Lung disease - resources

MedlinePlus

Resources - lung disease ... The following organizations are good resources for information on lung disease : American Lung Association -- www.lung.org National Heart, Lung, and Blood Institute -- www.nhlbi.nih.gov ...

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.).

Rheumatoid lung disease

MedlinePlus

Lung disease - rheumatoid arthritis; Rheumatoid nodules; Rheumatoid lung ... Lung problems are common in rheumatoid arthritis. They often cause no symptoms. The cause of lung disease associated with rheumatoid arthritis is unknown. Sometimes, the medicines used to ...

Indium Lung Disease

PubMed Central

Nakano, Makiko; Omae, Kazuyuki; Takeuchi, Koichiro; Chonan, Tatsuya; Xiao, Yong-long; Harley, Russell A.; Roggli, Victor L.; Hebisawa, Akira; Tallaksen, Robert J.; Trapnell, Bruce C.; Day, Gregory A.; Saito, Rena; Stanton, Marcia L.; Suarthana, Eva; Kreiss, Kathleen

2012-01-01

Background: Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. Methods: To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. Results: Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. Conclusions: Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies. PMID:22207675

The role of nailfold capillaroscopy in interstitial lung diseases - can it differentiate idiopathic cases from collagen tissue disease associated interstitial lung diseases?

PubMed

Çakmakçı Karadoğan, Dilek; Balkarlı, Ayşe; Önal, Özgür; Altınışık, Göksel; Çobankara, Veli

2015-01-01

Nailfold capillaroscopy (NFC) is a non-invasive diagnostic test that is mostly used for early diagnosis of collagen tissue diseases (CTDs). We aimed to evaluate whether NFC findings could be a clue for discriminating idiopathic interstitial lung diseases (ILD) from CTD associated ILDs (CTD-ILD). Additionally it was aimed to determine whether NFC could be helpful in discriminating usual interstitial pneumonia (UIP) pattern from non-specific interstitial pneumonia (NSIP) pattern. We grouped patients into three main groups: 15 CTD-ILD, 18 idiopathic ILD, and 17 patients in the control group. The CTD-ILD group was split into two subgroups: 8 patients with Sjögren's syndrome (SJS)-associated ILD and 7 with rheumatoid arthritis (RA)-associated ILD. The idiopathic-ILD group consisted of 10 idiopathic NSIP and 8 IPF patients. The control group consisted of 10 SJS and 7 RA patients without lung disease. None of the patients were on acute exacerbation at the time of examination, and none had Reynaud's phenomenon. Mean capillary density was significantly reduced only in the CTD-ILD group as compared to the control group (p= 0.006). In subgroup analysis, it was determined that RA-ILD, IPF, and SJS-ILD subgroups had more severe capillaroscopic abnormalities. Mean capillary density in patients with the UIP pattern was reduced compared to patients with the NSIP pattern and those in the control group; p values were 0.008 and < 0.001, respectively. This study is to be the first describing and comparing the nailfold capillaroscopic findings of patients with NSIP and UIP patterns. NFC findings can be helpful in discriminating UIP patterns from NSIP patterns. But to show its role in differentiating idiopathic disease, more studies with more patients are needed.

Variations of flow in human airways as a consequence of lung diseases

NASA Astrophysics Data System (ADS)

Lizal, Frantisek; Stejskal, David; Belka, Miloslav; Jedelsky, Jan; Jicha, Miroslav; Brat, Kristian; Herout, Vladimir; Lizalova Sujanska, Elena

2018-06-01

The efficiency of drug delivery administered by inhalation depends, among other factors, such as size and shape of aerosol particles, significantly also on the flow in the airways. As many lung diseases change both the breathing pattern and the shape of airways, we focus in this study on the influence of several selected diseases on the distribution of flow between the lung lobes and on changes the diseases induce on the course of flowrate. First, we present results of a literature survey focused on the published records of pathological breathing patterns. In the second part, we describe the newly designed breathing simulator and the implementation of the patterns into it. The last part is focused on the experimental verification of fidelity of the simulated breathing patterns.

Rheumatoid arthritis-associated interstitial lung disease: lung inflammation evaluated with high resolution computed tomography scan is correlated to rheumatoid arthritis disease activity.

PubMed

Pérez-Dórame, Renzo; Mejía, Mayra; Mateos-Toledo, Heidegger; Rojas-Serrano, Jorge

2015-01-01

To describe the association between rheumatoid arthritis disease activity (RA) and interstitial lung damage (inflammation and fibrosis), in a group of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). A retrospective study of RA patients with interstitial lung disease (restrictive pattern in lung function tests and evidence of interstitial lung disease in high resolution computed tomography (HRCT)). Patients were evaluated to exclude other causes of pulmonary disease. RA disease activity was measured with the CDAI index. Interstitial lung inflammation and fibrosis were determined by Kazerooni scale. We compared Kazerooni ground-glass score with the nearest CDAI score to HRCT date scan of the first medical evaluation at our institution. In nine patients, we compared the first ground-glass score with a second one after treatment with DMARDs and corticosteroids. Spearman's rank correlation coefficient was used to evaluate association between RA disease activity and the Kazerooni ground-glass and fibrosis scores. Thirty-four patients were included. A positive correlation between CDAI and ground-glass scores was found (rs=0.3767, P<0.028). Fibrosis and CDAI scores were not associated (rs=-0.0747, P<0.6745). After treatment, a downward tendency in the ground-glass score was observed (median [IQR]): (2.33 [2,3] vs. 2 [1.33-2.16]), P<0.056, along with a lesser CDAI score (27 [8-43] vs. 9 [5-12]), P<0.063. There is a correlation between RA disease activity and ground-glass appearance in the HRCT of RA-ILD patients. These results suggest a positive association between RA disease activity and lung inflammation in RA-ILD. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Case-based lung image categorization and retrieval for interstitial lung diseases: clinical workflows.

PubMed

Depeursinge, Adrien; Vargas, Alejandro; Gaillard, Frédéric; Platon, Alexandra; Geissbuhler, Antoine; Poletti, Pierre-Alexandre; Müller, Henning

2012-01-01

Clinical workflows and user interfaces of image-based computer-aided diagnosis (CAD) for interstitial lung diseases in high-resolution computed tomography are introduced and discussed. Three use cases are implemented to assist students, radiologists, and physicians in the diagnosis workup of interstitial lung diseases. In a first step, the proposed system shows a three-dimensional map of categorized lung tissue patterns with quantification of the diseases based on texture analysis of the lung parenchyma. Then, based on the proportions of abnormal and normal lung tissue as well as clinical data of the patients, retrieval of similar cases is enabled using a multimodal distance aggregating content-based image retrieval (CBIR) and text-based information search. The global system leads to a hybrid detection-CBIR-based CAD, where detection-based and CBIR-based CAD show to be complementary both on the user's side and on the algorithmic side. The proposed approach is in accordance with the classical workflow of clinicians searching for similar cases in textbooks and personal collections. The developed system enables objective and customizable inter-case similarity assessment, and the performance measures obtained with a leave-one-patient-out cross-validation (LOPO CV) are representative of a clinical usage of the system.

Artificial intelligence in diagnosis of obstructive lung disease: current status and future potential.

PubMed

Das, Nilakash; Topalovic, Marko; Janssens, Wim

2018-03-01

The application of artificial intelligence in the diagnosis of obstructive lung diseases is an exciting phenomenon. Artificial intelligence algorithms work by finding patterns in data obtained from diagnostic tests, which can be used to predict clinical outcomes or to detect obstructive phenotypes. The purpose of this review is to describe the latest trends and to discuss the future potential of artificial intelligence in the diagnosis of obstructive lung diseases. Machine learning has been successfully used in automated interpretation of pulmonary function tests for differential diagnosis of obstructive lung diseases. Deep learning models such as convolutional neural network are state-of-the art for obstructive pattern recognition in computed tomography. Machine learning has also been applied in other diagnostic approaches such as forced oscillation test, breath analysis, lung sound analysis and telemedicine with promising results in small-scale studies. Overall, the application of artificial intelligence has produced encouraging results in the diagnosis of obstructive lung diseases. However, large-scale studies are still required to validate current findings and to boost its adoption by the medical community.

Genomic Medicine and Lung Diseases

PubMed Central

Center, David M.; Schwartz, David A.; Solway, Julian; Gail, Dorothy; Laposky, Aaron D.

2012-01-01

The recent explosion of genomic data and technology points to opportunities to redefine lung diseases at the molecular level; to apply integrated genomic approaches to elucidate mechanisms of lung pathophysiology; and to improve early detection, diagnosis, and treatment of lung diseases. Research is needed to translate genomic discoveries into clinical applications, such as detecting preclinical disease, predicting patient outcomes, guiding treatment choices, and most of all identifying potential therapeutic targets for lung diseases. The Division of Lung Diseases in the National Heart, Lung, and Blood Institute convened a workshop, “Genomic Medicine and Lung Diseases,” to discuss the potential for integrated genomics and systems approaches to advance 21st century pulmonary medicine and to evaluate the most promising opportunities for this next phase of genomics research to yield clinical benefit. Workshop sessions included (1) molecular phenotypes, molecular biomarkers, and therapeutics; (2) new technology and opportunity; (3) integrative genomics; (4) molecular anatomy of the lung; (5) novel data and information platforms; and (6) recommendations for exceptional research opportunities in lung genomics research. PMID:22652029

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

Directional Multi-scale Modeling of High-Resolution Computed Tomography (HRCT) Lung Images for Diffuse Lung Disease Classification

NASA Astrophysics Data System (ADS)

Vo, Kiet T.; Sowmya, Arcot

A directional multi-scale modeling scheme based on wavelet and contourlet transforms is employed to describe HRCT lung image textures for classifying four diffuse lung disease patterns: normal, emphysema, ground glass opacity (GGO) and honey-combing. Generalized Gaussian density parameters are used to represent the detail sub-band features obtained by wavelet and contourlet transforms. In addition, support vector machines (SVMs) with excellent performance in a variety of pattern classification problems are used as classifier. The method is tested on a collection of 89 slices from 38 patients, each slice of size 512x512, 16 bits/pixel in DICOM format. The dataset contains 70,000 ROIs of those slices marked by experienced radiologists. We employ this technique at different wavelet and contourlet transform scales for diffuse lung disease classification. The technique presented here has best overall sensitivity 93.40% and specificity 98.40%.

