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

Post-tuberculous lung function impairment in a tuberculosis reference clinic in Cameroon.

PubMed

Mbatchou Ngahane, Bertrand Hugo; Nouyep, Junior; Nganda Motto, Malea; Mapoure Njankouo, Yacouba; Wandji, Adeline; Endale, Mireille; Afane Ze, Emmanuel

2016-05-01

After completion of treatment, a proportion of pulmonary TB (pTB) patients experience lung function impairment which can influence their quality of life. This study aimed to determine the prevalence of lung function impairment in patients treated for pTB and investigate its associated factors. A cross-sectional study was conducted in TB clinic of the Douala Laquintinie Hospital in Cameroon. Patients aged 15 and above who were treated for pTB between 2008 and 2012 were included in the study. Demographic data, respiratory symptoms prior TB diagnosis, comorbidities and chest radiography findings prior to TB treatment were collected. All participants underwent spirometric measurements. Airflow obstruction was defined as a post-bronchodilation FEV1/FVC <70% with FVC >80%, restrictive defects as an FEV1/FVC ratio of ≥70% with an FVC <80% predicted, and mixed defects as FVC of <80% predicted and an FEV1/FVC ratio of <70%. Lung function impairment was defined by the presence of at least one of these three abnormalities. Logistic regression analysis was employed to investigate risk factors of lung function impairment. Of a total of 269 participants included in the study, 146 (54.3%) were male. The median age of participants was 33 years. The median duration of symptoms before diagnosis of TB was 4 weeks [interquartile range (IQR) 3-8]. The prevalence of lung function impairment was 45.4% (95% CI 39-51). The multivariate analysis identified duration of symptoms [OR 1.08; 95% CI (1.01-1.15)] and fibrotic pattern [OR 3.54; 95% CI (1.40-8.95)] as independent risk factors for lung function impairment. Post-tuberculous pulmonary function impairment is frequent in Douala. Sensitization of patient with symptoms of pulmonary TB for an earlier visit to healthcare facilities could reduce the impact of pTB on lung function of patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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

PubMed Central

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

2015-01-01

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

Alcohol and Airways Function in Health and Disease

PubMed Central

Sisson, Joseph H.

2007-01-01

The volatility of alcohol promotes the movement of alcohol from the bronchial circulation across the airway epithelium and into the conducting airways of the lung. The exposure of the airways through this route likely accounts for many of the biologic effects of alcohol on lung airway functions. The impact of alcohol on lung airway functions is dependent on the concentration, duration and route of exposure. Brief exposure to mild concentrations of alcohol may enhance mucociliary clearance, stimulates bronchodilation and probably attenuates the airway inflammation and injury observed in asthma and COPD. Prolonged and heavy exposure to alcohol impairs mucociliary clearance, may complicate asthma management and likely worsens outcomes including lung function and mortality in COPD patients. Non-alcohol congeners and alcohol metabolites act as triggers for airway disease exacerbations especially in atopic asthmatics and in Asian populations who have a reduced capacity to metabolize alcohol. Research focused on the mechanisms of alcohol-mediated changes in airway functions has identified specific mechanisms that mediate alcohol effects within the lung airways. These include prominent roles for the second messengers calcium and nitric oxide, regulatory kinases including PKG and PKA, alcohol and acetaldehyde-metabolizing enzymes such as aldehyde dehydrogenase type 2 (ALDH2). The role alcohol may play in the pathobiology of airway mucus, bronchial blood flow, airway smooth muscle regulation and the interaction with other airway exposure agents, such as cigarette smoke, represent opportunities for future investigation. PMID:17764883

Alcohol and airways function in health and disease.

PubMed

Sisson, Joseph H

2007-08-01

The volatility of alcohol promotes the movement of alcohol from the bronchial circulation across the airway epithelium and into the conducting airways of the lung. The exposure of the airways through this route likely accounts for many of the biologic effects of alcohol on lung airway functions. The effect of alcohol on lung airway functions is dependent on the concentration, duration, and route of exposure. Brief exposure to mild concentrations of alcohol may enhance mucociliary clearance, stimulates bronchodilation, and probably attenuates the airway inflammation and injury observed in asthma and chronic obstructive pulmonary disease (COPD). Prolonged and heavy exposure to alcohol impairs mucociliary clearance, may complicate asthma management, and likely worsens outcomes including lung function and mortality in COPD patients. Nonalcohol congeners and alcohol metabolites act as triggers for airway disease exacerbations especially in atopic asthmatics and in Asian populations who have a reduced capacity to metabolize alcohol. Research focused on the mechanisms of alcohol-mediated changes in airway functions has identified specific mechanisms that mediate alcohol effects within the lung airways. These include prominent roles for the second messengers calcium and nitric oxide, regulatory kinases including PKG and PKA, alcohol- and acetaldehyde-metabolizing enzymes such as aldehyde dehydrogenase 2. The role alcohol may play in the pathobiology of airway mucus, bronchial blood flow, airway smooth muscle regulation, and the interaction with other airway exposure agents, such as cigarette smoke, represents opportunities for future investigation.

Involvement of MicroRNAs in Lung Cancer Biology and Therapy

PubMed Central

Liu, Xi; Sempere, Lorenzo F.; Guo, Yongli; Korc, Murray; Kauppinen, Sakari; Freemantle, Sarah J.; Dmitrovsky, Ethan

2011-01-01

MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression. Expression profiles of specific miRNAs have improved cancer diagnosis and classification and even provided prognostic information in many human cancers, including lung cancer. Tumor suppressive and oncogenic miRNAs were uncovered in lung carcinogenesis. The biological functions of these miRNAs in lung cancer were recently validated in well characterized cellular, murine transgenic as well as transplantable lung cancer models and in human paired normal-malignant lung tissue banks and tissue arrays. Tumor suppressive and oncogenic miRNAs that were identified in lung cancer will be reviewed here. Emphasis is placed on highlighting those functionally validated miRNAs that are not only biomarkers of lung carcinogenesis, but also candidate pharmacologic targets. How these miRNA findings advance an understanding of lung cancer biology and could improve lung cancer therapy are discussed in this article. PMID:21420030

Donor predicted post-operative forced expiratory volume in one second predicts recipients' best forced expiratory volume in one second following size-reduced lung transplantation.

PubMed

Inci, Ilhan; Irani, Sarosh; Kestenholz, Peter; Benden, Christian; Boehler, Annette; Weder, Walter

2011-01-01

The limited number of available grafts is one of the major obstacles of lung transplantation. Size-reduced lung transplantation allows the use of oversized grafts for small recipients. Optimal lung size matching is vital to achieve best functional outcome and avoid potential problems when using oversized grafts. We hypothesise that donor-predicted postoperative forced expiratory volume in 1s (ppoFEV1) correlates with the recipient best FEV1 after size-reduced lung transplant, being useful for the estimation of function outcome. All patients undergoing size-reduced or standard bilateral lung transplantation were included (1992-2007). Donor ppoFEV1 was calculated and corrected with respect to size reduction and correlated with recipient measured best FEV1 post-transplant. In addition, pre- and postoperative clinical data including surgical complications and outcome of all size-reduced lung transplant recipients were compared with standard lung transplant recipients. A total of 61 size-reduced lung transplant recipients (lobar transplants, n=20; anatomic or non-anatomic resection, n=41) were included and compared to 145 standard transplants. The mean donor-recipient height difference was statistically significant between the two groups (p=0.0001). The mean donor ppoFEV1 was comparable with recipient best FEV1 (2.7±0.6 vs 2.6±0.7 l). There was a statistically significant correlation between donor ppoFEV1 and recipient best FEV1 (p=0.01, r=0.688). The 30-day mortality rate and 3-month, 1- and 5-year survival rates were comparable between the two groups. In size-reduced lung transplantation, postoperative recipient best FEV1 could be predicted from donor-calculated and corrected FEV1 with respect to its size reduction. Compared to standard lung transplantation, equivalent morbidity, mortality and functional results could be obtained after size-reduced lung transplantation. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

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

PubMed

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

2014-11-01

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

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.

PPAR-γ in innate and adaptive lung immunity.

PubMed

Nobs, Samuel Philip; Kopf, Manfred

2018-05-16

The transcription factor PPAR-γ (peroxisome proliferator-activated receptor-γ) is a key regulator of lung immunity exhibiting multiple cell type specific roles in controlling development and function of the lung immune system. It is strictly required for the generation of alveolar macrophages by controlling differentiation of fetal lung monocyte precursors. Furthermore, it plays an important role in lung allergic inflammation by licensing lung dendritic cell t helper 2 (Th2) priming capacity as well as acting as a master transcription factor for pathogenic Th2 cells. Due to this plethora of functions and its involvement in multiple pulmonary diseases including asthma and pulmonary alveolar proteinosis, understanding the role of PPAR-γ in lung immunity is an important subject of ongoing research. ©2018 Society for Leukocyte Biology.

Pulmonary Function in Flight (PuFF) Experiment

NASA Technical Reports Server (NTRS)

2003-01-01

In this International Space Station (ISS) onboard photo, Expedition Six Science Officer Donald R. Pettit works to set up the Pulmonary Function in Flight (PuFF) experiment hardware in the Destiny Laboratory. Expedition Six is the fourth and final crew to perform the PuFF experiment. The PuFF experiment was developed to better understand what effects long term exposure to microgravity may have on the lungs. The focus is on measuring changes in the everness of gas exchange in the lungs, and on detecting changes in respiratory muscle strength. It allows astronauts to measure blood flow through the lungs, the ability of the lung to take up oxygen, and lung volumes. Each PuFF session includes five lung function tests, which involve breathing only cabin air. For each planned extravehicular (EVA) activity, a crew member performs a PuFF test within one week prior to the EVA. Following the EVA, those crew members perform another test to document the effect of exposure of the lungs to the low-pressure environment of the space suits. This experiment utilizes the Gas Analyzer System for Metabolic Analysis Physiology, or GASMAP, located in the Human Research Facility (HRF), along with a variety of other Puff equipment including a manual breathing valve, flow meter, pressure-flow module, pressure and volume calibration syringes, and disposable mouth pieces.

Lung functions among patients with pulmonary tuberculosis in Dar es Salaam - a cross-sectional study.

PubMed

Manji, Mohamed; Shayo, Grace; Mamuya, Simon; Mpembeni, Rose; Jusabani, Ahmed; Mugusi, Ferdinand

2016-04-23

Approximately 40-60 % of patients remain sufferers of sequela of obstructive, restrictive or mixed patterns of lung disease despite treatment for pulmonary tuberculosis (PTB). The prevalence of these abnormalities in Tanzania remains unknown. A descriptive cross-sectional study was carried out among 501 patients with PTB who had completed at least 20 weeks of treatment. These underwent spirometry and their lung functions were classified as normal or abnormal (obstructive, restrictive or mixed). Logistic regression models were used to explore factors associated with abnormal lung functions. Abnormal lung functions were present in 371 (74 %) patients. There were 210 (42 %) patients with obstructive, 65 (13 %) patients with restrictive and 96 (19 %) patients with mixed patterns respectively. Significant factors associated with abnormal lung functions included recurrent PTB (Adj OR 2.8, CI 1.274 - 6.106), Human Immunodeficiency Virus (HIV) negative status (Adj OR 1.7, CI 1.055 - 2.583), age more than 40 years (Adj OR 1.7, CI 1.080 - 2.804) and male sex (Adj OR 1.7, CI 1.123 - 2.614). The prevalence of abnormal lung functions is high and it is associated with male sex, age older than 40 years, recurrent PTB and HIV negative status.

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

PubMed

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

2017-07-12

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

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.

Invited commentary: on population subgroups, mathematics, and interventions.

PubMed

Jacobs, David R; Meyer, Katie A

2011-02-15

New sex-specific equations, each with race/ethnic-specific intercept, for predicted lung function illustrate a methodological point, that complex differences between groups may not imply interactions with other predictors, such as age and height. The new equations find that race/ethnic identity does not interact with either age or height in the prediction equations, although there are race/ethnic-specific offsets. Further study is warranted of the effect of possible small race/ethnic interactions on disease classification. Additional study of repeated measures of lung function is warranted, given that the new equations were developed in cross-sectional designs. Predicting lung function is more than a methodological exercise. Predicted values are important in disease diagnosis and monitoring. It is suggested that measurement and tracking of lung function throughout young adulthood could be used to provide an early warning of potential long-term lung function losses to encourage improvement of risky behaviors including smoking and failure to maintain normal body weight in the general population.

Lung function and exhaled nitric oxide in healthy unsedated African infants

PubMed Central

Gray, Diane; Willemse, Lauren; Visagie, Ane; Smith, Emilee; Czövek, Dorottya; Sly, Peter D; Hantos, Zoltán; Hall, Graham L; Zar, Heather J

2015-01-01

Background and objective Population-appropriate lung function reference data are essential to accurately identify respiratory disease and measure response to interventions. There are currently no reference data in African infants. The aim was to describe normal lung function in healthy African infants. Methods Lung function was performed on healthy South African infants enrolled in a birth cohort study, the Drakenstein child health study. Infants were excluded if they were born preterm or had a history of neonatal respiratory distress or prior respiratory tract infection. Measurements, made during natural sleep, included the forced oscillation technique, tidal breathing, exhaled nitric oxide and multiple breath washout measures. Results Three hundred sixty-three infants were tested. Acceptable and repeatable measurements were obtained in 356 (98%) and 352 (97%) infants for tidal breathing analysis and exhaled nitric oxide outcomes, 345 (95%) infants for multiple breath washout and 293 of the 333 (88%) infants for the forced oscillation technique. Age, sex and weight-for-age z score were significantly associated with lung function measures. Conclusions This study provides reference data for unsedated infant lung function in African infants and highlights the importance of using population-specific data. PMID:26134556

Optical techniques in pulmonary medicine. SPIE photonics West.

PubMed

Suter, Melissa J; Lam, Stephen; Brenner, Matthew

2012-04-01

There is ongoing interest in the emerging field of pulmonary photonic-based diagnostics. Potential clinical need areas that are being actively investigated at this time include airway and peripheral lung cancer diagnostics, pulmonary parenchymal and interstitial disorders, alveolar structure function, inhalation injury, ciliary function analysis, asthma and obstructive lung diseases.

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

PubMed

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

2012-08-01

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

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

Personality and Lung Function in Older Adults.

PubMed

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

2017-10-01

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

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

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.

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

PubMed

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

2016-12-01

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

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

Lung perfusion measured using magnetic resonance imaging: New tools for physiological insights into the pulmonary circulation.

PubMed

Hopkins, Susan R; Prisk, G Kim

2010-12-01

Since the lung receives the entire cardiac output, sophisticated imaging techniques are not required in order to measure total organ perfusion. However, for many years studying lung function has required physiologists to consider the lung as a single entity: in imaging terms as a single voxel. Since imaging, and in particular functional imaging, allows the acquisition of spatial information important for studying lung function, these techniques provide considerable promise and are of great interest for pulmonary physiologists. In particular, despite the challenges of low proton density and short T2* in the lung, noncontrast MRI techniques to measure pulmonary perfusion have several advantages including high reliability and the ability to make repeated measurements under a number of physiologic conditions. This brief review focuses on the application of a particular arterial spin labeling (ASL) technique, ASL-FAIRER (flow sensitive inversion recovery with an extra radiofrequency pulse), to answer physiologic questions related to pulmonary function in health and disease. The associated measurement of regional proton density to correct for gravitational-based lung deformation (the "Slinky" effect (Slinky is a registered trademark of Pauf-Slinky incorporated)) and issues related to absolute quantification are also discussed. Copyright © 2010 Wiley-Liss, Inc.

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.

Serum Methylarginines and Spirometry-Measured Lung Function in Older Adults

PubMed Central

McEvoy, Mark A.; Schofield, Peter W.; Smith, Wayne T.; Agho, Kingsley; Mangoni, Arduino A.; Soiza, Roy L.; Peel, Roseanne; Hancock, Stephen J.; Carru, Ciriaco; Zinellu, Angelo; Attia, John R.

2013-01-01

Rationale Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function. PMID:23690915

Ex Vivo Lung Perfusion: Establishment and Operationalization in Iran.

PubMed

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

2017-02-01

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

77 FR 44198 - Approval and Promulgation of Implementation Plans; State of Florida: New Source Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-27

....e., lung disease, decreased lung function asthma attacks and certain cardiovascular issues... with heart and lung diseases. For more details regarding health effects and PM 2.5 see EPA's Web site...'' and ``minor source baseline date'' (including trigger dates) to establish the PM 2.5 NAAQS specific...

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

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

Heterozygous Vangl2Looptail mice reveal novel roles for the planar cell polarity pathway in adult lung homeostasis and repair

PubMed Central

Poobalasingam, Thanushiyan; Yates, Laura L.; Walker, Simone A.; Pereira, Miguel; Gross, Nina Y.; Ali, Akmol; Kolatsi-Joannou, Maria; Jarvelin, Marjo-Riitta; Pekkanen, Juha; Papakrivopoulou, Eugenia; Long, David A.; Griffiths, Mark; Wagner, Darcy; Königshoff, Melanie; Hind, Matthew; Minelli, Cosetta; Lloyd, Clare M.

2017-01-01

ABSTRACT Lung diseases impose a huge economic and health burden worldwide. A key aspect of several adult lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), including emphysema, is aberrant tissue repair, which leads to an accumulation of damage and impaired respiratory function. Currently, there are few effective treatments available for these diseases and their incidence is rising. The planar cell polarity (PCP) pathway is critical for the embryonic development of many organs, including kidney and lung. We have previously shown that perturbation of the PCP pathway impairs tissue morphogenesis, which disrupts the number and shape of epithelial tubes formed within these organs during embryogenesis. However, very little is known about the role of the PCP pathway beyond birth, partly because of the perinatal lethality of many PCP mouse mutant lines. Here, we investigate heterozygous Looptail (Lp) mice, in which a single copy of the core PCP gene, Vangl2, is disrupted. We show that these mice are viable but display severe airspace enlargement and impaired adult lung function. Underlying these defects, we find that Vangl2Lp/+ lungs exhibit altered distribution of actin microfilaments and abnormal regulation of the actin-modifying protein cofilin. In addition, we show that Vangl2Lp/+ lungs exhibit many of the hallmarks of tissue damage, including an altered macrophage population, abnormal elastin deposition and elevated levels of the elastin-modifying enzyme, Mmp12, all of which are observed in emphysema. In vitro, disruption of VANGL2 impairs directed cell migration and reduces the rate of repair following scratch wounding of human alveolar epithelial cells. Moreover, using population data from a birth cohort of young adults, all aged 31, we found evidence of an interactive effect between VANGL2 and smoking on lung function. Finally, we show that PCP genes VANGL2 and SCRIB are significantly downregulated in lung tissue from patients with emphysema. Our data reveal an important novel role for the PCP pathway in adult lung homeostasis and repair and shed new light on the genetic factors which may modify destructive lung diseases such as emphysema. PMID:28237967

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

PubMed

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

2013-10-14

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

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.

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

PubMed Central

Sundar, Isaac K.; Ahmad, Tanveer; Yao, Hongwei; Hwang, Jae-woong; Gerloff, Janice; Lawrence, B. Paige; Sellix, Michael T.; Rahman, Irfan

2015-01-01

Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations. PMID:25923474

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).

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

PubMed

Bokov, P; Delclaux, C

2016-02-01

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

Normal expiratory flow rate and lung volumes in patients with combined emphysema and interstitial lung disease: a case series and literature review.

PubMed

Heathcote, Karen L; Cockcroft, Donald W; Fladeland, Derek A; Fenton, Mark E

2011-01-01

Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

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

PubMed Central

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

2015-01-01

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

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.

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.

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

PubMed Central

2011-01-01

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

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

PubMed

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

1994-07-01

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

Small Nodules Localization on CT Images of Lungs

NASA Astrophysics Data System (ADS)

Snezhko, E. V.; Kharuzhyk, S. A.; Tuzikov, A. V.; Kovalev, V. A.

2017-05-01

According to the World Health Organization (WHO) lung cancer remains the leading cause of death of men among all malignant tumors [1, 2]. One of the reasons of such a statistics is the fact that the lung cancer is hardly diagnosed on the yearly stages when it is almost asymptomatic. The purpose of this paper is to present a Computer-Aided Diagnosis (CAD) software developed for assistance of early detection of nodules in CT lung images including solitary pulmonary nodules (SPN) as well as multiple nodules. The efficiency of nodule localization was intended to be as high as the level of the best practice. The software developed supports several functions including lungs segmentation, selection of nodule candidates and nodule candidates filtering.

International Space Station (ISS)

NASA Image and Video Library

2003-01-16

In this International Space Station (ISS) onboard photo, Expedition Six Science Officer Donald R. Pettit works to set up the Pulmonary Function in Flight (PuFF) experiment hardware in the Destiny Laboratory. Expedition Six is the fourth and final crew to perform the PuFF experiment. The PuFF experiment was developed to better understand what effects long term exposure to microgravity may have on the lungs. The focus is on measuring changes in the everness of gas exchange in the lungs, and on detecting changes in respiratory muscle strength. It allows astronauts to measure blood flow through the lungs, the ability of the lung to take up oxygen, and lung volumes. Each PuFF session includes five lung function tests, which involve breathing only cabin air. For each planned extravehicular (EVA) activity, a crew member performs a PuFF test within one week prior to the EVA. Following the EVA, those crew members perform another test to document the effect of exposure of the lungs to the low-pressure environment of the space suits. This experiment utilizes the Gas Analyzer System for Metabolic Analysis Physiology, or GASMAP, located in the Human Research Facility (HRF), along with a variety of other Puff equipment including a manual breathing valve, flow meter, pressure-flow module, pressure and volume calibration syringes, and disposable mouth pieces.

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

PubMed

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

2016-01-27

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

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

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 physiology during ECS resuscitation of DCD donors followed by in situ assessment of lung function.

PubMed

Reoma, Junewai L; Rojas, Alvaro; Krause, Eric M; Obeid, Nabeel R; Lafayette, Nathan G; Pohlmann, Joshua R; Padiyar, Niru P; Punch, Jeffery D; Cook, Keith E; Bartlett, Robert H

2009-01-01

Extracorporeal cardiopulmonary support (ECS) of donors after cardiac death (DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in vivo method to assess if lungs are suitable for transplantation from DCD donors after ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10 min of warm ischemia. Cannulae were placed into the right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90 min with lungs inflated, group 1 (n = 5) or deflated, group 2 (n = 3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-ventricular (bi-VAD) system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1-hr assessment period. The oxygenator was turned off, and ventilation was restarted. Flows, blood gases, PA and left atrial pressures, and compliance were recorded. In both the groups, LA pressure was <15 mm Hg during ECS. During the lung assessment period, PA flows were 1.4-2.2 L/min. PO2 was >300 mm Hg, with normal PCO2. Extracorporeal cardiopulmonary support resuscitation of DCD donors is feasible and allows for assessment of function before procurement. Extracorporeal cardiopulmonary support does not cause pulmonary congestion, and the lungs retain adequate function for transplantation. Compliance correlated with lung function.

LUNG PHYSIOLOGY DURING ECS RESUSCITATION OF DCD DONORS FOLLOWED BY IN-SITU ASSESSMENT OF LUNG FUNCTION

PubMed Central

Reoma, Junewai L.; Rojas, Alvaro; Krause, Eric M.; Obeid, Nabeel R.; Lafayette, Nathan G.; Pohlmann, Joshua R.; Padiyar, Niru P.; Punch, Jeffery D; Cook, Keith E.; Bartlett, Robert H

2009-01-01

Extracorporeal cardiopulmonary support(ECS) of donors following cardiac death(DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in-vivo method to assess if lungs are suitable for transplantation from DCD donors following ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10min. of warm ischemia. Cannulas were placed into right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90min with lungs inflated, Group 1 (n=5) or deflated Group 2 (n=3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-VAD system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1hr assessment period. The oxygenator was turned off, and ventilation restarted. Flows, blood gases, pulmonary artery and left atrial pressures, and compliance were recorded. In both groups: LA pressure was <15mmHg during ECS. During the lung assessment period, PA flows were 1.4−2.2 liter/min. PO2 was >300mmHg, with normal PCO2. ECS resuscitation of DCD donors is feasible and allows for assessment of function prior to procurement. ECS does not cause pulmonary congestion, and lungs retain adequate function for transplantation. Compliance correlated with lung function. PMID:19506464

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

PubMed Central

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

2015-01-01

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

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

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

PubMed Central

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

2012-01-01

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

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.

Pulmonary health effects of agriculture.

PubMed

Nordgren, Tara M; Bailey, Kristina L

2016-03-01

Occupational exposures in the agricultural industry are associated with numerous lung diseases, including chronic obstructive pulmonary disease, asthma, hypersensitivity pneumonitis, lung cancer, and interstitial lung diseases. Efforts are ongoing to ascertain contributing factors to these negative respiratory outcomes and improve monitoring of environmental factors leading to disease. In this review, recently published studies investigating the deleterious effects of occupational exposures in the agricultural industry are discussed. Occupational exposures to numerous agricultural environment aerosols, including pesticides, fungi, and bacteria are associated with impaired respiratory function and disease. Increases in certain farming practices, including mushroom and greenhouse farming, present new occupational exposure concerns. Improved detection methods may provide opportunities to better monitor safe exposure levels to known lung irritants. In the agricultural industry, occupational exposures to organic and inorganic aerosols lead to increased risk for lung disease among workers. Increased awareness of respiratory risks and improved monitoring of agricultural environments are necessary to limit pulmonary health risks to exposed populations.

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

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

Nitrogen mustard is a vesicant that causes damage to the respiratory tract. In these studies, we characterized the acute effects of nitrogen mustard on lung structure, inflammatory mediator expression, and pulmonary function, with the goal of identifying mediators potentially involved in toxicity. Treatment of rats (male Wistar, 200-225 g) with nitrogen mustard (mechlorethamine hydrochloride, i.t., 0.25 mg/kg) resulted in marked histological changes in the respiratory tract, including necrotizing bronchiolitis, thickening of alveolar septa, and inflammation which was evident within 24 h. This was associated with increases in bronchoalveolar lavage protein and cells, confirming injury to alveolar epithelial regions of themore » lung. Nitrogen mustard administration also resulted in increased expression of inducible nitric oxide synthase and cyclooxygenase-2, pro-inflammatory proteins implicated in lung injury, in alveolar macrophages and alveolar and bronchial epithelial cells. Expression of connective tissue growth factor and matrix metalloproteinase-9, mediators regulating extracellular matrix turnover was also increased, suggesting that pathways leading to chronic lung disease are initiated early in the pathogenic process. Following nitrogen mustard exposure, alterations in lung mechanics and function were also observed. These included decreases in baseline static compliance, end-tidal volume and airway resistance, and a pronounced loss of methacholine responsiveness in resistance, tissue damping and elastance. Taken together, these data demonstrate that nitrogen mustard induces rapid structural and inflammatory changes in the lung which are associated with altered lung functioning. Understanding the nature of the injury induced by nitrogen mustard and related analogs may aid in the development of efficacious therapies for treatment of pulmonary injury resulting from exposure to vesicants.« less

Clinical measures, smoking, radon exposure, and risk of lung cancer in uranium miners.

PubMed Central

Finkelstein, M M

1996-01-01

OBJECTIVES: Exposure to the radioactive daughters of radon is associated with increased risk of lung cancer in mining populations. An investigation of incidence of lung cancer following a clinical survey of Ontario uranium miners was undertaken to explore whether risk associated with radon is modified by factors including smoking, radiographic silicosis, clinical symptoms, the results of lung function testing, and the temporal pattern of radon exposure. METHODS: Miners were examined in 1974 by a respiratory questionnaire, tests of lung function, and chest radiography. A random selection of 733 (75%) of the original 973 participants was followed up by linkage to the Ontario Mortality and Cancer Registries. RESULTS: Incidence of lung cancer was increased threefold. Risk of lung cancer among miners who had stopped smoking was half that of men who continued to smoke. There was no interaction between smoking and radon exposure. Men with lung function test results consistent with airways obstruction had an increased risk of lung cancer, even after adjustment for cigarette smoking. There was no association between radiographic silicosis and risk of lung cancer. Lung cancer was associated with exposures to radon daughters accumulated in a time window four to 14 years before diagnosis, but there was little association with exposures incurred earlier than 14 years before diagnosis. Among the men diagnosed with lung cancer, the mean and median dose rates were 2.6 working level months (WLM) a year and 1.8 WLM/year in the four to 14 year exposure window. CONCLUSIONS: Risk of lung cancer associated with radon is modified by dose and time from exposure. Risk can be substantially decreased by stopping smoking. PMID:8943835

28 CFR 79.61 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... The term includes in situ lung cancers. (m) Readily available documentation means documents in the... injury means structural or functional damage to the kidney tubules that results in renal disease and... resulting in chronic renal dysfunction. (j) Nonmalignant respiratory disease means fibrosis of the lung...

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.

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

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.

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.

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.

Matrix metalloproteinases: their functional role in lung cancer.

PubMed

Merchant, Neha; Nagaraju, Ganji Purnachandra; Rajitha, Balney; Lammata, Saipriya; Jella, Kishore Kumar; Buchwald, Zachary S; Lakka, Sajani S; Ali, Arif N

2017-08-01

Lung malignancy is the foremost cause of cancer-related deaths globally and is frequently related to long-term tobacco smoking. Recent studies reveal that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared with non-malignant lung tissue. MMPs are zinc-dependent proteases and are involved in the degradation of extracellular matrix (ECM). Several investigations have shown that MMPs manipulate the activity of non-ECM molecules, including cytokines, growth factors and receptors that control the tumor microenvironment. In this review, we have summarized and critically reviewed the published works on the role of MMPs in non-small-cell lung cancer. We have also explored the structure of MMPs, their various types and roles in lung cancer metastasis including invasion, migration and angiogenesis. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2015-03-14

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

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

PubMed

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

2015-11-01

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

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

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

PubMed

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

2014-09-25

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

Lung Parenchymal Mechanics

PubMed Central

Suki, Béla; Stamenovic, Dimitrije; Hubmayr, Rolf

2014-01-01

The lung parenchyma comprises a large number of thin-walled alveoli, forming an enormous surface area, which serves to maintain proper gas exchange. The alveoli are held open by the transpulmonary pressure, or prestress, which is balanced by tissues forces and alveolar surface film forces. Gas exchange efficiency is thus inextricably linked to three fundamental features of the lung: parenchymal architecture, prestress, and the mechanical properties of the parenchyma. The prestress is a key determinant of lung deformability that influences many phenomena including local ventilation, regional blood flow, tissue stiffness, smooth muscle contractility, and alveolar stability. The main pathway for stress transmission is through the extracellular matrix. Thus, the mechanical properties of the matrix play a key role both in lung function and biology. These mechanical properties in turn are determined by the constituents of the tissue, including elastin, collagen, and proteoglycans. In addition, the macroscopic mechanical properties are also influenced by the surface tension and, to some extent, the contractile state of the adherent cells. This article focuses on the biomechanical properties of the main constituents of the parenchyma in the presence of prestress and how these properties define normal function or change in disease. An integrated view of lung mechanics is presented and the utility of parenchymal mechanics at the bedside as well as its possible future role in lung physiology and medicine are discussed. PMID:23733644

RAGE and tobacco smoke: insights into modeling chronic obstructive pulmonary disease

PubMed Central

Robinson, Adam B.; Stogsdill, Jeffrey A.; Lewis, Joshua B.; Wood, Tyler T.; Reynolds, Paul R.

2012-01-01

Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and airspace remodeling, leading to airflow limitation that is not completely reversible. Smoking is the leading risk factor for compromised lung function stemming from COPD pathogenesis. First- and second-hand cigarette smoke contain thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic lung inflammation and destructive alveolar remodeling. Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors primarily expressed by diverse lung cells. RAGE expression increases following cigarette smoke exposure and expression is elevated in the lungs of patients with COPD. RAGE is responsible in part for inducing pro-inflammatory signaling pathways that culminate in expression and secretion of several cytokines, chemokines, enzymes, and other mediators. In the current review, new transgenic mouse models that conditionally over-express RAGE in pulmonary epithelium are discussed. When RAGE is over-expressed throughout embryogenesis, apoptosis in the peripheral lung causes severe lung hypoplasia. Interestingly, apoptosis in RAGE transgenic mice occurs via conserved apoptotic pathways also known to function in advanced stages of COPD. RAGE over-expression in the adult lung models features of COPD including pronounced inflammation and loss of parenchymal tissue. Understanding the biological contributions of RAGE during cigarette smoke-induced inflammation may provide critically important insight into the pathology of COPD. PMID:22934052

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

PubMed

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

2015-09-21

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

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.

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

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

PubMed

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

2016-01-01

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

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

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.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2018-01-01

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

Revascularization of decellularized lung scaffolds: principles and progress

PubMed Central

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

2015-01-01

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

Occupational Lung Disease Risk and Exposure to Butter-Flavoring Chemicals After Implementation of Controls at a Microwave Popcorn Plant

PubMed Central

Kanwal, Richard; Kullman, Greg; Fedan, Kathleen B.; Kreiss, Kathleen

2011-01-01

Objectives After an outbreak of severe lung disease among workers exposed to butter-flavoring chemicals at a microwave popcorn plant, we determined whether or not lung disease risk declined after implementation of exposure controls. Methods National Institute for Occupational Safety and Health staff performed eight serial cross-sectional medical and industrial hygiene surveys at the plant from November 2000 through August 2003. Medical surveys included standardized questionnaires and spirometry testing. Industrial hygiene surveys measured levels of production-related air contaminants, including butter-flavoring chemicals such as diacetyl. All diacetyl concentrations above detectable limits were corrected for the effects of absolute humidity and days to sample extraction. Results Ventilation and isolation of the production process resulted in one to three orders of magnitude reductions in diacetyl air concentrations in different areas of the plant. Workers with past high exposures had stable chest symptoms over time; nasal, eye, and skin irritation symptoms declined. New workers had lower symptom prevalences and higher lung function than workers with past high exposures, and they did not worsen over time. In workers who had at least three spirometry tests, those with past high exposures were more likely to experience rapid declines in lung function than new workers. Conclusions Implemented controls lowered exposures to butter-flavoring chemicals and decreased lung disease risk for much of the plant workforce. Some workers with continuing potential for intermittent, short-term peak and measurable time-weighted exposures remain at risk and should use respiratory protection and have regularly scheduled spirometry to detect rapid lung function declines that may be work-related. Close follow-up of such workers is likely to yield additional information on risks due to peak and time-weighted exposure levels. PMID:21800743

Occupational lung disease risk and exposure to butter-flavoring chemicals after implementation of controls at a microwave popcorn plant.

PubMed

Kanwal, Richard; Kullman, Greg; Fedan, Kathleen B; Kreiss, Kathleen

2011-01-01

After an outbreak of severe lung disease among workers exposed to butter-flavoring chemicals at a microwave popcorn plant, we determined whether or not lung disease risk declined after implementation of exposure controls. National Institute for Occupational Safety and Health staff performed eight serial cross-sectional medical and industrial hygiene surveys at the plant from November 2000 through August 2003. Medical surveys included standardized questionnaires and spirometry testing. Industrial hygiene surveys measured levels of production-related air contaminants, including butter-flavoring chemicals such as diacetyl. All diacetyl concentrations above detectable limits were corrected for the effects of absolute humidity and days to sample extraction. Ventilation and isolation of the production process resulted in one to three orders of magnitude reductions in diacetyl air concentrations in different areas of the plant. Workers with past high exposures had stable chest symptoms over time; nasal, eye, and skin irritation symptoms declined. New workers had lower symptom prevalences and higher lung function than workers with past high exposures, and they did not worsen over time. In workers who had at least three spirometry tests, those with past high exposures were more likely to experience rapid declines in lung function than new workers. Implemented controls lowered exposures to butter-flavoring chemicals and decreased lung disease risk for much of the plant workforce. Some workers with continuing potential for intermittent, short-term peak and measurable time-weighted exposures remain at risk and should use respiratory protection and have regularly scheduled spirometry to detect rapid lung function declines that may be work-related. Close follow-up of such workers is likely to yield additional information on risks due to peak and time-weighted exposure levels.

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.

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.

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.

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

PubMed Central

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

2015-01-01

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

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/.

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

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

PubMed

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

2014-06-01

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

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

PubMed

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

2015-06-01

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

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

PubMed

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

2003-02-01

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

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.

The association between substantiated childhood maltreatment, asthma and lung function: A prospective investigation.

PubMed

Abajobir, Amanuel Alemu; Kisely, Steve; Williams, Gail; Strathearn, Lane; Suresh, Sadasivam; Najman, Jake Moses

2017-10-01

Asthma reflects multiple and likely complex causal pathways. We investigate the possibility that childhood maltreatment is one such causal pathway. Childhood maltreatment can be interpreted as a form of early life adversity and like other life adversities may predict a range of negative health outcomes, including asthma. A total of 3762 young adults (52.63% female) from the Mater Hospital-University of Queensland Study of Pregnancy (MUSP) participated in this study. MUSP is a prospective Australian birth cohort study of mothers consecutively recruited during their first antenatal clinic visit at Brisbane's Mater Hospital from 1981 to 1983. The study followed both mother-child dyads to the age of 21years after birth. Participants reported whether they had been diagnosed by a physician with asthma by the 21-year follow-up. Trained research assistants also performed gender- and height-standardized lung function tests using a Spirobank G spirometer system attached to a laptop computer. We linked this dataset with data obtained from the child protection services and which comprised all substantiated cases of childhood maltreatment in the MUSP cohort. Substantiations of childhood maltreatment included children in an age range of 0-14years. The experience of any childhood maltreatment, particularly emotional abuse, was independently associated with self-reported physician-diagnosed asthma by the 21-year follow-up. The association was no longer significant after adjustment for a range of confounders and covariates in neglected children. Childhood maltreatment, including multiple events, was not associated with lung function in adjusted models. Childhood maltreatment, including emotional abuse, was associated with lifetime ever asthma. This was in contrast to the absence of an association with objective measures of lung function. More research is indicated on the effect of childhood maltreatment on lung function using objective measures. In the meantime, there should be a greater awareness of the potential impact of childhood maltreatment on the potential to develop asthma, as well as of the possibility that asthma in adulthood may precede childhood maltreatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Maternal Electroacupuncture on Perinatal Nicotine Exposure-Induced Lung Phenotype in Offspring.

