and manganese exposure on lung function in school children from an e-waste recycling area and the role of oxidative stress in this process were evaluated. We recruited school children (n=144, 8-13 years) from an e-waste recycling area in China compared with the control. Spirometry was performed to assess lung function status. The blood levels of chromium, nickel and manganese, antioxidant enzyme activities and lipid peroxidation of the subjects were examined. The concentrations of blood manganese (bMn) and serum nickel (sNi) in the exposed group were significantly higher than those in controls for all three age groups. The forced vital capacity value of boys aged 8-9 years was significantly lower than that of the control. Malondialdehyde levels and superoxide dismutase activities increased significantly in children aged 8-9 years from e-waste environment, but catalase activities declined. School children from an e-waste recycling area were exposed to high levels of the three transition metals. The accumulation of bMn and sNi may be risk factors for oxidative damage and decreased pulmonary function.

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

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

PubMed

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

2017-11-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-28

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

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

PubMed

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

2017-10-01

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

Dynamic hyperinflation after metronome-paced hyperventilation in COPD--a 2 year follow-up.

PubMed

Hannink, Jorien; Lahaije, Anke; Bischoff, Erik; van Helvoort, Hanneke; Dekhuijzen, Richard; Schermer, Tjard; Heijdra, Yvonne

2010-11-01

In contrast to the decline in FEV(1), the behavior of dynamic hyperinflation (DH) over time is unknown in patients with COPD. Metronome-paced hyperventilation (MPH) is a simple applicable surrogate for exercise to detect DH. To evaluate changes in MPH-induced DH during two years follow-up in mild-to-severe COPD patients. Additionally, influence of smoking status on DH and the relation between DH and other lung function parameters were assessed. Patients were recruited from a randomized controlled trial conducted in general practice. Measurements of lung function and DH were performed at baseline and after 12 and 24 months. DH was assessed by MPH with breathing frequency set at twice the baseline rate. Change in inspiratory capacity after MPH was used to reflect change in end-expiratory lung volume and therefore DH, presuming constant total lung capacity. During follow-up, 68 patients completed all measurements. DH increased by 0.23±0.06L (p≤0.001). No significant changes in FEV(1) %pred were seen. Smokers had lower FEV(1) and a more rapid decline than non-smokers. DH in smokers increased more over time compared to non-smokers. The amount of DH correlated positively with resting inspiratory capacity. After two years, a significant increase in MPH-induced DH in COPD patients was demonstrated, which was not accompanied by a decline in FEV(1). It might be that DH is a sensitive measure to track consequences of changes in airflow obstruction. Copyright © 2010 Elsevier Ltd. All rights reserved.

Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice.

PubMed

Tanaka, Ken-Ichiro; Sato, Keizo; Aoshiba, Kazutetsu; Azuma, Arata; Mizushima, Tohru

2012-06-15

Bronchodilators (such as ipratropium bromide), steroids (such as fluticasone propionate), and newly developed anti-inflammatory drugs (such as roflumilast) are used for patients with chronic obstructive pulmonary disease (COPD). We recently reported that lecithinized superoxide dismutase (PC-SOD) confers a protective effect in mouse models of COPD. We here examined the therapeutic effect of the combined administration of PC-SOD with ipratropium bromide on pulmonary emphysema and compared the effect of PC-SOD to other types of drugs. The severity of emphysema in mice was assessed by various criteria. Lung mechanics (elastance) and respiratory function (ratio of forced expiratory volume in the first 0.05 s to forced vital capacity) were assessed. Administration of PC-SOD by inhalation suppressed elastase-induced pulmonary emphysema, alteration of lung mechanics, and respiratory dysfunction. The concomitant intratracheal administration of ipratropium bromide did not alter the ameliorating effects of PC-SOD. Administration of ipratropium bromide, fluticasone propionate, or roflumilast alone did not suppress the elastase-induced increase in the pulmonary level of superoxide anion, pulmonary inflammatory response, pulmonary emphysema, alteration of lung mechanics, or respiratory dysfunction as effectively as did PC-SOD. PC-SOD, but not the other drugs, showed a therapeutic effect even when the drug was administered after the development of emphysema. PC-SOD also suppressed the cigarette smoke-induced pulmonary inflammatory response and increase in airway resistance. Based on these results, we consider that the inhalation of PC-SOD would be therapeutically beneficial for COPD.

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

PubMed Central

2011-01-01

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

Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury

PubMed Central

Zhang, Yi; Jiang, Ge; Sauler, Maor; Lee, Patty J.