The impact of coexisting lung diseases on outcomes in patients with pathological Stage I non-small-cell lung cancer.

PubMed

Tao, Hiroyuki; Onoda, Hideko; Okabe, Kazunori; Matsumoto, Tsuneo

2018-06-01

Cigarette smoking is a well-known cause of interstitial lung disease (ILD), pulmonary emphysema and lung cancer. Coexisting pulmonary disease can affect prognosis in patients with lung cancer. The aim of this study was to determine the influence of pulmonary disease on outcomes in patients with a smoking history who had undergone surgery for pathological Stage I non-small-cell lung cancer. Medical records of 257 patients with a smoking history who underwent surgery for pathological Stage I non-small-cell lung cancer between June 2009 and December 2014 were reviewed. Coexisting ILDs were evaluated using high-resolution computed tomography. The degree of pulmonary emphysema was determined using image analysis software according to the Goddard classification. The impact of clinicopathological factors on outcome was evaluated. Among the 257 patients, ILDs were detected via high-resolution computed tomography in 60 (23.3%) patients; of these, usual interstitial pneumonia (UIP) patterns and non-UIP patterns were seen in 25 (9.7%) and 35 (13.6%) patients, respectively. The degree of pulmonary emphysema was classified as none, mild and moderate and included 50 (19.5%), 162 (63.0%) and 45 (17.5%) patients, respectively. The 5-year overall survival, cancer-specific survival and relapse-free survival were 80.7%, 88.0% and 74.9%, respectively, during a median follow-up period of 50.5 months. In multivariate analysis, the presence of a UIP pattern was shown to be an independent risk factor for poor outcome. The presence of a UIP-pattern ILD on high-resolution computed tomography images was shown to be a risk factor for poor outcome in patients with a smoking history who had undergone surgery for pathological Stage I non-small-cell lung cancer.

Interstitial lung disease - adults - discharge

MedlinePlus

... lung disease Pulmonary alveolar proteinosis Rheumatoid lung disease Sarcoidosis Patient Instructions Eating extra calories when sick - adults ... team. Related MedlinePlus Health Topics Interstitial Lung Diseases Sarcoidosis Browse the Encyclopedia A.D.A.M., Inc. ...

Quantitative Stratification of Diffuse Parenchymal Lung Diseases

PubMed Central

Raghunath, Sushravya; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Maldonado, Fabien; Peikert, Tobias; Moua, Teng; Ryu, Jay H.; Bartholmai, Brian J.; Robb, Richard A.

2014-01-01

Diffuse parenchymal lung diseases (DPLDs) are characterized by widespread pathological changes within the pulmonary tissue that impair the elasticity and gas exchange properties of the lungs. Clinical-radiological diagnosis of these diseases remains challenging and their clinical course is characterized by variable disease progression. These challenges have hindered the introduction of robust objective biomarkers for patient-specific prediction based on specific phenotypes in clinical practice for patients with DPLD. Therefore, strategies facilitating individualized clinical management, staging and identification of specific phenotypes linked to clinical disease outcomes or therapeutic responses are urgently needed. A classification schema consistently reflecting the radiological, clinical (lung function and clinical outcomes) and pathological features of a disease represents a critical need in modern pulmonary medicine. Herein, we report a quantitative stratification paradigm to identify subsets of DPLD patients with characteristic radiologic patterns in an unsupervised manner and demonstrate significant correlation of these self-organized disease groups with clinically accepted surrogate endpoints. The proposed consistent and reproducible technique could potentially transform diagnostic staging, clinical management and prognostication of DPLD patients as well as facilitate patient selection for clinical trials beyond the ability of current radiological tools. In addition, the sequential quantitative stratification of the type and extent of parenchymal process may allow standardized and objective monitoring of disease, early assessment of treatment response and mortality prediction for DPLD patients. PMID:24676019

Surgical lung biopsy in transplant patients with diffuse lung disease: how much worse when the lung is the graft?

PubMed

Bertolotti, Alejandro; Defranchi, Sebastián; Vigliano, Carlos; Haberman, Diego; Favaloro, Roberto

2013-07-01

There are no data that compare the clinical presentation and results of surgical lung biopsy (SLB) for diffuse lung disease (DLD) in lung transplant patients, in contrast to individuals with other type of solid organ grafts. Our objective was to compare the clinical picture, radiologic pattern, pathology results, and outcomes of SLB for DLD in these two subsets of patients. We retrospectively reviewed the clinical records of transplant patients undergoing SLB for DLD at our institution between 2004 and 2011. Patients with lung transplants and those with other transplants were compared. During the study period, 1,232 solid organ transplants were done at our institution. Of these, 49 patients (4%) had DLD that needed SLB for diagnosis, and 24 of these patients had a lung transplant. Dyspnea and a radiologic reticular pattern were more frequent in lung transplant patients, 21 of 24 vs 11 of 25 (p = 0.001) and 14 of 24 vs 7 of 25 (p = 0.03), respectively. Although postoperative complications and in-hospital deaths were more common in lung transplant patients, the differences were not statistically significant. Having the SLB performed for diagnosis, as opposed to being conducted for DLD that did not improve on medical treatment, had a protective effect on multivariate analysis (hazard ratio, 0.39; 95% confidence interval, 0.16 to 0.96; p = 0.042). A prior lung transplant was the only independent predictor of survival (hazard ratio, 4.62; 95% confidence interval, 1.53 to 13.92, p = 0.006). It is relatively uncommon for a solid organ transplant patient with DLD to require a SLB. Clinical and radiologic presentation differ in patients with lung transplants compared with other transplants. Postoperative outcomes are not significantly different between the groups. SLB performed early in the course of the disease might be beneficial. Having a lung transplant is a significant negative predictor of survival. Copyright © 2013 The Society of Thoracic Surgeons. Published by

Automated diagnosis of interstitial lung diseases and emphysema in MDCT imaging

NASA Astrophysics Data System (ADS)

Fetita, Catalin; Chang Chien, Kuang-Che; Brillet, Pierre-Yves; Prêteux, Françoise

2007-09-01

Diffuse lung diseases (DLD) include a heterogeneous group of non-neoplasic disease resulting from damage to the lung parenchyma by varying patterns of inflammation. Characterization and quantification of DLD severity using MDCT, mainly in interstitial lung diseases and emphysema, is an important issue in clinical research for the evaluation of new therapies. This paper develops a 3D automated approach for detection and diagnosis of diffuse lung diseases such as fibrosis/honeycombing, ground glass and emphysema. The proposed methodology combines multi-resolution 3D morphological filtering (exploiting the sup-constrained connection cost operator) and graph-based classification for a full characterization of the parenchymal tissue. The morphological filtering performs a multi-level segmentation of the low- and medium-attenuated lung regions as well as their classification with respect to a granularity criterion (multi-resolution analysis). The original intensity range of the CT data volume is thus reduced in the segmented data to a number of levels equal to the resolution depth used (generally ten levels). The specificity of such morphological filtering is to extract tissue patterns locally contrasting with their neighborhood and of size inferior to the resolution depth, while preserving their original shape. A multi-valued hierarchical graph describing the segmentation result is built-up according to the resolution level and the adjacency of the different segmented components. The graph nodes are then enriched with the textural information carried out by their associated components. A graph analysis-reorganization based on the nodes attributes delivers the final classification of the lung parenchyma in normal and ILD/emphysematous regions. It also makes possible to discriminate between different types, or development stages, among the same class of diseases.

Hypothalamic digoxin, hemispheric chemical dominance, and interstitial lung disease.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-10-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with idiopathic pulmonary fibrosis and in individuals of differing hemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of idiopathic pulmonary fibrosis. All 15 cases of interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. The isoprenoidal metabolites--digoxin, dolichol, and ubiquinone, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, tyrosine/tryptophan catabolic patterns, free radical metabolism, glycoconjugate metabolism, and RBC membrane composition--were assessed in idiopathic pulmonary fibrosis as well as in individuals with differing hemispheric dominance. In patients with idiopathic pulmonary fibrosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in patients with idiopathic pulmonary fibrosis. Isoprenoid pathway dysfunction con tributes to the pathogenesis of idiopathic pulmonary fibrosis. The biochemical patterns obtained in interstitial lung disease are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. However, all the patients with interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Interstitial lung disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Is Previous Respiratory Disease a Risk Factor for Lung Cancer?