PubMed

Ji, Bo; Zhao, Guo-Zhen; Sakurai, Reiko; Cao, Yu; Zhang, Zi-Jian; Wang, Dan; Yan, Ming-Na; Rehan, Virender K

2016-08-01

Pregnant women exposed to tobacco smoke predispose the offspring to many adverse consequences including an altered lung development and function. There is no effective therapeutic intervention to block the effects of smoke exposure on the developing lung. Clinical and animal studies demonstrate that acupuncture can modulate a variety of pathophysiological processes, including those involving the respiratory system; however, whether acupuncture affects the lung damage caused by perinatal smoke exposure is not known. To determine the effect of acupuncture on perinatal nicotine exposure on the developing lung, pregnant rat dams were administered (1) saline, (2) nicotine, or (3) nicotine + electroacupuncture (EA). Nicotine was administered (1 mg/kg subcutaneously) once a day and EA was applied to both "Zusanli" (ST 36) points. Both interventions were administered from gestational day 6 to postnatal day 21 (PND21), following which pups were sacrificed. Lungs, blood, and brain were collected to examine markers of lung injury, repair, and hypothalamic pituitary adrenal (HPA) axis. Concomitant EA application blocked nicotine-induced changes in lung morphology, lung peroxisome proliferator-activated receptor γ and wingless-int signaling, two key lung developmental signaling pathways, hypothalamic pituitary adrenal axis (hypothalamic corticotropic releasing hormone and lung glucocorticoid receptor levels), and plasma β-endorphin levels. Electroacupuncture blocks the nicotine-induced changes in lung developmental signaling pathways and the resultant myogenic lung phenotype, known to be present in the affected offspring. We conclude that EA is a promising novel intervention against the smoke exposed lung damage to the developing lung.

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

PubMed

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

2017-11-01

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

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

PubMed Central

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

2013-01-01

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

Nuclear Factor-Kappa-B Signaling in Lung Development and Disease: One Pathway, Numerous Functions

PubMed Central

Alvira, Cristina M

2014-01-01

In contrast to other organs, the lung completes a significant portion of its development after term birth. During this stage of alveolarization, division of the alveolar ducts into alveolar sacs by secondary septation, and expansion of the pulmonary vasculature by means of angiogenesis markedly increase the gas exchange surface area of the lung. However, postnatal completion of growth renders the lung highly susceptible to environmental insults such as inflammation that disrupt this developmental program. This is particularly evident in the setting of preterm birth, where impairment of alveolarization causes bronchopulmonary dysplasia, a chronic lung disease associated with significant morbidity. The nuclear factor κ-B (NFκB) family of transcription factors are ubiquitously expressed, and function to regulate diverse cellular processes including proliferation, survival, and immunity. Extensive evidence suggests that activation of NFκB is important in the regulation of inflammation and in the control of angiogenesis. Therefore, NFκB-mediated downstream effects likely influence the lung response to injury and may also mediate normal alveolar development. This review summarizes the main biologic functions of NFκB, and highlights the regulatory mechanisms that allow for diversity and specificity in downstream gene activation. This is followed by a description of the pro and anti-inflammatory functions of NFκB in the lung, and of NFκB-mediated angiogenic effects. Finally, this review summarizes the clinical and experimental data that support a role for NFκB in mediating postnatal angiogenesis and alveolarization, and discusses the challenges that remain in developing therapies that can selectively block the detrimental functions of NFκB yet preserve the beneficial effects. Birth Defects Research (Part A) 100:202–216, 2014. © 2014 Wiley Periodicals, Inc. PMID:24639404

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

PubMed

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

2018-02-01

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

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.

Resident alveolar macrophages are master regulators of arrested alveolarization in experimental bronchopulmonary dysplasia.

PubMed

Kalymbetova, Tatiana V; Selvakumar, Balachandar; Rodríguez-Castillo, José Alberto; Gunjak, Miša; Malainou, Christina; Heindl, Miriam Ruth; Moiseenko, Alena; Chao, Cho-Ming; Vadász, István; Mayer, Konstantin; Lohmeyer, Jürgen; Bellusci, Saverio; Böttcher-Friebertshäuser, Eva; Seeger, Werner; Herold, Susanne; Morty, Rory E

2018-06-01

Trophic functions for macrophages are emerging as key mediators of developmental processes, including bone, vessel, and mammary gland development. Yolk sac-derived macrophages mature in the distal lung shortly after birth. Myeloid-lineage macrophages are recruited to the lung and are activated under pathological conditions. These pathological conditions include bronchopulmonary dysplasia (BPD), a common complication of preterm birth characterized by stunted lung development, where the formation of alveoli is blocked. No study has addressed causal roles for immune cells in lung alveolarization. We employed antibody-based and transgenic death receptor-based depletion approaches to deplete or prevent lung recruitment of immune cell populations in a hyperoxia-based mouse model of BPD. Neither neutrophils nor exudate macrophages (which might include lung interstitial macrophages) contributed to structural perturbations to the lung that were provoked by hyperoxia; however, cells of the Csf1r-expressing monocyte/macrophage lineage were implicated as causal mediators of stunted lung development. We propose that resident alveolar macrophages differentiate into a population of CD45 + CD11c + SiglecF + CD11b + CD68 + MHCII + cells, which are activated by hyperoxia, and contribute to disturbances to the structural development of the immature lung. This is the first report that causally implicates immune cells in pathological disturbances to postnatal lung organogenesis. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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

PubMed

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

1999-05-01

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

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.

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

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

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

2014-06-01

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

Correlation of lung surface area to apoptosis and proliferation in human emphysema.

PubMed

Imai, K; Mercer, B A; Schulman, L L; Sonett, J R; D'Armiento, J M

2005-02-01

Pulmonary emphysema is associated with alterations in matrix proteins and protease activity. These alterations may be linked to programmed cell death by apoptosis, potentially influencing lung architecture and lung function. To evaluate apoptosis in emphysema, lung tissue was analysed from 10 emphysema patients and six individuals without emphysema (normal). Morphological analysis revealed alveolar cells in emphysematous lungs with convoluted nuclei characteristic of apoptosis. DNA fragmentation was detected using terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL) and gel electrophoresis. TUNEL revealed higher apoptosis in emphysematous than normal lungs. Markers of apoptosis, including active caspase-3, proteolytic fragment of poly (ADP-ribose) polymerase, Bax and Bad, were detected in emphysematous lungs. Linear regression showed that apoptosis was inversely correlated with surface area. Emphysematous lungs demonstrated lower surface areas and increased cell proliferation. There was no correlation between apoptosis and proliferation, suggesting that, although both events increase during emphysema, they are not in equilibrium, potentially contributing to reduced lung surface area. In summary, cell-based mechanisms associated with emphysematous parenchymal damage include increased apoptosis and cell proliferation. Apoptosis correlated with airspace enlargement, supporting epidemiological evidence of the progressive nature of emphysema. These data extend the understanding of cell dynamics and structural changes within the lung during emphysema pathogenesis.

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

PubMed

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

2009-04-15

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

Cross sectional study on lung function of coke oven workers: a lung function surveillance system from 1978 to 1990

PubMed Central

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

2002-01-01

Aims: To determine the association between lung function of coke oven workers and exposure to coke oven emissions. Methods: Lung function data and detailed work histories for workers in recovery coke ovens of a steelworks were extracted from a lung function surveillance system. Multiple regressions were employed to determine significant predictors for lung function indices. The first sets of lung function tests for 613 new starters were pooled to assess the selection bias. The last sets of lung function tests for 834 subjects with one or more year of coke oven history were pooled to assess determinants of lung function. Results: Selection bias associated with the recruitment process was not observed among the exposure groups. For subjects with a history of one or more years of coke oven work, each year of working in the most exposed "operation" position was associated with reductions in FEV1 of around 9 ml (p = 0.006, 95% CI: 3 ml to 16 ml) and in FVC of around 12 ml (p = 0.002, 95% CI: 4 ml to 19 ml). Negative effects of smoking on lung function were also observed. Conclusions: Exposure to coke oven emissions was found to be associated with lower FEV1 and FVC. Effects of work exposure on lung function are similar to those found in other studies. PMID:12468747

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

PubMed

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

2014-09-01

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

Causes of death of patients with lung cancer.

PubMed

Nichols, Larry; Saunders, Rachel; Knollmann, Friedrich D

2012-12-01

The causes of death for patients with lung cancer are inadequately described. To categorize the immediate and contributing causes of death for patients with lung cancer. The autopsies from 100 patients who died of lung cancer between 1990 and February 2011 were analyzed. Tumor burden was judged the immediate cause of death in 30 cases, including 26 cases of extensive metastases and 4 cases with wholly or primarily lung tumor burden (causing respiratory failure). Infection was the immediate cause of death for 20 patients, including 8 with sepsis and 12 with pneumonia. Complications of metastatic disease were the immediate causes of death in 18 cases, including 6 cases of hemopericardium from pericardial metastases, 3 from myocardial metastases, 3 from liver metastases, and 3 from brain metastases. Other immediate causes of death were pulmonary hemorrhage (12 cases), pulmonary embolism (10 cases, 2 tumor emboli), and pulmonary diffuse alveolar damage (7 cases). From a functional (pathophysiologic) perspective, respiratory failure could be regarded as the immediate cause of death (or mechanism of death) in 38 cases, usually because of a combination of lung conditions, including emphysema, airway obstruction, pneumonia, hemorrhage, embolism, resection, and lung injury in addition to the tumor. For 94 of the 100 patients, there were contributing causes of death, with an average of 2.5 contributing causes and up to 6 contributing causes of death. The numerous and complex ways lung cancer kills patients pose a challenge for efforts to extend and improve their lives.

Wheezing

MedlinePlus

... done include: Blood work, possibly including arterial blood gases Chest x-ray Lung function tests A hospital ... 2018, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

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.

Polysaccharide K and Coriolus versicolor extracts for lung cancer: a systematic review.

PubMed

Fritz, Heidi; Kennedy, Deborah A; Ishii, Mami; Fergusson, Dean; Fernandes, Rochelle; Cooley, Kieran; Seely, Dugald

2015-05-01

Polysaccharide K, also known as PSK or Krestin, is derived from the Coriolus versicolor mushroom and is widely used in Japan as an adjuvant immunotherapy for a variety of cancer including lung cancer. Despite reported benefits, there has been no English language synthesis of PSK for lung cancer. To address this knowledge gap, we conducted a systematic review of PSK for the treatment of lung cancer. We searched PubMed, EMBASE, CINAHL, the Cochrane Library, AltHealth Watch, and the Library of Science and Technology from inception to August 2014 for clinical and preclinical evidence pertaining to the safety and efficacy of PSK or other Coriolus versicolor extracts for lung cancer. Thirty-one reports of 28 studies were included for full review and analysis. Six studies were randomized controlled trials, 5 were nonrandomized controlled trials, and 17 were preclinical studies. Nine of the reports were Japanese language publications. Fifteen of 17 preclinical studies supported anticancer effects for PSK through immunomodulation and potentiation of immune surveillance, as well as through direct tumor inhibiting actions in vivo that resulted in reduced tumor growth and antimetastatic effects. Nonrandomized controlled trials showed improvement of various survival measures including median survival and 1-, 2-, and 5-year survival. Randomized controlled trials showed benefits on a range of endpoints, including immune parameters and hematological function, performance status and body weight, tumor-related symptoms such as fatigue and anorexia, as well as survival. Although there were conflicting results for impact on some of the tumor-related symptoms and median survival, overall most randomized controlled trials supported a positive impact for PSK on these endpoints. PSK was safely administered following and in conjunction with standard radiation and chemotherapy. PSK may improve immune function, reduce tumor-associated symptoms, and extend survival in lung cancer patients. Larger, more rigorous randomized controlled trials for PSK in lung cancer patients are warranted. © The Author(s) 2015.

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

PubMed

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

2012-01-01

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

Brain-Derived Neurotrophic Factor in the Airways

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed Central

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

2016-01-01

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

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

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

PubMed

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

2017-08-24

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

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

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.

Clinical Outcomes of Paramyxovirus Infections in Lung Transplant Recipients Treated With Oral Ribavirin: A Two-Center Case Series.

PubMed

Garcia, Bryan; Sharma, Nirmal; Johnson, Kevin; Salgado, Juan; Wille, Keith

2017-10-31

Paramyxoviruses contribute to morbidity and mortality after lung transplant and are associated with bronchiolitis obliterans syndrome. Oral ribavirin has been used off-label for treatment of paramyxoviruses in immunosuppressed patients; however, data supporting its use for this purpose are lacking. We conducted a retrospective review to evaluate clinical outcomes of lung transplant recipients infected with paramyxoviruses and received treatment with oral ribavirin at 2 tertiary referral centers. Patients who were diagnosed with paramyxovirus infection by polymerase chain reaction testing between January 2011 and December 2014 and who received oral ribavirin were included. Clinical outcomes included pulmonary function testing, infection severity, and adverse events related to treatment. Twenty-six patients were diagnosed with a paramyxovirus and received oral ribavirin. The changes in mean forced expiratory volume 1 second from preinfection to infection onset and from infection onset to postinfection were significant (1.79 ± 0.13 to 1.61 ± 0.12 L and 1.61 ± 0.12L to 1.74 ± 0.12 L; P = .0001). Similar results were seen in subgroup analysis when respiratory syncytial virus and parainfluenza infections were evaluated independently. Use of oral ribavirin for treatment of paramyxovirus infections in lung transplant recipients was safe and associated with recovery of lung function.

Factors Associated with Life Expectancy in Patients with Metastatic Spine Disease from Adenocarcinoma of the Lung

PubMed Central

Goodwin, C. Rory; Khattab, Mohamed H.; Sankey, Eric W.; Elder, Benjamin D.; Kosztowski, Thomas A.; Sarabia-Estrada, Rachel; Bydon, Ali; Witham, Timothy F.; Wolinsky, Jean-Paul; Gokaslan, Ziya L.; Sciubba, Daniel M.

2015-01-01

Study Design Retrospective study. Objective Our objective was to identify preoperative prognostic factors associated with survival in patients with spinal metastasis from lung carcinoma. Methods A retrospective analysis of 26 patients diagnosed with lung carcinoma metastatic to the spinal column was performed to determine factors associated with survival. We used 3 months survival as the clinical cutoff for whether surgical intervention should be performed. We analyzed patients who survived less than 3 months compared with those who survived more than 3 months. Demographic, preoperative, operative, and postoperative factors including functional scores were collected for analysis. Results The median survival for all patients in our study was 3.5 months. We found a statistically significant difference between the group that survived less than 3 months and the group that survived greater than 3 months in terms of extrathoracic metastasis, visceral metastasis, and average postoperative modified Rankin score. Conclusion Determining which patients with lung cancer spinal metastases will benefit from surgical intervention is often dictated by the patient's predicted life expectancy. Factors associated with poorer prognosis include age, functional status, visceral metastases, and extrathoracic metastases. Although the prognosis for patients with lung cancer spinal metastases is poor, some patients may experience long-term benefit from surgical intervention. PMID:26430597

Cold stress aggravates inflammatory responses in an LPS-induced mouse model of acute lung injury

NASA Astrophysics Data System (ADS)

Joo, Su-Yeon; Park, Mi-Ju; Kim, Kyun-Ha; Choi, Hee-Jung; Chung, Tae-Wook; Kim, Yong Jin; Kim, Joung Hee; Kim, Keuk-Jun; Joo, Myungsoo; Ha, Ki-Tae

2016-08-01

Although the relationship between environmental cold temperature and susceptibility to respiratory infection is generally accepted, the effect of ambient cold temperature on host reactivity in lung inflammation has not been fully studied. To examine the function of ambient cold temperature on lung inflammation, mice were exposed to 4 °C for 8 h each day for 14 days. In the lungs of mice exposed to cold stress, inflammatory cells in bronchoalveolar lavage (BAL) fluid and lung tissues were slightly increased by about twofold. However, the structures of pulmonary epithelial cells were kept within normal limits. Next, we examined the effect of cold stress on the inflammatory responses in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The infiltration of neutrophils and inflammation of lung tissue determined by histology were significantly increased by exposure to ambient cold temperature. In addition, the production of pro-inflammatory cytokines including interleukin (IL)-12, IL-17, and monokine induced by gamma interferon (MIG) was elevated by exposure to cold stress. Therefore, we suggest that cold stress is a factor that exacerbates lung inflammation including ALI. To our knowledge, this is the first report on the relationship between cold stress and severity of lung inflammation.

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.

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.

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.

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-04-01

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

Tranexamic Acid Attenuates The Loss of Lung Barrier Function in a Rat Model of Polytrauma And Hemorrhage With Resuscitation.

PubMed

Wu, Xiaowu; Dubick, Michael A; Schwacha, Martin G; Cap, Andrew P; Darlington, Daniel N

2017-04-01

Severe trauma, hemorrhage, and resuscitation can lead to a trauma-related acute lung injury that involves rapid infiltration of immune cells and platelets. This infiltration involves exymatic degradation of matrix proteins, including plasmin, and causes loss of barrier function. Since tranexamic acid (TXA) inhibits plasminogen/ plasmin binding to target substrates, it may attenuate loss of barrier function after severe trauma, hemorrhage, and resuscitation. Sprague-Dawley rats were subjected to polytrauma (laparotomy, and trauma to intestines, liver, right leg skeletal muscle, and right femur fracture), then bled 40% of their blood volume. One hour after completion of polytrauma and hemorrhage, resuscitation was begun with fresh whole blood (FWB) or FWB with prior bolus administration of TXA (10 mg/kg in 0.2 mL). Polytrauma, hemorrhage, and resuscitation with FWB led to an elevation in lung water content that was significantly reduced with TXA administration. Polytrauma and hemorrhage led to rise in the number of neutrophils/monocytes and platelets in the lungs, and a rise in myeloperoxidase (MPO), neutrophil elastase and complement C5a content. While resuscitation with FWB significantly reduced the cellular infiltrate and MPO, FWB/TXA further reduced the levels of neutrophil/monocytes, neutrophil elastase, and complement C5a. Polytrauma and hemorrhage led to rise in lung plasmin activity that was significantly reduced with either FWB or FWB/TXA resuscitation. Severe trauma and hemorrhage leads to increases in lung water content, and immune cell, platelets, MPO, elastase, and C5a content in lung tissue, all markers of inflammation and acute lung injury. The addition of TXA to FWB resuscitation markedly attenuated the rise in these parameters suggesting its utility in treating acute lung injury.

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.

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

Lung Structure and the Intrinsic Challenges of Gas Exchange

PubMed Central

Hsia, Connie C.W.; Hyde, Dallas M.; Weibel, Ewald R.

2016-01-01

Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to all lung units within a confined thoracic space, to build a large gas exchange surface associated with minimal barrier thickness and a microvascular network to accommodate the entire right ventricular cardiac output while withstanding cyclic mechanical stresses that increase several folds from rest to exercise. Intricate regulatory mechanisms at every level ensure that the dynamic capacities of ventilation, perfusion, diffusion, and chemical binding to hemoglobin are commensurate with usual metabolic demands and periodic extreme needs for activity and survival. This article reviews the structural design of mammalian and human lung, its functional challenges, limitations, and potential for adaptation. We discuss (i) the evolutionary origin of alveolar lungs and its advantages and compromises, (ii) structural determinants of alveolar gas exchange, including architecture of conducting bronchovascular trees that converge in gas exchange units, (iii) the challenges of matching ventilation, perfusion, and diffusion and tissue-erythrocyte and thoracopulmonary interactions. The notion of erythrocytes as an integral component of the gas exchanger is emphasized. We further discuss the signals, sources, and limits of structural plasticity of the lung in alveolar hypoxia and following a loss of lung units, and the promise and caveats of interventions aimed at augmenting endogenous adaptive responses. Our objective is to understand how individual components are matched at multiple levels to optimize organ function in the face of physiological demands or pathological constraints. PMID:27065169

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

PubMed

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

2014-01-01

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

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

PubMed

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

2010-07-01

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

Pulmonary Screening in Subjects after the Fontan Procedure.

PubMed

Liptzin, Deborah R; Di Maria, Michael V; Younoszai, Adel; Narkewicz, Michael R; Kelly, Sarah L; Wolfe, Kelly R; Veress, Livia A

2018-05-07

To review the pulmonary findings of the first 51 patients who presented to our interdisciplinary single-ventricle clinic after undergoing the Fontan procedure. We performed an Institutional Review Board-approved retrospective review of 51 patients evaluated following the Fontan procedure. Evaluation included history, physical examination, pulmonary function testing, and 6-minute walk. Descriptive statistics were used to describe the population and testing data. Sixty-one percent of the patients had a pulmonary concern raised during the visit. Three patients had plastic bronchitis. Abnormal lung function testing was present in 46% of patients. Two-thirds (66%) of the patients had significant desaturation during the 6-minute walk test. Patients who underwent a fenestrated Fontan procedure and those who underwent unfenestrated Fontan were compared in terms of saturation and 6-minute walk test results. Sleep concerns were present in 45% of the patients. Pulmonary morbidities are common in patients after Fontan surgery and include plastic bronchitis, abnormal lung function, desaturations with walking, and sleep concerns. Abnormal lung function and obstructive sleep apnea may stress the Fontan circuit and may have implications for cognitive and emotional functioning. A pulmonologist involved in the care of patients after Fontan surgery can assist in screening for comorbidities and recommend interventions. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

Franklin, Meredith; Fruin, Scott

2017-08-01

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

Physical activity levels early after lung transplantation.

PubMed

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

2015-04-01

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

Respiratory function in wind instrument players.

PubMed

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

2009-01-01

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

Programming of respiratory health in childhood: influence of outdoor air pollution.

PubMed

Wright, Rosalind J; Brunst, Kelly J

2013-04-01

This overview highlights recent experimental and epidemiological evidence for the programming effects of outdoor air pollution exposures during early development on lung function and chronic respiratory disorders, such as asthma and related allergic disorders. Air pollutants may impact anatomy and/or physiological functioning of the lung and interrelated systems. Programming effects may result from pollutant-induced shifts in a number of molecular, cellular, and physiological states and their interacting systems. Specific key regulatory systems susceptible to programming may influence lung development and vulnerability to respiratory diseases, including both central and peripheral components of neuroendocrine pathways and autonomic nervous system (ANS) functioning which, in turn, influence the immune system. Starting in utero, environmental factors, including air pollutants, may permanently organize these systems toward trajectories of enhanced pediatric (e.g., asthma, allergy) as well as adult disease risk (e.g., chronic obstructive pulmonary disease). Evidence supports a central role of oxidative stress in the toxic effects of air pollution. Additional research suggests xenobiotic metabolism and subcellular components, such as mitochondria are targets of ambient air pollution and play a role in asthma and allergy programming. Mechanisms operating at the level of the placenta are being elucidated. Epigenetic mechanisms may be at the roots of adaptive developmental programming. Optimal coordinated functioning of many complex processes and their networks of interaction are necessary for normal lung development and the maintenance of respiratory health. Outdoor air pollution may play an important role in early programming of respiratory health and is potentially amenable to intervention.

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.

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.

Research Advances in Resistance to Platinum-based Chemotherapy in Lung Cancer.

PubMed

Zhang, Yajuan; Chang, De; Zhang, Jianpeng

2017-02-20

Platinum-based chemotherapy is the the cornerstone of treatment of many cancers. Combinations of platinum drugs with other agents are still the mainstream therapies for non-small cell lung cancer,showing significant effectiveness in an early phase. Along with the treatment,the tumor cells can become resistant to chemotherapy drugs,which affect the efficacy and prognosis. The mechanisms of drug resistance are complicated,including abnormal expressions of membrane proteins,enhanced DNA repair functions,abnormal regulation mechanisms of apoptosis,and enhanced cellular detoxification function. In this article we summarize some of the main mechanisms of platinum resistance in lung cancer cells,with an attempt to identify new potential target analogues or inhibitors and improve the efficacies of the combined use of platinum-based drugs.

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

PubMed Central

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

2015-01-01

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

Paraneoplastic syndromes associated with lung cancer

PubMed Central

Kanaji, Nobuhiro; Watanabe, Naoki; Kita, Nobuyuki; Bandoh, Shuji; Tadokoro, Akira; Ishii, Tomoya; Dobashi, Hiroaki; Matsunaga, Takuya

2014-01-01

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau’s syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer. PMID:25114839

Cardiorespiratory Interactions in Paediatrics: 'It's (almost always) the circulation stupid!'

PubMed

Rigby, M L; Rosenthal, M

2017-03-01

The interaction of the heart and lungs is probably the most important aspect of life and survival. Fortunately, it is not difficult to understand the fundamentals. The purpose of the lungs and their ventilation is to present oxygen to the circulation via the alveoli and to receive carbon dioxide from the circulation and then expel it. The relations of the heart and lungs and the matching of blood flow to the various organs with ventilation and lung perfusion may be disrupted by a variety of congenital or acquired heart malformations. They include those giving rise to an increased or reduced pulmonary blood flow, elevated pulmonary venous pressure or external physical pressure on the airways or lung parenchyma. Respiratory disorders which compromise cardiac function include states with reduced alveolar ventilation, those with a barrier to ventilation or perfusion, ventilation/perfusion mismatch and pulmonary vascular disease. There is also a fascinating group in which congenital disorders of the heart and lung co-exist to produce very particular modes of abnormal cardiopulmonary interaction. Copyright © 2016. Published by Elsevier Ltd.

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

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.

[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).

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.

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

PubMed

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

2016-07-27

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

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

PubMed

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

2018-07-01

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

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

PubMed

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

2007-02-15

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

Therapeutic approach to respiratory infections in lung transplantation.

PubMed

Clajus, Carolina; Blasi, Francesco; Welte, Tobias; Greer, Mark; Fuehner, Thomas; Mantero, Marco

2015-06-01

Lung transplant recipients (LTRs) are at life-long risk for infections and disseminated diseases owing to their immunocompromised state. Besides organ failure and sepsis, infection can trigger acute and chronic graft rejection which increases mortality. Medical prophylaxis and treatment are based on comprehensive diagnostic work-up including previous history of infection and airway colonisation to reduce long-term complications and mortality. Common bacterial pathogens include Pseudomonas and Staphylococcus, whilst Aspergillus and Cytomegalovirus (CMV) are respectively the commonest fungal and viral pathogens. Clinical symptoms can be various in lung transplant recipients presenting an asymptomatic to severe progress. Regular control of infection parameters, daily lung function testing and lifelong follow-up in a specialist transplant centre are mandatory for early detection of bacterial, viral and fungal infections. After transplantation each patient receives intensive training with rules of conduct concerning preventive behaviour and to recognize early signs of post transplant complications. Early detection of infection and complications are important goals to reduce major complications after lung transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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

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

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

1975-11-01

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

Lungs from donation after circulatory death donors: an alternative source to brain-dead donors? Midterm results at a single institution.

PubMed

Zych, Bartlomiej; Popov, Aron-Frederik; Amrani, Mohamed; Bahrami, Toufan; Redmond, Karen Christina; Krueger, Heike; Carby, Martin; Simon, André Ruediger

2012-09-01

Donor organ shortage remains to be the major limitation in lung transplantation, and donation after circulatory death (DCD) might represent one way to alleviate this problem. DCD was introduced to our institution in 2007 and has been a part of our clinical routine since then. Here, we present the mid-term results of lung transplantation from DCD in a single institution and compare the outcomes with the lung recipient cohort receiving lungs from donation after brain death (DBD). Since initiation of the DCD programme in March 2007, of the 157 lung transplantations performed, 26 (16.5%) were retrieved from DCD donors, with 25 double- and 1 single-lung transplants being performed. Results were compared with standard DBD transplantations. Analyses included, amongst others, donor characteristics, survival, prevalence of primary graft dysfunction, acute rejection, lung function tests during follow-up, onset of bronchiolitis obliterans syndrome (BOS) as well as duration of mechanical ventilation, hospital and intensive care unit length of stay. While there was no significant difference between lung function, BOS and survival between the two groups, lungs from DCD donors had a higher PaO(2) (median; interquartile range) 498.3 (451.5; 525) vs. DBD 442.5 (371.25; 502) kPa before retrieval (P = 0.009). There was also a longer total ischaemic time in the DCD vs. DBD group: 320 min (298.75; 393.25) vs. 285.5 min (240; 373) (P = 0.025). All other parameters were comparable. Medium-term results after lung transplantation with organs procured after circulatory death are comparable with those obtained after standard lung transplantation. Therefore, DCD could be used to significantly increase the donor pool.

Inhibition of the purinergic pathway prolongs mouse lung allograft survival.

PubMed

Liu, Kaifeng; Vergani, Andrea; Zhao, Picheng; Ben Nasr, Moufida; Wu, Xiao; Iken, Khadija; Jiang, Dawei; Su, Xiaofeng; Fotino, Carmen; Fiorina, Paolo; Visner, Gary A

2014-08-01

Lung transplantation has limited survival with current immunosuppression. ATP is released from activated T cells, which act as costimulatory molecules through binding to the purinergic receptor P2XR7. We investigated the role of blocking the ATP/purinergic pathway, primarily P2XR7, using its inhibitor oxidized ATP (oATP) in modulating rejection of mouse lung allografts. Mouse lung transplants were performed using mice with major histocompatibility complex mismatch, BALB/c to C57BL6. Recipients received suramin or oATP, and lung allografts were evaluated 15 to ≥ 60 days after transplantation. Recipients were also treated with oATP after the onset of moderate to severe rejection to determine its ability to rescue lung allografts. Outcomes measures included lung function, histology, thoracic imaging, and allo-immune responses. Blocking purinergic receptors with the nonselective inhibitor suramin or with the P2XR7-selective inhibitor oATP reduced acute rejection and prolonged lung allograft survival for ≥ 60 days with no progression in severity. There were fewer inflammatory cells within lung allografts, less rejection, and improved lung function, which was maintained over time. CD4 and CD8 T cells were reduced within lung allografts with impaired activation with prolonged impairment of CD8 responses. In vitro, oATP reduced CD8 activation of Th1 inflammatory cytokines IFN-γ and TNF-α and cytolytic machinery, granzyme B. Cotreatment with immunosuppressive agents, cyclosporine, rapamycin, or CTLA-4Ig resulted in no additive benefits, and oATP alone resulted in better outcomes than cyclosporine alone. This study illustrates a potential new pathway to target in hopes of prolonging survival of lung transplant recipients.

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.

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

PubMed

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

2018-04-15

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

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

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

PubMed

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

2016-11-01

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

Predictors of oxygen desaturation during submaximal exercise in 8,000 patients.

PubMed

Hadeli, K O; Siegel, E M; Sherrill, D L; Beck, K C; Enright, P L

2001-07-01

To determine predictors of oxygen desaturation during submaximal exercise in patients with various lung diseases. This retrospective case series used pulmonary function laboratory results from all patients referred to a major tertiary-care center. All patients > or = 35 years old who underwent spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), lung volumes, and pulse oximetry during 3-min submaximal step-test exercise during 1996 were included (4,545 men and 3,472 women). Logistic regression models, correcting for gender, age, and weight, determined the odds ratios (ORs) for oxygen desaturation of > or = 4% during exercise for each category of lung function abnormality (compared to those with entirely normal lung function). Approximately 74% of the patients had airways obstruction, while only 5.6% had restriction of lung volumes. One third of those with obstruction had a low DLCO, compared to 56% with restriction, while 2.7% had a low DLCO without obstruction or restriction. The risk of oxygen desaturation during submaximal exercise was very high (OR, 34) in patients with restriction and low DLCO (as in interstitial lung disease) and in patients with obstruction and low DLCO (as in COPD; OR, 18), intermediate (OR, 9) in patients with only a low DLCO, and lowest in those with a normal DLCO (OR, 4 if restricted; OR, 2 if obstructed). A cut point of DLCO < 62% predicted resulted in 75% sensitivity and specificity for exercise desaturation. No untoward cardiac events occurred in any patients during or following the submaximal exercise tests. The risk of oxygen desaturation during submaximal exercise is very high in patients with a low DLCO. Submaximal exercise tests are safe, even in elderly patients with heart and lung diseases.

Impact of spirometry feedback and brief motivational counseling on long term smoking outcomes: A comparison of smokers with and without lung impairment

PubMed Central

McClure, Jennifer B.; Ludman, Evette J.; Grothaus, Lou; Pabiniak, Chester; Richards, Julie

2009-01-01

Objective We compared long-term outcomes among smokers with and without impaired lung functioning who received brief counseling highlighting their spirometric test results. Methods Participants in this analysis all received a brief motivational intervention for smoking cessation including spirometric testing and feedback (~20 minutes), were advised to quit smoking, offered free access to a phone-based smoking cessation program, and followed for one year. Outcomes were analyzed for smokers with (n = 99) and without (n = 168) impaired lung function. Results Participants with lung impairment reported greater use of self-help cessation materials at 6 months, greater use of non-study-provided counseling services at 6 and 12 months, higher 7-day PPA rates at 6 months, and were more likely to talk with their doctor about their spirometry results. Conclusion Further research is warranted to determine if spirometry feedback has a differential treatment effect among smokers with and without lung impairment. Practice Implications It is premature to make practice recommendations based on these data. PMID:20434863

Impact of spirometry feedback and brief motivational counseling on long-term smoking outcomes: a comparison of smokers with and without lung impairment.

PubMed

McClure, Jennifer B; Ludman, Evette J; Grothaus, Lou; Pabiniak, Chester; Richards, Julie

2010-08-01

We compared long-term outcomes among smokers with and without impaired lung functioning who received brief counseling highlighting their spirometric test results. Participants in this analysis all received a brief motivational intervention for smoking cessation including spirometric testing and feedback ( approximately 20 min), were advised to quit smoking, offered free access to a phone-based smoking cessation program, and followed for one year. Outcomes were analyzed for smokers with (n=99) and without (n=168) impaired lung function. Participants with lung impairment reported greater use of self-help cessation materials at 6 months, greater use of non-study-provided counseling services at 6 and 12 months, higher 7-day PPA rates at 6 months, and were more likely to talk with their doctor about their spirometry results. Further research is warranted to determine if spirometry feedback has a differential treatment effect among smokers with and without lung impairment. It is premature to make practice recommendations based on these data. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Acute kidney injury after liver, heart, and lung transplants: dialysis modality, predictors of renal function recovery, and impact on survival.

PubMed

Pham, Phuong-Thu T; Slavov, Carmen; Pham, Phuong-Chi T

2009-07-01

Recipients of nonrenal organ transplants including the liver, heart, and lung are at risk for developing acute kidney injury (AKI) and chronic kidney disease (CKD). Underlying hepatic or cardiopulmonary failure, prolonged intraoperative hemodynamic instability, and the use of calcineurin inhibitors and nephrotoxic medications have all been suggested to be contributory. The incidence of perioperative AKI has been reported to occur in 17% to 95% in liver transplant recipients, 5% to 30% in heart transplant recipients, and 5% to 60% in recipients of lung transplants. Among those who develop AKI, renal replacement therapy is required in 5% to 35%, 5% to 15%, and 8% to 10% in liver, heart, and lung transplant recipients, respectively. The current article presents an overview of the literature on the choice of dialysis modality and its associated advantages and disadvantages in the management of AKI after liver, heart, and lung transplants. Predictive factors for renal function recovery and the impact of AKI and CKD on survival will also be discussed.

Long Noncoding RNAs in Lung Cancer.

PubMed

Roth, Anna; Diederichs, Sven

2016-01-01

Despite great progress in research and treatment options, lung cancer remains the leading cause of cancer-related deaths worldwide. Oncogenic driver mutations in protein-encoding genes were defined and allow for personalized therapies based on genetic diagnoses. Nonetheless, diagnosis of lung cancer mostly occurs at late stages, and chronic treatment is followed by a fast onset of chemoresistance. Hence, there is an urgent need for reliable biomarkers and alternative treatment options. With the era of whole genome and transcriptome sequencing technologies, long noncoding RNAs emerged as a novel class of versatile, functional RNA molecules. Although for most of them the mechanism of action remains to be defined, accumulating evidence confirms their involvement in various aspects of lung tumorigenesis. They are functional on the epigenetic, transcriptional, and posttranscriptional level and are regulators of pathophysiological key pathways including cell growth, apoptosis, and metastasis. Long noncoding RNAs are gaining increasing attention as potential biomarkers and a novel class of druggable molecules. It has become clear that we are only beginning to understand the complexity of tumorigenic processes. The clinical integration of long noncoding RNAs in terms of prognostic and predictive biomarker signatures and additional cancer targets could provide a chance to increase the therapeutic benefit. Here, we review the current knowledge about the expression, regulation, biological function, and clinical relevance of long noncoding RNAs in lung cancer.

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.

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

PubMed

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

2018-06-30

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

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.

Perfluorodecalin lavage of a longstanding lung atelectasis in a child with spinal muscle atrophy.

PubMed

Henrichsen, Thore; Lindenskov, Paal H H; Shaffer, Thomas H; Loekke, Ruth J V; Fugelseth, Drude; Lindemann, Rolf

2012-04-01

Persistent lung atelectasis is difficult to treat and perfluorochemical (PFC) liquid may be an option for bronchioalveolar lavage (BAL). A 4-year-old girl with spinal muscle atrophy was admitted in respiratory failure. On admission, the X-ray confirmed the persistence of total right-sided lung atelectasis, which had been present for 14 months. She was endotracheally intubated and ventilated from the day of admission. BAL with normal saline was performed twice without improvement. Following failed extubation and being dependent on continuous respiratory support, a trial of BAL using PFC liquid (Perfluorodecalin HP) was carried out. The PFC was delivered through the endotracheal tube on three consecutive days. A loading dose of 3 ml/kg was administered, followed by a varying dose in order to more effectively lavage the lungs. She tolerated the procedure well the first 2 days, although there were no clinical signs of improvement in the atelectasis. Intentionally, higher inflation pressures were applied after PFC instillation on day 3. Chest X-ray then showed hazy infiltrates on her left lung and she required more ventilatory support. However, lung infiltrates cleared over the next 3 days. A tracheotomy was done 6 days after the last PFC instillation. She had a slow recovery and was successfully decanulated. Clinical improvement of lung function was seen including less need of BiPAP and oxygen. A chest CT scan showed then functional lung tissue appearing in the previous total atelectatic right lung. Lavage with PFC can safely be performed with a therapeutic effect in a child with unilateral total lung atelectasis. Copyright © 2011 Wiley Periodicals, Inc.

The impact of aging on epithelial barriers.

PubMed

Parrish, Alan R

2017-10-02

The epithelium has many critical roles in homeostasis, including an essential responsibility in establishing tissue barriers. In addition to the fundamental role in separating internal from external environment, epithelial barriers maintain nutrient, fluid, electrolyte and metabolic waste balance in multiple organs. While, by definition, barrier function is conserved, the structure of the epithelium varies across organs. For example, the skin barrier is a squamous layer of cells with distinct structural features, while the lung barrier is composed of a very thin single cell to minimize diffusion space. With the increased focus on age-dependent alterations in organ structure and function, there is an emerging interest in the impact of age on epithelial barriers. This review will focus on the impact of aging on the epithelial barrier of several organs, including the skin, lung, gastrointestinal tract and the kidney, at a structural and functional level.