2013-01-01

The lung endothelium is a major target for inflammatory and oxidative stress. Heme oxygenase-1 (HO-1) induction is a crucial defense mechanism during oxidant challenges, such as hyperoxia. The role of lung endothelial HO-1during hyperoxia in vivo is not well defined. We engineered lentiviral vectors with microRNA (miRNA) sequences controlled by vascular endothelium cadherin (VE-cad) to study the specific role of lung endothelial HO-1. Wild-type (WT) murine lung endothelial cells (MLECs) or WT mice were treated with lentivirus and exposed to hyperoxia (95% oxygen). We detected HO-1 knockdown (∼55%) specifically in the lung endothelium. MLECs and lungs showed approximately a 2-fold increase in apoptosis and ROS generation after HO-1 silencing. We also demonstrate for the first time that silencing endothelial HO-1 has the same effect on lung injury and survival as silencing HO-1 in multiple lung cell types and that HO-1 regulates caspase 3 activation and autophagy in endothelium during hyperoxia. These studies demonstrate the utility of endothelial-targeted gene silencing in vivo using lentiviral miRNA constructs to assess gene function and that endothelial HO-1 is an important determinant of survival during hyperoxia.—Zhang, Y., Jiang, G., Sauler, M., Lee, P. J. Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury. PMID:23771928

[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.

Achromobacter xylosoxidans infection in an adult cystic fibrosis unit in Madrid.

PubMed

Llorca Otero, Laura; Girón Moreno, Rosa; Buendía Moreno, Buenaventura; Valenzuela, Claudia; Guiu Martínez, Alba; Alarcón Cavero, Teresa

2016-03-01

Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Although the rate of colonization by this microorganism is variable, prevalence is increasing in CF units. A microbiological/clinical study was conducted on of adult CF patients harboring A. xylosoxidans. Identification and susceptibility testing were performed using MicroScan (Siemens). Decline in lung function was assessed using the variable, annual percentage loss of FEV1 (forced expiratory volume in 1s). A. xylosoxidans was isolated in 18 (19.8%) of 91 patients over a 14-year period. Mean age was 26.6 years (18-39 years). Nine patients (9.8%) were chronically colonized. Piperacillin/tazobactam and imipenem were the most active antibiotics. Mean annual decline in lung function in chronically colonized patients was 2.49%. A. xylosoxidans is a major pathogen in CF. A decreased lung function was observed among patients who were chronically colonized by A. xylosoxidans. Antibiotic therapy should be started early in order to prevent chronic colonization by this microorganism. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Preparation for a first-in-man lentivirus trial in patients with cystic fibrosis

PubMed Central

Alton, Eric W F W; Beekman, Jeffery M; Boyd, A Christopher; Brand, June; Carlon, Marianne S; Connolly, Mary M; Chan, Mario; Conlon, Sinead; Davidson, Heather E; Davies, Jane C; Davies, Lee A; Dekkers, Johanna F; Doherty, Ann; Gea-Sorli, Sabrina; Gill, Deborah R; Griesenbach, Uta; Hasegawa, Mamoru; Higgins, Tracy E; Hironaka, Takashi; Hyndman, Laura; McLachlan, Gerry; Inoue, Makoto; Hyde, Stephen C; Innes, J Alastair; Maher, Toby M; Moran, Caroline; Meng, Cuixiang; Paul-Smith, Michael C; Pringle, Ian A; Pytel, Kamila M; Rodriguez-Martinez, Andrea; Schmidt, Alexander C; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Toshner, Richard; Tsugumine, Shu; Wasowicz, Marguerite W; Zhu, Jie

2017-01-01

We have recently shown that non-viral gene therapy can stabilise the decline of lung function in patients with cystic fibrosis (CF). However, the effect was modest, and more potent gene transfer agents are still required. Fuson protein (F)/Hemagglutinin/Neuraminidase protein (HN)-pseudotyped lentiviral vectors are more efficient for lung gene transfer than non-viral vectors in preclinical models. In preparation for a first-in-man CF trial using the lentiviral vector, we have undertaken key translational preclinical studies. Regulatory-compliant vectors carrying a range of promoter/enhancer elements were assessed in mice and human air–liquid interface (ALI) cultures to select the lead candidate; cystic fibrosis transmembrane conductance receptor (CFTR) expression and function were assessed in CF models using this lead candidate vector. Toxicity was assessed and ‘benchmarked’ against the leading non-viral formulation recently used in a Phase IIb clinical trial. Integration site profiles were mapped and transduction efficiency determined to inform clinical trial dose-ranging. The impact of pre-existing and acquired immunity against the vector and vector stability in several clinically relevant delivery devices was assessed. A hybrid promoter hybrid cytosine guanine dinucleotide (CpG)- free CMV enhancer/elongation factor 1 alpha promoter (hCEF) consisting of the elongation factor 1α promoter and the cytomegalovirus enhancer was most efficacious in both murine lungs and human ALI cultures (both at least 2-log orders above background). The efficacy (at least 14% of airway cells transduced), toxicity and integration site profile supports further progression towards clinical trial and pre-existing and acquired immune responses do not interfere with vector efficacy. The lead rSIV.F/HN candidate expresses functional CFTR and the vector retains 90–100% transduction efficiency in clinically relevant delivery devices. The data support the progression of the F/HN-pseudotyped lentiviral vector into a first-in-man CF trial in 2017. PMID:27852956