PubMed Central

Denholm, Rachel; Schüz, Joachim; Straif, Kurt; Stücker, Isabelle; Jöckel, Karl-Heinz; Brenner, Darren R.; De Matteis, Sara; Boffetta, Paolo; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Landi, Maria Teresa; Caporaso, Neil; Siemiatycki, Jack; Ahrens, Wolfgang; Pohlabeln, Hermann; Zaridze, David; Field, John K.; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Kendzia, Benjamin; Peters, Susan; Behrens, Thomas; Vermeulen, Roel; Brüning, Thomas; Kromhout, Hans

2014-01-01

Rationale: Previous respiratory diseases have been associated with increased risk of lung cancer. Respiratory conditions often co-occur and few studies have investigated multiple conditions simultaneously. Objectives: Investigate lung cancer risk associated with chronic bronchitis, emphysema, tuberculosis, pneumonia, and asthma. Methods: The SYNERGY project pooled information on previous respiratory diseases from 12,739 case subjects and 14,945 control subjects from 7 case–control studies conducted in Europe and Canada. Multivariate logistic regression models were used to investigate the relationship between individual diseases adjusting for co-occurring conditions, and patterns of respiratory disease diagnoses and lung cancer. Analyses were stratified by sex, and adjusted for age, center, ever-employed in a high-risk occupation, education, smoking status, cigarette pack-years, and time since quitting smoking. Measurements and Main Results: Chronic bronchitis and emphysema were positively associated with lung cancer, after accounting for other respiratory diseases and smoking (e.g., in men: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.20–1.48 and OR, 1.50; 95% CI, 1.21–1.87, respectively). A positive relationship was observed between lung cancer and pneumonia diagnosed 2 years or less before lung cancer (OR, 3.31; 95% CI, 2.33–4.70 for men), but not longer. Co-occurrence of chronic bronchitis and emphysema and/or pneumonia had a stronger positive association with lung cancer than chronic bronchitis “only.” Asthma had an inverse association with lung cancer, the association being stronger with an asthma diagnosis 5 years or more before lung cancer compared with shorter. Conclusions: Findings from this large international case–control consortium indicate that after accounting for co-occurring respiratory diseases, chronic bronchitis and emphysema continue to have a positive association with lung cancer. PMID:25054566

Computerized scheme for detection of diffuse lung diseases on CR chest images

NASA Astrophysics Data System (ADS)

Pereira, Roberto R., Jr.; Shiraishi, Junji; Li, Feng; Li, Qiang; Doi, Kunio

2008-03-01

We have developed a new computer-aided diagnostic (CAD) scheme for detection of diffuse lung disease in computed radiographic (CR) chest images. One hundred ninety-four chest images (56 normals and 138 abnormals with diffuse lung diseases) were used. The 138 abnormal cases were classified into three levels of severity (34 mild, 60 moderate, and 44 severe) by an experienced chest radiologist with use of five different patterns, i.e., reticular, reticulonodular, nodular, air-space opacity, and emphysema. In our computerized scheme, the first moment of the power spectrum, the root-mean-square variation, and the average pixel value were determined for each region of interest (ROI), which was selected automatically in the lung fields. The average pixel value and its dependence on the location of the ROI were employed for identifying abnormal patterns due to air-space opacity or emphysema. A rule-based method was used for determining three levels of abnormality for each ROI (0: normal, 1: mild, 2: moderate, and 3: severe). The distinction between normal lungs and abnormal lungs with diffuse lung disease was determined based on the fractional number of abnormal ROIs by taking into account the severity of abnormalities. Preliminary results indicated that the area under the ROC curve was 0.889 for the 44 severe cases, 0.825 for the 104 severe and moderate cases, and 0.794 for all cases. We have identified a number of problems and reasons causing false positives on normal cases, and also false negatives on abnormal cases. In addition, we have discussed potential approaches for improvement of our CAD scheme. In conclusion, the CAD scheme for detection of diffuse lung diseases based on texture features extracted from CR chest images has the potential to assist radiologists in their interpretation of diffuse lung diseases.

Analysis of speckle patterns in phase-contrast images of lung tissue

NASA Astrophysics Data System (ADS)

Kitchen, M. J.; Paganin, D.; Lewis, R. A.; Yagi, N.; Uesugi, K.

2005-08-01

Propagation-based phase-contrast images of mice lungs have been obtained at the SPring-8 synchrotron research facility. Such images exhibit a speckled intensity pattern that bears a superficial resemblance to alveolar structures. This speckle results from focussing effects as projected air-filled alveoli form aberrated compound refractive lenses. An appropriate phase-retrieval algorithm has been utilized to reconstruct the approximate projected lung tissue thickness from single-phase-contrast mice chest radiographs. The results show projected density variations across the lung, highlighting regions of low density corresponding to air-filled regions. Potentially, this offers a better method than conventional radiography for detecting lung diseases such as fibrosis, emphysema and cancer, though this has yet to be demonstrated. As such, the approach can assist in continuing studies of lung function utilizing propagation-based phase-contrast imaging.

What Are Asbestos-Related Lung Diseases?

MedlinePlus

... Back To Health Topics / Asbestos-Related Lung Diseases Asbestos-Related Lung Diseases Also known as What Is ... as the peritoneum (PER-ih-to-NE-um). Asbestos-Related Lung Diseases Figure A shows the location ...

Occupational lung diseases.

PubMed

Furlow, Bryant

2011-01-01

Chest radiography and high-resolution computed tomography are indispensable tools in the detection, classification and characterization of occupational lung diseases that are caused by inhaling mineral particles such as asbestos, silicon-containing rock dust and other tissue-damaging antigens, nanomaterials and toxins. Radiographic evidence of occupational lung disease is interpreted with a patient's clinical signs and symptoms and a detailed occupational history in mind because of high variability in radiographic findings. This Directed Reading reviews the history, epidemiology, functional anatomy, pathobiology and medical diagnostic imaging of occupational lung diseases associated with inhalation of fine particulates in the workplace. This article is a Directed Reading. Your access to Directed Reading quizzes for continuing education credit is determined by your CE preference. For access to other quizzes, go to www.asrt.org/store.

Interstitial Lung Disease due to Siderosis in a Lathe Machine Worker.

PubMed

Gothi, D; Satija, B; Kumar, S; Kaur, Omkar

2015-01-01

Since its first description in 1936, siderosis of lung has been considered a benign pneumoconiosis due to absence of significant clinical symptoms or respiratory impairment. Subsequently, authors have questioned the non-fibrogenic property of iron. However, siderosis causing interstitial lung disease with usual interstitial pneumonia (UIP) pattern has not been described in the past. We report a case of UIP on high resolution computed tomography, proven to be siderosis on transbronchial lung biopsy in a lathe machine worker.

Occupational lung diseases in Australia.

PubMed

Hoy, Ryan F; Brims, Fraser

2017-11-20

Occupational exposures are an important determinant of respiratory health. International estimates note that about 15% of adult-onset asthma, 15% of chronic obstructive pulmonary disease and 10-30% of lung cancer may be attributable to hazardous occupational exposures. One-quarter of working asthmatics either have had their asthma caused by work or adversely affected by workplace conditions. Recently, cases of historical occupational lung diseases have been noted to occur with new exposures, such as cases of silicosis in workers fabricating kitchen benchtops from artificial stone products. Identification of an occupational cause of a lung disease can be difficult and requires maintaining a high index of suspicion. When an occupational lung disease is identified, this may facilitate a cure and help to protect coworkers. Currently, very little information is collected regarding actual cases of occupational lung diseases in Australia. Most assumptions about many occupational lung diseases are based on extrapolation from overseas data. This lack of information is a major impediment to development of targeted interventions and timely identification of new hazardous exposures. All employers, governments and health care providers in Australia have a responsibility to ensure that the highest possible standards are in place to protect workers' respiratory health.

Pulmonary Hypertension in Parenchymal Lung Disease

PubMed Central

Tsangaris, Iraklis; Tsaknis, Georgios; Anthi, Anastasia; Orfanos, Stylianos E.

2012-01-01

Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lung diseases such as interstitial lung diseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lung diseases, some of which are very common, the available data is limited. In this paper, we try to browse in the latest available data regarding the occurrence, pathogenesis, and treatment of PH in chronic parenchymal lung diseases. PMID:23094153

Classification of diffuse lung diseases: why and how.

PubMed

Hansell, David M

2013-09-01

The understanding of complex lung diseases, notably the idiopathic interstitial pneumonias and small airways diseases, owes as much to repeated attempts over the years to classify them as to any single conceptual breakthrough. One of the many benefits of a successful classification scheme is that it allows workers, within and between disciplines, to be clear that they are discussing the same disease. This may be of particular importance in the recruitment of individuals for a clinical trial that requires a standardized and homogeneous study population. Different specialties require fundamentally different things from a classification: for epidemiologic studies, a classification that requires categorization of individuals according to histopathologic pattern is not usually practicable. Conversely, a scheme that simply divides diffuse parenchymal disease into inflammatory and noninflammatory categories is unlikely to further the understanding about the pathogenesis of disease. Thus, for some disease groupings, for example, pulmonary vasculopathies, there may be several appropriate classifications, each with its merits and demerits. There has been an interesting shift in the past few years, from the accepted primacy of histopathology as the sole basis on which the classification of parenchymal lung disease has rested, to new ways of considering how these entities relate to each other. Some inventive thinking has resulted in new classifications that undoubtedly benefit patients and clinicians in their endeavor to improve management and outcome. The challenge of understanding the logic behind current classifications and their shortcomings are explored in various examples of lung diseases.

Particles causing lung disease

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

Kilburn, K.H.

1984-04-01

The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of anmore » agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. 164 references, 1 figure, 2 tables.« less

The 'fragmented' scintigraphic lung pattern in pulmonary lymphangitic carcinomatosis secondary to breast cancer.