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

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

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

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.

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.

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

PubMed

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

2016-05-01

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

Lung Structure and the Intrinsic Challenges of Gas Exchange.

PubMed

Hsia, Connie C W; Hyde, Dallas M; Weibel, Ewald R

2016-03-15

Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to all lung units within a confined thoracic space, to build a large gas exchange surface associated with minimal barrier thickness and a microvascular network to accommodate the entire right ventricular cardiac output while withstanding cyclic mechanical stresses that increase several folds from rest to exercise. Intricate regulatory mechanisms at every level ensure that the dynamic capacities of ventilation, perfusion, diffusion, and chemical binding to hemoglobin are commensurate with usual metabolic demands and periodic extreme needs for activity and survival. This article reviews the structural design of mammalian and human lung, its functional challenges, limitations, and potential for adaptation. We discuss (i) the evolutionary origin of alveolar lungs and its advantages and compromises, (ii) structural determinants of alveolar gas exchange, including architecture of conducting bronchovascular trees that converge in gas exchange units, (iii) the challenges of matching ventilation, perfusion, and diffusion and tissue-erythrocyte and thoracopulmonary interactions. The notion of erythrocytes as an integral component of the gas exchanger is emphasized. We further discuss the signals, sources, and limits of structural plasticity of the lung in alveolar hypoxia and following a loss of lung units, and the promise and caveats of interventions aimed at augmenting endogenous adaptive responses. Our objective is to understand how individual components are matched at multiple levels to optimize organ function in the face of physiological demands or pathological constraints. Copyright © 2016 John Wiley & Sons, Inc.

Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.

PubMed

Dransfield, Mark T; Kunisaki, Ken M; Strand, Matthew J; Anzueto, Antonio; Bhatt, Surya P; Bowler, Russell P; Criner, Gerard J; Curtis, Jeffrey L; Hanania, Nicola A; Nath, Hrudaya; Putcha, Nirupama; Roark, Sarah E; Wan, Emily S; Washko, George R; Wells, J Michael; Wendt, Christine H; Make, Barry J

2017-02-01

Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up. We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV 1 decline based on reported exacerbations or acute respiratory events. In subjects with COPD, exacerbations were associated with excess FEV 1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23-151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV 1 decline. Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease. Trials are needed to test existing and novel therapies in subjects with early/mild COPD to potentially reduce the risk of progressing to more advanced lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).

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

PubMed

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

2015-01-01

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

Functional Imaging of the Lungs with Gas Agents

PubMed Central

Kruger, Stanley J.; Nagle, Scott K.; Couch, Marcus J.; Ohno, Yoshiharu; Albert, Mitchell; Fain, Sean B.

2015-01-01

This review focuses on the state-of-the-art of the three major classes of gas contrast agents used in magnetic resonance imaging (MRI) – hyperpolarized (HP) gas, molecular oxygen, and fluorinated gas – and their application to clinical pulmonary research. During the past several years there has been accelerated development of pulmonary MRI. This has been driven in part by concerns regarding ionizing radiation using multi-detector computed tomography (CT). However, MRI also offers capabilities for fast multi-spectral and functional imaging using gas agents that are not technically feasible with CT. Recent improvements in gradient performance and radial acquisition methods using ultra-short echo time (UTE) have contributed to advances in these functional pulmonary MRI techniques. Relative strengths and weaknesses of the main functional imaging methods and gas agents are compared and applications to measures of ventilation, diffusion, and gas exchange are presented. Functional lung MRI methods using these gas agents are improving our understanding of a wide range of chronic lung diseases, including chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis (CF) in both adults and children. PMID:26218920

Clinically important FEV1 declines among coal miners: an exploration of previously unrecognised determinants

PubMed Central

Wang, M. L.; Petsonk, E. L.; Beeckman, L. A.; Wagner, G. R.

1999-01-01

OBJECTIVES: The relation between occupational exposure to dust and loss of ventilatory lung function is now well established. However, many exposures during work and other activities might also have important roles in determining clinically important losses of lung function. In this study, we attempted to explore additional plausible determinants of exposures and other potential risk factors for clinically important decline in forced expiratory volume in 1 second (FEV1) during work in dusty trades. METHODS: The study was performed in 264 underground coal miners whose lung function had been followed up for an average of 11 years. With an extensive follow up questionnaire, miners were asked about their occupational and non-occupational exposures, smoking, personal and family medical history, and living conditions during childhood. RESULTS: Several variables of the mine environment (as well as previously recognised effects of mining work and region) were found to be associated with excess decline in FEV1, including work in roof bolting, exposure to explosive blasting, and to control dust spraying water that had been stored in holding tanks. Use of respiratory protection seemed to reduce the risk of decline in FEV1. Other factors that were found to be associated with declines in pulmonary function included smoking, body mass, weight gain, childhood pneumonia, and childhood exposure in the home to passive tobacco smoke and possibly smoke due to wood and coal fuels. Miners with excessive decline in FEV1 were less likely to be working in mining jobs at follow up. CONCLUSIONS: These findings suggest the existence of additional risk factors for decline in lung function in dusty trades, and may be useful in developing additional approaches to the prevention of chronic respiratory disease.   PMID:10658541

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

PubMed

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

2015-06-01

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

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

Role of natural killer cells in lung cancer.

PubMed

Aktaş, Ozge Nur; Öztürk, Ayşe Bilge; Erman, Baran; Erus, Suat; Tanju, Serhan; Dilege, Şükrü

2018-06-01

One of the key immune cells involved in the pathogenesis of lung cancer is natural killer (NK) cells and these cells are novel targets for therapeutic applications in lung cancer. The purpose of this review is to summarize the current literature on lung cancer pathogenesis with a focus on the interaction between NK cells and smoking, how these factors are related to the pathogenesis of lung cancer and how NK cell-based immunotherapy effect lung cancer survival. The relevant literature from PubMed and Medline databases is reviewed in this article. The cytolytic potential of NK cells are reduced in lung cancer and increasing evidence suggests that improving NK cell functioning may induce tumor regression. Recent clinical trials on NK cell-based novel therapies such as cytokines including interleukin (IL)-15, IL-12 and IL-2, NK-92 cell lines and allogenic NK cell immunotherapy showed promising results with less adverse effects on the lung cancer survival. The NK cell targeting strategy has not yet been approved for lung cancer treatment. More clinical studies focusing on the role of NK cells in lung cancer pathogenesis are warranted to develop novel NK cell-based therapeutic approaches for the treatment of lung cancer.

Promotion of Lung Health: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

PubMed Central

Budinger, G. R. Scott; Escobar, Gabriel J.; Hansel, Nadia N.; Hanson, Corrine K.; Huffnagle, Gary B.; Buist, A. Sonia

2014-01-01

Lung-related research primarily focuses on the etiology and management of diseases. In recent years, interest in primary prevention has grown. However, primary prevention also includes “health promotion” (actions in a population that keep an individual healthy). We encourage more research on population-based (public health) strategies that could not only maximize lung health but also mitigate “normal” age-related declines—not only for spirometry but across multiple measures of lung health. In developing a successful strategy, a “life course” approach is important. Unfortunately, we are unable to achieve the full benefit of this approach until we have better measures of lung health and an improved understanding of the normal trajectory, both over an individual’s life span and possibly across generations. We discuss key questions in lung health promotion, with an emphasis on the upper (healthier) end of the distribution of lung functioning and resiliency and briefly summarize the few interventions that have been studied to date. We conclude with suggestions regarding the most promising future research for this important, but largely neglected, area of lung research. PMID:24754821

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.

Lung function parameters improve prediction of VO2peak in an elderly population: The Generation 100 study.

PubMed

Hassel, Erlend; Stensvold, Dorthe; Halvorsen, Thomas; Wisløff, Ulrik; Langhammer, Arnulf; Steinshamn, Sigurd

2017-01-01

Peak oxygen uptake (VO2peak) is an indicator of cardiovascular health and a useful tool for risk stratification. Direct measurement of VO2peak is resource-demanding and may be contraindicated. There exist several non-exercise models to estimate VO2peak that utilize easily obtainable health parameters, but none of them includes lung function measures or hemoglobin concentrations. We aimed to test whether addition of these parameters could improve prediction of VO2peak compared to an established model that includes age, waist circumference, self-reported physical activity and resting heart rate. We included 1431 subjects aged 69-77 years that completed a laboratory test of VO2peak, spirometry, and a gas diffusion test. Prediction models for VO2peak were developed with multiple linear regression, and goodness of fit was evaluated. Forced expiratory volume in one second (FEV1), diffusing capacity of the lung for carbon monoxide and blood hemoglobin concentration significantly improved the ability of the established model to predict VO2peak. The explained variance of the model increased from 31% to 48% for men and from 32% to 38% for women (p<0.001). FEV1, diffusing capacity of the lungs for carbon monoxide and hemoglobin concentration substantially improved the accuracy of VO2peak prediction when added to an established model in an elderly population.

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.

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

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2015-01-01

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

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.

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.

Transbronchial biopsies safely diagnose amyloid lung disease

PubMed Central

Govender, Praveen; Keyes, Colleen M.; Hankinson, Elizabeth A.; O’Hara, Carl J.; Sanchorawala, Vaishali; Berk, John L.

2018-01-01

Background Autopsy identifies lung involvement in 58–92% of patients with the most prevalent forms of systemic amyloidoses. In the absence of lung biopsies, amyloid lung disease often goes unrecognized. Report of a death following transbronchial biopsies in a patient with systemic amyloidosis cautioned against the procedure in this patient cohort. We reviewed our experience with transbronchial biopsies in patients with amyloidosis to determine the safety and utility of bronchoscopic lung biopsies. Methods We identified patients referred to the Amyloidosis Center at Boston Medical Center with lung amyloidosis diagnosed by transbronchial lung biopsies (TBBX). Amyloid typing was determined by immunohistochemistry or mass spectrometry. Standard end organ assessments, including pulmonary function test (PFT) and chest tomography (CT) imaging, and extra-thoracic biopsies established the extent of disease. Results Twenty-five (21.7%) of 115 patients with lung amyloidosis were diagnosed by TBBX. PFT classified 33.3% with restrictive physiology, 28.6% with obstructive disease, and 9.5% mixed physiology; 9.5% exhibited isolated diffusion defects while 19% had normal pulmonary testing. Two view chest or CT imaging identified focal opacities in 52% of cases and diffuse interstitial disease in 48%. Amyloid type and disease extent included 68% systemic AL disease, 16% localized (lung limited) AL disease, 12% ATTR disease, and 4% AA amyloidosis. Fluoroscopy was not used during biopsy. No procedure complications were reported. Conclusions Our case series of 25 patients supports the use of bronchoscopic transbronchial biopsies for diagnosis of parenchymal lung amyloidosis. Normal PFTs do not rule out the histologic presence of amyloid lung disease. PMID:28393574

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

NASA Astrophysics Data System (ADS)

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

2011-03-01

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

Sources of household air pollution: The association with lung function and respiratory symptoms in middle-aged adult.

PubMed

Devien, Laurent; Giovannelli, Jonathan; Cuny, Damien; Matran, Régis; Amouyel, Philippe; Hulo, Sébastien; Edmé, Jean Louis; Dauchet, Luc

2018-07-01

The objective of the present study was to investigate the relationship between sources of household air pollution, respiratory symptoms and lung function. 3039 adults aged from 40 to 65 participated in the 2011-2013 ELISABET cross-sectional survey in northern France. Lung function was measured using spirometry. During a structured interview, respiratory symptoms, household fuels, exposure to moulds, and use of ventilation were recorded on a questionnaire. The self-reported presence of mould in at least two rooms (not including the bathroom and the kitchen) was associated with a 2.5% lower predicted forced expiratory volume in 1 s (95% confidence interval, -4.7 to -0.29; p-trend <0.05) and a higher risk of wheezing (p-trend < 0.001). Visible condensation was associated with wheezing (p < .05) and chronic cough (p < .05). There were no significant associations with the type of household fuel or inadequate ventilation/aeration. Similar results were found when the analyses were restricted to participants without known respiratory disease. Our results suggest that the presence of mould (known to be associated with more severe asthma symptoms) could also have an impact on respiratory symptoms and lung function in the general population and in populations without known respiratory disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Employment status and work-related difficulties in lung cancer survivors compared with the general population.

PubMed

Kim, Young Ae; Yun, Young Ho; Chang, Yoon Jung; Lee, Jongmog; Kim, Moon Soo; Lee, Hyun-Sung; Zo, Jae Ill; Kim, Jhingook; Choi, Yong Soo; Shim, Young Mog; Yoon, Seok-Jun

2014-03-01

To investigate the employment status of lung cancer survivors and the work-related problems they face. Although the number of lung cancer survivors is increasing, little is known about their employment and work-related issues. We enrolled 830 lung cancer survivors 12 months after lung cancer curative surgery (median time after diagnosis, 4.11 years) and 1000 volunteers from the general population. All participants completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30-item and a questionnaire that included items relating to their jobs. We used logistic regression analysis to identify independent predictors of unemployment. The employment rate of lung cancer survivors decreased from 68.6% at the time of diagnosis to 38.8% after treatment, which was significantly lower than the employment rate of the general population (63.5%; adjusted odds ratio = 2.31, 95% confidence interval: 1.66-3.22). The posttreatment unemployment rate was higher for women than for men. Among survivors, employment was inversely associated with older age, household income, number of comorbidities, and poor social functioning. Fatigue (78.6%) was the most common work-related problem reported by survivors. Lung cancer survivors experienced more difficulties in employment than did the general population. Age, monthly household income, number of comorbidities, and social functioning appear to be important factors influencing employment status. These findings suggest that lung cancer survivors need support to cope with the financial impact of cancer.

Correction of Spinal Deformity on a Lung Transplantation Recipient.

PubMed

Andrés Peiró, José Vicente; Granell, Joan Bagó; Moret, Montserrat Feliu; Galdó, Antonio Moreno

2017-01-01

The coexistence of lung disease and scoliosis entails a dramatic situation. There are no papers reporting scoliosis surgery in patients who suffered lung transplantation. To describe the case of a patient who underwent surgery to correct progressive spinal deformity after two consecutive lung transplants. Case report, including review of patient records, imaging and pulmonary function tests, and literature review. A 9-year-old woman diagnosed of idiopathic pulmonary fibrosis and progressive scoliosis underwent lung transplant. Retransplantation of right lung was performed at the age of 14 due to chronic rejection. When she was 16, respiratory function was stable and spinal deformity severely impaired her quality of life. Patient and family demanded a surgical correction. At that moment, she had severe osteoporosis and immunosuppression as a result of anti-rejection therapy. The pattern was a severe double thoracic curve T1-T6 89° and T7-L1 139°. To correct it, a posterior instrumented spine fusion from T2 to L4 using a hybrid configuration was performed. No significant complications occurred in perioperative, postoperative, and midterm follow-up periods. Solid fusion was achieved and patient was satisfied with surgery. Unfortunately, chronic lung graft rejection worsened her long-term general status. Scoliosis surgery on lung transplant recipients is feasible, regardless of potential complications related to immunosuppression and osteoporosis. The goal is to improve quality of life. Copyright © 2016 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

A Catalog of Genes Homozygously Deleted in Human Lung Cancer and the Candidacy of PTPRD as a Tumor Suppressor Gene

PubMed Central

Kohno, Takashi; Otsuka, Ayaka; Girard, Luc; Sato, Masanori; Iwakawa, Reika; Ogiwara, Hideaki; Sanchez-Cespedes, Montse; Minna, John D.; Yokota, Jun

2010-01-01

A total of 176 genes homozygously deleted in human lung cancer were identified by DNA array-based whole genome scanning of 52 lung cancer cell lines and subsequent genomic PCR in 74 cell lines, including the 52 cell lines scanned. One or more exons of these genes were homozygously deleted in one (1%) to 20 (27%) cell lines. These genes included known tumor suppressor genes, e.g., CDKN2A/p16, RB1, and SMAD4, and candidate tumor suppressor genes whose hemizygous or homozygous deletions were reported in several types of human cancers, such as FHIT, KEAP1, and LRP1B/LRP-DIP. CDKN2A/p16 and p14ARF located in 9p21 were most frequently deleted (20/74, 27%). The PTPRD gene was most frequently deleted (8/74, 11%) among genes mapping to regions other than 9p21. Somatic mutations, including a nonsense mutation, of the PTPRD gene were detected in 8/74 (11%) of cell lines and 4/95 (4%) of surgical specimens of lung cancer. Reduced PTPRD expression was observed in the majority (>80%) of cell lines and surgical specimens of lung cancer. Therefore, PTPRD is a candidate tumor suppressor gene in lung cancer. Microarray-based expression profiling of 19 lung cancer cell lines also indicated that some of the 176 genes, such as KANK and ADAMTS1, are preferentially inactivated by epigenetic alterations. Genetic/epigenetic as well as functional studies of these 176 genes will increase our understanding of molecular mechanisms behind lung carcinogenesis. PMID:20073072

Scleroderma Related Lung Disease: Is There a Pathogenic Role for Adipokines?

PubMed Central

Haley, Shannon; Shah, Dilip; Romero, Freddy; Summer, Ross

2013-01-01

Scleroderma is a systemic autoimmune disease of unknown etiology whose hallmark features include endothelial cell dysfunction, fibroblast proliferation and immune dysregulation. Although virtually any organ can be pathologically involved in scleroderma, lung complications including interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading cause of death in patients with this condition. Currently, the molecular mechanisms leading to development of scleroderma-related lung disease are poorly understood; however, the systemic nature of this condition has led many to implicate circulating factors in the pathogenesis of some of its organ impairment. In this article, we focus on a new class of circulating factors derived from adipose-tissue called adipokines, which are known to be altered in scleroderma. Recently, the adipokines adiponectin and leptin have been found to regulate biological activities in endothelial, fibroblast and immune cell types in lung and in many other tissues. The pleiotropic nature of these circulating factors and their functional activity on many cell types implicated in the pathogenesis of ILD and PAH suggest these hormones may play a mechanistic role in the onset and/or progression of scleroderma-related lung diseases. PMID:24173692

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

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

PubMed

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

2017-01-01

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

Identification of Key Transcription Factors Associated with Lung Squamous Cell Carcinoma

PubMed Central

Zhang, Feng; Chen, Xia; Wei, Ke; Liu, Daoming; Xu, Xiaodong; Zhang, Xing; Shi, Hong

2017-01-01

Background Lung squamous cell carcinoma (lung SCC) is a common type of lung cancer, but its mechanism of pathogenesis is unclear. The aim of this study was to identify key transcription factors in lung SCC and elucidate its mechanism. Material/Methods Six published microarray datasets of lung SCC were downloaded from Gene Expression Omnibus (GEO) for integrated bioinformatics analysis. Significance analysis of microarrays was used to identify differentially expressed genes (DEGs) between lung SCC and normal controls. The biological functions and signaling pathways of DEGs were mapped in the Gene Otology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, respectively. A transcription factor gene regulatory network was used to obtain insights into the functions of DEGs. Results A total of 1,011 genes, including 539 upregulated genes and 462 downregulated genes, were filtered as DEGs between lung SCC and normal controls. DEGs were significantly enriched in cell cycle, DNA replication, p53 signaling pathway, pathways in cancer, adherens junction, and cell adhesion molecules signaling pathways. There were 57 transcription factors identified, which were used to construct a regulatory network. The network consisted of 736 interactions between 49 transcription factors and 486 DEGs. NFIC, BRCA1, and NFATC2 were the top 3 transcription factors that had the highest connectivity with DEGs and that regulated 83, 82, and 75 DEGs in the network, respectively. Conclusions NFIC, BRCA1, and NFATC2 might be the key transcription factors in the development of lung SCC by regulating the genes involved in cell cycle and DNA replication pathways. PMID:28081052

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

PubMed

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

2015-08-15

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

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

Tobacco as a Reproductive and Developmental Toxicant

EPA Science Inventory

Maternal cigarette smoking has long been known to result in effects on offspring including lower birthweight and neurobehavioral effects. Continuing studies have expanded the list of adverse outcomes in offspring to include Sudden Infant Death Syndrome, impaired lung function, an...

[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.

Computed tomography in pulmonary sarcoidosis

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

Lynch, D.A.; Webb, W.R.; Gamsu, G.

1989-05-01

We studied the high resolution CT (HRCT) scans of 15 patients with biopsy-proven sarcoidosis and correlated the findings with pulmonary function tests (12 patients), 67Ga scans (10 patients), bronchoalveolar lavage (five patients), recent transbronchial biopsy (six patients), and recent open lung biopsy (three patients). The HRCT features included small nodules, thickened interlobular septa, patchy focal increase in lung density, honeycombing, and central conglomeration of vessels and bronchi. Active alveolitis was present by gallium scanning criteria in 5 of 10 cases. By bronchoalveolar lavage criteria, activity was present in three of five cases. Patchy increase in density may correlate with activemore » alveolitis as seen on /sup 67/Ga scanning. High resolution CT was better than chest X-radiography for demonstration of patchy increase in density and for distinguishing nodules from septal thickening. Both nodules and patchy density were partly reversible following therapy. Nodular densities seen on CT correlated with the presence of granulomata on histology. Resting pulmonary function tests correlated poorly with presence and extent of lung disease on HRCT. The presence on HRCT of focal fine nodules, patchy focal increase in lung density, and central crowding of bronchi and vessels should suggest the diagnosis of sarcoidosis. In some patients, HRCT can identify unsuspected parenchymal lung disease and document the reversible components of sarcoid lung disease.« less

Stage-dependent and locus-specific role of histone demethylase Jumonji D3 (JMJD3) in the embryonic stages of lung development.

PubMed

Li, Qingtian; Wang, Helen Y; Chepelev, Iouri; Zhu, Qingyuan; Wei, Gang; Zhao, Keji; Wang, Rong-Fu

2014-07-01

Histone demethylases have emerged as important players in developmental processes. Jumonji domain containing-3 (Jmjd3) has been identified as a key histone demethylase that plays a critical role in the regulation of gene expression; however, the in vivo function of Jmjd3 in embryonic development remains largely unknown. To this end, we generated Jmjd3 global and conditional knockout mice. Global deletion of Jmjd3 induces perinatal lethality associated with defective lung development. Tissue and stage-specific deletion revealed that Jmjd3 is dispensable in the later stage of embryonic lung development. Jmjd3 ablation downregulates the expression of genes critical for lung development and function, including AQP-5 and SP-B. Jmjd3-mediated alterations in gene expression are associated with locus-specific changes in the methylation status of H3K27 and H3K4. Furthermore, Jmjd3 is recruited to the SP-B promoter through interactions with the transcription factor Nkx2.1 and the epigenetic protein Brg1. Taken together, these findings demonstrate that Jmjd3 plays a stage-dependent and locus-specific role in the mouse lung development. Our study provides molecular insights into the mechanisms by which Jmjd3 regulates target gene expression in the embryonic stages of lung development.

Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

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

Venkatramani, Rajkumar, E-mail: rvenkatramani@chla.usc.edu; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California; Kamath, Sunil

Purpose: To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials: We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results: We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The followingmore » pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V{sub 22} (volume of lung exposed to a radiation dose ≥22 Gy) and V{sub 30} (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V{sub dose} (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Conclusions: Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed dose should be used to perform risk stratification of patients receiving lung irradiation.« less

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.

Anatomical pulmonary magnetic resonance imaging segmentation for regional structure-function measurements of asthma

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

Guo, F.; Graduate Program in Biomedical Engineering, University of Western Ontario, London, Ontario N6A 5B9; Svenningsen, S.

Purpose: Pulmonary magnetic-resonance-imaging (MRI) and x-ray computed-tomography have provided strong evidence of spatially and temporally persistent lung structure-function abnormalities in asthmatics. This has generated a shift in their understanding of lung disease and supports the use of imaging biomarkers as intermediate endpoints of asthma severity and control. In particular, pulmonary {sup 1}H MRI can be used to provide quantitative lung structure-function measurements longitudinally and in response to treatment. However, to translate such biomarkers of asthma, robust methods are required to segment the lung from pulmonary {sup 1}H MRI. Therefore, their objective was to develop a pulmonary {sup 1}H MRI segmentationmore » algorithm to provide regional measurements with the precision and speed required to support clinical studies. Methods: The authors developed a method to segment the left and right lung from {sup 1}H MRI acquired in 20 asthmatics including five well-controlled and 15 severe poorly controlled participants who provided written informed consent to a study protocol approved by Health Canada. Same-day spirometry and plethysmography measurements of lung function and volume were acquired as well as {sup 1}H MRI using a whole-body radiofrequency coil and fast spoiled gradient-recalled echo sequence at a fixed lung volume (functional residual capacity + 1 l). We incorporated the left-to-right lung volume proportion prior based on the Potts model and derived a volume-proportion preserved Potts model, which was approximated through convex relaxation and further represented by a dual volume-proportion preserved max-flow model. The max-flow model led to a linear problem with convex and linear equality constraints that implicitly encoded the proportion prior. To implement the algorithm, {sup 1}H MRI was resampled into ∼3 × 3 × 3 mm{sup 3} isotropic voxel space. Two observers placed seeds on each lung and on the background of 20 pulmonary {sup 1}H MR images in a randomized dataset, on five occasions, five consecutive days in a row. Segmentation accuracy was evaluated using the Dice-similarity-coefficient (DSC) of the segmented thoracic cavity with comparison to five-rounds of manual segmentation by an expert observer. The authors also evaluated the root-mean-squared-error (RMSE) of the Euclidean distance between lung surfaces, the absolute, and percent volume error. Reproducibility was measured using the coefficient of variation (CoV) and intraclass correlation coefficient (ICC) for two observers who repeated segmentation measurements five-times. Results: For five well-controlled asthmatics, forced expiratory volume in 1 s (FEV{sub 1})/forced vital capacity (FVC) was 83% ± 7% and FEV{sub 1} was 86 ± 9%{sub pred}. For 15 severe, poorly controlled asthmatics, FEV{sub 1}/FV C = 66% ± 17% and FEV{sub 1} = 72 ± 27%{sub pred}. The DSC for algorithm and manual segmentation was 91% ± 3%, 92% ± 2% and 91% ± 2% for the left, right, and whole lung, respectively. RMSE was 4.0 ± 1.0 mm for each of the left, right, and whole lung. The absolute (percent) volume errors were 0.1 l (∼6%) for each of right and left lung and ∼0.2 l (∼6%) for whole lung. Intra- and inter-CoV (ICC) were <0.5% (>0.91%) for DSC and <4.5% (>0.93%) for RMSE. While segmentation required 10 s including ∼6 s for user interaction, the smallest detectable difference was 0.24 l for algorithm measurements which was similar to manual measurements. Conclusions: This lung segmentation approach provided the necessary and sufficient precision and accuracy required for research and clinical studies.« less

Constrictive Bronchiolitis in Cystic Fibrosis Adolescents with Refractory Pulmonary Decline.

PubMed

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

2016-12-01

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

Fibulin-1 functions as a prognostic factor in lung adenocarcinoma.

PubMed

Cui, Yuan; Liu, Jian; Yin, Hai-Bing; Liu, Yi-Fei; Liu, Jun-Hua

2015-09-01

Fibulin-1 is a member of the fibulin gene family, characterized by tandem arrays of epidermal growth factor-like domains and a C-terminal fibulin-type module. Fibulin-1 plays important roles in a range of cellular functions including morphology, growth, adhesion and mobility. It acts as a tumor suppressor gene in cutaneous melanoma, prostate cancer and gastric cancer. However, whether fibulin-1 also acts as a tumor suppressor gene in lung adenocarcinoma remains unknown. We also determined the association of fibulin-1 expression with various clinical and pathological parameters, which would show its potential role in clinical prognosis. We investigated and followed up 140 lung adenocarcinoma patients who underwent lung resection without pre- and post-operative systemic chemotherapy at the Affiliated Hospital of Nantong University from 2009 to 2013. Western blot assay and immunohistochemistry were used to evaluate the expression of fibulin-1 in lung adenocarcinoma tissues. We then analyzed the correlations between fibulin-1 expression and clinicopathological variables as well as the patients' overall survival rate. Both western blot assay and immunohistochemistry demonstrated that the level of fibulin-1 was downregulated in human lung adenocarcinoma tissues compared with that of normal lung tissues. Fibulin-1 expression significantly correlated with histological differentiation (P = 0.046), clinical stage (P< 0.01), lymph node status (P = 0.038) and expression of Ki-67 (P = 0.013). More importantly, multivariate analysis revealed that fibulin-1 was an independent prognostic marker for lung adenocarcinoma, and high expression of fibulin-1 was significantly associated with better prognosis of lung adenocarcinoma patients. The results supported our hypothesis that fibulin-1 can act as a prognostic factor in lung adenocarcinoma progression. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2015-06-01

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

Advanced Techniques in Pulmonary Function Test Analysis Interpretation and Diagnosis

PubMed Central

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

1980-01-01

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

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

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.

Rheumatoid arthritis-related interstitial lung disease (RA-ILD): methotrexate and the severity of lung disease are associated to prognosis.

PubMed

Rojas-Serrano, Jorge; Herrera-Bringas, Denisse; Pérez-Román, Diana I; Pérez-Dorame, Renzo; Mateos-Toledo, Heidegger; Mejía, Mayra

2017-07-01

Interstitial lung disease (ILD) is a severe rheumatoid arthritis (RA) manifestation. The worst survival has been associated with usual interstitial pneumonia (UIP) definitive pattern in high-resolution chest tomography (HRCT) scans. Moreover, the use of methotrexate in RA-ILD is controversial. Our aim was to evaluate prognostic factors including methotrexate in an RA-ILD cohort and their association with survival. RA-ILD patients referred for medical evaluation and treatment at a single center were included. At the baseline, pulmonary function tests were carried out and a HRCT was obtained. A radiologist evaluated the ILD tomographic pattern and the extent of lung disease. Patients were considered as receiving methotrexate therapy if this drug was specifically prescribed for the treatment of RA-ILD at the beginning of follow up. Seventy-eight patients were included. UIP definite pattern in HRCT was not associated to worse survival. Variables associated with mortality reflected the severity of lung disease. Treatment with methotrexate was associated with survival (HR 0.13, 95% CI 0.02-0.64); older patients had worse prognosis (HR 1.04, 95% CI 1.003-1.09). After adjusting for confounding variables, methotrexate was strongly associated with survival. Methotrexate treatment during follow up was associated with survival. The severity of lung disease and not the tomographic pattern is associated with mortality; older patients had worse prognosis.

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

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

PubMed

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

2017-01-01

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

Aging effects on airflow dynamics and lung function in human bronchioles

PubMed Central

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

2017-01-01

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

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.

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

PubMed

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

2017-05-01

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

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

PubMed

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

2015-09-01

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

Lung function in children in relation to ethnicity, physique and socio-economic factors

PubMed Central

Lum, Sooky; Bountziouka, Vassiliki; Sonnappa, Samatha; Wade, Angie; Cole, Tim J; Harding, Seeromanie; Wells, Jonathan CK; Griffiths, Chris; Treleaven, Philip; Bonner, Rachel; Kirkby, Jane; Lee, Simon; Raywood, Emma; Legg, Sarah; Sears, Dave; Cottam, Philippa; Feyeraband, Colin; Stocks, Janet

2015-01-01

Question Can ethnic differences in spirometry be attributed to differences in physique and socio-economic factors? Methods Assessments were undertaken in 2171 London primary school-children on two occasions a year apart whenever possible, as part of the Size and Lung function In Children study. Measurements included spirometry, detailed anthropometry, 3-D photonic scanning for regional body shape, body composition, information on ethnic ancestry, birth and respiratory history, socio-economic circumstances and tobacco smoke exposure. Results Technically acceptable spirometry was obtained from 1901 children (mean age: 8.3yrs (range: 5.2-11.8yrs), 46% boys, 35% White; 29% Black-African origin; 24% South-Asian; 12% Other/mixed) on 2767 test occasions. After adjusting for sex, age and height, FEV1 was 1.32, 0.89 and 0.51 z-score units lower in Black, South-Asian and Other ethnicity children respectively, when compared with White children, with similar decrements for FVC (p<0.001 for all). Although further adjustment for sitting height and chest width reduced differences attributable to ethnicity by up to 16%, significant differences persisted after adjusting for all potential determinants including socio-economic circumstances. Answer Ethnic differences in spirometric lung function persist despite adjusting for a wide range of potential determinants, including body physique and socio-economic circumstances, emphasising the need to use ethnic-specific equations when interpreting results. PMID:26493801

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

PubMed

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

2014-06-01

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

Potential Role of Lung Ventilation Scintigraphy in the Assessment of COPD

PubMed Central

Cukic, Vesna; Begic, Amela

2014-01-01

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

Association of sweat chloride concentration at time of diagnosis and CFTR genotype with mortality and cystic fibrosis phenotype.

PubMed

McKone, Edward F; Velentgas, Priscilla; Swenson, Anna J; Goss, Christopher H

2015-09-01

The extent to which sweat chloride concentration predicts survival and clinical phenotype independently of CFTR genotype in cystic fibrosis is not well understood. We analyzed the US Cystic Fibrosis Foundation Patient Registry data using Cox regression to examine the relationship between sweat chloride concentration (<60, 60-<80, ≥80mmol/L), CFTR genotype (high and lower risk for lung function decline), and survival and mixed linear regression to examine the relationship between sweat chloride, CFTR genotype, and measures of lung function and growth. When included in the same model, CFTR genotype, but not sweat chloride, was independently associated with survival and with lung function, height, and BMI. Among patients with unclassified CFTR genotype, sweat chloride was an independent predictor of survival (<60 HR 0.53 [0.37, 0.77], 60-<80 0.51 [0.42, 0.63]). Sweat chloride concentration may be a useful predictor of mortality and clinical phenotype when CFTR genotype functional class is unclassified. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

PubMed Central

Esnault, Stephane; Kelly, Elizabeth A.

2017-01-01

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

Plant Polyphenols as Chemopreventive Agents for Lung Cancer

PubMed Central

Amararathna, Madumani; Johnston, Michael R.; Rupasinghe, H. P. Vasantha

2016-01-01

Lung cancer may be prevented by a diet rich in fruits and vegetables as they are enriched with dietary antioxidant polyphenols, such as flavonoids, proanthocyanidins, lignans, stilbenes, and phenolic acids. Dietary polyphenols exert a wide range of beneficial biological functions beyond their antioxidative properties and are involved in regulation of cell survival pathways leading to anticarcinogenic and antimutagenic functions. There are sufficient evidence from in vitro, in vivo, and epidemiological studies to suggest that the dietary intervention of polyphenols in cancer prevention, including the chemopreventive ability of dietary polyphenols, act against lung carcinogens. Cohort and epidemiological studies in selected risk populations have evaluated clinical effects of polyphenols. Polyphenols have demonstrated three major actions: antioxidative activity, regulation of phase I and II enzymes, and regulation of cell survival pathways against lung carcinogenesis. They have also shown an inverse association of lung cancer occurrences among high risk populations who consumed considerable amounts of fruits and vegetables in their daily diet. In in vitro cell culture experimental models, polyphenols bind with electrophilic metabolites from carcinogens, inactivate cellular oxygen radicals, prevent membrane lipid peroxidation and DNA oxidative damage, and adduct formation. Further, polyphenols enhance the detoxifying enzymes such as the phase II enzymes, glutathione transferases and glucuronosyl transferases. PMID:27548149

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.

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.

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

PubMed

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

2017-07-01

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

Association of 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.

Lung function declines in patients with pulmonary sarcoidosis and increased respiratory epithelial permeability to sup 99m Tc-DTPA

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

Chinet, T.; Dusser, D.; Labrune, S.

1990-02-01

Respiratory epithelial clearance of {sup 99m}Tc-DTPA (RC-Tc-DTPA) and pulmonary function tests (PFT) were determined at intervals of 6 or 12 months in 37 untreated, nonsmoking patients with sarcoidosis over a period of 6 to 36 months. PFT included the measurements of total lung capacity (TLC), vital capacity (VC), FEV1, and diffusing capacity for carbon monoxide. No difference was found between the respiratory clearance of {sup 113m}In-DTPA (2.25 +/- 1.00%/min) and RC-Tc-DTPA (2.29 +/- 1.11%/min) in eight patients with pulmonary sarcoidosis. Pulmonary function decreased 15% or more in at least 2 function tests during 11 follow-up periods, but it remained stablemore » during 47 follow-up periods. In patients whose lung function deteriorated, RC-Tc-DTPA increased to 3.51 +/- 1.55%/min; in contrast, in patients whose lung function remained stable, regardless of the initial values, RC-Tc-DTPA was normal (1.00 +/- 0.50%/min; p less than 0.001). In eight patients who were treated with corticosteroids, RC-Tc-DTPA decreased from 3.48 +/- 1.31%/min to 1.56 +/- 0.64%/min (p less than 0.001), and PFT improved. We conclude that in nonsmokers with pulmonary sarcoidosis, increased RC-Tc-DTPA is not related to dissociation of 99mTc from DTPA, RC-Tc-DTPA is increased when pulmonary function decreases, and, when increased, RC-Tc-DTPA decreases with corticosteroid therapy.« less

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

The histone demethylase PHF8 is an oncogenic protein in human non-small cell lung cancer

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

Shen, Yuzhou; Pan, Xufeng; Zhao, Heng, E-mail: hengzhao1966@sina.com

2014-08-15

Highlights: • PHF8 overexpresses in human NSCLC and predicts poor survival. • PHF8 regulates lung cancer cell growth and transformation. • PHF8 regulates apoptosis in human lung cancer cells. • PHF8 promotes miR-21 expression in human lung cancer. • MiR-21 is critically essential for PHF8 function in human lung cancer cells. - Abstract: PHF8 is a JmjC domain-containing protein and erases repressive histone marks including H4K20me1 and H3K9me1/2. It binds to H3K4me3, an active histone mark usually located at transcription start sites (TSSs), through its plant homeo-domain, and is thus recruited and enriched in gene promoters. PHF8 is involved inmore » the development of several types of cancer, including leukemia, prostate cancer, and esophageal squamous cell carcinoma. Herein we report that PHF8 is an oncogenic protein in human non-small cell lung cancer (NSCLC). PHF8 is up-regulated in human NSCLC tissues, and high PHF8 expression predicts poor survival. Our in vitro and in vivo evidence demonstrate that PHF8 regulates lung cancer cell proliferation and cellular transformation. We found that PHF8 knockdown induces DNA damage and apoptosis in lung cancer cells. PHF8 promotes miR-21 expression in human lung cancer, and miR-21 knockdown blocks the effects of PHF8 on proliferation and apoptosis of lung cancer cells. In summary, PHF8 promotes lung cancer cell growth and survival by regulating miR-21.« less

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

PubMed

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

2013-05-01

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

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

Arsenic Compromises Conducting Airway Epithelial Barrier Properties in Primary Mouse and Immortalized Human Cell Cultures

PubMed Central

Sherwood, Cara L.; Liguori, Andrew E.; Olsen, Colin E.; Lantz, R. Clark; Burgess, Jefferey L.; Boitano, Scott

2013-01-01

Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb)] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE) cell model we found that both micromolar (3.9 μM) and submicromolar (0.8 μM) arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl) Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-). We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway. PMID:24349408

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

PubMed

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

2018-05-01

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

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

PubMed

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

1993-01-01

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

Estimation of Lung Ventilation

NASA Astrophysics Data System (ADS)

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

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

Reduction of Pulmonary Function After Surgical Lung Resections of Different Volume

PubMed Central

Cukic, Vesna

2014-01-01

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

m6A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression.