PubMed

Vattimo, A V; Burroni, L; Bertelli, P; Vella, A; Volterrani, D

1998-01-01

Pulmonary lymphangitic carcinomatosis (PLC) is an unusual presentation of diffuse infiltrative lung disease. In this report we present two cases secondary to breast cancer; the diagnosis was made by means of transbronchial lung biopsy or postmortem examination. The goal of this study was to analyze the scintigraphic pattern of pulmonary perfusion performed with technetium-99m macroaggregated albumin (99mTc-MAA) in the hope of achieving improved recognition of PLC and its subsequent diagnosis. Upon admission, both patients underwent routine clinical exams followed by chest X-rays. The second patient also underwent CT examination, and both were ultimately examined using pulmonary perfusion scintigraphy with 99mTc-MAA. In the various exams performed, the most reliable and easily identified diagnostic finding turned out to be a characteristic 'fragmented' lung pattern revealed with the perfusion lung scan. Unfortunately, in both cases the patients' conditions rapidly worsened and death occurred shortly following scintigraphy. We were able to conclude that the recognition of the mentioned fragmented scintigraphic lung pattern may be useful in suspected PLC, whereas the nonspecific clinical presentation of this pathology makes diagnosis extremely difficult, with the most significant results being achieved through a comparison of scintigraphic and high resolution CT data.

Inflammatory myofibroblastic tumor of the lung with unique histological pattern and association with Sjögren's disease and systemic lupus erythematosus.

PubMed

Shlopov, Boris V; French, Samuel W

2011-10-01

Inflammatory myofibroblastic tumor (IMT) of the lung is a rare condition. Radiological properties and clinical presentation of this disease can mimic malignant process. We present a case of IMT of the lung in a 58 year old female patient with a single lung nodule. Tumor was unencapsulated, firm, and well circumscribed. Microscopically tumor had multinodular structure with single or multiple small blood vessels in the center of each nodule surrounded in circular pattern by connective tissue containing spindle cells embedded into the thick layers of extracellular matrix. Extracellular matrix was identified as type I and type III collagen fibrils embedded into type IV collagen and laminin. The tumor was surrounded by T-, B-lymphocytes and polyclonal plasma cells. Histological organization of this lesion's stromal component was unique, but cell composition was similar to inflammatory pseudotumor of the lung. In addition, tumor tissue sections exhibited strong positivity for IgG, weak positivity for IgA, 1Cq, but were negative for IgM, and C3. Mutational analysis of the EGFR, KRAS genes and ALK locus rearrangement were performed and did not reveal any mutations. This is the first report of an IMT associated with Sjögren's disease, systemic lupus erythematosus and Non-Hodgkin lymphoma developing in the lungs. Patient was clinically followed up for 18 months and no recurrence of the tumor observed. Copyright © 2011 Elsevier Inc. All rights reserved.

Retinal vascular changes in preterm infants: heart and lung diseases and plus disease.

PubMed

Arriola-Lopez, Andrea Elizabeth; Martinez-Perez, M Elena; Martinez-Castellanos, Maria Ana

2017-12-01

To report the retinal vascular features of preterm infants with congenital heart disease (CHD), lung disease (pulmonary hypertension [PH] and bronchopulmonary dysplasia [BPD]), and ROP with plus disease to determine whether these disease entities are distinguishable on the basis of retinal vessel morphology. The medical records of preterm infants with CHD, lung disease, and ROP with plus disease were reviewed retrospectively. Qualitative vascular findings were validated using computer-based software to analyze 25 representative images, each corresponding to one infant's eye. The images were organized into five groups, based on clinical information. Vessel diameter (d) and tortuosity index (TI) were measured. A total of 106 infants (mean gestational age, 30.5 ± 2.22 weeks) were initially included. Ophthalmologic evaluation of preterm infants with CHD and lung diseases showed vascular tortuosity without vasodilation at the posterior pole as well as in the periphery. Quantitative analysis showed that venular diameter was significantly increased in the plus disease group (P = 0.0022) compared to other groups. There was significantly less tortuosity in both arterioles and venules in BPD (P < 0.001, P = 0.0453) compared with plus group. The patterns of retinal vascular tortuosity observed in preterm infants may be unique to different systemic congestive conditions and could have therapeutic implications. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. 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.

Exhaled Aerosol Pattern Discloses Lung Structural Abnormality: A Sensitivity Study Using Computational Modeling and Fractal Analysis

PubMed Central

Xi, Jinxiang; Si, Xiuhua A.; Kim, JongWon; Mckee, Edward; Lin, En-Bing

2014-01-01

Background Exhaled aerosol patterns, also called aerosol fingerprints, provide clues to the health of the lung and can be used to detect disease-modified airway structures. The key is how to decode the exhaled aerosol fingerprints and retrieve the lung structural information for a non-invasive identification of respiratory diseases. Objective and Methods In this study, a CFD-fractal analysis method was developed to quantify exhaled aerosol fingerprints and applied it to one benign and three malign conditions: a tracheal carina tumor, a bronchial tumor, and asthma. Respirations of tracer aerosols of 1 µm at a flow rate of 30 L/min were simulated, with exhaled distributions recorded at the mouth. Large eddy simulations and a Lagrangian tracking approach were used to simulate respiratory airflows and aerosol dynamics. Aerosol morphometric measures such as concentration disparity, spatial distributions, and fractal analysis were applied to distinguish various exhaled aerosol patterns. Findings Utilizing physiology-based modeling, we demonstrated substantial differences in exhaled aerosol distributions among normal and pathological airways, which were suggestive of the disease location and extent. With fractal analysis, we also demonstrated that exhaled aerosol patterns exhibited fractal behavior in both the entire image and selected regions of interest. Each exhaled aerosol fingerprint exhibited distinct pattern parameters such as spatial probability, fractal dimension, lacunarity, and multifractal spectrum. Furthermore, a correlation of the diseased location and exhaled aerosol spatial distribution was established for asthma. Conclusion Aerosol-fingerprint-based breath tests disclose clues about the site and severity of lung diseases and appear to be sensitive enough to be a practical tool for diagnosis and prognosis of respiratory diseases with structural abnormalities. PMID:25105680

The Lung Microbiome, Immunity, and the Pathogenesis of Chronic Lung Disease.

PubMed

O'Dwyer, David N; Dickson, Robert P; Moore, Bethany B

2016-06-15

The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The microbiome of the lung has relatively less bacterial biomass when compared with the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration, and relative growth within its communities. Chronic lung disease alters these factors. Many forms of chronic lung disease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lung disease may reside in deciphering the complex interactions between the host, pathogen, and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships. Copyright © 2016 by The American Association of Immunologists, Inc.

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

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

PubMed

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

2009-01-01

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

Early interstitial lung disease in microscopic polyangiitis: Case report and literature review.

PubMed

García-Nava, Marcos; Mateos-Toledo, Heidegger; Guevara-Canseco, Ana Patricia Georgina; Infante-González, Cesar Eduardo; Reyes-Nava, Diego Alberto; Estrada-Castro, Emilio

Microscopic polyangiitis (MPA) is a systemic disease included in the Chapel Hill 2012 Classification as necrotizing vasculitis affecting capillaries, venules and arterioles. It usually expresses antineutrophil cytoplasmic antibodies (ANCA) and has a perinuclear immunofluorescence pattern and correlation with anti-myeloperoxidase (MPO) antibodies. Capillaritis with alveolar hemorrhage is the most common manifestation of lung disease. Interstitial lung disease (ILD) is uncommon, with usual interstitial pneumonia being the predominant pattern. However, other patterns such as organizing pneumonia have been described. No guidelines exist for treating patients with ILD and, currently, ANCA-associated vasculitis (AAV) is managed along the lines of small vessel vasculitis. The prognosis with this association is uncertain, with possibilities of relapse and a fatal outcome. We present a case in which ILD was the first manifestation of MPA, without alveolar hemorrhage, with subsequent renal involvement and, in which, the established treatment produced a significant clinical improvement. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Differential expression patterns of housekeeping genes increase diagnostic and prognostic value in lung cancer

PubMed Central

Chang, Yu-Chun; Ding, Yan; Dong, Lingsheng; Zhu, Lang-Jing; Jensen, Roderick V.

2018-01-01

Background Using DNA microarrays, we previously identified 451 genes expressed in 19 different human tissues. Although ubiquitously expressed, the variable expression patterns of these “housekeeping genes” (HKGs) could separate one normal human tissue type from another. Current focus on identifying “specific disease markers” is problematic as single gene expression in a given sample represents the specific cellular states of the sample at the time of collection. In this study, we examine the diagnostic and prognostic potential of the variable expressions of HKGs in lung cancers. Methods Microarray and RNA-seq data for normal lungs, lung adenocarcinomas (AD), squamous cell carcinomas of the lung (SQCLC), and small cell carcinomas of the lung (SCLC) were collected from online databases. Using 374 of 451 HKGs, differentially expressed genes between pairs of sample types were determined via two-sided, homoscedastic t-test. Principal component analysis and hierarchical clustering classified normal lung and lung cancers subtypes according to relative gene expression variations. We used uni- and multi-variate cox-regressions to identify significant predictors of overall survival in AD patients. Classifying genes were selected using a set of training samples and then validated using an independent test set. Gene Ontology was examined by PANTHER. Results This study showed that the differential expression patterns of 242, 245, and 99 HKGs were able to distinguish normal lung from AD, SCLC, and SQCLC, respectively. From these, 70 HKGs were common across the three lung cancer subtypes. These HKGs have low expression variation compared to current lung cancer markers (e.g., EGFR, KRAS) and were involved in the most common biological processes (e.g., metabolism, stress response). In addition, the expression pattern of 106 HKGs alone was a significant classifier of AD versus SQCLC. We further highlighted that a panel of 13 HKGs was an independent predictor of overall

Mitochondria in Lung Diseases

PubMed Central

Aravamudan, Bharathi; Thompson, Michael A.; Pabelick, Christina M.; Prakash, Y. S.