PubMed

Liu, Jiqin; Ren, Dangli; Du, Zhenhua; Wang, Hekong; Zhang, Hua; Jin, Ying

2018-08-25

N 6 -Methyladenosine (m 6 A) represents the most prevalent internal modification in mammalian mRNAs. Emerging evidences suggest that m 6 A modification is profoundly implicated in many biological processes, including cancer development. However, limited knowledge is available about the functional importance of m 6 A in lung cancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, we first identified fat mass- and obesity-associated protein (FTO) as a prognostic factor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but not other m 6 A modification genes including METTL3, METTL14 and ALKBH5, was the major dysregulated factor responsible for aberrant m 6 A modification in LUSC. Loss-of-function studies suggested that FTO knockdown effectively inhibited cell proliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520 cells. Furthermore, overexpression of FTO, but not its mutant form, facilitated the malignant phenotypes of CHLH-1 cells. Mechanistically, FTO enhanced MZF1 expression by reducing m 6 A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. Taken together, our study demonstrates the functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Transcriptional profiling of host gene expression in chicken embryo lung cells infected with laryngotracheitis virus

PubMed Central

2010-01-01

Background Infection by infectious laryngotracheitis virus (ILTV; gallid herpesvirus 1) causes acute respiratory diseases in chickens often with high mortality. To better understand host-ILTV interactions at the host transcriptional level, a microarray analysis was performed using 4 × 44 K Agilent chicken custom oligo microarrays. Results Microarrays were hybridized using the two color hybridization method with total RNA extracted from ILTV infected chicken embryo lung cells at 0, 1, 3, 5, and 7 days post infection (dpi). Results showed that 789 genes were differentially expressed in response to ILTV infection that include genes involved in the immune system (cytokines, chemokines, MHC, and NF-κB), cell cycle regulation (cyclin B2, CDK1, and CKI3), matrix metalloproteinases (MMPs) and cellular metabolism. Differential expression for 20 out of 789 genes were confirmed by quantitative reverse transcription-PCR (qRT-PCR). A bioinformatics tool (Ingenuity Pathway Analysis) used to analyze biological functions and pathways on the group of 789 differentially expressed genes revealed that 21 possible gene networks with intermolecular connections among 275 functionally identified genes. These 275 genes were classified into a number of functional groups that included cancer, genetic disorder, cellular growth and proliferation, and cell death. Conclusion The results of this study provide comprehensive knowledge on global gene expression, and biological functionalities of differentially expressed genes in chicken embryo lung cells in response to ILTV infections. PMID:20663125

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.

[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.

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.

Effect of pirfenidone on wound healing in lung transplant patients.

PubMed

Mortensen, Amber; Cherrier, Lauren; Walia, Rajat

2018-01-01

The drug pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor beta, a known contributor to wound healing. We evaluated whether patients taking pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether pirfenidone should be discontinued prior to listing to allow for a wash-out period. We retrospectively reviewed patients who underwent lung transplantation for pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January 2014 to December 2015. We describe 18 patients who took pirfenidone up to a month before transplant. Aside from one patient who experienced sternal dehiscence due to a surgical issue, all remaining patients did well with no evidence of airway dehiscence. Each of these 17 patients had been on pirfenidone for at least 30 days; nine patients had been on pirfenidone for over 90 days. Baseline characteristics including age, sex, body mass index, renal function, liver function, glucose level, pre-transplant corticosteroid use, and post-transplant immunosuppressant therapy were similar. In our experience, pirfenidone may be safely continued until lung transplantation. Only one patient in our series experienced impaired wound healing related to a surgical issue, even when pirfenidone was continued until lung transplantation. We found no evidence of impaired wound healing or airway complications after lung transplantation in patients who were treated with pirfenidone before lung transplantation.

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.

Matrix composition and mechanics of decellularized lung scaffolds.

PubMed

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

2012-01-01

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

Detection of early subclinical lung disease in children with cystic fibrosis by lung ventilation imaging with hyperpolarised gas MRI.

PubMed

Marshall, Helen; Horsley, Alex; Taylor, Chris J; Smith, Laurie; Hughes, David; Horn, Felix C; Swift, Andrew J; Parra-Robles, Juan; Hughes, Paul J; Norquay, Graham; Stewart, Neil J; Collier, Guilhem J; Teare, Dawn; Cunningham, Steve; Aldag, Ina; Wild, Jim M

2017-08-01

Hyperpolarised 3 He ventilation-MRI, anatomical lung MRI, lung clearance index (LCI), low-dose CT and spirometry were performed on 19 children (6-16 years) with clinically stable mild cystic fibrosis (CF) (FEV 1 >-1.96), and 10 controls. All controls had normal spirometry, MRI and LCI. Ventilation-MRI was the most sensitive method of detecting abnormalities, present in 89% of patients with CF, compared with CT abnormalities in 68%, LCI 47% and conventional MRI 22%. Ventilation defects were present in the absence of CT abnormalities and in patients with normal physiology, including LCI. Ventilation-MRI is thus feasible in young children, highly sensitive and provides additional information about lung structure-function relationships. 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/.

Comprehensive outcomes after lung retransplantation: a single center review.

PubMed

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

2018-05-13

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

A conserved post-transcriptional BMP2 switch in lung cells.

PubMed

Jiang, Shan; Fritz, David T; Rogers, Melissa B

2010-05-15

An ultra-conserved sequence in the bone morphogenetic protein 2 (BMP2) 3' untranslated region (UTR) markedly represses BMP2 expression in non-transformed lung cells. In contrast, the ultra-conserved sequence stimulates BMP2 expression in transformed lung cells. The ultra-conserved sequence functions as a post-transcriptional cis-regulatory switch. A common single-nucleotide polymorphism (SNP, rs15705, +A1123C), which has been shown to influence human morphology, disrupts a conserved element within the ultra-conserved sequence and altered reporter gene activity in non-transformed lung cells. This polymorphism changed the affinity of the BMP2 RNA for several proteins including nucleolin, which has an increased affinity for the C allele. Elevated BMP2 synthesis is associated with increased malignancy in mouse models of lung cancer and poor lung cancer patient prognosis. Understanding the cis- and trans-regulatory factors that control BMP2 synthesis is relevant to the initiation or progression of pathologies associated with abnormal BMP2 levels. (c) 2010 Wiley-Liss, Inc.

Antibody-mediated rejection of the lung: A consensus report of the International Society for Heart and Lung Transplantation.

PubMed

Levine, Deborah J; Glanville, Allan R; Aboyoun, Christina; Belperio, John; Benden, Christian; Berry, Gerald J; Hachem, Ramsey; Hayes, Don; Neil, Desley; Reinsmoen, Nancy L; Snyder, Laurie D; Sweet, Stuart; Tyan, Dolly; Verleden, Geert; Westall, Glen; Yusen, Roger D; Zamora, Martin; Zeevi, Adriana

2016-04-01

Antibody-mediated rejection (AMR) is a recognized cause of allograft dysfunction in lung transplant recipients. Unlike AMR in other solid-organ transplant recipients, there are no standardized diagnostic criteria or an agreed-upon definition. Hence, a working group was created by the International Society for Heart and Lung Transplantation with the aim of determining criteria for pulmonary AMR and establishing a definition. Diagnostic criteria and a working consensus definition were established. Key diagnostic criteria include the presence of antibodies directed toward donor human leukocyte antigens and characteristic lung histology with or without evidence of complement 4d within the graft. Exclusion of other causes of allograft dysfunction increases confidence in the diagnosis but is not essential. Pulmonary AMR may be clinical (allograft dysfunction which can be asymptomatic) or sub-clinical (normal allograft function). This consensus definition will have clinical, therapeutic and research implications. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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.

Association of incidental emphysema with annual lung function decline and future development of airflow limitation

PubMed Central

Koo, Hyeon-Kyoung; Jin, Kwang Nam; Kim, Deog Kyeom; Chung, Hee Soon; Lee, Chang-Hoon

2016-01-01

Objectives Emphysema is one of the prognostic factors for rapid lung function decline in patients with COPD, but the impact of incidentally detected emphysema on population without spirometric abnormalities has not been evaluated. This study aimed to determine whether emphysema detected upon computed tomography (CT) screening would accelerate the rate of lung function decline and influence the possibility of future development of airflow limitation in a population without spirometric abnormalities. Materials and methods Subjects who participated in a routine screening for health checkup and follow-up pulmonary function tests for at least 3 years between 2004 and 2010 were retrospectively enrolled. The percentage of low-attenuation area below −950 Hounsfield units (%LAA−950) was calculated automatically. A calculated value of %LAA−950 that exceeded 10% was defined as emphysema. Adjusted annual lung function decline was analyzed using random-slope, random-intercept mixed linear regression models. Results A total of 628 healthy subjects within the normal range of spriometric values were included. Multivariable analysis showed that the emphysema group exhibited a faster decline in forced vital capacity (−33.9 versus −18.8 mL/year; P=0.02). Emphysema was not associated with the development of airflow limitation during follow-up. Conclusion Incidental emphysema quantified using CT scan was significantly associated with a more rapid decline in forced vital capacity in the population with normative spirometric values. However, an association between emphysema and future development of airflow limitation was not observed. PMID:26893550

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.

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

PubMed

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

2010-01-01

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

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

PubMed

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

2017-05-01

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

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

PubMed

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

2011-07-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-08-01

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

From COPD epidemiology to studies of pathophysiological disease mechanisms: challenges with regard to study design and recruitment process: Respiratory and Cardiovascular Effects in COPD (KOLIN).

PubMed

Lindberg, Anne; Linder, Robert; Backman, Helena; Eriksson Ström, Jonas; Frølich, Andreas; Nilsson, Ulf; Rönmark, Eva; Johansson Strandkvist, Viktor; Behndig, Annelie F; Blomberg, Anders

2017-01-01

Background : Chronic obstructive pulmonary disease (COPD) is a largely underdiagnosed disease including several phenotypes. In this report, the design of a study intending to evaluate the pathophysiological mechanism in COPD in relation to the specific phenotypes non-rapid and rapid decline in lung function is described together with the recruitment process of the study population derived from a population based study. Method : The OLIN COPD study includes a population-based COPD cohort and referents without COPD identified in 2002-04 ( n  = 1986), and thereafter followed annually since 2005. Lung function decline was estimated from baseline in 2002-2004 to 2010 (first recruitment phase) or to 2012/2013 (second recruitment phase). Individuals who met the predefined criteria for the following four groups were identified; group A) COPD grade 2-3 with rapid decline in FEV 1 and group B) COPD grade 2-3 without rapid decline in FEV 1 (≥60 and ≤30 ml/year, respectively), group C) ever-smokers, and group D) non-smokers with normal lung function. Groups A-C included ever-smokers with >10 pack years. The intention was to recruit 15 subjects in each of the groups A-D. Results : From the database groups A-D were identified; group A n  = 37, group B n  = 29, group C n  = 41, and group D n  = 55. Fifteen subjects were recruited from groups C and D, while this goal was not reached in the groups A ( n  = 12) and B ( n  = 10). The most common reasons for excluding individuals identified as A or B were comorbidities contraindicating bronchoscopy, or inflammatory diseases/immune suppressive medication expected to affect the outcome. Conclusion : The study is expected to generate important results regarding pathophysiological mechanisms associated with rate of decline in lung function among subjects with COPD and the in-detail described recruitment process, including reasons for non-participation, is a strength when interpreting the results in forthcoming studies.

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

PubMed

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

2017-03-01

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

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

PubMed

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

2016-11-01

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

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

PubMed

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

2014-05-01

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

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.

The role of STATs in lung carcinogenesis: an emerging target for novel therapeutics.

PubMed

Karamouzis, Michalis V; Konstantinopoulos, Panagiotis A; Papavassiliou, Athanasios G

2007-05-01

The signal transducer and activator of transcription (STAT) proteins are a family of latent cytoplasmic transcription factors, which form dimers when activated by cytokine receptors, tyrosine kinase growth factor receptors as well as non-receptor tyrosine kinases. Dimeric STATs translocate to the nucleus, where they bind to specific DNA-response elements in the promoters of target genes, thereby inducing unique gene expression programs often in association with other transcription regulatory proteins. The functional consequence of different STAT proteins activation varies, as their target genes play diverse roles in normal cellular/tissue functions, including growth, apoptosis, differentiation and angiogenesis. Certain activated STATs have been implicated in human carcinogenesis, albeit only few studies have focused into their role in lung tumours. Converging evidence unravels their molecular interplays and complex multipartite regulation, rendering some of them appealing targets for lung cancer treatment with new developing strategies.

A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer

PubMed Central

Wilson, Frederick H.; Johannessen, Cory M.; Piccioni, Federica; Tamayo, Pablo; Kim, Jong Wook; Van Allen, Eliezer M.; Corsello, Steven M.; Capelletti, Marzia; Calles, Antonio; Butaney, Mohit; Sharifnia, Tanaz; Gabriel, Stacey B.; Mesirov, Jill P.; Hahn, William C.; Engelman, Jeffrey A.; Meyerson, Matthew; Root, David E.; Jänne, Pasi A.; Garraway, Levi A.

2015-01-01

Summary We conducted a large-scale functional genetic study to characterize mechanisms of resistance to ALK inhibition in ALK-dependent lung cancer cells. We identify members of known resistance pathways and additional putative resistance drivers. Among the latter were members of the P2Y purinergic receptor family of G-protein coupled receptors (P2Y1, P2Y2, and P2Y6). P2Y receptors mediated resistance in part through a protein kinase C (PKC)-dependent mechanism. Moreover, PKC activation alone was sufficient to confer resistance to ALK inhibitors whereas combined ALK and PKC inhibition restored sensitivity. We observed enrichment of gene signatures associated with several resistance drivers (including P2Y receptors) in crizotinib-resistant ALK-rearranged lung tumors compared to treatment-naïve controls, supporting a role for identified resistance mechanisms in clinical resistance. PMID:25759024

Rehabilitation Nutrition for Possible Sarcopenic Dysphagia After Lung Cancer Surgery: A Case Report.

PubMed

Wakabayashi, Hidetaka; Uwano, Rimiko

2016-06-01

Sarcopenic dysphagia is characterized by the loss of swallowing muscle mass and function associated with generalized loss of skeletal muscle mass and function. In this report, the authors describe a patient with possible sarcopenic dysphagia after lung cancer surgery and was treated subsequently by rehabilitation nutrition. A 71-year-old man with lung cancer experienced complications of an acute myocardial infarction and pneumonia after surgery. He was ventilated artificially, and a tracheotomy was performed. The patient received diagnoses of malnutrition, severe sarcopenia, and possible sarcopenic dysphagia. His dysphagia was improved by a combination of dysphagia rehabilitation including physical and speech therapy and an improvement in nutrition initiated by a nutrition support team. Finally, he no longer had dysphagia and malnutrition. Sarcopenic dysphagia should be considered in patients with sarcopenia and dysphagia. Rehabilitation nutrition using a combination of both rehabilitation and nutritional care management is presumptively useful for treating sarcopenic dysphagia.

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.

Mathematical modelling of a human external respiratory system

NASA Technical Reports Server (NTRS)

1977-01-01

A closed system of algebraic and common differential equations solved by computer is investigated. It includes equations which describe the activity pattern of the respiratory center, the phrenic nerve, the thrust produced by the diaphragm as a function of the lung volume and discharge frequency of the phrenic nerve, as well as certain relations of the lung stretch receptors and chemoreceptors on various lung and blood characteristics, equations for lung biomechanics, pulmonary blood flow, alveolar gas exchange and capillary blood composition equations to determine various air and blood flow and gas exchange parameters, and various gas mixing and arterial and venous blood composition equations, to determine other blood, air and gas mixing characteristics. Data are presented by means of graphs and tables, and some advantages of this model over others are demonstrated by test results.

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

PubMed Central

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

2015-01-01

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

Microbial colonization and lung function in adolescents with cystic fibrosis.

PubMed

Hector, Andreas; Kirn, Tobias; Ralhan, Anjali; Graepler-Mainka, Ute; Berenbrinker, Sina; Riethmueller, Joachim; Hogardt, Michael; Wagner, Marlies; Pfleger, Andreas; Autenrieth, Ingo; Kappler, Matthias; Griese, Matthias; Eber, Ernst; Martus, Peter; Hartl, Dominik

2016-05-01

With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern of bacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preserved lung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa. Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. Collectively, this study identified potentially protective and harmful microbial colonization patterns in adolescent CF patients. Further studies in different patient cohorts are required to evaluate these microbial patterns and to assess their clinical relevance. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Spirometry, Static Lung Volumes, and Diffusing Capacity.

PubMed

Vaz Fragoso, Carlos A; Cain, Hilary C; Casaburi, Richard; Lee, Patty J; Iannone, Lynne; Leo-Summers, Linda S; Van Ness, Peter H

2017-09-01

Spirometric Z-scores from the Global Lung Initiative (GLI) rigorously account for age-related changes in lung function and are thus age-appropriate when establishing spirometric impairments, including a restrictive pattern and air-flow obstruction. However, GLI-defined spirometric impairments have not yet been evaluated regarding associations with static lung volumes (total lung capacity [TLC], functional residual capacity [FRC], and residual volume [RV]) and gas exchange (diffusing capacity). We performed a retrospective review of pulmonary function tests in subjects ≥40 y old (mean age 64.6 y), including pre-bronchodilator measures for: spirometry ( n = 2,586), static lung volumes by helium dilution with inspiratory capacity maneuver ( n = 2,586), and hemoglobin-adjusted single-breath diffusing capacity ( n = 2,508). Using multivariable linear regression, adjusted least-squares means (adj LS Means) were calculated for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity. The adj LS Means were expressed with and without height-cubed standardization and stratified by GLI-defined spirometry, including normal ( n = 1,251), restrictive pattern ( n = 663), and air-flow obstruction (mild, [ n = 128]; moderate, [ n = 150]; and severe, [ n = 394]). Relative to normal spirometry, restrictive-pattern had lower adj LS Means for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity ( P ≤ .001). Conversely, relative to normal spirometry, mild, moderate, and severe air-flow obstruction had higher adj LS Means for FRC and RV ( P < .001). However, only mild and moderate air-flow obstruction had higher adj LS Means for TLC ( P < .001), while only moderate and severe air-flow obstruction had higher adj LS Means for RV/TLC ( P < .001) and lower adj LS Means for hemoglobin-adjusted single-breath diffusing capacity ( P < .001). Notably, TLC (calculated as FRC + inspiratory capacity) was not increased in severe air-flow obstruction ( P ≥ .11) because inspiratory capacity decreased with increasing air-flow obstruction ( P < .001), thus opposing the increased FRC ( P < .001). Finally, P values were similar whether adj LS Means were height-cubed standardized. A GLI-defined spirometric restrictive pattern is strongly associated with a restrictive ventilatory defect (decreased TLC, FRC, and RV), while GLI-defined spirometric air-flow obstruction is strongly associated with hyperinflation (increased FRC) and air trapping (increased RV and RV/TLC). Both spirometric impairments were strongly associated with impaired gas exchange (decreased hemoglobin-adjusted single-breath diffusing capacity). Copyright © 2017 by Daedalus Enterprises.

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

PubMed

McGeachie, M J; Yates, K P; Zhou, X; Guo, F; Sternberg, A L; Van Natta, M L; Wise, R A; Szefler, S J; Sharma, S; Kho, A T; Cho, M H; Croteau-Chonka, D C; Castaldi, P J; Jain, G; Sanyal, A; Zhan, Y; Lajoie, B R; Dekker, J; Stamatoyannopoulos, J; Covar, R A; Zeiger, R S; Adkinson, N F; Williams, P V; Kelly, H W; Grasemann, H; Vonk, J M; Koppelman, G H; Postma, D S; Raby, B A; Houston, I; Lu, Q; Fuhlbrigge, A L; Tantisira, K G; Silverman, E K; Tonascia, J; Weiss, S T; Strunk, R C

2016-05-12

Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Aspergillus fumigatus colonization in cystic fibrosis: implications for lung function?

PubMed

de Vrankrijker, A M M; van der Ent, C K; van Berkhout, F T; Stellato, R K; Willems, R J L; Bonten, M J M; Wolfs, T F W

2011-09-01

Aspergillus fumigatus is commonly found in the respiratory secretions of patients with cystic fibrosis (CF). Although allergic bronchopulmonary aspergillosis (ABPA) is associated with deterioration of lung function, the effects of A. fumigatus colonization on lung function in the absence of ABPA are not clear. This study was performed in 259 adults and children with CF, without ABPA. A. fumigatus colonization was defined as positivity of >50% of respiratory cultures in a given year. A cross-sectional analysis was performed to study clinical characteristics associated with A. fumigatus colonization. A retrospective cohort analysis was performed to study the effect of A. fumigatus colonization on lung function observed between 2002 and 2007. Longitudinal data were analysed with a linear mixed model. Sixty-one of 259 patients were at least intermittently colonized with A. fumigatus. An association was found between A. fumigatus colonization and increased age and use of inhaled antibiotics. In the longitudinal analysis, 163 patients were grouped according to duration of colonization. After adjustment for confounders, there was no significant difference in lung function between patients colonized for 0 or 1 year and patients with 2-3 or more than 3 years of colonization (p 0.40 and p 0.64) throughout the study. There was no significant difference in lung function decline between groups. Although colonization with A. fumigatus is more commonly found in patients with more severe lung disease and increased treatment burden, it is not independently associated with lower lung function or more severe lung function decline over a 5-year period. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

Diesel exhaust particle promotes tumor lung metastasis via the induction of BLT1-mediated neutrophilic lung inflammation.

PubMed

Li, Wenjing; Liu, Ting; Xiong, Yingluo; Lv, Jiaoyan; Cui, Xinyi; He, Rui

2018-06-05

BLT1, the primary functional receptor of Leukotriene B4 (LTB4), is involved in tissue inflammation by mediating leukocyte recruitment, and recently LTB4-dependent inflammation was reported to promote lung tumor growth. Exposure to diesel exhaust particle (DEP), the major component of particulate matter 2.5 (PM 2.5 ), can elicit lung inflammation, which may increase the risk of lung cancer. However, it remains unknown about the critical factors mediating DEP-induced lung inflammation and the subsequent effect on tumor metastasis. In this study, we found that DEP exposure led to acute lung inflammation, characterized by abundant infiltration of neutrophils and elevated lung levels in LTB4, as well as several pro-inflammatory cytokines and chemokines, including IL-1β, IL-6, TNF-α, CXCL1/2. Furthermore, DEP exposure promoted lung metastasis of 3LL and 4T1 cells. BLT1 blockade by its specific antagonist U75302 significantly inhibited neutrophilic lung inflammation following DEP exposure. Importantly, BLT1 blockade before the onset of inflammation significantly reduced DEP-enhanced lung metastasis, which was associated with greatly decreased infiltrating neutrophils in lungs. Interestingly, BLT1 blockade after the occurrence of lung metastases had no effect on the magnitude of lung metastasis, suggesting that inhibition of BLT1-mediated lung inflammation was insufficient to suppress established metastatic tumor. Administration of BLT2 inhibitor LY255283 fails to inhibit DEP-induced lung inflammation and tumor metastasis. Collectively, our results demonstrate that DEP exposure causes BLT1-mediated lung neutrophilic inflammation, which is critical for tumor lung metastasis, and suggest that interruption of the LTB4-BLT1 axis could be useful for preventing PM 2.5 -induced inflammation and subsequent susceptible to lung metastasis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Lung function in North American Indian children: reference standards for spirometry, maximal expiratory flow volume curves, and peak expiratory flow.

PubMed

Wall, M A; Olson, D; Bonn, B A; Creelman, T; Buist, A S

1982-02-01

Reference standards of lung function was determined in 176 healthy North American Indian children (94 girls, 82 boys) 7 to 18 yr of age. Spirometry, maximal expiratory flow volume curves, and peak expiratory flow rate were measured using techniques and equipment recommended by the American Thoracic Society. Standing height was found to be an accurate predictor of lung function, and prediction equations for each lung function variable are presented using standing height as the independent variable. Lung volumes and expiratory flow rates in North American Indian children were similar to those previously reported for white and Mexican-American children but were greater than those in black children. In both boys and girls, lung function increased in a curvilinear fashion. Volume-adjusted maximal expiratory flow rates after expiring 50 or 75% of FVC tended to decrease in both sexes as age and height increased. Our maximal expiratory flow volume curve data suggest that as North American Indian children grow, lung volume increases at a slightly faster rate than airway size does.

Physiologic Basis for Improved Pulmonary Function after Lung Volume Reduction

PubMed Central

Fessler, Henry E.; Scharf, Steven M.; Ingenito, Edward P.; McKenna, Robert J.; Sharafkhaneh, Amir

2008-01-01

It is not readily apparent how pulmonary function could be improved by resecting portions of the lung in patients with emphysema. In emphysema, elevation in residual volume relative to total lung capacity reduces forced expiratory volumes, increases inspiratory effort, and impairs inspiratory muscle mechanics. Lung volume reduction surgery (LVRS) better matches the size of the lungs to the size of the thorax containing them. This restores forced expiratory volumes and the mechanical advantage of the inspiratory muscles. In patients with heterogeneous emphysema, LVRS may also allow space occupied by cysts to be reclaimed by more normal lung. Newer, bronchoscopic methods for lung volume reduction seek to achieve similar ends by causing localized atelectasis, but may be hindered by the low collateral resistance of emphysematous lung. Understanding of the mechanisms of improved function after LVRS can help select patients more likely to benefit from this approach. PMID:18453348

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

PubMed

Koman, Patricia D; Mancuso, Peter

2017-07-17

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

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.

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

PubMed

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

2017-05-05

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

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.

The Role of Nicotine in the Effects of Maternal Smoking during Pregnancy on Lung Development and Childhood Respiratory Disease. Implications for Dangers of E-Cigarettes

PubMed Central

McEvoy, Cindy T.

2016-01-01

Use of e-cigarettes, especially among the young, is increasing at near-exponential rates. This is coupled with a perception that e-cigarettes are safe and with unlimited advertising geared toward vulnerable populations, the groups most likely to smoke or vape during pregnancy. There is now wide appreciation of the dangers of maternal smoking during pregnancy and the lifelong consequences this has on offspring lung function, including the increased risk of childhood wheezing and subsequent asthma. Recent evidence strongly supports that much of the effect of smoking during pregnancy on offspring lung function is mediated by nicotine, making it highly likely that e-cigarette use during pregnancy will have the same harmful effects on offspring lung function and health as do conventional cigarettes. In fact, the evidence for nicotine being the mediator of harm of conventional cigarettes may be most compelling for its effects on lung development. This raises concerns about both the combined use of e-cigarettes plus conventional cigarettes by smokers during pregnancy as well as the use of e-cigarettes by e-cigarette–only users who think them safe or by those sufficiently addicted to nicotine to not be able to quit e-cigarette usage during pregnancy. Thus, it is important for health professionals to be aware of the risks of e-cigarette usage during pregnancy, particularly as it pertains to offspring respiratory health. PMID:26756937

The Role of Nicotine in the Effects of Maternal Smoking during Pregnancy on Lung Development and Childhood Respiratory Disease. Implications for Dangers of E-Cigarettes.

PubMed

Spindel, Eliot R; McEvoy, Cindy T

2016-03-01

Use of e-cigarettes, especially among the young, is increasing at near-exponential rates. This is coupled with a perception that e-cigarettes are safe and with unlimited advertising geared toward vulnerable populations, the groups most likely to smoke or vape during pregnancy. There is now wide appreciation of the dangers of maternal smoking during pregnancy and the lifelong consequences this has on offspring lung function, including the increased risk of childhood wheezing and subsequent asthma. Recent evidence strongly supports that much of the effect of smoking during pregnancy on offspring lung function is mediated by nicotine, making it highly likely that e-cigarette use during pregnancy will have the same harmful effects on offspring lung function and health as do conventional cigarettes. In fact, the evidence for nicotine being the mediator of harm of conventional cigarettes may be most compelling for its effects on lung development. This raises concerns about both the combined use of e-cigarettes plus conventional cigarettes by smokers during pregnancy as well as the use of e-cigarettes by e-cigarette-only users who think them safe or by those sufficiently addicted to nicotine to not be able to quit e-cigarette usage during pregnancy. Thus, it is important for health professionals to be aware of the risks of e-cigarette usage during pregnancy, particularly as it pertains to offspring respiratory health.

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

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

PubMed

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

2005-12-01

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

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

PubMed

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

2017-09-01

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

Sirolimus alters lung pathology and viral load following influenza A virus infection.

PubMed

Alsuwaidi, Ahmed R; George, Junu A; Almarzooqi, Saeeda; Hartwig, Stacey M; Varga, Steven M; Souid, Abdul-Kader

2017-07-11

Inhibitors of mTOR, such as sirolimus, have been shown to induce thymus involution and inflammatory lung disease in mice. The latter effect supports the role of this serine/threonine kinase in ameliorating lung inflammation. Other studies have shown sirolimus reduces/delays lung disease associated with various strains of influenza A virus (IAV). Thus, the effects of mTOR inhibitors on influenza infection deserve further studies. Here, we examined the changes in lung viral copies, pathology and pulmonary function associated with IAV (A/PR/8/34) infection in mice treated with sirolimus. Body weight loss peaked between days 6-11 post-infection and was more severe in IAV-infected mice that were administered sirolimus as compared to mice that received IAV alone (p = 0.030). Natural log viral gene copies, mean ± SD per mg lung tissue, in IAV-infected mice that were administered sirolimus were 17.31 ± 1.27 on day 4, 19.31 ± 7.46 on day 10, and 0 on day 25. The corresponding number of copies in mice that received IAV alone were 18.56 ± 0.95 on day 4 (p = 0.132), 1.52 ± 1.39 on day 10 (p = 0.008), and 0 on day 25. Lung pathology was evident on days 4, 10, and 25 post infection, with mean ± SD inflammatory score of 9.0 ± 4.5 in IAV-infected mice that were administered sirolimus, as compared to 11.5 ± 4.5 (p = 0.335) in mice received IAV alone (maximum score, 26.0). Impaired lung function was evident in IAV-infected mice on days 4 and 10, as demonstrated by increased airway resistance and decreased compliance. In this model, the effects of sirolimus on influenza infection included severe weight loss and modified viral replication, respiratory function and lung inflammation. The adverse events associated with sirolimus treatment are consistent with its potent immunosuppressive activity and, thus, preclude its use in IAV infection.

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

Sex Steroid Signaling: Implications for Lung Diseases

PubMed Central

Sathish, Venkatachalem; Martin, Yvette N.; Prakash, Y.S.

2015-01-01

There is increasing recognition that the sex hormones (estrogen, progesterone, and testosterone) have biological and pathophysiological actions in peripheral, non-reproductive organs, including the lung. Clinically, sex differences in the incidence, morbidity and mortality of lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, lung cancer and pulmonary hypertension have been noted, although intrinsic sex differences vs. the roles of sex steroids are still not well-understood. Accordingly, it becomes important to ask the following questions: 1) Which sex steroids are involved? 2) How do they affect different components of the lung under normal circumstances? 3) How does sex steroid signaling change in or contribute to lung disease, and in this regard, are sex steroids detrimental or beneficial? As our understanding of sex steroid signaling in the lung improves, it is important to consider whether such information can be used to develop new therapeutic strategies to target lung diseases, perhaps in both sexes or in a sex-specific manner. In this review, we focus on the basics of sex steroid signaling, and the current state of knowledge regarding how they influence structure and function of specific lung components across the life span and in the context of some important lung diseases. We then summarize the potential for sex steroids as useful biomarkers and therapeutic targets in these lung diseases as a basis for future translational research in the area of gender and individualized medicine. PMID:25595323

Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling

PubMed Central

Sellamuthu, Rajendran; Umbright, Christina; Li, Shengqiao; Kashon, Michael; Joseph, Pius

2015-01-01

A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatics analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top ranking biological functions perturbed by silica exposure in A549 cells and rat lungs. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study may result in better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure. PMID:22087542

The effects of ozone exposure and associated injury mechanisms on the central nervous system.

PubMed

Martínez-Lazcano, Juan Carlos; González-Guevara, Edith; del Carmen Rubio, María; Franco-Pérez, Javier; Custodio, Verónica; Hernández-Cerón, Miguel; Livera, Carlos; Paz, Carlos

2013-01-01

Ozone (O3) is a component of photochemical smog, which is a major air pollutant and demonstrates properties that are harmful to health because of the toxic properties that are inherent to its powerful oxidizing capabilities. Environmental O3 exposure is associated with many symptoms related to respiratory disorders, which include loss of lung function, exacerbation of asthma, airway damage, and lung inflammation. The effects of O3 are not restricted to the respiratory system or function - adverse effects within the central nervous system (CNS) such as decreased cognitive response, decrease in motor activity, headaches, disturbances in the sleep-wake cycle, neuronal dysfunctions, cell degeneration, and neurochemical alterations have also been described; furthermore, it has also been proposed that O3 could have epigenetic effects. O3 exposure induces the reactive chemical species in the lungs, but the short half-life of these chemical species has led some authors to attribute the injurious mechanisms observed within the lungs to inflammatory processes. However, the damage to the CNS induced by O3 exposure is not well understood. In this review, the basic mechanisms of inflammation and activation of the immune system by O3 exposure are described and the potential mechanisms of damage, which include neuroinflammation and oxidative stress, and the signs and symptoms of disturbances within the CNS caused by environmental O3 exposure are discussed.

Changes in Regional Ventilation During Treatment and Dosimetric Advantages of CT Ventilation Image Guided Radiation Therapy for Locally Advanced Lung Cancer.

PubMed

Yamamoto, Tokihiro; Kabus, Sven; Bal, Matthieu; Bzdusek, Karl; Keall, Paul J; Wright, Cari; Benedict, Stanley H; Daly, Megan E

2018-05-04

Lung functional image guided radiation therapy (RT) that avoids irradiating highly functional regions has potential to reduce pulmonary toxicity following RT. Tumor regression during RT is common, leading to recovery of lung function. We hypothesized that computed tomography (CT) ventilation image-guided treatment planning reduces the functional lung dose compared to standard anatomic image-guided planning in 2 different scenarios with or without plan adaptation. CT scans were acquired before RT and during RT at 2 time points (16-20 Gy and 30-34 Gy) for 14 patients with locally advanced lung cancer. Ventilation images were calculated by deformable image registration of four-dimensional CT image data sets and image analysis. We created 4 treatment plans at each time point for each patient: functional adapted, anatomic adapted, functional unadapted, and anatomic unadapted plans. Adaptation was performed at 2 time points. Deformable image registration was used for accumulating dose and calculating a composite of dose-weighted ventilation used to quantify the lung accumulated dose-function metrics. The functional plans were compared with the anatomic plans for each scenario separately to investigate the hypothesis at a significance level of 0.05. Tumor volume was significantly reduced by 20% after 16 to 20 Gy (P = .02) and by 32% after 30 to 34 Gy (P < .01) on average. In both scenarios, the lung accumulated dose-function metrics were significantly lower in the functional plans than in the anatomic plans without compromising target volume coverage and adherence to constraints to critical structures. For example, functional planning significantly reduced the functional mean lung dose by 5.0% (P < .01) compared to anatomic planning in the adapted scenario and by 3.6% (P = .03) in the unadapted scenario. This study demonstrated significant reductions in the accumulated dose to the functional lung with CT ventilation image-guided planning compared to anatomic image-guided planning for patients showing tumor regression and changes in regional ventilation during RT. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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

PubMed

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

2008-08-01

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

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.

Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures.

PubMed

Schweitzer, Kelly S; Chen, Steven X; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J; Hubbard, Walter C; Kim, Elena S; Lai, Xianyin; Wang, Mu; Kranz, William D; Carroll, Clinton J; Ray, Bruce D; Bittman, Robert; Goodpaster, John; Petrache, Irina

2015-07-15

The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

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.

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.

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

PubMed

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

2015-03-01

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

Cost and effectiveness of lung lobectomy by video-assisted thoracic surgery for lung cancer

PubMed Central

Mafé, Juan J.; Planelles, Beatriz; Asensio, Santos; Cerezal, Jorge; Inda, María-del-Mar; Lacueva, Javier; Esteban, Maria-Dolores; Hernández, Luis; Martín, Concepción; Baschwitz, Benno

2017-01-01

Background Video-assisted thoracic surgery (VATS) emerged as a minimally invasive surgery for diseases in the field of thoracic surgery. We herein reviewed our experience on thoracoscopic lobectomy for early lung cancer and evaluated Health System use. Methods A cost-effectiveness study was performed comparing VATS vs. open thoracic surgery (OPEN) for lung cancer patients. Demographic data, tumor localization, dynamic pulmonary function tests [forced vital capacity (FVC), forced expiratory volume in one second (FEV1), diffusion capacity (DLCO) and maximal oxygen uptake (VO2max)], surgical approach, postoperative details, and complications were recorded and analyzed. Results One hundred seventeen patients underwent lung resection by VATS (n=42, 36%; age: 63±9 years old, 57% males) or OPEN (n=75, 64%; age: 61±11 years old, 73% males). Pulmonary function tests decreased just after surgery with a parallel increasing tendency during first 12 months. VATS group tended to recover FEV1 and FVC quicker with significantly less clinical and post-surgical complications (31% vs. 53%, P=0.015). Costs including surgery and associated hospital stay, complications and costs in the 12 months after surgery were significantly lower for VATS (P<0.05). Conclusions The VATS approach surgery allowed earlier recovery at a lower cost than OPEN with a better cost-effectiveness profile. PMID:28932560

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

NASA Astrophysics Data System (ADS)

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

2009-04-01

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

Combined effect of urinary monohydroxylated polycyclic aromatic hydrocarbons and impaired lung function on diabetes.