2014-01-01

Summary Mitochondria are autonomous cellular organelles that oversee a variety of functions such as metabolism, energy production, calcium buffering, and cell fate determination. Regulation of their morphology and diverse activities beyond energy production are being recognized as playing major roles in cellular health and dysfunction. This review is aimed at summarizing what is known regarding mitochondrial contributions to pathogenesis of lung diseases. Emphasis is given to understanding the importance of structural and functional aspects of mitochondria in both normal cellular function (based on knowledge from other cell types) and in development and modulation of lung diseases such as asthma, COPD, cystic fibrosis and cancer. Emerging techniques that allow examination of mitochondria, and potential strategies to target mitochondria in the treatment of lung diseases are also discussed. PMID:23978003

Intersections of lung progenitor cells, lung disease and lung cancer.

PubMed

Kim, Carla F

2017-06-30

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

Gastroesophageal reflux and lung disease.

PubMed

Meyer, Keith C

2015-08-01

Gastroesophageal reflux (GER) can cause respiratory symptoms and may trigger, drive and/or worsen airway disorders, interstitial lung diseases and lung allograft dysfunction. Whether lifestyle changes and acid suppression alone can counter and prevent the adverse effects of GER on the respiratory tract remains unclear. Recent data suggest that antireflux surgery may be more effective in preventing lung disease progression in patients with idiopathic pulmonary fibrosis or lung transplant recipients who have evidence of allograft dysfunction associated with the presence of excessive GER. Additional research and clinical trials are needed to determine the role of GER in various lung disorders and identify which interventions are most efficacious in preventing the respiratory consequences of gastroesophageal reflux disease. In addition, measuring biomarkers that indicate that gastric refluxate has been aspirated into the lower respiratory tract (e.g., pepsin and bile acid concentrations in bronchoalveolar lavage fluid) may prove helpful in both diagnosis and therapeutic decision making.

VARIATION OF LUNG DEPOSITION OF MICRON SIZE PARTICLES WITH LUNG VOLUME AND BREATHING PATTERN

EPA Science Inventory

Lung volume and breathing pattern are the source of inter-and intra-subject variability of lung deposition of inhaled particles. Controlling these factors may help optimize delivery of aerosol medicine to the target site within the lung. In the present study we measured total lu...

The Lung Microbiome, Immunity and the Pathogenesis of Chronic Lung Disease1

PubMed Central

O’Dwyer, David N.; Dickson, Robert P.; Moore, Bethany B.

2016-01-01

The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The microbiome of the lung has relatively less bacterial biomass when compared to the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration and relative growth within its communities. Chronic lung disease alters these factors. Many forms of chronic lung disease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lung disease may reside in deciphering the complex interactions between the host, pathogen and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships. PMID:27260767

Lung Manifestations in the Rheumatic Diseases.

PubMed

Doyle, Tracy J; Dellaripa, Paul F

2017-12-01

Lung ailments in rheumatic diseases present unique challenges for diagnosis and management and are a source of significant morbidity and mortality for patients. Unlike the idiopathic interstitial pneumonias, patients with rheumatic diseases experience lung disease in the context of a systemic disease that may make it more difficult to recognize and that may present greater risks with treatment. Despite recent advances in our awareness of these diseases, there is still a significant lack of understanding of natural history to elucidate which patients will have disease that is progressive and thus warrants treatment. What we do know is that a subset of patients with rheumatic disease experience parenchymal lung disease that can prognostically resemble idiopathic pulmonary fibrosis, such as in rheumatoid arthritis, and that others can have aggressive inflammatory lung disease in the context of autoimmune myositis, systemic sclerosis, or an undifferentiated autoimmune process. As we enter into a paradigm shift where we view lung health as a cornerstone of our care of patients with rheumatic diseases, we hopefully will improve our ability to identify those patients at highest risk for pulmonary disease and progression, and offer emerging treatments which will result in better outcomes and a better quality of life. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease.

PubMed

Kwon, Yong-Soo; Koh, Won-Jung

2016-05-01

Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed.

Right Ventricular Dysfunction in Chronic Lung Disease

PubMed Central

Kolb, Todd M.; Hassoun, Paul M.

2012-01-01

Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, except during acute exacerbations of chronic lung disease or when multiple co-morbidities are present. Treatment is targeted at correcting hypoxia and improving pulmonary gas exchange and mechanics. There are presently no convincing data to support the use of pulmonary hypertension-specific therapies in patients with right ventricular dysfunction secondary to chronic lung disease. PMID:22548815

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.

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

Meta-markers for the differential diagnosis of lung cancer and lung disease.

PubMed

Kim, Yong-In; Ahn, Jung-Mo; Sung, Hye-Jin; Na, Sang-Su; Hwang, Jaesung; Kim, Yongdai; Cho, Je-Yoel

2016-10-04

Misdiagnosis of lung cancer remains a serious problem due to the difficulty of distinguishing lung cancer from other respiratory lung diseases. As a result, the development of serum-based differential diagnostic biomarkers is in high demand. In this study, 198 clinical serum samples from non-cancer lung disease and lung cancer patients were analyzed using nLC-MRM-MS for the levels of seven lung cancer biomarker candidates. When the candidates were assessed individually, only SERPINEA4 showed statistically significant changes in the serum levels. The MRM results and clinical information were analyzed using a logistic regression analysis to select model for the best 'meta-marker', or combination of biomarkers for differential diagnosis. Also, under consideration of statistical interaction, variables having low significance as a single factor but statistically influencing on meta-marker model were selected. Using this probabilistic classification, the best meta-marker was determined to be made up of two proteins SERPINA4 and PON1 with age factor. This meta-marker showed an enhanced differential diagnostic capability (AUC=0.915) for distinguishing the two patient groups. Our results suggest that a statistical model can determine optimal meta-markers, which may have better specificity and sensitivity than a single biomarker and thus improve the differential diagnosis of lung cancer and lung disease patients. Diagnosing lung cancer commonly involves the use of radiographic methods. However, an imaging-based diagnosis may fail to differentiate lung cancer from non-cancerous lung disease. In this study, we examined several serum proteins in the sera of 198 lung cancer and non-cancerous lung disease patients by multiple-reaction monitoring. We then used a combination of variables to generate a meta-marker model that is useful as a differential diagnostic biomarker. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Lung disease

MedlinePlus

... cell cancer - CT scan Secondhand smoke and lung cancer Yellow nail syndrome Respiratory system References Kraft M. Approach to the patient with respiratory disease. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: ...

Associations between Dietary Patterns and Post-Bronchodilation Lung Function in the SAPALDIA Cohort.

PubMed

Steinemann, Nina; Grize, Leticia; Pons, Marco; Rothe, Thomas; Stolz, Daiana; Turk, Alexander; Schindler, Christian; Brombach, Christine; Probst-Hensch, Nicole

2018-05-04

Chronic obstructive pulmonary disease (COPD) is not restricted to smokers. Dietary habits may contribute to the disease occurrence. Epidemiological studies point to a protective effect of fruit and vegetable intake against COPD. To investigate the associations between dietary patterns and parameters of lung function related to COPD in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). Data were included from the second follow-up assessment of the SAPALDIA cohort in 2010-2011 using a food frequency questionnaire. Principal component factor analysis was used to derive dietary patterns, whose association with FEV1, FEV1/FVC, FEF2575, and COPD was investigated by applying multivariate regression analyses. After adjustment for potential confounders, the "prudent dietary pattern" characterised by the predominant food groups vegetables, fruits, water, tea and coffee, fish, and nuts was positively associated with FEV1 (increase of 40 mL per SD, p < 0.001). Also for factor 3 ("high-carbohydrate diet"), we found a significant positive association with FEV1 (with an increase per SD of 36 mL, p = 0.006). The main results are consistent with a protective effect of a diet rich in fruits, vegetables, fish, and nuts against age-related chronic respiratory disease. If confirmed in prospective cohorts, our results may guide nutritional counselling towards respiratory health promotion. © 2018 The Author(s) Published by S. Karger AG, Basel.

Multisource Transfer Learning With Convolutional Neural Networks for Lung Pattern Analysis.

PubMed

Christodoulidis, Stergios; Anthimopoulos, Marios; Ebner, Lukas; Christe, Andreas; Mougiakakou, Stavroula

2017-01-01

Early diagnosis of interstitial lung diseases is crucial for their treatment, but even experienced physicians find it difficult, as their clinical manifestations are similar. In order to assist with the diagnosis, computer-aided diagnosis systems have been developed. These commonly rely on a fixed scale classifier that scans CT images, recognizes textural lung patterns, and generates a map of pathologies. In a previous study, we proposed a method for classifying lung tissue patterns using a deep convolutional neural network (CNN), with an architecture designed for the specific problem. In this study, we present an improved method for training the proposed network by transferring knowledge from the similar domain of general texture classification. Six publicly available texture databases are used to pretrain networks with the proposed architecture, which are then fine-tuned on the lung tissue data. The resulting CNNs are combined in an ensemble and their fused knowledge is compressed back to a network with the original architecture. The proposed approach resulted in an absolute increase of about 2% in the performance of the proposed CNN. The results demonstrate the potential of transfer learning in the field of medical image analysis, indicate the textural nature of the problem and show that the method used for training a network can be as important as designing its architecture.