PubMed

Hou, Jian; Sun, Huizhen; Xiao, Lili; Zhou, Yun; Yin, Wenjun; Xu, Tian; Cheng, Juan; Chen, Weihong; Yuan, Jing

2016-07-01

Associations of type 2 diabetes with exposure to polycyclic aromatic hydrocarbons and reduced lung function have been reported. The aim of the present study was to investigate effect of reduced lung function and exposure to background PAHs on diabetes. A total of 2730 individuals were drawn from the Wuhan-Zhuhai (WHZH) Cohort Study (n=3053). Participants completed physical examination, measurement of lung function and urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs). Risk factors for type 2 diabetes were identified by multiple logistic regression analysis, and the presence of additive interaction between levels of urinary OH-PAHs and lower lung function was evaluated by calculation of the relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP). Urinary OH-PAHs levels was positively associated with type 2 diabetes among individuals with impaired lung function (p<0.05). Forced expiratory volume in one second (FEV1, odd ratio (OR): 0.664, 95% confidence interval (CI): 0.491-0.900) and forced vital capacity (FVC, OR: 0.693, 95% CI: 0.537-0.893) were negatively associated with diabetes among individuals. Additive interaction of higher urinary levels of OH-PAHs and lower FVC (RERI: 0.679, 95% CI: 0.120-1.238); AP: 0.427, 95% CI: 0.072-0.782) was associated with diabetes. Exposure to background PAHs was related to diabetes among individuals with lower lung function. Urinary levels of OH-PAHs and reduced lung function had an additive effect on diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Can Stem Cells be Used to Generate New Lungs? Ex Vivo Lung Bioengineering with Decellularized Whole Lung Scaffolds

PubMed Central

Wagner, Darcy E.; Bonvillain, Ryan W.; Jensen, Todd J.; Girard, Eric D.; Bunnell, Bruce A.; Finck, Christine M.; Hoffman, Andrew M.; Weiss, Daniel J.

2013-01-01

For patients with end-stage lung diseases, lung transplantation is the only available therapeutic option. However, the number of suitable donor lungs is insufficient and lung transplants are complicated by significant graft failure and complications of immunosuppressive regimens. An alternative to classic organ replacement is desperately needed. Engineering of bioartificial organs using either natural or synthetic scaffolds is an exciting new potential option for generation of functional pulmonary tissue for human clinical application. Natural organ scaffolds can be generated by decellularization of native tissues; these acellular scaffolds retain the native organ ultrastructure and can be seeded with autologous cells toward the goal of regenerating functional tissues. Several decellularization strategies have been employed for lung, however, there is no consensus on the optimal approach. A variety of cell types have been investigated as potential candidates for effective recellularization of acellular lung scaffolds. Candidate cells that might be best utilized are those which can be easily and reproducibly isolated, expanded in vitro, seeded onto decellularized matrices, induced to differentiate into pulmonary lineage cells, and which survive to functional maturity. Whole lung cell suspensions, endogenous progenitor cells, embryonic and adult stem cells, and induced pluripotent stem (iPS) cells have been investigated for their applicability to repopulate acellular lung matrices. Ideally, patient-derived autologous cells would be used for lung recellularization as they have the potential to reduce the need for post-transplant immunosuppression. Several studies have performed transplantation of rudimentary bioengineered lung scaffolds in animal models with limited, short-term functionality but much further study is needed. PMID:23614471

Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: role of oxidative stress and ceramides.

PubMed

Schweitzer, Kelly S; Hatoum, Hadi; Brown, Mary Beth; Gupta, Mehak; Justice, Matthew J; Beteck, Besem; Van Demark, Mary; Gu, Yuan; Presson, Robert G; Hubbard, Walter C; Petrache, Irina

2011-12-01

The epithelial and endothelial cells lining the alveolus form a barrier essential for the preservation of the lung respiratory function, which is, however, vulnerable to excessive oxidative, inflammatory, and apoptotic insults. Whereas profound breaches in this barrier function cause pulmonary edema, more subtle changes may contribute to inflammation. The mechanisms by which cigarette smoke (CS) exposure induce lung inflammation are not fully understood, but an early alteration in the epithelial barrier function has been documented. We sought to investigate the occurrence and mechanisms by which soluble components of mainstream CS disrupt the lung endothelial cell barrier function. Using cultured primary rat microvascular cell monolayers, we report that CS induces endothelial cell barrier disruption in a dose- and time-dependent manner of similar magnitude to that of the epithelial cell barrier. CS exposure triggered a mechanism of neutral sphingomyelinase-mediated ceramide upregulation and p38 MAPK and JNK activation that were oxidative stress dependent and that, along with Rho kinase activation, mediated the endothelial barrier dysfunction. The morphological changes in endothelial cell monolayers induced by CS included actin cytoskeletal rearrangement, junctional protein zonula occludens-1 loss, and intercellular gap formation, which were abolished by the glutathione modulator N-acetylcysteine and ameliorated by neutral sphingomyelinase inhibition. The direct application of ceramide recapitulated the effects of CS, by disrupting both endothelial and epithelial cells barrier, by a mechanism that was redox and apoptosis independent and required Rho kinase activation. Furthermore, ceramide induced dose-dependent alterations of alveolar microcirculatory barrier in vivo, measured by two-photon excitation microscopy in the intact rat. In conclusion, soluble components of CS have direct endothelial barrier-disruptive effects that could be ameliorated by glutathione modulators or by inhibitors of neutral sphingomyelinase, p38 MAPK, JNK, and Rho kinase. Amelioration of endothelial permeability may alleviate lung and systemic vascular dysfunction associated with smoking-related chronic obstructive lung diseases.

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.

Native American ancestry, lung function, and COPD in Costa Ricans.

PubMed

Chen, Wei; Brehm, John M; Boutaoui, Nadia; Soto-Quiros, Manuel; Avila, Lydiana; Celli, Bartolome R; Bruse, Shannon; Tesfaigzi, Yohannes; Celedón, Juan C

2014-04-01

Whether Native American ancestry (NAA) is associated with COPD or lung function in a racially admixed Hispanic population is unknown. We recruited 578 Costa Ricans with and without COPD into a hybrid case-control/family-based cohort, including 316 members of families of index case subjects. All participants completed questionnaires and spirometry and gave a blood sample for DNA extraction. Genome-wide genotyping was conducted with the Illumina Human610-Quad and HumanOmniExpress BeadChip kits (Illumina Inc), and individual ancestral proportions were estimated from these genotypic data and reference panels. For unrelated individuals, linear or logistic regression was used for the analysis of NAA and COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage II or greater) or lung function. For extended families, linear mixed models and generalized estimating equations were used for the analysis. All models were adjusted for age, sex, educational level, and smoking behavior; models for FEV1 were also adjusted for height. The average proportion of European, Native American, and African ancestry among participants was 62%, 35%, and 3%, respectively. After adjustment for current smoking and other covariates, NAA was inversely associated with COPD (OR per 10% increment, 0.55; 95% CI, 0.41-0.75) but positively associated with FEV1, FVC, and FEV1/FVC. After additional adjustment for pack-years of smoking, the association between NAA and COPD or lung function measures was slightly attenuated. We found that about 31% of the estimated effect of NAA on COPD is mediated by pack-years of smoking. NAA is inversely associated with COPD but positively associated with FEV1 or FVC in Costa Ricans. Ancestral effects on smoking behavior partly explain the findings for COPD but not for FEV1 or FVC.

Native American Ancestry, Lung Function, and COPD in Costa Ricans

PubMed Central

Chen, Wei; Brehm, John M.; Boutaoui, Nadia; Soto-Quiros, Manuel; Avila, Lydiana; Celli, Bartolome R.; Bruse, Shannon; Tesfaigzi, Yohannes

2014-01-01

Background: Whether Native American ancestry (NAA) is associated with COPD or lung function in a racially admixed Hispanic population is unknown. Methods: We recruited 578 Costa Ricans with and without COPD into a hybrid case-control/family-based cohort, including 316 members of families of index case subjects. All participants completed questionnaires and spirometry and gave a blood sample for DNA extraction. Genome-wide genotyping was conducted with the Illumina Human610-Quad and HumanOmniExpress BeadChip kits (Illumina Inc), and individual ancestral proportions were estimated from these genotypic data and reference panels. For unrelated individuals, linear or logistic regression was used for the analysis of NAA and COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage II or greater) or lung function. For extended families, linear mixed models and generalized estimating equations were used for the analysis. All models were adjusted for age, sex, educational level, and smoking behavior; models for FEV1 were also adjusted for height. Results: The average proportion of European, Native American, and African ancestry among participants was 62%, 35%, and 3%, respectively. After adjustment for current smoking and other covariates, NAA was inversely associated with COPD (OR per 10% increment, 0.55; 95% CI, 0.41-0.75) but positively associated with FEV1, FVC, and FEV1/FVC. After additional adjustment for pack-years of smoking, the association between NAA and COPD or lung function measures was slightly attenuated. We found that about 31% of the estimated effect of NAA on COPD is mediated by pack-years of smoking. Conclusions: NAA is inversely associated with COPD but positively associated with FEV1 or FVC in Costa Ricans. Ancestral effects on smoking behavior partly explain the findings for COPD but not for FEV1 or FVC. PMID:24306962

A prospective cohort study among new Chinese coal miners: the early pattern of lung function change.

PubMed

Wang, M-L; Wu, Z-E; Du, Q-G; Petsonk, E L; Peng, K-L; Li, Y-D; Li, S-K; Han, G-H; Atffield, M D

2005-11-01

To investigate the early pattern of longitudinal change in forced expiratory volume in 1 second (FEV1) among new Chinese coal miners, and the relation between coal mine dust exposure and the decline of lung function. The early pattern of lung function changes in 317 newly hired Chinese underground coal miners was compared to 132 referents. This three year prospective cohort study involved a pre-employment and 15 follow up health surveys, including a questionnaire and spirometry tests. Twice a month, total and respirable dust area sampling was done. The authors used a two stage analysis and a linear mixed effects model approach to analyse the longitudinal spirometry data, and to investigate the changes in FEV1 over time, controlling for age, height, pack years of smoking, mean respirable dust concentration, the room temperature during testing, and the groupxtime interaction terms. FEV1 change over time in new miners is non-linear. New miners experience initial rapid FEV1 declines, primarily during the first year of mining, little change during the second year, and partial recovery during the third year. Both linear and quadratic time trends in FEV1 change are highly significant. Smoking miners lost more FEV1 than non-smokers. Referents, all age less than 20 years, showed continued lung growth, whereas the miners who were under age 20 exhibited a decline in FEV1. Dust and smoking affect lung function in young, newly hired Chinese coal miners. FEV1 change over the first three years of employment is non-linear. The findings have implications for both methods and interpretation of medical screening in coal mining and other dusty work: during the first several years of employment more frequent testing may be desirable, and caution is required in interpreting early FEV1 declines.

Physical complications in acute lung injury survivors: a two-year longitudinal prospective study.

PubMed

Fan, Eddy; Dowdy, David W; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A; Sevransky, Jonathan E; Shanholtz, Carl; Himmelfarb, Cheryl R Dennison; Desai, Sanjay V; Ciesla, Nancy; Herridge, Margaret S; Pronovost, Peter J; Needham, Dale M

2014-04-01

Survivors of severe critical illness frequently develop substantial and persistent physical complications, including muscle weakness, impaired physical function, and decreased health-related quality of life. Our objective was to determine the longitudinal epidemiology of muscle weakness, physical function, and health-related quality of life and their associations with critical illness and ICU exposures. A multisite prospective study with longitudinal follow-up at 3, 6, 12, and 24 months after acute lung injury. Thirteen ICUs from four academic teaching hospitals. Two hundred twenty-two survivors of acute lung injury. None. At each time point, patients underwent standardized clinical evaluations of extremity, hand grip, and respiratory muscle strength; anthropometrics (height, weight, mid-arm circumference, and triceps skin fold thickness); 6-minute walk distance, and the Medical Outcomes Short-Form 36 health-related quality of life survey. During their hospitalization, survivors also had detailed daily evaluation of critical illness and related treatment variables. Over one third of survivors had objective evidence of muscle weakness at hospital discharge, with most improving within 12 months. This weakness was associated with substantial impairments in physical function and health-related quality of life that persisted at 24 months. The duration of bed rest during critical illness was consistently associated with weakness throughout 24-month follow-up. The cumulative dose of systematic corticosteroids and use of neuromuscular blockers in the ICU were not associated with weakness. Muscle weakness is common after acute lung injury, usually recovering within 12 months. This weakness is associated with substantial impairments in physical function and health-related quality of life that continue beyond 24 months. These results provide valuable prognostic information regarding physical recovery after acute lung injury. Evidence-based methods to reduce the duration of bed rest during critical illness may be important for improving these long-term impairments.

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.

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

Sanchez-Nieto, Beatriz, E-mail: bsanchez@fis.puc.cl; Goset, Karen C.; Caviedes, Ivan

Purpose: To propose multivariate predictive models for changes in pulmonary function tests ({Delta}PFTs) with respect to preradiotherapy (pre-RT) values in patients undergoing RT for breast cancer and lymphoma. Methods and Materials: A prospective study was designed to measure {Delta}PFTs of patients undergoing RT. Sixty-six patients were included. Spirometry, lung capacity (measured by helium dilution), and diffusing capacity of carbon monoxide tests were used to measure lung function. Two lung definitions were considered: paired lung vs. irradiated lung (IL). Correlation analysis of dosimetric parameters (mean lung dose and the percentage of lung volume receiving more than a threshold dose) and {Delta}PFTsmore » was carried out to find the best dosimetric predictor. Chemotherapy, age, smoking, and the selected dose-volume parameter were considered as single and interaction terms in a multivariate analysis. Stability of results was checked by bootstrapping. Results: Both lung definitions proved to be similar. Modeling was carried out for IL. Acute and late damage showed the highest correlations with volumes irradiated above {approx}20 Gy (maximum R{sup 2} = 0.28) and {approx}40 Gy (maximum R{sup 2} = 0.21), respectively. RT alone induced a minor and transitory restrictive defect (p = 0.013). Doxorubicin-cyclophosphamide-paclitaxel (Taxol), when administered pre-RT, induced a late, large restrictive effect, independent of RT (p = 0.031). Bootstrap values confirmed the results. Conclusions: None of the dose-volume parameters was a perfect predictor of outcome. Thus, different predictor models for {Delta}PFTs were derived for the IL, which incorporated other nondosimetric parameters mainly through interaction terms. Late {Delta}PFTs seem to behave more serially than early ones. Large restrictive defects were demonstrated in patients pretreated with doxorubicin-cyclophosphamide-paclitaxel.« less

Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer.

PubMed

Zhang, X; Miao, X; Sun, T; Tan, W; Qu, S; Xiong, P; Zhou, Y; Lin, D

2005-06-01

The FAS and FASL system plays a key role in regulating apoptotic cell death and corruption of this signalling pathway has been shown to participate in immune escape and tumorigenesis. There is reduced expression of FAS but elevated expression of FASL in many types of human cancers including lung cancer. We recently reported an association between functional polymorphisms in FAS (-1377G-->A) and FASL (-844T-->C) and risk of oesophageal cancer. To examine the contribution of these polymorphisms to risk of developing lung cancer. Genotypes of 1000 lung cancer patients and 1270 controls were analysed by PCR based restriction fragment length polymorphism. Associations with risk of lung cancer were estimated by logistic regression. Compared with non-carriers, there was a 1.6 fold excess risk of developing lung cancer for carriers of the FAS -1377AA genotype (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.21 to 2.10; p = 0.001), and 1.8 fold excess risk (OR 1.79, 95% CI 1.26 to 2.52; p = 0.001) for carriers of FASL -844CC. Gene-gene interaction of FAS and FASL polymorphisms increased risk of lung cancer in a multiplicative manner (OR for the carriers of both FAS -1377AA and FASL -844CC genotypes 4.18, 95% CI 2.83 to 6.18). Gene-environment interaction of FAS or FASL polymorphism and smoking associated with increased risk of lung cancer was also found. These results are consistent with our initial findings in oesophageal cancer and further support the hypothesis that the FAS and FASL triggered apoptosis pathway plays an important role in human carcinogenesis.

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

Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

PubMed Central

Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

2014-01-01

Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and/or treating alcohol-related pulmonary disorders. PMID:24940828

The Aging Lung: Clinical and Imaging Findings and the Fringe of Physiological State.

PubMed

Schröder, T H; Storbeck, B; Rabe, K F; Weber, C

2015-06-01

Since aspects of demographic transition have become an essential part of socioeconomic, medical and health-care research in the last decades, it is vital for the radiologist to discriminate between normal ageing related effects and abnormal imaging findings in the elderly. This article reviews functional and structural aspects of the ageing lung and focuses on typical ageing related radiological patterns. • The physiological aging process of the thoracic organs shows typical structural and functional aspects.• Mild interstitial fibrosis and focal parenchymal abnormalities like septal thickening can be diagnosed frequently - whereas a clinical correlate is often lacking.• With increasing patient age, the influence by various intrinsic and extrinsic factors (including comorbidities of the patient, and drug inhalation toxicants) also increases.• A growing spectrum of imaging techniques (including functional cardiopulmonary MRI, MRI spectroscopy, hybrid-techniques) is confronted by rare empiric data in the very old people (aging 80 years and older). © Georg Thieme Verlag KG Stuttgart · New York.

Extracorporeal membrane oxygenation as a bridge to lung transplant: midterm outcomes.

PubMed

Bermudez, Christian A; Rocha, Rodolfo V; Zaldonis, Diana; Bhama, Jay K; Crespo, Maria M; Shigemura, Norihisa; Pilewski, Joseph M; Sappington, Penny L; Boujoukos, Arthur J; Toyoda, Yoshiya

2011-10-01

Extracorporeal membrane oxygenation (ECMO) is used occasionally as a bridge to lung transplantation. The impact on mid-term survival is unknown. We analyzed outcomes after lung transplant over a 19-year period in patients who received ECMO support. From March 1991 to October 2010, 1,305 lung transplants were performed at our institution. Seventeen patients (1.3%) were supported with ECMO before lung transplant. Diagnoses included retransplantation (n = 6), pulmonary fibrosis (n = 6), cystic fibrosis (n = 4), and chronic obstructive pulmonary disease (n = 1). Fifteen patients underwent double lung transplant, one patient had single left lung transplant and one patient had a heart-lung transplant. Venovenous and venoarterial ECMO were implanted in eight and nine cases, respectively. Median duration of support was 3.2 days (range, 1 to 49 days). Mean patient follow-up was 2.3 years. Thirty-day, 1-year, and 3-year survivals were 81%, 74%, and 65%, respectively, for the supported patients and 93%, 78%, and 62% in the control group (p = 0.56). Two-year survival was not affected by ECMO type, with survival of five out of nine patients supported by venoarterial ECMO vs seven out of eight patients supported by venovenous ECMO (p = 0.17). At 1- year follow-up, allograft function for the ECMO-supported patients did not differ from the control group (forced expiratory volume in one second, 2.35 L vs 2.09 L, p = 0.39) (forced vital capacity, 3.06 L vs 2.71 L, p = 0.34). Extracorporeal membrane oxygenation as a bridge to lung transplantation is associated with higher perioperative mortality but acceptable mid-term survival in carefully selected patients. Late allograft function did not differ in patients who received ECMO support before lung transplant from those who did not receive ECMO. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

WE-AB-202-01: Evaluating the Toxicity Reduction with CT-Ventilation Functional Avoidance Radiation Therapy

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

Vinogradskiy, Y; Miyasaka, Y; Kadoya, N

Purpose: CT-ventilation is an exciting new imaging modality that uses 4DCTs to calculate lung ventilation. Studies have proposed to use 4DCT-ventilation imaging for functional avoidance radiotherapy which implies designing treatment plans to spare functional portions of the lung. Although retrospective studies have been performed to evaluate the dosimetric gains to functional lung; no work has been done to translate the dosimetric gains to an improvement in pulmonary toxicity. The purpose of our work was to evaluate the potential reduction in toxicity for 4DCT-ventilation based functional avoidance. Methods: 70 lung cancer patients with 4DCT imaging were used for the study. CT-ventilationmore » maps were calculated using the patient’s 4DCT, deformable image registrations, and a density-change-based algorithm. Radiation pneumonitis was graded using imaging and clinical information. Log-likelihood methods were used to fit a normal-tissue-complication-probability (NTCP) model predicting grade 2+ radiation pneumonitis as a function of doses (mean and V20) to functional lung (>15% ventilation). For 20 patients a functional plan was generated that reduced dose to functional lung while meeting RTOG 0617-based constraints. The NTCP model was applied to the functional plan to determine the reduction in toxicity with functional planning Results: The mean dose to functional lung was 16.8 and 17.7 Gy with the functional and clinical plans respectively. The corresponding grade 2+ pneumonitis probability was 26.9% with the clinically-used plan and 24.6% with the functional plan (8.5% reduction). The V20-based grade 2+ pneumonitis probability was 23.7% with the clinically-used plan and reduced to 19.6% with the functional plan (20.9% reduction). Conclusion: Our results revealed a reduction of 9–20% in complication probability with functional planning. To our knowledge this is the first study to apply complication probability to convert dosimetric results to toxicity improvement. The results presented in the current work provide seminal data for prospective clinical trials in functional avoidance. YV discloses funding from State of Colorado. TY discloses National Lung Cancer Partnership; Young Investigator Research grant.« less

Respiratory pathogens mediate the association between lung function and temperature in cystic fibrosis.

PubMed

Collaco, Joseph M; Raraigh, Karen S; Appel, Lawrence J; Cutting, Garry R

2016-11-01

Mean annual ambient temperature is a replicated environmental modifier of cystic fibrosis (CF) lung disease with warmer temperatures being associated with lower lung function. The mechanism of this relationship is not completely understood. However, Pseudomonas aeruginosa, a pathogen that infects the lungs of CF individuals and decreases lung function, also has a higher prevalence in individuals living in warmer climates. We therefore investigated the extent to which respiratory pathogens mediated the association between temperature and lung function. Thirteen respiratory pathogens observed on CF respiratory cultures were assessed in multistep fashion using clustered linear and logistic regression to determine if any mediated the association between temperature and lung function. Analysis was performed in the CF Twin-Sibling Study (n=1730; primary population); key findings were then evaluated in the U.S. CF Foundation Data Registry (n=15,174; replication population). In the primary population, three respiratory pathogens (P. aeruginosa, mucoid P. aeruginosa, and methicillin-resistant Staphylococcus aureus) mediated the association between temperature and lung function. P. aeruginosa accounted for 19% of the association (p=0.003), mucoid P. aeruginosa for 31% (p=0.001), and MRSA for 13% (p=0.023). The same three pathogens mediated association in the replication population (7%, p<0.001; 7%, p=0.002; and 4%, (p=0.002), respectively). Three important respiratory pathogens in CF mediate the association between lower lung function and warmer temperatures. These findings have implications for understanding regional variations in clinical outcomes, and interpreting results of epidemiologic studies and clinical trials that encompass regions with different ambient temperatures. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Pulmonary function response and effects of antioxidant genetic polymorphisms in healthy young adults exposed to low concentration ozone.

EPA Science Inventory

Rational: Ozone is known to induce a variety of pulmonary effects including decrement of spirometric lung function and inflammatory reaction, and antioxidant genes are known to play an important role in modulating the effects. It is unclear, however, if such effects may occur at...

Lung function gain in preterm infants with and without bronchopulmonary dysplasia.

PubMed

Sanchez-Solis, Manuel; Perez-Fernandez, Virginia; Bosch-Gimenez, Vicente; Quesada, Juan J; Garcia-Marcos, Luis

2016-09-01

The aim of our study was to determine whether the development of lung function, during the first 2 years of life, is different in preterm infants who suffered or did not suffer from Bronchopulmonary dysplasia (BPD). We also assessed the role of nutritional status and growth in that development. Lung function tests were performed in 71 preterm infants at two time points: 6 months of corrected age and 1 year after. FVC, FEV0.5, FEF75 , and FEF25-75 were obtained from maximal expiratory volume curves by means of the raised volume rapid thoraco-abdominal compression technique. When comparing lung function measurements, we found that FVC (P = 0.033) FEV0.5 (P = 0.044), FEF75 (P = 0.014), and FEF25-75 (P = 0.036) were significantly lower in BPD infants. We did not find any catch-up of lung function during the study time, in neither the whole group of children nor within the BPD or non-BPD groups. The increase in lung function was directly proportional to the increase in weight and length. The multivariate analysis showed that the increase in z-score of FVC (P = 0.043), FEV0.5 (P = 0.015), and FEF75 (P = 0.042), was related with the height velocity during the study period. Infants who suffered from BPD have lower lung function (FVC, FEV0.5 , FEF75 , and FEF25-75 ), than those non-BPD, at two different time points 1 year apart. During the study period, there was no lung function catch-up in either BPD or non-BPD infants. The increase in length is closely associated to the increase in lung function. Pediatr Pulmonol. 2016; 51:936-942. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Gene-by-environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma.

PubMed

Bunyavanich, S; Boyce, J A; Raby, B A; Weiss, S T

2012-02-01

Distinct receptors likely exist for leukotriene (LT)E(4), a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE(4)-induced airways inflammation, and P2Y12 antagonism attenuates house dust mite-induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied. To test for association between variants in the P2Y12 gene (P2RY12) and lung function in human subjects with asthma, and to examine for gene-by-environment interaction with house dust mite exposure. Nineteen single nucleotide polymorphisms (SNPs) in P2RY12 were genotyped in 422 children with asthma and their parents (n = 1266). Using family based methods, we tested for associations between these SNPs and five lung function measures. We performed haplotype association analyses and tested for gene-by-environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons. Five SNPs in P2RY12 were associated with multiple lung function measures (P-values 0.006–0.025). Haplotypes in P2RY12 were also associated with lung function (P-values 0.0055–0.046). House dust mite exposure modulated associations between P2RY12 and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction P-values 0.0028–0.040). The P2RY12 variants were associated with lung function in a large family-based asthma cohort. House dust mite exposure caused significant gene-by-environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment.

Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.

PubMed

Hobbs, Brian D; de Jong, Kim; Lamontagne, Maxime; Bossé, Yohan; Shrine, Nick; Artigas, María Soler; Wain, Louise V; Hall, Ian P; Jackson, Victoria E; Wyss, Annah B; London, Stephanie J; North, Kari E; Franceschini, Nora; Strachan, David P; Beaty, Terri H; Hokanson, John E; Crapo, James D; Castaldi, Peter J; Chase, Robert P; Bartz, Traci M; Heckbert, Susan R; Psaty, Bruce M; Gharib, Sina A; Zanen, Pieter; Lammers, Jan W; Oudkerk, Matthijs; Groen, H J; Locantore, Nicholas; Tal-Singer, Ruth; Rennard, Stephen I; Vestbo, Jørgen; Timens, Wim; Paré, Peter D; Latourelle, Jeanne C; Dupuis, Josée; O'Connor, George T; Wilk, Jemma B; Kim, Woo Jin; Lee, Mi Kyeong; Oh, Yeon-Mok; Vonk, Judith M; de Koning, Harry J; Leng, Shuguang; Belinsky, Steven A; Tesfaigzi, Yohannes; Manichaikul, Ani; Wang, Xin-Qun; Rich, Stephen S; Barr, R Graham; Sparrow, David; Litonjua, Augusto A; Bakke, Per; Gulsvik, Amund; Lahousse, Lies; Brusselle, Guy G; Stricker, Bruno H; Uitterlinden, André G; Ampleford, Elizabeth J; Bleecker, Eugene R; Woodruff, Prescott G; Meyers, Deborah A; Qiao, Dandi; Lomas, David A; Yim, Jae-Joon; Kim, Deog Kyeom; Hawrylkiewicz, Iwona; Sliwinski, Pawel; Hardin, Megan; Fingerlin, Tasha E; Schwartz, David A; Postma, Dirkje S; MacNee, William; Tobin, Martin D; Silverman, Edwin K; Boezen, H Marike; Cho, Michael H

2017-03-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10 -6 ) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

Radiation-induced pulmonary gene expression changes are attenuated by the CTGF antibody Pamrevlumab.

PubMed

Sternlicht, Mark D; Wirkner, Ute; Bickelhaupt, Sebastian; Lopez Perez, Ramon; Tietz, Alexandra; Lipson, Kenneth E; Seeley, Todd W; Huber, Peter E

2018-01-18

Fibrosis is a delayed side effect of radiation therapy (RT). Connective tissue growth factor (CTGF) promotes the development of fibrosis in multiple settings, including pulmonary radiation injury. To better understand the cellular interactions involved in RT-induced lung injury and the role of CTGF in these responses, microarray expression profiling was performed on lungs of irradiated and non-irradiated mice, including mice treated with the anti-CTGF antibody pamrevlumab (FG-3019). Between group comparisons (Welch's t-tests) and principal components analyses were performed in Genespring. At the mRNA level, the ability of pamrevlumab to prolong survival and ameliorate RT-induced radiologic, histologic and functional lung deficits was correlated with the reversal of a clear enrichment in mast cell, macrophage, dendritic cell and mesenchymal gene signatures. Cytokine, growth factor and matrix remodeling genes that are likely to contribute to RT pneumonitis and fibrosis were elevated by RT and attenuated by pamrevlumab, and likely contribute to the cross-talk between enriched cell-types in injured lung. CTGF inhibition had a normalizing effect on select cell-types, including immune cells not typically regarded as being regulated by CTGF. These results suggest that interactions between RT-recruited cell-types are critical to maintaining the injured state; that CTGF plays a key role in this process; and that pamrevlumab can ameliorate RT-induced lung injury in mice and may provide therapeutic benefit in other immune and fibrotic disorders.

Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis.

PubMed

Solanki, Hitendra S; Advani, Jayshree; Khan, Aafaque Ahmad; Radhakrishnan, Aneesha; Sahasrabuddhe, Nandini A; Pinto, Sneha M; Chang, Xiaofei; Prasad, Thottethodi Subrahmanya Keshava; Mathur, Premendu Prakash; Sidransky, David; Gowda, Harsha; Chatterjee, Aditi

2017-08-01

Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke. Using high resolution Orbitrap Velos mass spectrometer, we identified the hyperphosphorylation of 493 sites, which corresponds to 341 proteins and 195 hypophosphorylated sites, mapping to 142 proteins upon smoke exposure (2.0-fold change). We report differential phosphorylation of multiple kinases, including PAK6, EPHA4, LYN, mitogen-activated protein kinase, and phosphatases, including TMEM55B, PTPN14, TIGAR, among others, in response to chronic cigarette smoke exposure. Bioinformatics analysis revealed that the molecules differentially phosphorylated upon chronic exposure of cigarette smoke are associated with PI3K/AKT/mTOR and CDC42-PAK signaling pathways. These signaling networks are involved in multiple cellular processes, including cell polarity, cytoskeletal remodeling, cellular migration, protein synthesis, autophagy, and apoptosis. The present study contributes to emerging proteomics insights on cigarette smoke mediated global signaling in lung cells, which in turn may aid in development of precision medicine therapeutics and postgenomics biomarkers.

Work-related symptoms and dose-response relationships for personal exposures and pulmonary function among woodworkers.

PubMed

Mandryk, J; Alwis, K U; Hocking, A D

1999-05-01

Four sawmills, a wood chipping mill, and five joineries in New South Wales, Australia, were studied for the effects of personal exposure to wood dust, endotoxins. (1-->3)-beta-D-glucans, Gram-negative bacteria, and fungi on lung function among woodworkers. Personal inhalable and respirable dust sampling was carried out. The lung function tests of workers were conducted before and after a workshift. The mean percentage cross-shift decrease in lung function was markedly high for woodworkers compared with the controls. Dose-response relationships among personal exposures and percentage cross-shift decrease in lung function and percentage predicted lung function were more pronounced among joinery workers compared with sawmill and chip mill workers. Woodworkers had markedly high prevalence of regular cough, phlegm, and chronic bronchitis compared with controls. Significant associations were found between percentage cross-shift decrease in FVC and regular phlegm and blocked nose among sawmill and chip mill workers. Both joinery workers and sawmill and chip mill workers showed significant relationships between percentage predicted lung function (FVC, FEV1, FEV1/FVC, FEF25-75%) and respiratory symptoms. Wood dust and biohazards associated with wood dust are potential health hazards and should be controlled.

Lung vital capacity and oxygen saturation in adults with cerebral palsy

PubMed Central

Lampe, Renée; Blumenstein, Tobias; Turova, Varvara; Alves-Pinto, Ana

2014-01-01

Background Individuals with infantile cerebral palsy have multiple disabilities. The most conspicuous syndrome being investigated from many aspects is motor movement disorder with a spastic gait pattern. The lung function of adults with spasticity attracts less attention in the literature. This is surprising because decreased thoracic mobility and longstanding scoliosis should have an impact on lung function. With increasing age and the level of disability, individuals become susceptible to lung infections and reflux illness, and these are accompanied by increased aspiration risk. This study examined, with different methods, to what extent adults with congenital cerebral palsy and acquired spastic paresis – following traumatic brain injury – showed restriction of lung function. It also assessed the contribution of disability level on this restriction. Methods The oxygen saturation of 46 adults with a diagnosis of cerebral palsy was measured with an oximeter. Lung vital capacity was measured with a mobile spirometer and excursion of the thorax was clinically registered. The gross motor function levels and the presence or absence of scoliosis were determined. Results A significantly positive correlation between lung vital capacity and chest expansion was established. Both the lung vital capacity and the thorax excursion decreased with increases in gross motor function level. Oxygen saturation remained within the normal range in all persons, in spite of reduced values of the measured lung parameters. No statistically significant dependency between lung vital capacity and oxygen saturation, and between chest expansion and oxygen saturation was found. The scoliotic deformities of the spine were associated with an additional decrease in the vital capacity, but this did not affect blood oxygen supply. Conclusion Despite the decreased chest expansion and the significantly reduced lung volume in adults with cerebral palsy, sufficient oxygen supply was registered. PMID:25525345

Abnormal lung function at preschool age asthma in adolescence?

PubMed

Lajunen, Katariina; Kalliola, Satu; Kotaniemi-Syrjänen, Anne; Sarna, Seppo; Malmberg, L Pekka; Pelkonen, Anna S; Mäkelä, Mika J

2018-05-01

Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate. This longitudinal study relates lung function assessed with impulse oscillometry (IOS) in preschool children to asthma in adolescence. Lung function was measured with IOS in 255 children with asthma-like symptoms aged 4-7 years. Baseline measurements were followed by exercise challenge and bronchodilation tests. At age 12-16 years, 121 children participated in the follow-up visit, when lung function was assessed with spirometry, followed by a bronchodilation test. Asthma symptoms and medication were recorded by a questionnaire and atopy defined by skin prick tests. Abnormal baseline values in preschool IOS were significantly associated with low lung function, the need for asthma medication, and asthma symptoms in adolescence. Preschool abnormal R5 at baseline (z-score ≥1.645 SD) showed 9.2 odds ratio (95%CI 2.7;31.7) for abnormal FEV1/FVC, use of asthma medication in adolescence, and 9.9 odds ratio (95%CI 2.9;34.4) for asthma symptoms. Positive exercise challenge and modified asthma-predictive index at preschool age predicted asthma symptoms and the need for asthma medication, but not abnormal lung function at teenage. Abnormal preschool IOS is associated with asthma and poor lung function in adolescence and might be utilised for identification of asthma persistence. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Early bronchopulmonary involvement in Crohn disease: a case report

PubMed Central

Valletta, Enrico; Bertini, Marina; Sette, Luciano; Braggion, Cesare; Pradal, Ugo; Zannoni, Marina

2001-01-01

Background Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease. Case presentation A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation. Conclusions Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD. PMID:11734067

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.

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

SU-E-J-87: Ventilation Weighting Effect On Mean Doses of Both Side Lungs for Patients with Advanced Stage Lung Cancer

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

Qu, H; Xia, P; Yu, N

Purpose: To study ventilation weighting effect on radiation doses to both side lungs for patients with advanced stage lung cancer. Methods: Fourteen patients with advanced stage lung cancer were included in this retrospective study. Proprietary software was developed to calculate the lung ventilation map based on 4DCT images acquired for radiation therapy. Two phases of inhale (0%) and exhale (50%) were used for the lung ventilation calculations. For each patient, the CT images were resampled to the same dose calculation resolution of 3mmx3mmx3mm. The ventilation distribution was then normalized by the mean value of the ventilation. The ventilation weighted dosemore » was calculated by applying linearly weighted ventilation to the dose of each pixel. The lung contours were automatically delineated from patient CT image with lung window, excluding the tumor and high density tissues. For contralateral and ipsilateral lungs, the mean lung doses from the original plan and ventilation weighted mean lung doses were compared using two tail t-Test. Results: The average of mean dose was 6.1 ±3.8Gy for the contralateral lungs, and 26.2 ± 14.0Gy for the ipsilateral lungs. The average of ventilation weighted dose was 6.3± 3.8Gy for the contralateral lungs and 24.6 ± 13.1Gy for the ipsilateral lungs. The statistics analysis shows the significance of the mean dose increase (p<0.015) for the contralateral lungs and decrease (p<0.005) for the ipsilateral lungs. Conclusion: Ventilation weighted doses were greater than the un-weighted doses for contralateral lungs and smaller for ipsilateral lungs. This Result may be helpful to understand the radiation dosimetric effect on the lung function and provide planning guidance for patients with advance stage lung cancer.« less

Effects of antenatal multiple micronutrient supplementation on lung function in mid-childhood: follow-up of a double-blind randomised controlled trial in Nepal

PubMed Central

Devakumar, D; Stocks, J; Ayres, JG; Kirkby, J; Yadav, SK; Saville, NM; Devereux, G; Wells, JCK; Manandhar, DS; Costello, A; Osrin, D

2015-01-01

A randomised trial of prenatal multiple micronutrient supplementation in Nepalese women increased birthweight and weight at two years of age in offspring, compared with those born to mothers who only received iron and folic acid supplements. Further follow-up of this cohort provided an opportunity to investigate the effect of antenatal multiple micronutrients on subsequent lung function, by measuring spirometry at 7-9 years of age in children born in the trial. 841 children (80% of the cohort) were seen at mean (SD) 8.5 (0.4) years. Technically successful spirometry results were obtained in 793 children (94.3%), 50% of whom had been randomised to micronutrient supplementation. Background characteristics, including anthropometry, were similar in the two allocation groups. Lung function was also similar, mean (95%CI) difference in z-scores (supplementation – control) being −0.08 (−0.19, 0.04) for FEV1; −0.05 (−0.17, 0.06) for FVC and −0.04 (−0.15, 0.07) for FEV1/FVC. Compared with healthy White children, FEV1 and FVC in the ‘healthy’ Nepalese children were ~1 z-score (~13%) lower, with no difference in FEV1/FVC. We conclude that, compared with routine iron and folic acid, multiple micronutrient supplementation during pregnancy has no effect on spirometric lung function in Nepalese children at 8.5 years of age. PMID:25700386

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.