Childhood interstitial lung diseases: an 18-year retrospective analysis.

PubMed

Soares, Jennifer J; Deutsch, Gail H; Moore, Paul E; Fazili, Mohammad F; Austin, Eric D; Brown, Rebekah F; Sokolow, Andrew G; Hilmes, Melissa A; Young, Lisa R

2013-10-01

Childhood interstitial lung diseases (ILD) occur in a variety of clinical contexts. Advances in the understanding of disease pathogenesis and use of standardized terminology have facilitated increased case ascertainment. However, as all studies have been performed at specialized referral centers, the applicability of these findings to general pulmonary practice has been uncertain. The objective of this study was to determine the historical occurrence of childhood ILD to provide information reflecting general pediatric pulmonary practice patterns. Childhood ILD cases seen at Vanderbilt Children's Hospital from 1994 to 2011 were retrospectively reviewed and classified according to the current pediatric diffuse lung disease histopathologic classification system. A total of 93 cases were identified, of which 91.4% were classifiable. A total of 68.8% (64/93) of subjects underwent lung biopsy in their evaluations. The largest classification categories were disorders related to systemic disease processes (24.7%), disorders of the immunocompromised host (24.7%), and disorders more prevalent in infancy (22.6%). Eight cases of neuroendocrine cell hyperplasia of infancy (NEHI) were identified, including 5 that were previously unrecognized before this review. Our findings demonstrate the general scope of childhood ILD and that these cases present within a variety of pediatric subspecialties. Retrospective review was valuable in recognizing more recently described forms of childhood ILD. As a significant portion of cases were classifiable based on clinical, genetic, and/or radiographic criteria, we urge greater consideration to noninvasive diagnostic approaches and suggest modification to the current childhood ILD classification scheme to accommodate the increasing number of cases diagnosed without lung biopsy.

HOX Genes in Human Lung

PubMed Central

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

2001-01-01

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

Simultaneous Subcutaneous and Lung Hydatid Disease.

PubMed

Karaarslan, Kerem; Koçal, Sedat; Durgun Yetim, Tülin

2017-03-01

Hydatid disease is still endemic in Turkey. The most common site is the liver, followed by the lungs; it is rarely observed in the other parts of the body. In this case, right lung and subclavicular subcutaneous hydatid cysts were simultaneously observed. Cystotomy and capitonnage via minithoracotomy were applied for the cyst in the lung, and the subclavicular subcutaneous hydatid cyst was completely excised. Histopathological diagnosis was confirmed. Cystic lesions localized in the body except the liver and lung hydatid disease should always assessing kept in mind. It should not be forgotten that the cyst in the lung and liver may be detected simultaneously in other parts of the body.

Lung cancer in connective tissue disease-associated interstitial lung disease: clinical features and impact on outcomes.

PubMed

Watanabe, Satoshi; Saeki, Keigo; Waseda, Yuko; Murata, Akari; Takato, Hazuki; Ichikawa, Yukari; Yasui, Masahide; Kimura, Hideharu; Hamaguchi, Yasuhito; Matsushita, Takashi; Yamada, Kazunori; Kawano, Mitsuhiro; Furuichi, Kengo; Wada, Takashi; Kasahara, Kazuo

2018-02-01

Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.

Challenges in pulmonary fibrosis · 3: Cystic lung disease

PubMed Central

Cosgrove, Gregory P; Frankel, Stephen K; Brown, Kevin K

2007-01-01

Cystic lung disease is a frequently encountered problem caused by a diverse group of diseases. Distinguishing true cystic lung disease from other entities, such as cavitary lung disease and emphysema, is important given the differing prognostic implications. In this paper the features of the cystic lung diseases are reviewed and contrasted with their mimics, and the clinical and radiographic features of both diffuse (pulmonary Langerhans' cell histiocytosis and lymphangioleiomyomatosis) and focal or multifocal cystic lung disease are discussed. PMID:17726170

Gastroesophageal Reflux Disease in Children with Interstitial Lung Disease.

PubMed

Dziekiewicz, M A; Karolewska-Bochenek, K; Dembiński, Ł; Gawronska, A; Krenke, K; Lange, J; Banasiuk, M; Kuchar, E; Kulus, M; Albrecht, P; Banaszkiewicz, A

2016-01-01

Gastroesophageal reflux disease is common in adult patients with interstitial lung disease. However, no data currently exist regarding the prevalence and characteristics of the disease in pediatric patients with interstitial lung disease. The aim of the present study was to prospectively assess the incidence of gastroesophageal reflux disease and characterize its features in children with interstitial lung disease. Gastroesophageal reflux disease was established based on 24 h pH-impedance monitoring (MII-pH). Gastroesophageal reflux episodes (GERs) were classified according to widely recognized criteria as acid, weakly acid, weakly alkaline, or proximal. Eighteen consecutive patients (15 boys, aged 0.2-11.6 years) were enrolled in the study. Gastroesophageal reflux disease was diagnosed in a half (9/18) of children. A thousand GERs were detected by MII-pH (median 53.5; IQR 39.0-75.5). Of these, 585 (58.5 %) episodes were acidic, 407 (40.7 %) were weakly acidic, and eight (0.8 %) were weakly alkaline. There were 637 (63.7 %) proximal GERs. The patients in whom gastroesophageal reflux disease was diagnosed had a significantly higher number of proximal and total GERs. We conclude that the prevalence of gastroesophageal reflux disease in children with interstitial lung disease is high; thus, the disease should be considered regardless of presenting clinical symptoms. A high frequency of non-acid and proximal GERs makes the MII-pH method a preferable choice for the detection of reflux episodes in this patient population.

Toxic Inhalational Injury-Associated Interstitial Lung Disease in Children

PubMed Central

Lee, Eun; Seo, Ju-Hee; Kim, Hyung Young; Yu, Jinho; Jhang, Won-Kyoung; Park, Seong-Jong; Kwon, Ji-Won; Kim, Byoung-Ju; Do, Kyung-Hyun; Cho, Young Ah; Kim, Sun-A; Jang, Se Jin

2013-01-01

Interstitial lung disease in children (chILD) is a group of disorders characterized by lung inflammation and interstitial fibrosis. In the past recent years, we noted an outbreak of child in Korea, which is possibly associated with inhalation toxicity. Here, we report a series of cases involving toxic inhalational injury-associated chILD with bronchiolitis obliterans pattern in Korean children. This study included 16 pediatric patients confirmed by lung biopsy and chest computed tomography, between February 2006 and May 2011 at Asan Medical Center Children's Hospital. The most common presenting symptoms were cough and dyspnea. The median age at presentation was 26 months (range: 12-47 months), with high mortality (44%). Histopathological analysis showed bronchiolar destruction and centrilobular distribution of alveolar destruction by inflammatory and fibroproliferative process with subpleural sparing. Chest computed tomography showed ground-glass opacities and consolidation in the early phase and diffuse centrilobular nodular opacity in the late phase. Air leak with severe respiratory difficulty was associated with poor prognosis. Although respiratory chemicals such as humidifier disinfectants were strongly considered as a cause of this disease, further studies are needed to understand the etiology and pathophysiology of the disease to improve the prognosis and allow early diagnosis and treatment. PMID:23772158

Advances in the treatment of rheumatic interstitial lung disease.

PubMed

Vassallo, Robert; Thomas, Charles F

2004-05-01

Interstitial lung disease frequently complicates the rheumatic diseases. The purpose of this review is to outline recent advances and current concepts regarding the management of these interstitial lung diseases. Several histologic lesions cause interstitial lung disease in rheumatic diseases, including nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, lymphocytic interstitial pneumonia, desquamative interstitial pneumonia, and acute interstitial pneumonia. Although the relative frequency of occurrence of these histopathologic lesions is not definitively established, it seems that nonspecific interstitial pneumonia accounts for a large proportion of rheumatic disease-associated interstitial lung diseases. Although usual interstitial pneumonia generally responds poorly to corticosteroid therapy, other forms of interstitial pneumonia are often steroid responsive and have a more favorable long-term prognosis. Pulmonary hypertension is increasingly recognized as a complication of these interstitial lung diseases. Treatment of pulmonary hypertension in these patients provides clinical benefit and may suppress pulmonary inflammation and fibrosis. Lung transplantation is a treatment option for selected patients with severe pulmonary involvement and limited life expectancy. Interstitial lung disease is common in the rheumatic diseases, may be caused by a variety of lesions that respond differently to treatment, and may lead to the development of pulmonary hypertension. Whether the prognosis of interstitial lung disease associated with rheumatic disease is similar to that associated with the idiopathic interstitial pneumonias is not known. Treatment of these interstitial lung diseases should take into account the specific histologic lesion, the activity of the underlying rheumatic disease, and associated pulmonary hypertension, if present. The diagnosis of a rheumatic disease is no longer an absolute contraindication to lung

Cyclophosphamide for connective tissue disease-associated interstitial lung disease.