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.

Sustained Effects of Sirolimus on Lung Function and Cystic Lung Lesions in Lymphangioleiomyomatosis

PubMed Central

Yao, Jianhua; Jones, Amanda M.; Julien-Williams, Patricia; Stylianou, Mario; Moss, Joel

2014-01-01

Rationale: Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis. Objectives: To determine whether sirolimus has beneficial effects on lung function, cystic areas, and adjacent lung parenchyma; whether these effects are sustained; and whether sirolimus is well tolerated by patients. Methods: Lung function decline over time, lung volume occupied by cysts (cyst score), and lung tissue texture in the vicinity of the cysts were quantified with a computer-aided diagnosis system in 38 patients. Then we compared cyst scores from the last study on sirolimus with studies done on sirolimus therapy. In 12 patients, we evaluated rates of change in lung function and cyst scores off and on sirolimus. Measurements and Main Results: Sirolimus reduced yearly declines in FEV1 (−2.3 ± 0.1 vs. 1.0 ± 0.3% predicted; P < 0.001) and diffusing capacity of carbon monoxide (−2.6 ± 0.1 vs. 0.9 ± 0.2% predicted; P < 0.001). Cyst scores 1.2 ± 0.8 years (30.5 ± 11.9%) and 2.5 ± 2 years (29.7 ± 12.1%) after initiating sirolimus were not significantly different from pretreatment values (28.4 ± 12.5%). In 12 patients followed for 5 years, a significant reduction in rates of yearly decline in FEV1 (−1.4 ± 0.2 vs. 0.3 ± 0.4% predicted; P = 0.025) was observed. Analyses of 104 computed tomography scans showed a nonsignificant (P = 0.23) reduction in yearly rates of change of cyst scores (1.8 ± 0.2 vs. 0.3 ± 0.3%; P = 0.23) and lung texture features. Despite adverse events, most patients were able to continue sirolimus therapy. Conclusions: Sirolimus therapy slowed down lung function decline and increase in cystic lesions. Most patients were able to tolerate sirolimus therapy. PMID:25329516

Impairment of pulmonary diffusion correlates with hypoxemic burden in central sleep apnea heart failure patients.

PubMed

Fox, Henrik; Koerber, Britta; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf

2017-09-01

Central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) are highly prevalent in heart failure (HF) and are linked to increased mortality. Impaired pulmonary diffusion capacity [DLCO] and [KCO]) have been suggested to play a key role in CSA-CSR pathophysiology. This study investigated the relationship between HF, CSR, DLCO and KCO in well-characterized HF patients. This prospective study included HF patients with CSR, all patients underwent full overnight polysomnography (PSG) and lung function testing. A total of 100 patients were included (age 70.7±9.7years, 95% male, body mass index 28.9±5.3kg/m 2 , left ventricular ejection fraction 33.5±7.7%, New York Heart Association class III 65%. DLCO and oxygenation were significantly correlated with hypoxemic burden (p<0.05). Mean oxygen saturation, oxygen desaturation, C-reactive protein level and pH were significantly associated with CSA-CSR severity (p<0.05). The finding that lung diffusion capacity is significantly associated with hypoxemic burden in HF patients with CSA-CSR highlights the important of lung function in HF patients. Copyright © 2017. Published by Elsevier B.V.

High-Resolution Time-Frequency Spectrum-Based Lung Function Test from a Smartphone Microphone

PubMed Central

Thap, Tharoeun; Chung, Heewon; Jeong, Changwon; Hwang, Ki-Eun; Kim, Hak-Ryul; Yoon, Kwon-Ha; Lee, Jinseok

2016-01-01

In this paper, a smartphone-based lung function test, developed to estimate lung function parameters using a high-resolution time-frequency spectrum from a smartphone built-in microphone is presented. A method of estimation of the forced expiratory volume in 1 s divided by forced vital capacity (FEV1/FVC) based on the variable frequency complex demodulation method (VFCDM) is first proposed. We evaluated our proposed method on 26 subjects, including 13 healthy subjects and 13 chronic obstructive pulmonary disease (COPD) patients, by comparing with the parameters clinically obtained from pulmonary function tests (PFTs). For the healthy subjects, we found that an absolute error (AE) and a root mean squared error (RMSE) of the FEV1/FVC ratio were 4.49% ± 3.38% and 5.54%, respectively. For the COPD patients, we found that AE and RMSE from COPD patients were 10.30% ± 10.59% and 14.48%, respectively. For both groups, we compared the results using the continuous wavelet transform (CWT) and short-time Fourier transform (STFT), and found that VFCDM was superior to CWT and STFT. Further, to estimate other parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF), regression analysis was conducted to establish a linear transformation. However, the parameters FVC, FEV1, and PEF had correlation factor r values of 0.323, 0.275, and −0.257, respectively, while FEV1/FVC had an r value of 0.814. The results obtained suggest that only the FEV1/FVC ratio can be accurately estimated from a smartphone built-in microphone. The other parameters, including FVC, FEV1, and PEF, were subjective and dependent on the subject’s familiarization with the test and performance of forced exhalation toward the microphone. PMID:27548164

Association of emphysema-like lung on cardiac computed tomography and mortality in persons without airflow obstruction: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study

PubMed Central

Oelsner, Elizabeth C.; Hoffman, Eric A.; Folsom, Aaron R.; Carr, J. Jeffrey; Enright, Paul L.; Kawut, Steven M.; Kronmal, Richard; Lederer, David; Lima, Joao A. C.; Lovasi, Gina S.; Shea, Steven; Barr, R. Graham

2015-01-01

Background Whereas low lung function is known to predict mortality in the general population, the prognostic significance of emphysema on computed tomography (CT) in persons without chronic obstructive pulmonary disease (COPD) remains uncertain. Objective To determine whether greater emphysema-like lung on CT is associated with all-cause mortality among persons without airflow obstruction or COPD in the general population. Design Prospective cohort study. Setting Population-based, multiethnic sample from 6 US communities. Participants 2965 participants ages 45-84 years without airflow obstruction on spirometry. Measurements Emphysema-like lung was defined on cardiac CT as the number of lung voxels less than -950 Hounsfield Units, and was adjusted for the number of total imaged lung voxels. Results Among 2965 participants, 50.9% of whom never smoked, there were 186 deaths over a median of 6.2 years. Greater emphysema-like lung was independently associated with increased mortality (adjusted hazard ratio [HR]1.14 per one-half of the interquartile range, 95% CI 1.04-1.24, P=0.004), adjusting for potential confounders including cardiovascular risk factors and the forced expiratory volume in one second. Generalized additive models supported a linear association between emphysema-like lung and mortality without evidence for a threshold. The association was of greatest magnitude among smokers, although multiplicative interaction terms did not support effect modification by smoking status. Limitations Cardiac CT scans did not include lung apices. The number of deaths was limited among subgroup analyses. Conclusions Emphysema-like lung on CT was associated with all-cause mortality among persons without airflow obstruction or COPD in a general population sample, particularly among smokers. Recognition of the independent prognostic significance of emphysema on CT among patients without COPD on spirometry is warranted. Primary Funding Source NIH/NHLBI. PMID:25506855

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.

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

PubMed Central

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

2014-01-01

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

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

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

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

2010-06-04

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

Influence of 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.

Secreted Phosphoprotein 1 Is a Determinant of Lung Function Development in Mice

PubMed Central

Martin, Timothy M.; Concel, Vincent J.; Upadhyay, Swapna; Bein, Kiflai; Brant, Kelly A.; George, Leema; Mitra, Ankita; Thimraj, Tania A.; Fabisiak, James P.; Vuga, Louis J.; Fattman, Cheryl; Kaminski, Naftali; Schulz, Holger; Leikauf, George D.

2014-01-01

Secreted phosphoprotein 1 (Spp1) is located within quantitative trait loci associated with lung function that was previously identified by contrasting C3H/HeJ and JF1/Msf mouse strains that have extremely divergent lung function. JF1/Msf mice with diminished lung function had reduced lung SPP1 transcript and protein during the peak stage of alveologenesis (postnatal day [P]14–P28) as compared with C3H/HeJ mice. In addition to a previously identified genetic variant that altered runt-related transcription factor 2 (RUNX2) binding in the Spp1 promoter, we identified another promoter variant in a putative RUNX2 binding site that increased the DNA protein binding. SPP1 induced dose-dependent mouse lung epithelial-15 cell proliferation. Spp1(−/−) mice have decreased specific total lung capacity/body weight, higher specific compliance, and increased mean airspace chord length (Lm) compared with Spp1(+/+) mice. Microarray analysis revealed enriched gene ontogeny categories, with numerous genes associated with lung development and/or respiratory disease. Insulin-like growth factor 1, Hedgehog-interacting protein, wingless-related mouse mammary tumor virus integration site 5A, and NOTCH1 transcripts decreased in the lung of P14 Spp1(−/−) mice as determined by quantitative RT-PCR analysis. SPP1 promotes pneumocyte growth, and mice lacking SPP1 have smaller, more compliant lungs with enlarged airspace (i.e., increased Lm). Microarray analysis suggests a dysregulation of key lung developmental transcripts in gene-targeted Spp1(−/−) mice, particularly during the peak phase of alveologenesis. In addition to its known roles in lung disease, this study supports SPP1 as a determinant of lung development in mice. PMID:24816281

Automated method and system for the alignment and correlation of images from two different modalities

DOEpatents

Giger, Maryellen L.; Chen, Chin-Tu; Armato, Samuel; Doi, Kunio

1999-10-26

A method and system for the computerized registration of radionuclide images with radiographic images, including generating image data from radiographic and radionuclide images of the thorax. Techniques include contouring the lung regions in each type of chest image, scaling and registration of the contours based on location of lung apices, and superimposition after appropriate shifting of the images. Specific applications are given for the automated registration of radionuclide lungs scans with chest radiographs. The method in the example given yields a system that spatially registers and correlates digitized chest radiographs with V/Q scans in order to correlate V/Q functional information with the greater structural detail of chest radiographs. Final output could be the computer-determined contours from each type of image superimposed on any of the original images, or superimposition of the radionuclide image data, which contains high activity, onto the radiographic chest image.

Idiopathic pulmonary fibrosis: a holistic approach to disease management in the antifibrotic age.

PubMed

Shaw, Jonathon; Marshall, Tracey; Morris, Helen; Hayton, Conal; Chaudhuri, Nazia

2017-11-01

Idiopathic pulmonary fibrosis (IPF) is the most common cause of interstitial lung disease (ILD) and carries a worse prognosis than many cancers. Until recently, there were no active treatment options available for patients with IPF, meaning palliation or lung transplantation in selected patients were the only options. The management of IPF has changed dramatically over the last decade with the advent of two antifibrotic agents; pirfenidone and nintedanib. These new agents have been shown to reduce decline in lung function and pirfenidone has been shown to reduce mortality. The changing landscape of IPF diagnosis and management present a number of issues that may be encountered including management of side effects related to antifibrotic therapy. This article aims to give an overview of the holistic approach to the management of patients with IPF, including antifibrotic management, symptom management and the invaluable role of the ILD specialist nurse.

Idiopathic pulmonary fibrosis: a holistic approach to disease management in the antifibrotic age

PubMed Central

Shaw, Jonathon; Marshall, Tracey; Morris, Helen; Chaudhuri, Nazia

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is the most common cause of interstitial lung disease (ILD) and carries a worse prognosis than many cancers. Until recently, there were no active treatment options available for patients with IPF, meaning palliation or lung transplantation in selected patients were the only options. The management of IPF has changed dramatically over the last decade with the advent of two antifibrotic agents; pirfenidone and nintedanib. These new agents have been shown to reduce decline in lung function and pirfenidone has been shown to reduce mortality. The changing landscape of IPF diagnosis and management present a number of issues that may be encountered including management of side effects related to antifibrotic therapy. This article aims to give an overview of the holistic approach to the management of patients with IPF, including antifibrotic management, symptom management and the invaluable role of the ILD specialist nurse. PMID:29268540

Mechanisms of lung aging.

PubMed

Brandenberger, Christina; Mühlfeld, Christian

2017-03-01

Lung aging is associated with structural remodeling, a decline of respiratory function and a higher susceptibility to acute and chronic lung diseases. Individual factors that modulate pulmonary aging include basic genetic configuration, environmental exposure, life-style and biography of systemic diseases. However, the actual aging of the lung takes place in pulmonary resident cells and is closely linked to aging of the immune system (immunosenescence). Therefore, this article reviews the current knowledge about the impact of aging on pulmonary cells and the immune system, without analyzing those factors that may accelerate the aging process in depth. Hallmarks of aging include alterations at molecular, cellular and cell-cell interaction levels. Because of the great variety of cell types in the lung, the consequences of aging display a broad spectrum of phenotypes. For example, aging is associated with more collagen and less elastin production by fibroblasts, thus increasing pulmonary stiffness and lowering compliance. Decreased sympathetic airway innervation may increase the constriction status of airway smooth muscle cells. Aging of resident and systemic immune cells leads to a pro-inflammatory milieu and reduced capacity of fighting infectious diseases. The current review provides an overview of cellular changes occurring with advancing age in general and in several cell types of the lung as well as of the immune system. Thereby, this survey not only aims at providing a better understanding of the mechanisms of pulmonary aging but also to identify gaps in knowledge that warrant further investigations.

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

PubMed

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

2018-03-17

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

Six minute walking test and carbon monoxide diffusing capacity for non-small cell lung cancer: easy performed tests in every day practice.

PubMed

Zarogoulidis, Paul; Kerenidi, Theodora; Huang, Haidong; Kontakiotis, Theodoros; Tremma, Ourania; Porpodis, Konstantinos; Kalianos, Anastasios; Rapti, Ageliki; Foroulis, Christoforos; Zissimopoulos, Athanasios; Courcoutsakis, Nikolaos; Zarogoulidis, Konstantinos

2012-12-01

Several studies have demonstrated that reduced lung function is a significant risk factor for lung cancer and increased surgical risk in patients with operable stages of lung cancer. The aim of the study was to perform pulmonary function tests and investigate which is a favorable respiratory function test for overall survival between lung cancer stages. Lung function tests were performed to lung cancer patients with non-small cell lung cancer of stage I, II, III and IV (241 patients in total). They had the last follow-up consecutively between December 2006 and July 2008. The staging was decided according to the sixth edition of TNM classification of NSCLC. The Forced Expiratory Volume in 1sec (FEV1), Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) were measured according to American Thoracic Society/European Respiratory Society guidelines. The 6 Minute Walking Test (6MWT) was measured according to the American Thoracic Society. There was a significant association of the DLCO upon diagnosis and overall survival for stage II (P<0.007) and IV (P<0.003). Furthermore, there was a significant association between 6MWT and overall survival for stage III (P<0.001) and stage IV (P<0.010). The significance for each lung function test is different among the stages of NSCLC. DLCO and 6MWT upon admission are the most valuable prognostic factors for overall survival of NSCLC.

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

PubMed

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

2016-08-01

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

Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

ClinicalTrials.gov

2017-04-12

Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

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

PubMed

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

2018-04-05

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

Respiratory symptoms and pulmonary function impairment among detergent plant workers in Jos, Northern Nigeria.

PubMed

Babashani, M; Iliyasu, Z; Ukoli, C O

2008-01-01

The industrial process of detergent production could be deleterious to lung function. This study describes respiratory symptoms and ventilatory function impairment among detergent workers in Jos, Northern Nigeria. Two hundred detergent plant workers and controls were studied for the presence of respiratory symptoms and ventilatory function impairment using the MRC questionnaire and Spirometry. A significantly higher proportion of exposed detergent workers 178 (87.0%) reported respiratory symptoms compared to 52 (26.0%) controls [OR=23; 95% CI=12.9-41.3] (P<0.001). Commonest symptoms include rhinitis (57.5% versus 11.0%) and cough (48.5% versus 15%). Symptoms were most prevalent in the packaging section. FEV1, FVC and PEFR were significantly reduced among exposed detergent workers. Similarly, the predicted values of PEFR, FVC and FEV1, were significantly reduced among smokers (P<0. 001). Respiratory symptoms are highly prevalent among detergent workers. This was associated with impaired pulmonary function. Protective equipment and periodic lung function tests could reduce these effects.

Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers

PubMed Central

Blakely, Collin M.; Watkins, Thomas B.K.; Wu, Wei; Gini, Beatrice; Chabon, Jacob J.; McCoach, Caroline E.; McGranahan, Nicholas; Wilson, Gareth A.; Birkbak, Nicolai J.; Olivas, Victor R.; Rotow, Julia; Maynard, Ashley; Wang, Victoria; Gubens, Matthew A.; Banks, Kimberly C.; Lanman, Richard B.; Caulin, Aleah F.; John, John St.; Cordero, Anibal R.; Giannikopoulos, Petros; Simmons, Andrew D.; Mack, Philip C.; Gandara, David R.; Husain, Hatim; Doebele, Robert C.; Riess, Jonathan W.; Diehn, Maximilian; Swanton, Charles; Bivona, Trever G.

2017-01-01

A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant protein product (e.g. EGFR inhibitor treatment in EGFR-mutant lung cancers). However, genetically-driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1122 EGFR-mutant lung cancer cell-free DNA samples and whole exome analysis of seven longitudinally collected tumor samples from an EGFR-mutant lung cancer patient, we identify critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers. We define new pathways limiting EGFR inhibitor response, including WNT/β-catenin and cell cycle gene (e.g. CDK4, CDK6) alterations. Tumor genomic complexity increases with EGFR inhibitor treatment and co-occurring alterations in CTNNB1, and PIK3CA exhibit non-redundant functions that cooperatively promote tumor metastasis or limit EGFR inhibitor response. This study challenges the prevailing single-gene driver oncogene view and links clinical outcomes to co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancer patients. PMID:29106415

PPAR Agonists for the Prevention and Treatment of Lung Cancer.

PubMed

Lakshmi, Sowmya P; Reddy, Aravind T; Banno, Asoka; Reddy, Raju C

2017-01-01

Lung cancer is the most common and most fatal of all malignancies worldwide. Furthermore, with more than half of all lung cancer patients presenting with distant metastases at the time of initial diagnosis, the overall prognosis for the disease is poor. There is thus a desperate need for new prevention and treatment strategies. Recently, a family of nuclear hormone receptors, the peroxisome proliferator-activated receptors (PPARs), has attracted significant attention for its role in various malignancies including lung cancer. Three PPARs, PPAR α , PPAR β / δ , and PPAR γ , display distinct biological activities and varied influences on lung cancer biology. PPAR α activation generally inhibits tumorigenesis through its antiangiogenic and anti-inflammatory effects. Activated PPAR γ is also antitumorigenic and antimetastatic, regulating several functions of cancer cells and controlling the tumor microenvironment. Unlike PPAR α and PPAR γ , whether PPAR β / δ activation is anti- or protumorigenic or even inconsequential currently remains an open question that requires additional investigation. This review of current literature emphasizes the multifaceted effects of PPAR agonists in lung cancer and discusses how they may be applied as novel therapeutic strategies for the disease.

A novel PHD-finger protein 14/KIF4A complex overexpressed in lung cancer is involved in cell mitosis regulation and tumorigenesis.

PubMed

Zhang, Lin; Huang, Qin; Lou, Jiatao; Zou, Liangjian; Wang, Yiguo; Zhang, Peng; Yang, Guang; Zhang, Junyi; Yu, Lan; Yan, Dai; Zhang, Chenyi; Qiao, Jing; Wang, Shuting; Wang, Sai; Xu, Yongdong; Ji, Hongbin; Chen, Zhengjun; Zhang, Zhe

2017-03-21

The plant homeodomain (PHD) finger-containing proteins have been implicated in many human diseases including cancer. In this study, we found that PHF14, a newly identified PHD finger protein, is highly expressed in lung cancer. The high expression level of PHF14 was associated with adenocarcinoma and poor survival in lung cancer patients. Knocking down PHF14 suppressed cancer cell growth and carcinogenesis, while over-expressing PHF14 promoted cell proliferation. During cell division, PHF14 directly bound to and co-localized with KIF4A (a nuclear motor protein involved in lung carcinogenesis) to form a functional complex. Similarly to the effect of KIF4A depletion, silencing PHF14 in several cell lines caused cell mitotic defects, prolonged M phase, and inhibited cell proliferation. What's more, these two proteins had a synergistic effect on cell proliferation and were significantly co-overexpressed in lung cancer tissues. Our data provide new insights into the biological significance of PHD finger proteins and imply that PHF14 may be a potential biomarker for lung cancer.

Targeting DDX3 with a small molecule inhibitor for lung cancer therapy

PubMed Central

Bol, Guus M; Vesuna, Farhad; Xie, Min; Zeng, Jing; Aziz, Khaled; Gandhi, Nishant; Levine, Anne; Irving, Ashley; Korz, Dorian; Tantravedi, Saritha; Heerma van Voss, Marise R; Gabrielson, Kathleen; Bordt, Evan A; Polster, Brian M; Cope, Leslie; van der Groep, Petra; Kondaskar, Atul; Rudek, Michelle A; Hosmane, Ramachandra S; van der Wall, Elsken; van Diest, Paul J; Tran, Phuoc T; Raman, Venu

2015-01-01

Lung cancer is the most common malignancy worldwide and is a focus for developing targeted therapies due to its refractory nature to current treatment. We identified a RNA helicase, DDX3, which is overexpressed in many cancer types including lung cancer and is associated with lower survival in lung cancer patients. We designed a first-in-class small molecule inhibitor, RK-33, which binds to DDX3 and abrogates its activity. Inhibition of DDX3 by RK-33 caused G1 cell cycle arrest, induced apoptosis, and promoted radiation sensitization in DDX3-overexpressing cells. Importantly, RK-33 in combination with radiation induced tumor regression in multiple mouse models of lung cancer. Mechanistically, loss of DDX3 function either by shRNA or by RK-33 impaired Wnt signaling through disruption of the DDX3–β-catenin axis and inhibited non-homologous end joining—the major DNA repair pathway in mammalian somatic cells. Overall, inhibition of DDX3 by RK-33 promotes tumor regression, thus providing a compelling argument to develop DDX3 inhibitors for lung cancer therapy. PMID:25820276

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.

Handgrip strength is associated with improved spirometry in adolescents

PubMed Central

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

2018-01-01

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

Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury.

PubMed

Spieth, Peter M; Carvalho, Alysson R; Pelosi, Paolo; Hoehn, Catharina; Meissner, Christoph; Kasper, Michael; Hübler, Matthias; von Neindorff, Matthias; Dassow, Constanze; Barrenschee, Martina; Uhlig, Stefan; Koch, Thea; de Abreu, Marcelo Gama

2009-04-15

Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies.

Astilbin alleviates sepsis-induced acute lung injury by inhibiting the expression of macrophage inhibitory factor in rats.

PubMed

Zhang, Hong-Bo; Sun, Li-Chao; Zhi, Li-da; Wen, Qian-Kuan; Qi, Zhi-Wei; Yan, Sheng-Tao; Li, Wen; Zhang, Guo-Qiang

2017-10-01

Sepsis is a systemic inflammatory response syndrome caused by severe infections. Astilbin is a dihydroflavonol derivative found in many medicinal and food plants with multiple pharmacological functions. To investigate the effects of astilbin on sepsis-induced acute lung injury (ALI), cecal ligation and puncture was performed on rats to establish a sepsis-induced ALI model; these rats were then treated with astilbin at different concentrations. Lung injury scores, including lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration were determined to evaluate the effects of astilbin on sepsis-induced ALI. We found that astilbin treatment significantly attenuates sepsis-induced lung injury and improves survival rate, lung injury scores, lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration. Astilbin treatment also dramatically decreased the production of inflammatory cytokines and chemokines in bronchoalveolar lavage fluid. Further, astilbin treatment inhibited the expression and production of macrophage inhibitory factor (MIF), which inhibits the inflammatory response. Collectively, these data suggest that astilbin has a protective effect against sepsis-induced ALI by inhibiting MIF-mediated inflammatory responses. This study provides a molecular basis for astilbin as a new medical treatment for sepsis-induced ALI.

Enhanced alveolar growth and remodeling in Guinea pigs raised at high altitude.

PubMed

Hsia, Connie C W; Carbayo, Juan J Polo; Yan, Xiao; Bellotto, Dennis J

2005-05-12

To examine the effects of chronic high altitude (HA) exposure on lung structure during somatic maturation, we raised male weanling guinea pigs at HA (3800m) for 1, 3, or 6 months, while their respective male littermates were simultaneously raised at low altitude (LA, 1200m). Under anaesthesia, airway pressure was measured at different lung volumes. The right lung was fixed at a constant airway pressure for morphometric analysis under light and electron microscopy. In animals raised at HA for 1 month, lung volume, alveolar surface area and alveolar-capillary blood volume (V(c)) were elevated above LA control values. Following 3-6 months of HA exposure, increases in lung volume and alveolar surface area persisted while the initial increase in V(c) normalized. Additional adaptation occurred, including a higher epithelial cell volume, septal tissue volume and capillary surface area, a lower alveolar duct volume and lower harmonic mean diffusion barrier resulting in higher membrane and lung diffusing capacities. These data demonstrate enhanced alveolar septal growth and progressive acinar remodeling during chronic HA exposure with long-term augmentation of alveolar dimensions as well as functional compensation in lung compliance and diffusive gas transport.

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

PubMed

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

2012-11-01

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

Combined Ventilation and Perfusion Imaging Correlates With the Dosimetric Parameters of Radiation Pneumonitis in Radiation Therapy Planning for Lung Cancer

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

Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp; Doi, Yoshiko; Nakashima, Takeo

2015-11-15

Purpose: The purpose of this study was to prospectively investigate clinical correlations between dosimetric parameters associated with radiation pneumonitis (RP) and functional lung imaging. Methods and Materials: Functional lung imaging was performed using four-dimensional computed tomography (4D-CT) for ventilation imaging, single-photon emission computed tomography (SPECT) for perfusion imaging, or both (V/Q-matched region). Using 4D-CT, ventilation imaging was derived from a low attenuation area according to CT numbers below different thresholds (vent-860 and -910). Perfusion imaging at the 10th, 30th, 50th, and 70th percentile perfusion levels (F10-F70) were defined as the top 10%, 30%, 50%, and 70% hyperperfused normal lung, respectively.more » All imaging data were incorporated into a 3D planning system to evaluate correlations between RP dosimetric parameters (where fV20 is the percentage of functional lung volume irradiated with >20 Gy, or fMLD, the mean dose administered to functional lung) and the percentage of functional lung volume. Radiation pneumonitis was evaluated using Common Terminology Criteria for Adverse Events version 4.0. Statistical significance was defined as a P value of <.05. Results: Sixty patients who underwent curative radiation therapy were enrolled (48 patients for non-small cell lung cancer, and 12 patients for small cell lung cancer). Grades 1, 2, and ≥3 RP were observed in 16, 44, and 6 patients, respectively. Significant correlations were observed between the percentage of functional lung volume and fV20 (r=0.4475 in vent-860 and 0.3508 in F30) or fMLD (r=0.4701 in vent-860 and 0.3128 in F30) in patients with grade ≥2 RP. F30∩vent-860 results exhibited stronger correlations with fV20 and fMLD in patients with grade ≥2 (r=0.5509 in fV20 and 0.5320 in fMLD) and grade ≥3 RP (r=0.8770 in fV20 and 0.8518 in fMLD). Conclusions: RP dosimetric parameters correlated significantly with functional lung imaging.« less

Role of CYP1A2 polymorphisms on lung cancer risk in a prospective study.

PubMed

Pavanello, Sofia; Fedeli, Ugo; Mastrangelo, Giuseppe; Rota, Federica; Overvad, Kim; Raaschou-Nielsen, Ole; Tjønneland, Anne; Vogel, Ulla

2012-06-01

Cytochrome P4501A2 (CYP1A2) is a key enzyme for lung carcinogen activation and lung inflammation. We studied the interactions of the CYP1A2 functional variants -3860G/A(rs2069514),-2467T/delT(rs3569413),-163C/A(rs762551)] with occupational/environmental carcinogenic exposures in the development of lung cancer in a case-control study nested in the Danish prospective cohort "Diet, Cancer and Health." At enrollment (1993-1997), blood samples for genotype analyses and information on lifestyle were collected 5 (mean value) years before the onset of the disease. The study population included 425 lung cancer cases and 786 subcohort members, who were gender- and age-matched. We found that -163A carriers were at increased risk of lung cancer (P=0.035) in a multivariate COX regression model, which was adjusted for personal habits (i.e., cumulative smoking, passive smoke at home, alcohol intake, and fruit intake) and occupational exposure. Additionally, the interaction between -2467delT and smoking increases lung cancer risk in males, especially light smokers (<21.5 pack-years, P=0.004). The increased lung cancer risk found in -163C carriers, independent of smoking status, and in -2467delT male smokers, suggests that these variants could influence lung cancer development through different mechanisms (i.e. lung carcinogen activation and lung inflammation). Copyright © 2012 Elsevier Inc. All rights reserved.

Sex steroid signaling: implications for lung diseases.

PubMed

Sathish, Venkatachalem; Martin, Yvette N; Prakash, Y S

2015-06-01

There is increasing recognition that sex hormones (estrogen, progesterone, and testosterone) have biological and pathophysiological actions in peripheral, non-reproductive organs, including the lung. Clinically, sex differences in the incidence, morbidity and mortality of lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, lung cancer and pulmonary hypertension have been noted, although intrinsic sex differences vs. the roles of sex steroids are still not well-understood. Accordingly, it becomes important to ask the following questions: 1) Which sex steroids are involved? 2) How do they affect different components of the lung under normal circumstances? 3) How does sex steroid signaling change in or contribute to lung disease, and in this regard, are sex steroids detrimental or beneficial? As our understanding of sex steroid signaling in the lung improves, it is important to consider whether such information can be used to develop new therapeutic strategies to target lung diseases, perhaps in both sexes or in a sex-specific manner. In this review, we focus on the basics of sex steroid signaling, and the current state of knowledge regarding how they influence structure and function of specific lung components across the life span and in the context of some important lung diseases. We then summarize the potential for sex steroids as useful biomarkers and therapeutic targets in these lung diseases as a basis for future translational research in the area of gender and individualized medicine. Copyright © 2015 Elsevier Inc. All rights reserved.

Shrinking lung syndrome as a manifestation of pleuritis: a new model based on pulmonary physiological studies.

PubMed

Henderson, Lauren A; Loring, Stephen H; Gill, Ritu R; Liao, Katherine P; Ishizawar, Rumey; Kim, Susan; Perlmutter-Goldenson, Robin; Rothman, Deborah; Son, Mary Beth F; Stoll, Matthew L; Zemel, Lawrence S; Sandborg, Christy; Dellaripa, Paul F; Nigrovic, Peter A

2013-03-01

The pathophysiology of shrinking lung syndrome (SLS) is poorly understood. We sought to define the structural basis for this condition through the study of pulmonary mechanics in affected patients. Since 2007, most patients evaluated for SLS at our institutions have undergone standardized respiratory testing including esophageal manometry. We analyzed these studies to define the physiological abnormalities driving respiratory restriction. Chest computed tomography data were post-processed to quantify lung volume and parenchymal density. Six cases met criteria for SLS. All presented with dyspnea as well as pleurisy and/or transient pleural effusions. Chest imaging results were free of parenchymal disease and corrected diffusing capacities were normal. Total lung capacities were 39%-50% of predicted. Maximal inspiratory pressures were impaired at high lung volumes, but not low lung volumes, in 5 patients. Lung compliance was strikingly reduced in all patients, accompanied by increased parenchymal density. Patients with SLS exhibited symptomatic and/or radiographic pleuritis associated with 2 characteristic physiological abnormalities: (1) impaired respiratory force at high but not low lung volumes; and (2) markedly decreased pulmonary compliance in the absence of identifiable interstitial lung disease. These findings suggest a model in which pleural inflammation chronically impairs deep inspiration, for example through neural reflexes, leading to parenchymal reorganization that impairs lung compliance, a known complication of persistently low lung volumes. Together these processes could account for the association of SLS with pleuritis as well as the gradual symptomatic and functional progression that is a hallmark of this syndrome.

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.

Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues.

PubMed

Anafi, Ron C; Pellegrino, Renata; Shockley, Keith R; Romer, Micah; Tufik, Sergio; Pack, Allan I

2013-05-30

Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed "sleep specific" changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time. Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a ubiquitous role in reducing cellular metabolic stress in both brain and peripheral tissues. Finally, our data suggest a novel role for sleep in synchronizing transcription in peripheral tissues.

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

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

Qu, H; Yu, N; Stephans, K

2014-06-01

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

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

Deregulated angiogenesis in chronic lung diseases: a possible role for lung mesenchymal progenitor cells (2017 Grover Conference Series)

PubMed Central

Kropski, Jonathan A.; Richmond, Bradley W.; Gaskill, Christa F.; Foronjy, Robert F.

2017-01-01

Chronic lung disease (CLD), including pulmonary fibrosis (PF) and chronic obstructive pulmonary disease (COPD), is the fourth leading cause of mortality worldwide. Both are debilitating pathologies that impede overall tissue function. A common co-morbidity in CLD is vasculopathy, characterized by deregulated angiogenesis, remodeling, and loss of microvessels. This substantially worsens prognosis and limits survival, with most current therapeutic strategies being largely palliative. The relevance of angiogenesis, both capillary and lymph, to the pathophysiology of CLD has not been resolved as conflicting evidence depicts angiogenesis as both reparative or pathologic. Therefore, we must begin to understand and model the underlying pathobiology of pulmonary vascular deregulation, alone and in response to injury induced disease, to define cell interactions necessary to maintain normal function and promote repair. Capillary and lymphangiogenesis are deregulated in both PF and COPD, although the mechanisms by which they co-regulate and underlie early pathogenesis of disease are unknown. The cell-specific mechanisms that regulate lung vascular homeostasis, repair, and remodeling represent a significant gap in knowledge, which presents an opportunity to develop targeted therapies. We have shown that that ABCG2pos multipotent adult mesenchymal stem or progenitor cells (MPC) influence the function of the capillary microvasculature as well as lymphangiogenesis. A balance of both is required for normal tissue homeostasis and repair. Our current models suggest that when lymph and capillary angiogenesis are out of balance, the non-equivalence appears to support the progression of disease and tissue remodeling. The angiogenic regulatory mechanisms underlying CLD likely impact other interstitial lung diseases, tuberous sclerosis, and lymphangioleiomyomatosis. PMID:29040010

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.

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.

Lung-resident eosinophils represent a distinct regulatory eosinophil subset

PubMed Central

Mesnil, Claire; Raulier, Stéfanie; Paulissen, Geneviève; Xiao, Xue; Birrell, Mark A.; Pirottin, Dimitri; Janss, Thibaut; Henket, Monique; Schleich, Florence N.; Radermecker, Marc; Thielemans, Kris; Gillet, Laurent; Thiry, Marc; Belvisi, Maria G.; Louis, Renaud; Desmet, Christophe; Bureau, Fabrice

2016-01-01

Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5–independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite–induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5–dependent peribronchial Siglec-FhiCD62L–CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions. PMID:27548519

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

Guards at the gate: physiological and pathological roles of tissue-resident innate lymphoid cells in the lung.

PubMed

Cheng, Hang; Jin, Chengyan; Wu, Jing; Zhu, Shan; Liu, Yong-Jun; Chen, Jingtao

2017-12-01

The lung is an important open organ and the primary site of respiration. Many life-threatening diseases develop in the lung, e.g., pneumonia, asthma, chronic obstructive pulmonary diseases (COPDs), pulmonary fibrosis, and lung cancer. In the lung, innate immunity serves as the frontline in both anti-irritant response and anti-tumor defense and is also critical for mucosal homeostasis; thus, it plays an important role in containing these pulmonary diseases. Innate lymphoid cells (ILCs), characterized by their strict tissue residence and distinct function in the mucosa, are attracting increased attention in innate immunity. Upon sensing the danger signals from damaged epithelium, ILCs activate, proliferate, and release numerous cytokines with specific local functions; they also participate in mucosal immune-surveillance, immune-regulation, and homeostasis. However, when their functions become uncontrolled, ILCs can enhance pathological states and induce diseases. In this review, we discuss the physiological and pathological functions of ILC subsets 1 to 3 in the lung, and how the pathogenic environment affects the function and plasticity of ILCs.

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.

Airway symptoms and lung function in the local population after the oil tank explosion in Gulen, Norway.

PubMed

Granslo, Jens-Tore; Bråtveit, Magne; Hollund, Bjørg Eli; Irgens, Ågot; Svanes, Cecilie; Magerøy, Nils; Moen, Bente Elisabeth

2012-12-12

Oil tanks containing a mixture of hydrocarbons, including sulphuric compounds, exploded and caught fire in an industrial harbour. This study assesses airway symptoms and lung function in the nearby population 1½ years after the explosion. A cross-sectional study included individuals ≥18 years old. Individuals living <6 km (sub-groups <3km and 3-6 km) from the accident site formed the exposed group, individuals living >20 km away formed a control group. A questionnaire and spirometry tests were completed by 223 exposed individuals (response rate men 70%, women 75%) and 179 control individuals (response rate men 51%, women 65%). Regression analyses included adjustment for smoking, occupational exposure, atopy, infection in the preceding month and age. Analyses of symptoms were also adjusted for stress reactions related to the accident. Exposed individuals experienced significantly more blocked nose (odds ratio 1.7 [95% confidence interval 1.0, 2.8]), rhinorrhoea (1.6 [1.1, 3.3]), nose irritation (3.4 [2.0, 5.9]), sore throat (3.1 [1.8, 5.5]), morning cough (3.5 [2.0, 5.5]), daily cough (2.2 [1.4, 3.7]), cough >3 months a year (2.9 [1.5, 5.3]) and cough with phlegm (1.9 [1.2, 3.1]) than control individuals. A significantly increasing trend was found for nose symptoms and cough, depending on the proximity of home address to explosion site (daily cough, 3-6km 1.8 [1.0, 3.1], <3km 3.0 [1.7, 6.4]). Lung function measurements were significantly lower in the exposed group than in the control group, FEV1 adjusted mean difference -123 mL [95% confidence interval -232, -14]), FEV1% predicted -2.5 [-5.5, 0.5], FVC -173 mL [- 297, -50], FVC% predicted -3.1 [- 5.9, -0.4], and airway obstruction (GOLD II/III). Based on cross sectional analyses, individuals living in an area with air pollution from an oil tank explosion had more airway symptoms and lower lung function than a control group 1½ years after the incident.