PubMed

Barnes, Hayley; Holland, Anne E; Westall, Glen P; Goh, Nicole Sl; Glaspole, Ian N

2018-01-03

-cyclophosphamide-containing therapies for at least six months, with follow-up of at least 12 months from the start of treatment. We imported studies identified by the search into a reference manager database. We retrieved the full-text versions of relevant studies, and two review authors independently extracted data. Primary outcomes were change in lung function (change in forced vital capacity (FVC) % predicted and diffusing capacity of the lung for carbon monoxide (DLCO) % predicted), adverse events, and health-related quality of life measures. Secondary outcomes included all-cause mortality, dyspnoea, cough, and functional exercise testing. When appropriate, we performed meta-analyses and subgroup analyses by severity of lung function, connective tissue disease diagnosis, and radiological pattern of fibrosis. We assessed the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and created 'Summary of findings' tables. We included in the analysis four trials with 495 participants (most with systemic sclerosis). We formed two separate comparisons: cyclophosphamide versus placebo (two trials, 195 participants) and cyclophosphamide versus mycophenolate (two trials, 300 participants). We found evidence to be of low quality, as dropout rates were high in the intervention groups, and as we noted a wide confidence interval around the effect with small differences, which affected the precision of results.The data demonstrates significant improvement in lung function with cyclophosphamide compared with placebo (post-treatment FVC % mean difference (MD) 2.83, 95% confidence interval (CI) 0.80 to 4.87; P = 0.006) but no significant difference in post-treatment DLCO (% MD -1.68, 95% CI -4.37 to 1.02; P = 0.22; two trials, 182 participants).Risk of adverse effects was increased in the cyclophosphamide treatment groups compared with the placebo groups, in particular, haematuria, leukopenia, and nausea, leading to a higher rate of withdrawal from cyclophosphamide

Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

PubMed

Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

2016-04-01

Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Update on flavoring-induced lung disease.

PubMed

Holden, Van K; Hines, Stella E

2016-03-01

Since the initial report of bronchiolitis obliterans in microwave popcorn workers, exposures to flavoring substances have been identified in a variety of food and flavor manufacturing facilities and in the consumer market. Attempts to decrease the risk of lung disease have included the use of flavoring substitutes; however, these chemicals may cause similar injury. This article reviews recent flavoring exposures and data on the pathogenesis, clinical characteristics, and surveillance of flavoring-induced lung disease. Diacetyl and 2,3-pentanedione exposures have occurred in food production facilities that make cookies, cereal, chocolate, and coffee. Airborne levels often exceed proposed occupational exposure limits. Cases of biopsy-proven bronchiolitis obliterans in heavy popcorn consumers have also been reported. New data demonstrate the presence of diacetyl and 2,3-pentanedione in flavored nicotine liquids used in electronic nicotine delivery systems. Diacetyl substitutes cause similar peri-bronchiolar fibrotic lesions in animal studies. Their use may continue to place workers at risk for flavoring-induced lung disease, which may present in forms beyond that of fixed airflow obstruction, contributing to delays in identifying and treating patients with flavoring-induced lung disease. Engineering controls, medical surveillance and personal protective equipment can limit flavorings exposure and risk for lung disease.

Bag-of-features approach for improvement of lung tissue classification in diffuse lung disease

NASA Astrophysics Data System (ADS)

Kato, Noriji; Fukui, Motofumi; Isozaki, Takashi

2009-02-01

Many automated techniques have been proposed to classify diffuse lung disease patterns. Most of the techniques utilize texture analysis approaches with second and higher order statistics, and show successful classification result among various lung tissue patterns. However, the approaches do not work well for the patterns with inhomogeneous texture distribution within a region of interest (ROI), such as reticular and honeycombing patterns, because the statistics can only capture averaged feature over the ROI. In this work, we have introduced the bag-of-features approach to overcome this difficulty. In the approach, texture images are represented as histograms or distributions of a few basic primitives, which are obtained by clustering local image features. The intensity descriptor and the Scale Invariant Feature Transformation (SIFT) descriptor are utilized to extract the local features, which have significant discriminatory power due to their specificity to a particular image class. In contrast, the drawback of the local features is lack of invariance under translation and rotation. We improved the invariance by sampling many local regions so that the distribution of the local features is unchanged. We evaluated the performance of our system in the classification task with 5 image classes (ground glass, reticular, honeycombing, emphysema, and normal) using 1109 ROIs from 211 patients. Our system achieved high classification accuracy of 92.8%, which is superior to that of the conventional system with the gray level co-occurrence matrix (GLCM) feature especially for inhomogeneous texture patterns.

Breathing pattern and chest wall volumes during exercise in patients with cystic fibrosis, pulmonary fibrosis and COPD before and after lung transplantation.

PubMed

Wilkens, H; Weingard, B; Lo Mauro, A; Schena, E; Pedotti, A; Sybrecht, G W; Aliverti, A

2010-09-01

Pulmonary fibrosis (PF), cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) often cause chronic respiratory failure (CRF). In order to investigate if there are different patterns of adaptation of the ventilatory pump in CRF, in three groups of lung transplant candidates with PF (n=9, forced expiratory volume in 1 s (FEV(1))=37+/-3% predicted, forced vital capacity (FVC)=32+/-2% predicted), CF (n=9, FEV(1)=22+/-3% predicted, FVC=30+/-3% predicted) and COPD (n=21, FEV(1)=21+/-1% predicted, FVC=46+/-2% predicted), 10 healthy controls and 16 transplanted patients, total and compartmental chest wall volumes were measured by opto-electronic plethysmography during rest and exercise. Three different breathing patterns were found during CRF in PF, CF and COPD. Patients with COPD were characterised by a reduced duty cycle at rest and maximal exercise (34+/-1%, p<0.001), while patients with PF and CF showed an increased breathing frequency (49+/-6 and 34+/-2/min, respectively) and decreased tidal volume (0.75+/-0.10 and 0.79+/-0.07 litres) (p<0.05). During exercise, end-expiratory chest wall and rib cage volumes increased significantly in patients with COPD and CF but not in those with PF. End-inspiratory volumes did not increase in CF and PF. The breathing pattern of transplanted patients was similar to that of healthy controls. There are three distinct patterns of CRF in patients with PF, CF and COPD adopted by the ventilatory pump to cope with the underlying lung disease that may explain why patients with PF and CF are prone to respiratory failure earlier than patients with COPD. After lung transplantation the chronic adaptations of the ventilatory pattern to advanced lung diseases are reversible and indicate that the main contributing factor is the lung itself rather than systemic effects of the disease.

[Estimation of pulmonary hypertension in lung and valvular heart diseases by perfusion lung scintigraphy].

PubMed

Fujii, T; Tanaka, M; Yazaki, Y; Kitabayashi, H; Koizumi, T; Kubo, K; Sekiguchi, M; Yano, K

1999-06-01

To estimate pulmonary hypertension, we measured postural differences in pulmonary blood flow for the lateral decubitus positions on perfusion lung scintigrams with Tc-99 m macro-aggregated albumin, applying the method devised by Tanaka et al (Eur J Nucl Med 17: 320-326, 1990). Utilizing a scintillation camera coupled to a minicomputer system, changes in the distribution of pulmonary blood flow caused by gravitational effects, namely, changes in the total count ratios for the right lung versus the left lung in the right and left lateral decubitus positions (R/L), were obtained for 44 patients with lung disease, 95 patients with valvular heart disease, and 23 normal subjects. Mean standard deviation in the R/L ratios was 3.09 +/- 1.28 for the normal subjects, 1.97 +/- 0.89 for the patients with lung disease, and 1.59 +/- 0.59 for the patients with valvular heart disease. The R/L ratios correlated with mean pulmonary arterial pressure and cardio-thoracic ratios in the lung disease and valvular heart disease groups, with pulmonary arteriolar resistance in the former, and with pulmonary capillary wedge pressure in the latter. Defining pulmonary hypertension (> 20 mmHg) as an R/L ratio of less than 1.81, which is the mean-1 standard deviation for normal subjects, the sensitivity and the specificity of the R/L ratio for the diagnosis of pulmonary hypertension were 62.9% and 76.2%, respectively, for the lung disease patients, and 80.3% and 61.8%, respectively, for the valvular heart disease patients. This method seems to be useful for the pathophysiologic evaluation of pulmonary perfusion in cases of lung disease and valvular heart disease.

Malfolded protein structure and proteostasis in lung diseases.

PubMed

Balch, William E; Sznajder, Jacob I; Budinger, Scott; Finley, Daniel; Laposky, Aaron D; Cuervo, Ana Maria; Benjamin, Ivor J; Barreiro, Esther; Morimoto, Richard I; Postow, Lisa; Weissman, Allan M; Gail, Dorothy; Banks-Schlegel, Susan; Croxton, Thomas; Gan, Weiniu

2014-01-01

Recent discoveries indicate that disorders of protein folding and degradation play a particularly important role in the development of lung diseases and their associated complications. The overarching purpose of the National Heart, Lung, and Blood Institute workshop on "Malformed Protein Structure and Proteostasis in Lung Diseases" was to identify mechanistic and clinical research opportunities indicated by these recent discoveries in proteostasis science that will advance our molecular understanding of lung pathobiology and facilitate the development of new diagnostic and therapeutic strategies for the prevention and treatment of lung disease. The workshop's discussion focused on identifying gaps in scientific knowledge with respect to proteostasis and lung disease, discussing new research advances and opportunities in protein folding science, and highlighting novel technologies with potential therapeutic applications for diagnosis and treatment.

Animal Models of Fibrotic Lung Disease

PubMed Central

Lawson, William E.; Oury, Tim D.; Sisson, Thomas H.; Raghavendran, Krishnan; Hogaboam, Cory M.