Pulmonary immunity and extracellular matrix interactions.

PubMed

O'Dwyer, David N; Gurczynski, Stephen J; Moore, Bethany B

2018-04-09

The lung harbors a complex immune system composed of both innate and adaptive immune cells. Recognition of infection and injury by receptors on lung innate immune cells is crucial for generation of antigen-specific responses by adaptive immune cells. The extracellular matrix of the lung, comprising the interstitium and basement membrane, plays a key role in the regulation of these immune systems. The matrix consists of several hundred assembled proteins that interact to form a bioactive scaffold. This template, modified by enzymes, acts to facilitate cell function and differentiation and changes dynamically with age and lung disease. Herein, we explore relationships between innate and adaptive immunity and the lung extracellular matrix. We discuss the interactions between extracellular matrix proteins, including glycosaminoglycans, with prominent effects on innate immune signaling effectors such as toll-like receptors. We describe the relationship of extracellular matrix proteins with adaptive immunity and leukocyte migration to sites of injury within the lung. Further study of these interactions will lead to greater knowledge of the role of matrix biology in lung immunity. The development of novel therapies for acute and chronic lung disease is dependent on a comprehensive understanding of these complex matrix-immunity interactions. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

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

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.

Clinical and Organizational Factors in the Initial Evaluation of Patients With Lung Cancer

PubMed Central

Jim Yeung, Sai-Ching; Tanoue, Lynn T.; Gould, Michael K.

2013-01-01

Background: This guideline is intended to provide an evidence-based approach to the initial evaluation of patients with known or suspected lung cancer. It also includes an assessment of the impact of timeliness of care and multidisciplinary teams on outcome. Methods: The applicable current medical literature was identified by a computerized search and evaluated using standardized methods. Recommendations were framed using the approach described by the Guidelines Oversight Committee of the American College of Chest Physicians. Data sources included MEDLINE and the Cochrane Database of Systematic Reviews. Results: Initial evaluation should include a thorough history and physical examination; CT imaging; pulmonary function tests; and hemoglobin, electrolyte, liver function, and calcium levels. Additional testing for distant metastases and paraneoplastic syndromes should be determined on the basis of these results. Paraneoplastic syndromes may have an adverse impact on cancer treatment, so they should be controlled rapidly with the goal of proceeding with definitive cancer treatment in a timely manner. Although the relationship between timeliness of care and survival is difficult to quantify, efforts to deliver timely care are reasonable and should be balanced with the need to attend to other dimensions of health-care quality (eg, safety, effectiveness, efficiency, equality, consistency with patient values and preferences). Quality care will require multiple disciplines. Although it is difficult to assess the impact, we suggest that a multidisciplinary team approach to care be used, particularly for patients requiring multimodality therapy. Conclusions: The initial evaluation of patients with lung cancer should include a thorough history and physical examination, pulmonary function tests, CT imaging, basic laboratory tests, and selective testing for distant metastases and paraneoplastic syndromes. PMID:23649435

Localization of essential rhombomeres for respiratory rhythm generation in bullfrog tadpoles using a binary search algorithm: Rhombomere 7 is essential for the gill rhythm and suppresses lung bursts before metamorphosis.

PubMed

Duchcherer, Maryana; Baghdadwala, Mufaddal I; Paramonov, Jenny; Wilson, Richard J A

2013-12-01

Frog metamorphosis includes transition from water breathing to air breathing but the extent to which such a momentous change in behavior requires fundamental changes in the organization of the brainstem respiratory circuit is unknown. Here, we combine a vertically mounted isolated brainstem preparation, "the Sheep Dip," with a search algorithm used in computer science, to identify essential rhombomeres for generation of ventilatory motor bursts in metamorphosing bullfrog tadpoles. Our data suggest that rhombomere 7, which in mammals hosts the PreBötC (PreBötzinger Complex; the likely inspiratory oscillator), is essential for gill and buccal bursts. Whereas rhombomere 5, in close proximity to a brainstem region associated with the mammalian expiratory oscillator, is essential for lung bursts at both stages. Therefore, we conclude there is no rhombomeric translocation of respiratory oscillators in bullfrogs as previously suggested. In premetamorphic tadpoles, functional ablation of rhombomere 7 caused ectopic expression of precocious lung bursts, suggesting the gill oscillator suppresses an otherwise functional lung oscillator in early development. Copyright © 2013 Wiley Periodicals, Inc.

Integrative approaches for modeling regulation and function of the respiratory system.

PubMed

Ben-Tal, Alona; Tawhai, Merryn H

2013-01-01

Mathematical models have been central to understanding the interaction between neural control and breathing. Models of the entire respiratory system-which comprises the lungs and the neural circuitry that controls their ventilation-have been derived using simplifying assumptions to compartmentalize each component of the system and to define the interactions between components. These full system models often rely-through necessity-on empirically derived relationships or parameters, in addition to physiological values. In parallel with the development of whole respiratory system models are mathematical models that focus on furthering a detailed understanding of the neural control network, or of the several functions that contribute to gas exchange within the lung. These models are biophysically based, and rely on physiological parameters. They include single-unit models for a breathing lung or neural circuit, through to spatially distributed models of ventilation and perfusion, or multicircuit models for neural control. The challenge is to bring together these more recent advances in models of neural control with models of lung function, into a full simulation for the respiratory system that builds upon the more detailed models but remains computationally tractable. This requires first understanding the mathematical models that have been developed for the respiratory system at different levels, and which could be used to study how physiological levels of O2 and CO2 in the blood are maintained. Copyright © 2013 Wiley Periodicals, Inc.

Airway Surface Dehydration Aggravates Cigarette Smoke-Induced Hallmarks of COPD in Mice.

PubMed

Seys, Leen J M; Verhamme, Fien M; Dupont, Lisa L; Desauter, Elke; Duerr, Julia; Seyhan Agircan, Ayca; Conickx, Griet; Joos, Guy F; Brusselle, Guy G; Mall, Marcus A; Bracke, Ken R

2015-01-01

Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown. We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na⁺ channel (βENaC). βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured. Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements. We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.

Prognostic value of serum zinc levels in patients with acute HC/zinc chloride smoke inhalation

PubMed Central

Xie, Fei; Zhang, Xingang; Xie, Lixin

2017-01-01

Abstract Hexachloroethane (HC)/zinc chloride (ZnCl, smoke bomb) exposure in the military setting results in lung injury which is uncommon and has been rarely described in previous studies. The aim of this study is to investigate the correlation between the serum zinc in patients with HC/ZnCl smoke inhalation lung injury and disease severity. A total of 15 patients with HC/ZnCl-related conditions were recruited in this study. The serum zinc level and the pulmonary function tests and liver function tests including total lung capacity (TLC), forced vital capacity (FVC), forced expiratory pressure in 1 second (FEV1), alanine aminotransferase (ALT), and aspartate transaminase (AST) were analyzed. Eleven cases had mild clinical manifestations. Four cases rapidly developed features typical of severe adult respiratory distress syndrome. The level of serum zinc was increased, but FVC, FEV1, and TLC was decreased significantly in the moderate and severe cases. In addition, the serum zinc level correlated well with the TLC, FVC, and FEV1 (r = −0.587, −0.626, −0.617, respectively; P = .027, .017, .019, respectively). The 4 cases in moderate and severe group had delayed impairment of liver functions after the accident. This study suggested that the serum zinc level may be associated with the severity of lung and liver injuries after HC/ZnCl smoke inhalation. PMID:28953660

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

Effects of budesonide on the lung functions, inflammation and apoptosis in a saline-lavage model of acute lung injury.

PubMed

Mokra, D; Kosutova, P; Balentova, S; Adamkov, M; Mikolka, P; Mokry, J; Antosova, M; Calkovska, A

2016-12-01

Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26.7 kPa in FiO 2 1.0. Then, one group of animals was treated with corticosteroid budesonide (Pulmicort susp inh, AstraZeneca; 0.25 mg/kg) given intratracheally by means of inpulsion regime of high-frequency jet ventilation, while another group was non-treated, and both groups were oxygen-ventilated for following 5 hours. Another group of animals served as healthy controls. After sacrifice of animals, left lung was saline-lavaged and protein content was measured and cells in the lavage fluid were determined microscopically. Right lung tissue was used for estimation of edema formation (expressed as wet/dry weight ratio), for histomorphological investigation, immunohistochemical determination of apoptosis of lung cells, and for determination of markers of inflammation and lung injury (IL-1β, IL-6, IL-8, TNF-α, IFNγ, esRAGE, caspase-3) by ELISA methods. Levels of several cytokines were estimated also in plasma. Repetitive lung lavage worsened gas exchange, induced lung injury, inflammation and lung edema and increased apoptosis of lung epithelial cells. Budesonide reduced lung edema, cell infiltration into the lung and apoptosis of epithelial cells and decreased concentrations of proinflammatory markers in the lung and blood. These changes resulted in improved ventilation. Concluding, curative intratracheal treatment with budesonide alleviated lung injury, inflammation, apoptosis of lung epithelial cells and lung edema and improved lung functions in a lavage model of ALI. These findings suggest a potential of therapy with inhaled budesonide also for patients with ARDS.

Design of the Endobronchial Valve for Emphysema Palliation Trial (VENT): a non-surgical method of lung volume reduction.

PubMed

Strange, Charlie; Herth, Felix J F; Kovitz, Kevin L; McLennan, Geoffrey; Ernst, Armin; Goldin, Jonathan; Noppen, Marc; Criner, Gerard J; Sciurba, Frank C

2007-07-03

Lung volume reduction surgery is effective at improving lung function, quality of life, and mortality in carefully selected individuals with advanced emphysema. Recently, less invasive bronchoscopic approaches have been designed to utilize these principles while avoiding the associated perioperative risks. The Endobronchial Valve for Emphysema PalliatioN Trial (VENT) posits that occlusion of a single pulmonary lobe through bronchoscopically placed Zephyr endobronchial valves will effect significant improvements in lung function and exercise tolerance with an acceptable risk profile in advanced emphysema. The trial design posted on Clinical trials.gov, on August 10, 2005 proposed an enrollment of 270 subjects. Inclusion criteria included: diagnosis of emphysema with forced expiratory volume in one second (FEV1) < 45% of predicted, hyperinflation (total lung capacity measured by body plethysmography > 100%; residual volume > 150% predicted), and heterogeneous emphysema defined using a quantitative chest computed tomography algorithm. Following standardized pulmonary rehabilitation, patients were randomized 2:1 to receive unilateral lobar placement of endobronchial valves plus optimal medical management or optimal medical management alone. The co-primary endpoint was the mean percent change in FEV1 and six minute walk distance at 180 days. Secondary end-points included mean percent change in St. George's Respiratory Questionnaire score and the mean absolute changes in the maximal work load measured by cycle ergometry, dyspnea (mMRC) score, and total oxygen use per day. Per patient response rates in clinically significant improvement/maintenance of FEV1 and six minute walk distance and technical success rates of valve placement were recorded. Apriori response predictors based on quantitative CT and lung physiology were defined. If endobronchial valves improve FEV1 and health status with an acceptable safety profile in advanced emphysema, they would offer a novel intervention for this progressive and debilitating disease. ClinicalTrials.gov: NCT00129584.

Human fetal lung morphometry at autopsy with new modeling to quantitate structural maturity.

PubMed

Lipsett, Jill

2017-06-01

To demonstrate a simplified morphometric procedure, including a new model for acinar structural maturity, applicable to autopsy fetal lung and present reference values for these parameters. Cases with autopsy consent for research were studied. To simplify analysis only critical morphometric parameters were measured to allow calculation of gas-exchange surface area. A total of 58 fetuses, 16-40 weeks were included. Subjects were rejected with any condition predisposing to pulmonary hypo/hyperplasia, significant maceration, or if lung weight/bodyweight or microscopy identified pulmonary hypoplasia or lung growth disorders. Lungs were inflation fixed, weights and volumes determined, sampled, then returned to the body. Volume densities (V V ) of parenchyma/non-parenchyma and air-space/gas-exchange tissue, gas-exchange surface density (S V ), and total surface area (SA) were determined. The number, mean radius, and septal thickness of modeled airspace-spheres were calculated. Equations were generated for each parameter function of gestation and bodyweight. From 16 to 40-week weights and volumes increased as power functions from ∼4 g/mL to ∼90 g/mL. Parenchyma/non-parenchyma changed little-75:25 (16 weeks) to 71:29 (term). Parenchyma was 10% airspace:90% tissue early and 50:50 by term. Gas-exchange S V increased from 175 to 450 cm 2 /cm 3 and total SA increased from 0.059 to 4.793 m 2 . There were 3.31 × 10 6 airspace-spheres, 12 µ radius, septal thickness 30 µ at 16 weeks, increasing to 56.92 × 10 6 , 26 µ radius, septal thickness 13 µ by term. Morphometry can feasibly be performed at autopsy, providing more informative quantitative data on lung structural development than current methods utilized. This reference data set compares well with published data. © 2017 Wiley Periodicals, Inc.

Decreased lung function with mediation of blood parameters linked to e-waste lead and cadmium exposure in preschool children.

PubMed

Zeng, Xiang; Xu, Xijin; Boezen, H Marike; Vonk, Judith M; Wu, Weidong; Huo, Xia

2017-11-01

Blood lead (Pb) and cadmium (Cd) levels have been associated with lower lung function in adults and smokers, but whether this also holds for children from electronic waste (e-waste) recycling areas is still unknown. To investigate the contribution of blood heavy metals and lung function levels, and the relationship among living area, the blood parameter levels, and the lung function levels, a total of 206 preschool children from Guiyu (exposed area), and Haojiang and Xiashan (reference areas) were recruited and required to undergo blood tests and lung function tests during the study period. Preschool children living in e-waste exposed areas were found to have a 1.37 μg/dL increase in blood Pb, 1.18 μg/L increase in blood Cd, and a 41.00 × 10 9 /L increase in platelet counts, while having a 2.82 g/L decrease in hemoglobin, 92 mL decrease in FVC and 86 mL decrease in FEV 1 . Each unit of hemoglobin (1 g/L) decline was associated with 5 mL decrease in FVC and 4 mL decrease in FEV 1 . We conclude that children living in e-waste exposed area have higher levels of blood Pb, Cd and platelets, and lower levels of hemoglobin and lung function. Hemoglobin can be a good predictor for lung function levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic effects of air pollution on lung function after lung transplantation in the Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) study.

PubMed

Benmerad, Meriem; Slama, Rémy; Botturi, Karine; Claustre, Johanna; Roux, Antoine; Sage, Edouard; Reynaud-Gaubert, Martine; Gomez, Carine; Kessler, Romain; Brugière, Olivier; Mornex, Jean-François; Mussot, Sacha; Dahan, Marcel; Boussaud, Véronique; Danner-Boucher, Isabelle; Dromer, Claire; Knoop, Christiane; Auffray, Annick; Lepeule, Johanna; Malherbe, Laure; Meleux, Frederik; Nicod, Laurent; Magnan, Antoine; Pison, Christophe; Siroux, Valérie

2017-01-01

An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs).The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6 months. The levels of air pollutants (nitrogen dioxide (NO 2 ), particulate matter with an aerodynamic cut-off diameter of x µm (PM x ) and ozone (O 3 )) at the patients' home address were averaged in the 12 months before each spirometry test. The effects of air pollutants on forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) in % predicted were estimated using mixed linear regressions. We assessed the effect modification of macrolide antibiotics in this relationship.Increased 12-month levels of pollutants were associated with lower levels of FVC % pred (-2.56%, 95% CI -3.86--1.25 for 5 µg·m -3 of PM 10 ; -0.75%, 95% CI -1.38--0.12 for 2 µg·m -3 of PM 2.5 and -2.58%, 95% CI -4.63--0.53 for 10 µg·m -3 of NO 2 ). In patients not taking macrolides, the deleterious association between PM and FVC tended to be stronger and PM 10 was associated with lower FEV 1 Our study suggests a deleterious effect of chronic exposure to air pollutants on lung function levels in LTRs, which might be modified with macrolides. Copyright ©ERS 2017.

Perinatal stress and early life programming of lung structure and function

PubMed Central

Wright, Rosalind J.

2010-01-01

Exposure to environmental toxins during critical periods of prenatal and/or postnatal development may alter the normal course of lung morphogenesis and maturation, potentially resulting in changes that affect both structure and function of the respiratory system. Moreover, these early effects may persist into adult life magnifying the potential public health impact. Aberrant or excessive pro-inflammatory immune responses, occurring both locally and systemically, that result in inflammatory damage to the airway are a central determinant of lung structure-function changes throughout life. Disruption of neuroendocrine function in early development, specifically the hypothalamic-pituitary-adrenal (HPA) axis, may alter functional status of the immune system. Autonomic nervous system (ANS) function (sympathovagal imbalance) is another integral component of airway function and immunity in childhood. This overview discusses the evidence linking psychological factors to alterations in these interrelated physiological processes that may, in turn, influence childhood lung function and identifies gaps in our understanding. PMID:20080145

Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy.

PubMed

Dane, D Merrill; Yan, Xiao; Tamhane, Rahul M; Johnson, Robert L; Estrera, Aaron S; Hogg, Deborah C; Hogg, Richard T; Hsia, Connie C W

2004-03-01

To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-CT)) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-CT) were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.

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.

Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway

PubMed Central

Hwang, Jae-Woong; Sundar, Isaac K.; Yao, Hongwei; Sellix, Michael T.; Rahman, Irfan

2014-01-01

Patients with obstructive lung diseases display abnormal circadian rhythms in lung function. We determined the mechanism whereby environmental tobacco/cigarette smoke (CS) modulates expression of the core clock gene BMAL1, through Sirtuin1 (SIRT1) deacetylase during lung inflammatory and injurious responses. Adult C57BL6/J and various mice mutant for SIRT1 and BMAL1 were exposed to both chronic (6 mo) and acute (3 and 10 d) CS, and we measured the rhythmic expression of clock genes, circadian rhythms of locomotor activity, lung function, and inflammatory and emphysematous responses in the lungs. CS exposure (100–300 mg/m3 particulates) altered clock gene expression and reduced locomotor activity by disrupting the central and peripheral clocks and increased lung inflammation, causing emphysema in mice. BMAL1 was acetylated and degraded in the lungs of mice exposed to CS and in patients with chronic obstructive pulmonary disease (COPD), compared with lungs of the nonsmoking controls, linking it mechanistically to CS-induced reduction of SIRT1. Targeted deletion of Bmal1 in lung epithelium augmented inflammation in response to CS, which was not attenuated by the selective SIRT1 activator SRT1720 (EC50=0.16 μM) in these mice. Thus, the circadian clock, specifically the enhancer BMAL1 in epithelium, plays a pivotal role, mediated by SIRT1-dependent BMAL1, in the regulation of CS-induced lung inflammatory and injurious responses.— Hwang, J.-W., Sundar, I. K., Yao, H., Sellix, M. T., Rahman, I. Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway. PMID:24025728

Serum periostin relates to type-2 inflammation and lung function in asthma: Data from the large population-based cohort Swedish GA(2)LEN.

PubMed

James, A; Janson, C; Malinovschi, A; Holweg, C; Alving, K; Ono, J; Ohta, S; Ek, A; Middelveld, R; Dahlén, B; Forsberg, B; Izuhara, K; Dahlén, S-E

2017-11-01

Periostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type 2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear. To examine circulating periostin in healthy controls and subjects with asthma from the general population with different severity and treatment profiles, both with and without chronic rhinosinusitis (CRS), in relation to other biomarkers and clinical characteristics. Serum periostin was examined by ELISA in 1100 subjects aged 17-76 from the Swedish Global Allergy and Asthma European Network (GA(2)LEN) study, which included 463 asthmatics with/without chronic rhinosinusitis (CRS), 98 individuals with CRS only, and 206 healthy controls. Clinical tests included measurement of lung function, Fraction of exhaled NO (FeNO), IgE, urinary eosinophil-derived neurotoxin (U-EDN), and serum eosinophil cationic protein (S-ECP), as well as completion of questionnaires regarding respiratory symptoms, medication, and quality of life. Although median periostin values showed no differences when comparing disease groups with healthy controls, multiple regression analyses revealed that periostin was positively associated with higher FeNO, U-EDN, and total IgE. In patients with asthma, an inverse relationship with lung function was also observed. Current smoking was associated with decreased periostin levels, whereas increased age and lower body mass index (BMI) related to higher periostin levels in subjects both with and without asthma. We confirm associations between periostin and markers of type 2 inflammation, as well as lung function, and identify novel constitutional factors of importance to the use of periostin as a phenotype-specific biomarker in asthma. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Role of PET/CT for precision medicine in lung cancer: perspective of the Society of Nuclear Medicine and Molecular Imaging.

PubMed

Greenspan, Bennett S

2017-12-01

This article discusses the role of PET/CT in contributing to precision medicine in lung cancer, and provides the perspective of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) on this process. The mission and vision of SNMMI are listed, along with the guidance provided by SNMMI to promote best practice in precision medicine. Basic principles of PET/CT are presented. An overview of the use of PET/CT imaging in lung cancer is discussed. In lung cancer patients, PET/CT is vitally important for optimal patient management. PET/CT is essential in determining staging and re-staging of disease, detecting recurrent or residual disease, evaluating response to therapy, and providing prognostic information. PET/CT is also critically important in radiation therapy planning by determining the extent of active disease, including an assessment of functional tumor volume. The current approach in tumor imaging is a significant advance over conventional imaging. However, recent advances suggest that therapeutic response criteria in the near future will be based on metabolic characteristics and will include the evaluation of biologic characteristics of tumors to further enhance the effectiveness of precision medicine in lung cancer, producing improved patient outcomes with less morbidity.

Prone position for the prevention of lung infection.

PubMed

Beuret, P

2002-04-01

Pulmonary infection is frequent in brain injured patients. It has been identified as an independent predictor of unfavorable neurological outcome, calling for attempts of prevention. We recently evaluated intermittent prone positioning for the prevention of ventilator-associated pneumonia (VAP) in comatose brain injured patients, in a randomized study. 25 patients were included in the prone position (PP) group: they were positioned on prone four hours once daily until they could get up to sit in an armchair; 26 patients were included in the supine position (SP) group. The main characteristics of the patients from the two groups were similar at randomization. The primary end-point was the incidence of lung worsening, defined by an increase in the Lung Injury Score by at least one point since the time of randomization. The incidence of lung worsening was lower in the PP group (12%) than in the SP group (50%) (p=0.003). The incidence of VAP was 38.4% in the SP group and 20% in the PP group (p=0.14). There was no serious complication attributable to prone positioning. In conclusion, the beneficial effect of prone positioning for prevention of lung infection in brain injured patients is not well established. However, in those patients, prone positioning is able to avoid the worsening of pulmonary function, especially in oxygenation.

miR-448 is a novel prognostic factor of lung squamous cell carcinoma and regulates cells growth and metastasis by targeting DCLK1.

PubMed

Shan, Changting; Fei, Fan; Li, Fengzhu; Zhuang, Bo; Zheng, Yulong; Wan, Yufeng; Chen, Jianhui

2017-05-01

MicroRNA-448 (miR-448) has been showed to be low-expressed and function as tumor suppressor in most human cancers. However, there are limited reports on the clinical significance and biological function of miR-448 in lung squamous cell carcinoma. In this study, we observed that miR-448 expression was decreased in lung squamous cell carcinoma tissues and cell lines. Meanwhile, miR-448 expression associated with differentiated degree, T classification (tumor size), N classification (lymph node metastasis), M classification (distant metastasis), clinical stage and prognosis of lung squamous cell carcinoma patients. In survival analysis, low expression of miR-448 was a poor independent prognostic factor for lung squamous cell carcinoma patients. Moreover, gain-of-function and loss-of-function studies showed miR-448 acted as a tumor suppressor regulating lung squamous cell carcinoma cells growth and metastasis. Furthermore, DCLK1 has been identified as a potential target for miR-448 to regulate lung squamous cell carcinoma cells growth and metastasis. In conclusion, miR-448 low-expression was a poor prognostic factor for lung squamous cell carcinoma patients, and miR-448 served as a tumor suppressor in lung squamous cell carcinoma cells via targeting DCLK1. Copyright © 2017. Published by Elsevier Masson SAS.

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

PubMed

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

2016-10-24

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

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

PubMed Central

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

2016-01-01

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

Alveolar type II cell transplantation restores pulmonary surfactant protein levels in lung fibrosis.

PubMed

Guillamat-Prats, Raquel; Gay-Jordi, Gemma; Xaubet, Antoni; Peinado, Victor I; Serrano-Mollar, Anna

2014-07-01

Alveolar Type II cell transplantation has been proposed as a cell therapy for the treatment of idiopathic pulmonary fibrosis. Its long-term benefits include repair of lung fibrosis, but its success partly depends on the restoration of lung homeostasis. Our aim was to evaluate surfactant protein restoration after alveolar Type II cell transplantation in an experimental model of bleomycin-induced lung fibrosis in rats. Lung fibrosis was induced by intratracheal instillation of bleomycin. Alveolar Type II cells were obtained from healthy animals and transplanted 14 days after bleomycin was administered. Furthermore, one group transplanted with alveolar macrophages and another group treated with surfactant were established to evaluate the specificity of the alveolar Type II cell transplantation. The animals were euthanized at 21 days after bleomycin instillation. Lung fibrosis was confirmed by a histologic study and an evaluation of the hydroxyproline content. Changes in surfactant proteins were evaluated by mRNA expression, Western blot and immunofluorescence studies. The group with alveolar Type II cell transplantation was the only one to show a reduction in the degree of lung fibrosis and a complete recovery to normal levels of surfactant proteins. One of the mechanisms involved in the beneficial effect of alveolar Type II cell transplantation is restoration of lung surfactant protein levels, which is required for proper respiratory function. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Relation between lung function, exercise capacity, and exposure to asbestos cement.

PubMed Central

Wollmer, P; Eriksson, L; Jonson, B; Jakobsson, K; Albin, M; Skerfving, S; Welinder, H

1987-01-01

A group of 137 male workers with known exposure (mean 20 fibre years per millilitre) to asbestos cement who had symptoms or signs of pulmonary disease was studied together with a reference group of 49 healthy industrial workers with no exposure to asbestos. Lung function measurements were made at rest and during exercise. Evidence of lung fibrosis was found as well as of obstructive airways disease in the exposed group compared with the reference group. Asbestos cement exposure was related to variables reflecting lung fibrosis but not to variables reflecting airflow obstruction. Smoking was related to variables reflecting obstructive lung disease. Exercise capacity was reduced in the exposed workers and was related to smoking and to lung function variables, reflecting obstructive airways disease. There was no significant correlation between exercise capacity and exposure to asbestos cement. PMID:3651353

Connective tissue-activating peptide III: a novel blood biomarker for early lung cancer detection.

PubMed

Yee, John; Sadar, Marianne D; Sin, Don D; Kuzyk, Michael; Xing, Li; Kondra, Jennifer; McWilliams, Annette; Man, S F Paul; Lam, Stephen

2009-06-10

There are no reliable blood biomarkers to detect early lung cancer. We used a novel strategy that allows discovery of differentially present proteins against a complex and variable background. Mass spectrometry analyses of paired pulmonary venous-radial arterial blood from 16 lung cancer patients were applied to identify plasma proteins potentially derived from the tumor microenvironment. Two differentially expressed proteins were confirmed in 64 paired venous-arterial blood samples using an immunoassay. Twenty-eight pre- and postsurgical resection peripheral blood samples and two independent, blinded sets of plasma from 149 participants in a lung cancer screening study (49 lung cancers and 100 controls) and 266 participants from the National Heart Lung and Blood Institute Lung Health Study (45 lung cancer and 221 matched controls) determined the accuracy of the two protein markers to detect subclinical lung cancer. Connective tissue-activating peptide III (CTAP III)/ neutrophil activating protein-2 (NAP-2) and haptoglobin were identified to be significantly higher in venous than in arterial blood. CTAP III/NAP-2 levels decreased after tumor resection (P = .01). In two independent population cohorts, CTAP III/NAP-2 was significantly associated with lung cancer and improved the accuracy of a lung cancer risk prediction model that included age, smoking, lung function (FEV(1)), and an interaction term between FEV(1) and CTAP III/NAP-2 (area under the curve, 0.84; 95% CI, 0.77 to 0.91) compared to CAPIII/NAP-2 alone. We identified CTAP III/NAP-2 as a novel biomarker to detect preclinical lung cancer. The study underscores the importance of applying blood biomarkers as part of a multimodal lung cancer risk prediction model instead of as stand-alone tests.

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.

Mitochondria in lung disease

PubMed Central

Cloonan, Suzanne M.; Choi, Augustine M.K.

2016-01-01

Mitochondria are a distinguishing feature of eukaryotic cells. Best known for their critical function in energy production via oxidative phosphorylation (OXPHOS), mitochondria are essential for nutrient and oxygen sensing and for the regulation of critical cellular processes, including cell death and inflammation. Such diverse functional roles for organelles that were once thought to be simple may be attributed to their distinct heteroplasmic genome, exclusive maternal lineage of inheritance, and ability to generate signals to communicate with other cellular organelles. Mitochondria are now thought of as one of the cell’s most sophisticated and dynamic responsive sensing systems. Specific signatures of mitochondrial dysfunction that are associated with disease pathogenesis and/or progression are becoming increasingly important. In particular, the centrality of mitochondria in the pathological processes and clinical phenotypes associated with a range of lung diseases is emerging. Understanding the molecular mechanisms regulating the mitochondrial processes of lung cells will help to better define phenotypes and clinical manifestations associated with respiratory disease and to identify potential diagnostic and therapeutic targets. PMID:26928034

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

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

Eslick, E; Kipritidis, J; Keall, P

2014-06-01

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

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.

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

Tucker, Susan L.; Liu, H. Helen; Wang, Shulian

Purpose: The aim of this study was to investigate the effect of radiation dose distribution in the lung on the risk of postoperative pulmonary complications among esophageal cancer patients. Methods and Materials: We analyzed data from 110 patients with esophageal cancer treated with concurrent chemoradiotherapy followed by surgery at our institution from 1998 to 2003. The endpoint for analysis was postsurgical pneumonia or acute respiratory distress syndrome. Dose-volume histograms (DVHs) and dose-mass histograms (DMHs) for the whole lung were used to fit normal-tissue complication probability (NTCP) models, and the quality of fits were compared using bootstrap analysis. Results: Normal-tissue complicationmore » probability modeling identified that the risk of postoperative pulmonary complications was most significantly associated with small absolute volumes of lung spared from doses {>=}5 Gy (VS5), that is, exposed to doses <5 Gy. However, bootstrap analysis found no significant difference between the quality of this model and fits based on other dosimetric parameters, including mean lung dose, effective dose, and relative volume of lung receiving {>=}5 Gy, probably because of correlations among these factors. The choice of DVH vs. DMH or the use of fractionation correction did not significantly affect the results of the NTCP modeling. The parameter values estimated for the Lyman NTCP model were as follows (with 95% confidence intervals in parentheses): n = 1.85 (0.04, {infinity}), m = 0.55 (0.22, 1.02), and D {sub 5} = 17.5 Gy (9.4 Gy, 102 Gy). Conclusions: In this cohort of esophageal cancer patients, several dosimetric parameters including mean lung dose, effective dose, and absolute volume of lung receiving <5 Gy provided similar descriptions of the risk of postoperative pulmonary complications as a function of Radiation dose distribution in the lung.« less

Lung volumes and lung volume recruitment in ARDS: a comparison between supine and prone position.

PubMed

Aguirre-Bermeo, Hernan; Turella, Marta; Bitondo, Maddalena; Grandjean, Juan; Italiano, Stefano; Festa, Olimpia; Morán, Indalecio; Mancebo, Jordi

2018-02-14

The use of positive end-expiratory pressure (PEEP) and prone position (PP) is common in the management of severe acute respiratory distress syndrome patients (ARDS). We conducted this study to analyze the variation in lung volumes and PEEP-induced lung volume recruitment with the change from supine position (SP) to PP in ARDS patients. The investigation was conducted in a multidisciplinary intensive care unit. Patients who met the clinical criteria of the Berlin definition for ARDS were included. The responsible physician set basal PEEP. To avoid hypoxemia, FiO 2 was increased to 0.8 1 h before starting the protocol. End-expiratory lung volume (EELV) and functional residual capacity (FRC) were measured using the nitrogen washout/washin technique. After the procedures in SP, the patients were turned to PP and 1 h later the same procedures were made in PP. Twenty-three patients were included in the study, and twenty were analyzed. The change from SP to PP significantly increased FRC (from 965 ± 397 to 1140 ± 490 ml, p = 0.008) and EELV (from 1566 ± 476 to 1832 ± 719 ml, p = 0.008), but PEEP-induced lung volume recruitment did not significantly change (269 ± 186 ml in SP to 324 ± 188 ml in PP, p = 0.263). Dynamic strain at PEEP decreased with the change from SP to PP (0.38 ± 0.14 to 0.33 ± 0.13, p = 0.040). As compared to supine, prone position increases resting lung volumes and decreases dynamic lung strain.

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.

75 FR 53907 - Revisions to the Arizona State Implementation Plan, Maricopa County

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-02

... health and the environment, including premature mortality, aggravation of respiratory and cardiovascular disease, decreased lung function, visibility impairment, and damage to vegetation and ecosystems. Section... protection, Air pollution control, Intergovernmental relations, Particulate matter, Reporting and...

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.

Towards a virtual lung: multi-scale, multi-physics modelling of the pulmonary system.

PubMed

Burrowes, K S; Swan, A J; Warren, N J; Tawhai, M H

2008-09-28

The essential function of the lung, gas exchange, is dependent on adequate matching of ventilation and perfusion, where air and blood are delivered through complex branching systems exposed to regionally varying transpulmonary and transmural pressures. Structure and function in the lung are intimately related, yet computational models in pulmonary physiology usually simplify or neglect structure. The geometries of the airway and vascular systems and their interaction with parenchymal tissue have an important bearing on regional distributions of air and blood, and therefore on whole lung gas exchange, but this has not yet been addressed by modelling studies. Models for gas exchange have typically incorporated considerable detail at the level of chemical reactions, with little thought for the influence of structure. To date, relatively little attention has been paid to modelling at the cellular or subcellular level in the lung, or to linking information from the protein structure/interaction and cellular levels to the operation of the whole lung. We review previous work in developing anatomically based models of the lung, airways, parenchyma and pulmonary vasculature, and some functional studies in which these models have been used. Models for gas exchange at several spatial scales are briefly reviewed, and the challenges and benefits from modelling cellular function in the lung are discussed.

Antihistamine medication may alleviate negative effects of prenatal exposure to polycyclic aromatic hydrocarbons (PAH) on lung function in children. Birth cohort prospective study.

PubMed

Jedrychowski, Wieslaw A; Perera, Frederica P; Maugeri, Umberto; Majewska, Renata; Spengler, Jack; Mroz, Elzbieta; Flak, Elzbieta; Klimaszewska-Rembiasz, Maria; Camman, David

2015-05-01

The main purpose of the present study was to test the hypothesis that the depressed lung growth attributable to prenatal exposure to polycyclic aromatic hydrocarbons (PAH) may be modified by the intake of antihistamine medications. Individual prenatal PAH exposure was assessed by personal air monitoring in 176 children who were followed over nine years, in the course of which outdoor residential air monitoring, allergic skin tests for indoor allergens, lung function tests (FVC, FEV(1), FEV(05), and FEF(25-75)) were performed. The analysis with the General Estimated Equation (GEE) showed no association between prenatal PAH exposure and lung function in the group of children who were reported to be antihistamine users. However, in the group of antihistamine non-users all lung function tests except for FEF(25-75) were significantly and inversely associated with prenatal airborne PAH exposure. The results of the study suggest that the intake of antihistamine medications in early childhood may inhibit the negative effect of fetal PAH exposure on lung growth and provides additional indirect evidence for the hypothesis that lung alterations in young children resulting from PAH exposure may be caused by the allergic inflammation within lung. © 2014 Wiley Periodicals, Inc.

[Lung scintigraphy].

PubMed

Schümichen, Carl; Schmidt, Matthias; Krause, Thomas

2018-06-01

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

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

Inhibition of glycogen synthase kinase-3β prevents activation of focal adhesion kinase after ischemia/reperfusion of the rat lung.

PubMed

Waldow, Thomas; Witt, Wolfgang; Matschke, Klaus

2010-01-01

Recent studies on the mechanisms of ischemic preconditioning in myocardial tissue have presented convincing evidence that multiple protective pathways converge on inhibition of glycogen synthase kinase-3β (GSK-3β). To directly address the role of GSK-3β in ischemia and reperfusion (I/R) of the lung, a rat model of left lung in situ ischemia was used. The specific non-competitive inhibitor of GSK-3β, TDZD-8, was injected (3 mg/kg, vehicle in controls) 5 min before the left lung hilum was occluded for 60 min. Animals in the ischemia group underwent the same treatment, but without administration of TDZD-8. Lung functional and biochemical parameters were determined at time points 15 min and 60 min reperfusion. Treatment with TDZD-8 improved gas exchange (arterial pO2), but I/R-induced inflammation (plasma interleukin-6, leukocyte invasion) was not affected. The I/R cycle induced a rapid (15 min reperfusion) increase of protein tyrosine phosphorylation, including the activating phosphorylation of focal adhesion kinase at Tyr397, Tyr407, Tyr577, and Tyr861, and the non-receptor kinase Src at Tyr416. The phosphorylation was blocked by the GSK inhibitor. This effect may be related to the reduced plasma level of the strong effector of focal adhesion kinase, transforming growth factor-β1, in the TDZD group. The underlying mechanisms are elusive, but they deserve further investigation, especially in relation to the early increase of lung permeability in this rat model of I/R injury. In conclusion, the results suggest that inhibition of GSK-3β improves rat lung function during an I/R cycle, but only during the early reperfusion phase.

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Early Changes in Clinical, Functional, and Laboratory Biomarkers in Workers at Risk of Indium Lung Disease

PubMed Central

Virji, M. Abbas; Trapnell, Bruce C.; Carey, Brenna; Healey, Terrance; Kreiss, Kathleen

2014-01-01

Rationale: Occupational exposure to indium compounds, including indium–tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood. Objectives: To determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities. Methods: Among indium–tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models. Measurements and Main Results: Eighty-seven (93%) of 94 indium–tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 μg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥ 1.0 μg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 μg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures. Conclusions: In indium–tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum biomarkers of lung disease. PMID:25295756

Lack of phosphoinositide 3-kinase-gamma attenuates ventilator-induced lung injury.

PubMed

Lionetti, Vincenzo; Lisi, Alberto; Patrucco, Enrico; De Giuli, Paolo; Milazzo, Maria Giovanna; Ceci, Simone; Wymann, Matthias; Lena, Annalisa; Gremigni, Vittorio; Fanelli, Vito; Hirsch, Emilio; Ranieri, V Marco

2006-01-01

G protein-coupled receptors may up-regulate the inflammatory response elicited by ventilator-induced lung injury but also regulate cell survival via protein kinase B (Akt) and extracellular signal regulated kinases 1/2 (ERK1/2). The G protein-sensitive phosphoinositide-3-kinase gamma (PI3Kgamma) regulates several cellular functions including inflammation and cell survival. We explored the role of PI3Kgamma on ventilator-induced lung injury. Prospective, randomized, experimental study. University animal research laboratory. Wild-type (PI3Kgamma), knock-out (PI3Kgamma ), and kinase-dead (PI3Kgamma) mice. Three ventilatory strategies (no stretch, low stretch, high stretch) were studied in an isolated, nonperfused model of acute lung injury (lung lavage) in PI3Kgamma, PI3Kgamma, and PI3Kgamma mice. Reduction in lung compliance, hyaline membrane formation, and epithelial detachment with high stretch were more pronounced in PI3Kgamma than in PI3Kgamma and PI3Kgamma (p < .01). Inflammatory cytokines and IkBalpha phosphorylation with high stretch did not differ among PI3Kgamma, PI3Kgamma, and PI3Kgamma. Apoptotic index (terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling) and caspase-3 (immunohistochemistry) with high stretch were larger (p < .01) in PI3Kgamma and PI3Kgamma than in PI3Kgamma. Electron microscopy showed that high stretch caused apoptotic changes in alveolar cells of PI3Kgamma mice whereas PI3Kgamma mice showed necrosis. Phosphorylation of Akt and ERK1/2 with high stretch was more pronounced in PI3Kgamma than in PI3Kgamma and PI3Kgamma (p < .01). Silencing PI3Kgamma seems to attenuate functional and morphological consequences of ventilator-induced lung injury independently of inhibitory effects on cytokines release but through the enhancement of pulmonary apoptosis.

Genetic variation predicting cisplatin cytotoxicity associated with overall survival in lung cancer patients receiving platinum-based chemotherapy †, ‡

PubMed Central

Tan, Xiang-Lin; Moyer, Ann M.; Fridley, Brooke L.; Schaid, Daniel J.; Niu, Nifang; Batzler, Anthony J.; Jenkins, Gregory D.; Abo, Ryan P.; Li, Liang; Cunningham, Julie M.; Sun, Zhifu; Yang, Ping; Wang, Liewei

2011-01-01

Purpose Inherited variability in the prognosis of lung cancer patients treated with platinum-based chemotherapy has been widely investigated. However, the overall contribution of genetic variation to platinum response is not well established. To identify novel candidate SNPs/genes, we performed a genome-wide association study (GWAS) for cisplatin cytotoxicity using lymphoblastoid cell lines (LCLs), followed by an association study of selected SNPs from the GWAS with overall survival (OS) in lung cancer patients. Experimental Design GWAS for cisplatin were performed with 283 ethnically diverse LCLs. 168 top SNPs were genotyped in 222 small cell and 961 non-small cell lung cancer (SCLC, NSCLC) patients treated with platinum-based therapy. Association of the SNPs with OS was determined using the Cox regression model. Selected candidate genes were functionally validated by siRNA knockdown in human lung cancer cells. Results Among 157 successfully genotyped SNPs, 9 and 10 SNPs were top SNPs associated with OS for patients with NSCLC and SCLC, respectively, although they were not significant after adjusting for multiple testing. Fifteen genes, including 7 located within 200 kb up or downstream of the four top SNPs and 8 genes for which expression was correlated with three SNPs in LCLs were selected for siRNA screening. Knockdown of DAPK3 and METTL6, for which expression levels were correlated with the rs11169748 and rs2440915 SNPs, significantly decreased cisplatin sensitivity in lung cancer cells. Conclusions This series of clinical and complementary laboratory-based functional studies identified several candidate genes/SNPs that might help predict treatment outcomes for platinum-based therapy of lung cancer. PMID:21775533

The large lungs of elite swimmers: an increased alveolar number?

PubMed

Armour, J; Donnelly, P M; Bye, P T

1993-02-01

In order to obtain further insight into the mechanisms relating to the large lung volumes of swimmers, tests of mechanical lung function, including lung distensibility (K) and elastic recoil, pulmonary diffusion capacity, and respiratory mouth pressures, together with anthropometric data (height, weight, body surface area, chest width, depth and surface area), were compared in eight elite male swimmers, eight elite male long distance athletes and eight control subjects. The differences in training profiles of each group were also examined. There was no significant difference in height between the subjects, but the swimmers were younger than both the runners and controls, and both the swimmers and controls were heavier than the runners. Of all the training variables, only the mean total distance in kilometers covered per week was significantly greater in the runners. Whether based on: (a) adolescent predicted values; or (b) adult male predicted values, swimmers had significantly increased total lung capacity ((a) 145 +/- 22%, (mean +/- SD) (b) 128 +/- 15%); vital capacity ((a) 146 +/- 24%, (b) 124 +/- 15%); and inspiratory capacity ((a) 155 +/- 33%, (b) 138 +/- 29%), but this was not found in the other two groups. Swimmers also had the largest chest surface area and chest width. Forced expiratory volume in one second (FEV1) was largest in the swimmers ((b) 122 +/- 17%) and FEV1 as a percentage of forced vital capacity (FEV1/FVC)% was similar for the three groups. Pulmonary diffusing capacity (DLCO) was also highest in the swimmers (117 +/- 18%). All of the other indices of lung function, including pulmonary distensibility (K), elastic recoil and diffusion coefficient (KCO), were similar. These findings suggest that swimmers may have achieved greater lung volumes than either runners or control subjects, not because of greater inspiratory muscle strength, or differences in height, fat free mass, alveolar distensibility, age at start of training or sternal length or chest depth, but by developing physically wider chests, containing an increased number of alveoli, rather than alveoli of increased size. However, in this cross-sectional study, hereditary factors cannot be ruled out, although we believe them to be less likely.

[Research advance on mechanism and application of HATs and HDACs in epithelial-mesenchymal transition of lung cancer].

PubMed

Chang, Rui; You, Jiacong; Zhou, Qinghua

2013-04-01

Lung cancer is one of the most common diseases that endanger health and life of people domestically. A number of recurrence and death of lung cancer originated from metastasis. As a key step in metastasis of lung cancer, epithelial to mesenchymal transition involved down-regulation of E-cadherin, as well as regulated by EMT transcription factors. HATs and HDACs is a protein family that catalyzes acetylation and deacetylation of histones. Not only they have vital functions in tumor pathogenesis, but also participate in the EMT of lung cancer. HATs and HDACs interact with certain EMT transcription factors. Moreover, the function of these EMT transcription factors may be regulated by acetylation, which has influence on EMT program in lung cancer. Therefore, this review introduces the event of HATs and HDACs function in EMT of lung cancer, and investigate the molecular mechanism of their interaction. Then, the potential of HDAC inhibitor utilization in the inhibition of EMT and lung cancer therapy were discussed, as to pave the way for the related basic research and clinical practice.

CFTR and lung homeostasis

PubMed Central

Matalon, Sadis

2014-01-01

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

Characteristic patterns in the fibrotic lung. Comparing idiopathic pulmonary fibrosis with chronic lung allograft dysfunction.

PubMed

Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver

2015-03-01

Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.

The potential impacts of climate variability and change on air pollution-related health effects in the United States.

PubMed Central

Bernard, S M; Samet, J M; Grambsch, A; Ebi, K L; Romieu, I

2001-01-01

Climate change may affect exposures to air pollutants by affecting weather, anthropogenic emissions, and biogenic emissions and by changing the distribution and types of airborne allergens. Local temperature, precipitation, clouds, atmospheric water vapor, wind speed, and wind direction influence atmospheric chemical processes, and interactions occur between local and global-scale environments. If the climate becomes warmer and more variable, air quality is likely to be affected. However, the specific types of change (i.e., local, regional, or global), the direction of change in a particular location (i.e., positive or negative), and the magnitude of change in air quality that may be attributable to climate change are a matter of speculation, based on extrapolating present understanding to future scenarios. There is already extensive evidence on the health effects of air pollution. Ground-level ozone can exacerbate chronic respiratory diseases and cause short-term reductions in lung function. Exposure to particulate matter can aggravate chronic respiratory and cardiovascular diseases, alter host defenses, damage lung tissue, lead to premature death, and possibly contribute to cancer. Health effects of exposures to carbon monoxide, sulfur dioxide, and nitrogen dioxide can include reduced work capacity, aggravation of existing cardiovascular diseases, effects on pulmonary function, respiratory illnesses, lung irritation, and alterations in the lung's defense systems. Adaptations to climate change should include ensuring responsiveness of air quality protection programs to changing pollution levels. Research needs include basic atmospheric science work on the association between weather and air pollutants; improving air pollution models and their linkage with climate change scenarios; and closing gaps in the understanding of exposure patterns and health effects. PMID:11359687

The potential impacts of climate variability and change on air pollution-related health effects in the United States.

PubMed

Bernard, S M; Samet, J M; Grambsch, A; Ebi, K L; Romieu, I

2001-05-01

Climate change may affect exposures to air pollutants by affecting weather, anthropogenic emissions, and biogenic emissions and by changing the distribution and types of airborne allergens. Local temperature, precipitation, clouds, atmospheric water vapor, wind speed, and wind direction influence atmospheric chemical processes, and interactions occur between local and global-scale environments. If the climate becomes warmer and more variable, air quality is likely to be affected. However, the specific types of change (i.e., local, regional, or global), the direction of change in a particular location (i.e., positive or negative), and the magnitude of change in air quality that may be attributable to climate change are a matter of speculation, based on extrapolating present understanding to future scenarios. There is already extensive evidence on the health effects of air pollution. Ground-level ozone can exacerbate chronic respiratory diseases and cause short-term reductions in lung function. Exposure to particulate matter can aggravate chronic respiratory and cardiovascular diseases, alter host defenses, damage lung tissue, lead to premature death, and possibly contribute to cancer. Health effects of exposures to carbon monoxide, sulfur dioxide, and nitrogen dioxide can include reduced work capacity, aggravation of existing cardiovascular diseases, effects on pulmonary function, respiratory illnesses, lung irritation, and alterations in the lung's defense systems. Adaptations to climate change should include ensuring responsiveness of air quality protection programs to changing pollution levels. Research needs include basic atmospheric science work on the association between weather and air pollutants; improving air pollution models and their linkage with climate change scenarios; and closing gaps in the understanding of exposure patterns and health effects.

Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury.

PubMed

Hong, Ji Young; Shin, Mi Hwa; Douglas, Ivor S; Chung, Kyung Soo; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Kim, Se Kyu; Chang, Joon; Kim, Young Sam; Park, Moo Suk

2016-11-01

Eph-Ephrin signalling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homoeostasis and repair after injury. Although previous studies have demonstrated that stimulation of the EphA receptor induces increased vascular permeability and inflammatory response in lung injury, the detailed mechanisms of EphA2 signalling are unknown. In the present study, we evaluated the role of EphA2 signalling in mice with lipopolysaccharide (LPS)-induced lung injury. Acute LPS exposure significantly up-regulated EphA2 and EphrinA1 expression. Compared with LPS+IgG mice (IgG instillation after LPS exposure), LPS+EphA2 mAb mice [EphA2 monoclonal antibody (mAb) instillation posttreatment after LPS exposure] had attenuated lung injury and reduced cell counts and protein concentration of bronchoalveolar lavage fluid (BALF). EphA2 mAb posttreatment down-regulated the expression of phosphoinositide 3-kinases (PI3K) 110γ, phospho-Akt, phospho-NF-κB p65, phospho-Src and phospho-S6K in lung lysates. In addition, inhibiting the EphA2 receptor augmented the expression of E-cadherin, which is involved in cell-cell adhesion. Our study identified EphA2 receptor as an unrecognized modulator of several signalling pathways-including PI3K-Akt-NF-kB, Src-NF-κB, E-cadherin and mTOR-in LPS-induced lung injury. These results suggest that EphA2 receptor inhibitors may function as novel therapeutic agents for LPS-induced lung injury. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema.

PubMed

Mondoñedo, Jarred R; Suki, Béla

2017-02-01

Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction.

Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema

PubMed Central

Mondoñedo, Jarred R.

2017-01-01

Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction. PMID:28182686

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

PubMed

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

2005-04-01

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

[MicroRNAs in diagnosis and prognosis in lung cancer].

PubMed

Avila-Moreno, Federico; Urrea, Francisco; Ortiz-Quintero, Blanca

2011-01-01

MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that regulate gene expression at the posttranscriptional level by blocking translation or inducing degradation of messenger RNA targets. It has been shown that miRNAs participate in a wide spectrum of essential biologic processes including cell cycle, differentiation, development, apoptosis and hematopoiesis, revealing one of the major regulators of human gene expression. Recent studies have shown evidences of abnormal expression of miRNAs in solid and hematological tumors, as well as the association of altered miRNAs with oncogenic or tumor suppressor functions, suggesting a key role of miRNAs in carcinogenesis. Moreover, unique profiles of altered miRNAs expression seem to allow distinction from normal tissue, prediction of disease outcomes, and evaluation of tumor aggressiveness in several types of cancer, including lung cancer. These unique and highly stable miRNAs patterns seems not to depend of age and race, and these characteristics highlight their potential diagnostic and prognosis utility. These findings are particularly promising for lung cancer, a worldwide leading cause of cancer-related deaths with a poor survival rate, despite the discovery of novel therapies. This review describes the potential of miRNAs as biomarkers for diagnosis, cancer classification and estimation of prognosis in lung cancer; and the approaches used to detect and quantify these miRNAs; including the current information about circulating miRNAs as potential biomarkers in lung cancer. This review also provides a description of miRNAs biogenesis, nomenclature and available database for miRNA sequences.

MMP12, lung function, and COPD in high-risk populations.

PubMed

Hunninghake, Gary M; Cho, Michael H; Tesfaigzi, Yohannes; Soto-Quiros, Manuel E; Avila, Lydiana; Lasky-Su, Jessica; Stidley, Chris; Melén, Erik; Söderhäll, Cilla; Hallberg, Jenny; Kull, Inger; Kere, Juha; Svartengren, Magnus; Pershagen, Göran; Wickman, Magnus; Lange, Christoph; Demeo, Dawn L; Hersh, Craig P; Klanderman, Barbara J; Raby, Benjamin A; Sparrow, David; Shapiro, Steven D; Silverman, Edwin K; Litonjua, Augusto A; Weiss, Scott T; Celedón, Juan C

2009-12-31

Genetic variants influencing lung function in children and adults may ultimately lead to the development of chronic obstructive pulmonary disease (COPD), particularly in high-risk groups. We tested for an association between single-nucleotide polymorphisms (SNPs) in the gene encoding matrix metalloproteinase 12 (MMP12) and a measure of lung function (prebronchodilator forced expiratory volume in 1 second [FEV(1)]) in more than 8300 subjects in seven cohorts that included children and adults. Within the Normative Aging Study (NAS), a cohort of initially healthy adult men, we tested for an association between SNPs that were associated with FEV(1) and the time to the onset of COPD. We then examined the relationship between MMP12 SNPs and COPD in two cohorts of adults with COPD or at risk for COPD. The minor allele (G) of a functional variant in the promoter region of MMP12 (rs2276109 [-82A-->G]) was positively associated with FEV(1) in a combined analysis of children with asthma and adult former and current smokers in all cohorts (P=2x10(-6)). This allele was also associated with a reduced risk of the onset of COPD in the NAS cohort (hazard ratio, 0.65; 95% confidence interval [CI], 0.46 to 0.92; P=0.02) and with a reduced risk of COPD in a cohort of smokers (odds ratio, 0.63; 95% CI, 0.45 to 0.88; P=0.005) and among participants in a family-based study of early-onset COPD (P=0.006). The minor allele of a SNP in MMP12 (rs2276109) is associated with a positive effect on lung function in children with asthma and in adults who smoke. This allele is also associated with a reduced risk of COPD in adult smokers. 2009 Massachusetts Medical Society

Lung Function Measurements in Rodents in Safety Pharmacology Studies

PubMed Central

Hoymann, Heinz Gerd

2012-01-01

The ICH guideline S7A requires safety pharmacology tests including measurements of pulmonary function. In the first step – as part of the “core battery” – lung function tests in conscious animals are requested. If potential adverse effects raise concern for human safety, these should be explored in a second step as a “follow-up study”. For these two stages of safety pharmacology testing, both non-invasive and invasive techniques are needed which should be as precise and reliable as possible. A short overview of typical in vivo measurement techniques is given, their advantages and disadvantages are discussed and out of these the non-invasive head-out body plethysmography and the invasive but repeatable body plethysmography in orotracheally intubated rodents are presented in detail. For validation purposes the changes in the respective parameters such as tidal midexpiratory flow (EF50) or lung resistance have been recorded in the same animals in typical bronchoconstriction models and compared. In addition, the technique of head-out body plethysmography has been shown to be useful to measure lung function in juvenile rats starting from day two of age. This allows safety pharmacology testing and toxicological studies in juvenile animals as a model for the young developing organism as requested by the regulatory authorities (e.g., EMEA Guideline 1/2008). It is concluded that both invasive and non-invasive pulmonary function tests are capable of detecting effects and alterations on the respiratory system with different selectivity and area of operation. The use of both techniques in a large number of studies in mice and rats in the last years have demonstrated that they provide useful and reliable information on pulmonary mechanics in safety pharmacology and toxicology testing, in investigations of respiratory disorders, and in pharmacological efficacy studies. PMID:22973226

Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis

USDA-ARS?s Scientific Manuscript database

Pulmonary neuroendocrine cells (PNECs) are proposed to be the first specialized cell type to appear in the lung, but their ontogeny remains obscure. Although studies of PNECs have suggested their involvement in a number of lung functions, neither their in vivo significance nor the molecular mechanis...

Imaging Lung Function in Mice Using SPECT/CT and Per-Voxel Analysis

PubMed Central

Jobse, Brian N.; Rhem, Rod G.; McCurry, Cory A. J. R.; Wang, Iris Q.; Labiris, N. Renée

2012-01-01

Chronic lung disease is a major worldwide health concern but better tools are required to understand the underlying pathologies. Ventilation/perfusion (V/Q) single photon emission computed tomography (SPECT) with per-voxel analysis allows for non-invasive measurement of regional lung function. A clinically adapted V/Q methodology was used in healthy mice to investigate V/Q relationships. Twelve week-old mice were imaged to describe normal lung function while 36 week-old mice were imaged to determine how age affects V/Q. Mice were ventilated with Technegas™ and injected with 99mTc-macroaggregated albumin to trace ventilation and perfusion, respectively. For both processes, SPECT and CT images were acquired, co-registered, and quantitatively analyzed. On a per-voxel basis, ventilation and perfusion were moderately correlated (R = 0.58±0.03) in 12 week old animals and a mean log(V/Q) ratio of −0.07±0.01 and standard deviation of 0.36±0.02 were found, defining the extent of V/Q matching. In contrast, 36 week old animals had significantly increased levels of V/Q mismatching throughout the periphery of the lung. Measures of V/Q were consistent across healthy animals and differences were observed with age demonstrating the capability of this technique in quantifying lung function. Per-voxel analysis and the ability to non-invasively assess lung function will aid in the investigation of chronic lung disease models and drug efficacy studies. PMID:22870297

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

NASA Astrophysics Data System (ADS)

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

2006-03-01

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

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.

Multiple Facets of cAMP Signalling and Physiological Impact: cAMP Compartmentalization in the Lung

PubMed Central

Oldenburger, Anouk; Maarsingh, Harm; Schmidt, Martina

2012-01-01

Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP) are currently used in the treatment of several chronic inflammatory disorders, including chronic obstructive pulmonary disease (COPD). Characteristics of COPD are airway obstruction, airway inflammation and airway remodelling, processes encompassed by increased airway smooth muscle mass, epithelial changes, goblet cell and submucosal gland hyperplasia. In addition to inflammatory cells, airway smooth muscle cells and (myo)fibroblasts, epithelial cells underpin a variety of key responses in the airways such as inflammatory cytokine release, airway remodelling, mucus hypersecretion and airway barrier function. Cigarette smoke, being next to environmental pollution the main cause of COPD, is believed to cause epithelial hyperpermeability by disrupting the barrier function. Here we will focus on the most recent progress on compartmentalized signalling by cAMP. In addition to G protein-coupled receptors, adenylyl cyclases, cAMP-specific phospho-diesterases (PDEs) maintain compartmentalized cAMP signalling. Intriguingly, spatially discrete cAMP-sensing signalling complexes seem also to involve distinct members of the A-kinase anchoring (AKAP) superfamily and IQ motif containing GTPase activating protein (IQGAPs). In this review, we will highlight the interaction between cAMP and the epithelial barrier to retain proper lung function and to alleviate COPD symptoms and focus on the possible molecular mechanisms involved in this process. Future studies should include the development of cAMP-sensing multiprotein complex specific disruptors and/or stabilizers to orchestrate cellular functions. Compartmentalized cAMP signalling regulates important cellular processes in the lung and may serve as a therapeutic target. PMID:24281338

Genetic variation in the prostaglandin E2 pathway is associated with primary graft dysfunction.

PubMed

Diamond, Joshua M; Akimova, Tatiana; Kazi, Altaf; Shah, Rupal J; Cantu, Edward; Feng, Rui; Levine, Matthew H; Kawut, Steven M; Meyer, Nuala J; Lee, James C; Hancock, Wayne W; Aplenc, Richard; Ware, Lorraine B; Palmer, Scott M; Bhorade, Sangeeta; Lama, Vibha N; Weinacker, Ann; Orens, Jonathan; Wille, Keith; Crespo, Maria; Lederer, David J; Arcasoy, Selim; Demissie, Ejigayehu; Christie, Jason D

2014-03-01

Biologic pathways with significant genetic conservation across human populations have been implicated in the pathogenesis of primary graft dysfunction (PGD). The evaluation of the role of recipient genetic variation in PGD has thus far been limited to single, candidate gene analyses. We sought to identify genetic variants in lung transplant recipients that are responsible for increased risk of PGD using a two-phase large-scale genotyping approach. Phase 1 was a large-scale candidate gene association study of the multicenter, prospective Lung Transplant Outcomes Group cohort. Phase 2 included functional evaluation of selected variants and a bioinformatics screening of variants identified in phase 1. After genetic data quality control, 680 lung transplant recipients were included in the analysis. In phase 1, a total of 17 variants were significantly associated with PGD, four of which were in the prostaglandin E2 family of genes. Among these were a coding variant in the gene encoding prostaglandin E2 synthase (PTGES2; P = 9.3 × 10(-5)) resulting in an arginine to histidine substitution at amino acid position 298, and three variants in a block containing the 5' promoter and first intron of the PTGER4 gene (encoding prostaglandin E2 receptor subtype 4; all P < 5 × 10(-5)). Functional evaluation in regulatory T cells identified that rs4434423A in the PTGER4 gene was associated with differential suppressive function of regulatory T cells. Further research aimed at replication and additional functional insight into the role played by genetic variation in prostaglandin E2 synthetic and signaling pathways in PGD is warranted.

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.

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

PubMed

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

2018-04-01

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

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

PubMed

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

2018-06-01

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

Activation and overexpression of Sirt1 attenuates lung fibrosis via P300.

PubMed

Zeng, Zhilin; Cheng, Sheng; Chen, Huilong; Li, Qinghai; Hu, Yinan; Wang, Qi; Zhu, Xianying; Wang, Jun

2017-05-13

Persistent fibroblast activation is a predominant feature of idiopathic pulmonary fibrosis (IPF), but the transcriptional and epigenetic mechanisms controlling this process are not well understood. Silent information regulator type-1 (Sirt1) is a member of class Ⅲ histone deacetylase with important regulatory roles in a variety of pathophysiologic processes, but its role in fibrotic lung diseases is not clearly elucidated. Sirt1 expression in lung tissues of IPF patients and in a mouse model of bleomycin (BLM)-induced lung fibrosis were evaluated by immunofluorescence. The function of Sirt1 in BLM-induced lung fibrosis in the mouse model or transforming growth factor β1 (TGF-β1)-mediated lung fibroblast cellular model was investigated by Sirt1 activation, overexpression and knockdown of Sirt1. Finally, the involvement of p300 signaling pathways was assessed. In this study, we found up-regulation of Sirt1 in BLM-induced lung fibrosis, as well as in the lungs of IPF patients, including in the aggregated pulmonary fibroblasts of fibrotic foci. Activation or overexpression of Sirt1 attenuated TGF-β1-mediated lung fibroblast differentiation and activation and diminished the severity of experimental lung fibrosis in mice. Whereas knockdown of Sirt1 promoted the pro-fibrogenic activity of TGF-β1 in lung fibroblasts. A potential mechanism for the role of Sirt1 in lung fibrosis was through regulating the expression of p300. Thus, we characterized Sirt1 as an important regulator of lung fibrosis and provides a proof of principle for activation or overexpression of Sirt1 as a potential novel therapeutic strategy for IPF. Copyright © 2017 Elsevier Inc. All rights reserved.

Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action.

PubMed

Ionescu, Lavinia; Byrne, Roisin N; van Haaften, Tim; Vadivel, Arul; Alphonse, Rajesh S; Rey-Parra, Gloria J; Weissmann, Gaia; Hall, Adam; Eaton, Farah; Thébaud, Bernard

2012-12-01

Mortality and morbidity of acute lung injury and acute respiratory distress syndrome remain high because of the lack of pharmacological therapies to prevent injury or promote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donor-derived cell engraftment, suggesting that MSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulating alveolar macrophage (AM) function. We tested the therapeutic effect of MSC-derived conditioned medium (CdM) compared with whole MSCs, lung fibroblasts, and fibroblast-CdM. Intratracheal MSCs and MSC-CdM significantly attenuated lipopolysaccharide (LPS)-induced lung neutrophil influx, lung edema, and lung injury as assessed by an established lung injury score. MSC-CdM increased arginase-1 activity and Ym1 expression in LPS-exposed AMs. In vivo, AMs from LPS-MSC and LPS-MSC CdM lungs had enhanced expression of Ym1 and decreased expression of inducible nitric oxide synthase compared with untreated LPS mice. This suggests that MSC-CdM promotes alternative macrophage activation to an M2 "healer" phenotype. Comparative multiplex analysis of MSC- and fibroblast-CdM demonstrated that MSC-CdM contained several factors that may confer therapeutic benefit, including insulin-like growth factor I (IGF-I). Recombinant IGF-I partially reproduced the lung protective effect of MSC-CdM. In summary, MSCs act through a paracrine activity. MSC-CdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/anti-inflammatory M2 macrophage phenotype in part via IGF-I.

Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action

PubMed Central

Ionescu, Lavinia; Byrne, Roisin N.; van Haaften, Tim; Vadivel, Arul; Alphonse, Rajesh S.; Rey-Parra, Gloria J.; Weissmann, Gaia; Hall, Adam; Eaton, Farah

2012-01-01

Mortality and morbidity of acute lung injury and acute respiratory distress syndrome remain high because of the lack of pharmacological therapies to prevent injury or promote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donor-derived cell engraftment, suggesting that MSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulating alveolar macrophage (AM) function. We tested the therapeutic effect of MSC-derived conditioned medium (CdM) compared with whole MSCs, lung fibroblasts, and fibroblast-CdM. Intratracheal MSCs and MSC-CdM significantly attenuated lipopolysaccharide (LPS)-induced lung neutrophil influx, lung edema, and lung injury as assessed by an established lung injury score. MSC-CdM increased arginase-1 activity and Ym1 expression in LPS-exposed AMs. In vivo, AMs from LPS-MSC and LPS-MSC CdM lungs had enhanced expression of Ym1 and decreased expression of inducible nitric oxide synthase compared with untreated LPS mice. This suggests that MSC-CdM promotes alternative macrophage activation to an M2 “healer” phenotype. Comparative multiplex analysis of MSC- and fibroblast-CdM demonstrated that MSC-CdM contained several factors that may confer therapeutic benefit, including insulin-like growth factor I (IGF-I). Recombinant IGF-I partially reproduced the lung protective effect of MSC-CdM. In summary, MSCs act through a paracrine activity. MSC-CdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/anti-inflammatory M2 macrophage phenotype in part via IGF-I. PMID:23023971

Nutritional state and lung disease in cystic fibrosis.

PubMed

Bakker, W

1992-10-01

The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the severity and progress of the pulmonary involvement associated with the disease. Many data support the view that malnutrition and deterioration of lung function are closely interrelated and interdependent, with each affecting the other, leading to a spiral decline in both. The occurrence of malnutrition appears to be associated with poor lung function and poor survival, and conversely prevention of malnutrition appears to be associated with better lung function and improved survival. Nutritional intervention may lead to an improvement in body weight, lung function and exercise tolerance, provided that the intervention is combined with exercise training in order to increase both respiratory and other muscle mass. These improvements can be preserved when patients have the stamina to continue with a high-energy, high-fat diet and daily exercise training at home.

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 biology, function and clinical implications of exosomes in lung cancer.

PubMed

Zhou, Li; Lv, Tangfeng; Zhang, Qun; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Song, Yong

2017-10-28

Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. In addition, we also discuss current challenges that might impede the clinical use of exosomes. Further studies on the functional roles of exosomes in lung cancer requires thorough research. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between the Type of Workplace and Lung Function in Copper Miners

PubMed Central

Gruszczyński, Leszek; Wojakowska, Anna; Ścieszka, Marek; Turczyn, Barbara; Schmidt, Edward

2016-01-01

The aim of the analysis was to retrospectively assess changes in lung function in copper miners depending on the type of workplace. In the groups of 225 operators, 188 welders, and 475 representatives of other jobs, spirometry was performed at the start of employment and subsequently after 10, 20, and 25 years of work. Spirometry Longitudinal Data Analysis software was used to estimate changes in group means for FEV1 and FVC. Multiple linear regression analysis was used to assess an association between workplace and lung function. Lung function assessed on the basis of calculation of longitudinal FEV1 (FVC) decline was similar in all studied groups. However, multiple linear regression model used in cross-sectional analysis revealed an association between workplace and lung function. In the group of welders, FEF75 was lower in comparison to operators and other miners as early as after 10 years of work. Simultaneously, in smoking welders, the FEV1/FVC ratio was lower than in nonsmokers (p < 0,05). The interactions between type of workplace and smoking (p < 0,05) in their effect on FVC, FEV1, PEF, and FEF50 were shown. Among underground working copper miners, the group of smoking welders is especially threatened by impairment of lung ventilatory function. PMID:27274987

Association of area socioeconomic status with lung function in children.

PubMed

Wu, Yi-Fan; Wu, Cho-Kai; Chen, Duan-Rung; Chie, Wei-Chu; Lee, Yungling Leo

2012-12-01

The study investigates the association between area-level socioeconomic status (SES) and children's lung function. Participants were 3994 seventh grade students from the Taiwan Children Health Study living in 14 communities in Taiwan and were recruited in 2007. Area-level SES predictors were population size, occupation type, income and education level. Hierarchical linear models (HLM) were used to examine the effects of area-level SES on lung function, after accounting for area air pollution and individual SES (parental education and family income). Areas with high income were independently associated with lower child lung function. The coefficients for log transformation of area tax per person in HLM were -47.8 (95% confidence interval (CI): -80.9, -14.8) in FEV(1), -43.8 (95% CI: -75.2, -12.5) in FVC, -93.4 (95% CI: -179.3, -7.5) in FEF(25-75) and -203.2 (95% CI: -349.1, -57.2) in PEF. All SES predictors influenced in the same direction and affected males more. The interaction of area tax per person with parental educational level was significant on PEF, suggesting significant association of greater parental education with lower lung function in children. High area SES was inversely associated with lung function in Taiwanese children. Copyright © 2012 Elsevier Inc. All rights reserved.

Exposure to industrial air pollutant emissions and lung function in children: Canadian Health Measures Survey, 2007 to 2011.

PubMed

Wong, Suzy L; Coates, Allan L; To, Teresa

2016-02-01

Long-term exposure to ambient air pollution has been associated with adverse effects on children's lung function. Few studies have examined lung function in relation to industrial emissions of air pollutants. This cross-sectional study was based on 2,833 respondents aged 6 to 18 for whom spirometry data were collected by the Canadian Health Measures Survey, 2007 to 2011. The weighted sum of industrial air emissions of nitrogen oxides (NOₓ) and fine particulate matter (PM2.5) within 25 km of the respondent's residence was derived using National Pollutant Release Inventory data. Multivariate linear regression was used to examine the relationship between NOₓ and PM2.5 emissions and forced vital capacity (FVC), the forced expiratory volume in 1 sec (FEV₁), and the ratio of the two (FEV₁/FVC). Industrial air emissions of NOₓ were not significantly associated with lung function among males or females. Emissions of PM2.5 were negatively associated with FEV₁ and FEV₁/FVC, but not FVC, among males. PM2.5 was not significantly related to lung function among females. The associations that emerged between lung function and industrial emissions of PM2.5 among males were consistent with airway obstruction. Further research is warranted to investigate the gender differences observed in this study.

Lung function imaging methods in Cystic Fibrosis pulmonary disease.

PubMed

Kołodziej, Magdalena; de Veer, Michael J; Cholewa, Marian; Egan, Gary F; Thompson, Bruce R

2017-05-17

Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis. X-ray phase-contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis lung assessment which provides dynamic morphological and functional information, albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI) is a non-ionising radiation imaging method that is garnering growing interest among researchers and clinicians working with Cystic Fibrosis patients. Recent advances in MRI have opened up the possibilities to observe lung function in real time to potentially allow sensitive and accurate assessment of disease progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be tailored to clinical needs. While MRI offers significant promise it still suffers from poor spatial resolution and the development of an objective scoring system especially for ventilation assessment.

The effects of danofloxacin and tilmicosin on neutrophil function and lung consolidation in beef heifer calves with induced Pasteurella (Mannheimia) haemolytica pneumonia.

PubMed

Fajt, V R; Apley, M D; Roth, J A; Frank, D E; Brogden, K A; Skogerboe, T L; Shostrom, V K; Chin, Y-L

2003-06-01

Pneumonia caused by Pasteurella (Mannheimia) haemolytica was induced in weaned beef heifer calves, approximately 6 months of age. Calves were treated at 20 h after challenge with therapeutic doses of danofloxacin or tilmicosin. Peripheral blood neutrophils were collected at 3, 24 and 48 h after treatment. The ex vivo effects on neutrophil function, neutrophil apoptosis, and hematological parameters were examined, as was the effect on percentage lung consolidation. Neutrophil function assays included random migration under agarose, cytochrome C reduction, iodination, Staphylococcus aureus ingestion, chemotaxis, and antibody-dependent and antibody-independent cell-mediated cytotoxicity. Apoptosis was determined using a cell death detection kit. Killing was performed at 72 h after treatment. Statistical comparisons were made among the three groups of challenged-treated animals: saline, danofloxacin, and tilmicosin. Comparisons were also made between nonchallenged nontreated animals (NCH) and challenged saline-treated animals. There were no significant differences for any of the neutrophil function assays or neutrophil apoptosis among the challenged-treated groups. This suggests that danofloxacin and tilmicosin have no clinically significant effects on neutrophil function or apoptosis. There were also no significant differences in percentage lung consolidation among the challenged-treated groups. Significant differences were found between the NCH calves and the challenged saline-treated calves in several neutrophil assays, which were attributed to effects of P. haemolytica infection.

Utilization of the organ care system for bilateral lung transplantation: preliminary results of a comparative study.

PubMed

Zeriouh, Mohamed; Sabashnikov, Anton; Mohite, Prashant N; Zych, Bartlomiej; Patil, Nikhil P; García-Sáez, Diana; Koch, Achim; Weymann, Alexander; Soresi, Simona; Wippermann, Jens; Wahlers, Thorsten; De Robertis, Fabio; Popov, Aron-Frederik; Simon, André R

2016-09-01

Lung transplantation (LTx) remains the gold standard for patients with end-stage lung disease. However, due to donor organ shortage and brain stem death-related lung injury, only a small proportion of lungs are used increasing the mortality rate on the waiting list. A portable normothermic continuous ex vivo perfusion using the organ care system (OCS) represents one of the tools to increase the pool of donor organs and to improve the function of marginal lungs. We sought to assess mid-term outcomes after LTx using OCS and to compare outcomes including overall survival and freedom from bronchiolitis obliterans syndrome (BOS) with those after conventional preservation. Included were 322 consecutive LTx performed at Harefield Hospital between January 2007 and December 2014. Recipients were divided into two groups depending on the organ storage strategy: the majority of patients (n = 308) were transplanted using lungs after cold storage (cold storage group), whereas 14 organs were preserved using OCS (OCS group). The primary end-points were overall survival and freedom from BOS after LTx. The secondary end-points were perioperative clinical characteristics and adverse events. There were no statistically significant differences in terms of most baseline donor and recipient characteristics. The percentage of heavy smokers among donors [8 (2.9%) vs 6 (42.9%), P < 0.001] and the median number of pack-years smoked by donors [14 (7;24) vs 25 (24;30), P = 0.026] were statistically higher in the OCS group. Patients from the OCS group had significantly better postoperative FEV1 at 3 [69 (54;86) vs 93 (87;89), P < 0.001] and 6 [77 (60;90) vs 94 (84;100), P = 0.006] months. There were no statistically significant differences in terms of cumulative survival and freedom from BOS between the two groups. Results after LTx using OCS are acceptable with excellent survival, and superior early outcome in terms of postoperative lung function despite higher risk in the OCS group. Further larger prospective trials are warranted to confirm our preliminary results and to elaborate long-term outcomes. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

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.