2013-01-01

Interstitial lung fibrosis can develop as a consequence of occupational or medical exposure, as a result of genetic defects, and after trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can develop in an idiopathic manner. The pathogenesis of each form of lung fibrosis remains poorly understood. They each result in a progressive loss of lung function with increasing dyspnea, and most forms ultimately result in mortality. To better understand the pathogenesis of lung fibrotic disorders, multiple animal models have been developed. This review summarizes the common and emerging models of lung fibrosis to highlight their usefulness in understanding the cell–cell and soluble mediator interactions that drive fibrotic responses. Recent advances have allowed for the development of models to study targeted injuries of Type II alveolar epithelial cells, fibroblastic autonomous effects, and targeted genetic defects. Repetitive dosing in some models has more closely mimicked the pathology of human fibrotic lung disease. We also have a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis. Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease. PMID:23526222

Global perspectives of emerging occupational and environmental lung diseases.

PubMed

Moitra, Subhabrata; Puri, Rajan; Paul, Devon; Huang, Yuh-Chin T

2015-03-01

New technologies continue to be introduced into the workplace and the environment. These novel technologies also bring in new hazards leading to evolving patterns of established occupational and environmental diseases, as well as novel conditions never before encountered. Many of these emerging conditions have appeared in media outlets or in the literature as case reports. These sentinel cases often serve as a warning sign for subsequent outbreaks. This review will discuss environmental and occupational lung diseases and exposures from a global perspective. These diseases and exposures include environmental exposure to asbestos and lung diseases, accelerated silicosis in sandblasting jean workers, coal worker's pneumoconiosis in surface coal miners, health effects of indoor air pollution from burning of biomass fuels and exposures to heavy metals and potential health effects from hydraulic fracturing (fracking). Other emerging conditions are also discussed, including smog in developing countries, sand storms in Asia and the Middle East and respiratory illnesses from nanoparticles and man-made fibres. Clinicians must remain vigilant for potential occupational and environmental exposures, especially when evaluating patients with unusual and unique presentation, so that occupational and environmental risk factors may be identified, and monitoring and preventive measures can be implemented early.

[Modern Views on Children's Interstitial Lung Disease].

PubMed

Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu

2015-01-01

Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article.

Mast cells in airway diseases and interstitial lung disease.

PubMed

Cruse, Glenn; Bradding, Peter

2016-05-05

Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease. Published by Elsevier B.V.

Interstitial lung disease

MedlinePlus

... for lung disease. These jobs include coal mining, sand blasting, and working on a ship. Treatment Treatment ... A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

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

Assessing the feasibility of a web-based registry for multiple orphan lung diseases: the Australasian Registry Network for Orphan Lung Disease (ARNOLD) experience.

PubMed

Casamento, K; Laverty, A; Wilsher, M; Twiss, J; Gabbay, E; Glaspole, I; Jaffe, A

2016-04-18

We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were sent regular emails between July 2009 and June 2014 requesting information on patients they had seen with any of 30 rare lung diseases. Prevalence rates were calculated using population statistics. Emails were sent to 649 Australian respiratory physicians and 65 in New Zealand. 231 (32.4%) physicians responded to emails a total of 1554 times (average 7.6 responses per physician). Prevalence rates of 30 rare lung diseases are reported. A multi-disease rare lung disease registry was implemented in the Australian and New Zealand health care settings that provided prevalence data on orphan lung diseases in this region but was limited by under reporting.

Classification algorithm of lung lobe for lung disease cases based on multislice CT images

NASA Astrophysics Data System (ADS)

Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Mishima, M.; Ohmatsu, H.; Tsuchida, T.; Eguchi, K.; Kaneko, M.; Moriyama, N.

2011-03-01

With the development of multi-slice CT technology, to obtain an accurate 3D image of lung field in a short time is possible. To support that, a lot of image processing methods need to be developed. In clinical setting for diagnosis of lung cancer, it is important to study and analyse lung structure. Therefore, classification of lung lobe provides useful information for lung cancer analysis. In this report, we describe algorithm which classify lungs into lung lobes for lung disease cases from multi-slice CT images. The classification algorithm of lung lobes is efficiently carried out using information of lung blood vessel, bronchus, and interlobar fissure. Applying the classification algorithms to multi-slice CT images of 20 normal cases and 5 lung disease cases, we demonstrate the usefulness of the proposed algorithms.

Fibred confocal fluorescence microscopy in the diagnosis of interstitial lung diseases.

PubMed

Meng, Peng; Tan, Gan Liang; Low, Su Ying; Takano, Angela; Ng, Yuen Li; Anantham, Devanand

2016-12-01

Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD. In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients' final diagnoses based on multi-disciplinary consensus. One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24-79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001). Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited.

A support vector machine classifier reduces interscanner variation in the HRCT classification of regional disease pattern in diffuse lung disease: Comparison to a Bayesian classifier

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

Chang, Yongjun; Lim, Jonghyuck; Kim, Namkug

2013-05-15

Purpose: To investigate the effect of using different computed tomography (CT) scanners on the accuracy of high-resolution CT (HRCT) images in classifying regional disease patterns in patients with diffuse lung disease, support vector machine (SVM) and Bayesian classifiers were applied to multicenter data. Methods: Two experienced radiologists marked sets of 600 rectangular 20 Multiplication-Sign 20 pixel regions of interest (ROIs) on HRCT images obtained from two scanners (GE and Siemens), including 100 ROIs for each of local patterns of lungs-normal lung and five of regional pulmonary disease patterns (ground-glass opacity, reticular opacity, honeycombing, emphysema, and consolidation). Each ROI was assessedmore » using 22 quantitative features belonging to one of the following descriptors: histogram, gradient, run-length, gray level co-occurrence matrix, low-attenuation area cluster, and top-hat transform. For automatic classification, a Bayesian classifier and a SVM classifier were compared under three different conditions. First, classification accuracies were estimated using data from each scanner. Next, data from the GE and Siemens scanners were used for training and testing, respectively, and vice versa. Finally, all ROI data were integrated regardless of the scanner type and were then trained and tested together. All experiments were performed based on forward feature selection and fivefold cross-validation with 20 repetitions. Results: For each scanner, better classification accuracies were achieved with the SVM classifier than the Bayesian classifier (92% and 82%, respectively, for the GE scanner; and 92% and 86%, respectively, for the Siemens scanner). The classification accuracies were 82%/72% for training with GE data and testing with Siemens data, and 79%/72% for the reverse. The use of training and test data obtained from the HRCT images of different scanners lowered the classification accuracy compared to the use of HRCT images from the same

Isolated lung transplantation for end-stage lung disease: a viable therapy.

PubMed

Egan, T M; Westerman, J H; Lambert, C J; Detterbeck, F C; Thompson, J T; Mill, M R; Keagy, B A; Paradowski, L J; Wilcox, B R

1992-04-01

Since January 1990, we have performed 29 isolated lung transplantations in 28 patients with end-stage lung disease (12 single, 16 bilateral). Recipient diagnoses were: cystic fibrosis (11), chronic obstructive pulmonary disease (6), pulmonary fibrosis (6), eosinophilic granulomatosis (1), postinfectious lung disease (1), adult respiratory distress syndrome (1), and primary pulmonary hypertension (2). There have been four deaths, two in patients with pulmonary fibrosis and two in patients with primary pulmonary hypertension. Four patients have undergone transplantation while on ventilatory support for respiratory failure (2 with cystic fibrosis, 1 having redo lung transplantation with cystic fibrosis, and 1 with adult respiratory distress syndrome); all of these have survived. Six patients required cardiopulmonary bypass, which was associated with increased transfusion requirement. All patients 2 months after discharge have returned to an active life-style, except for 2 patients who currently await retransplantation. Preoperative pulmonary rehabilitation has resulted in significant improvement in exercise performance in all patients. Immunosuppression consists of cyclosporine, azathioprine, and antilymphoblast globulin (University of Minnesota), withholding systemic steroids in the early postoperative period. We have employed bronchial omentopexy in all but four transplants; there has been one partial bronchial dehiscence, two instances of bronchomalacia requiring internal stenting, and one airway stenosis. Cytomegalovirus disease has been seen frequently (15 cases), but has responded well to treatment with ganciclovir. Other complication shave included one drug-related prolonged postoperative ventilation, thrombosis of a left lung after bilateral lung transplantation requiring retransplantation, five episodes of unilateral phrenic nerve palsy after bilateral lung transplantation (4 resolved), and the requirement of massive transfusion (greater than 10 units) in 5

Autoinflammatory disease in the lung.

PubMed

Scambler, Thomas; Holbrook, Jonathan; Savic, Sinisa; McDermott, Michael F; Peckham, Daniel

2018-04-19

Ascertaining the dominant cell type driving an immunological disease is essential to understanding the causal pathology and, therefore, selecting or developing an effective treatment. Classifying immunological diseases in this way has led to successful treatment regimens for many monogenic diseases; however, when the dominant cell type is unclear and there is no obvious causal genetic mutation, then identifying the correct disease classification and appropriate therapy can be challenging. In this review we focus on pulmonary immunological diseases where an innate immune signature has been identified as a predominant aspect of the immunopathology. We describe the molecular pathology of 'autoinflammatory diseases of the lung' and propose that small molecule and biological therapies, including recombinant interleukin-1 receptor antagonist, that target key innate immune pathways, are likely be beneficial in the control of pulmonary and systemic inflammation in these conditions. In addition, the successful use of macrolide antibiotics to treat lung infections in these conditions further confirms that the innate immune system is the key conductor of inflammation in these pulmonary diseases, as there is a strong body of evidence that macrolides are able to modulate the NLRP3 inflammasome and interleukin-1β and interleukin-18 secretion, both of which are central players in the innate immune response. Throughout this review we highlight the published evidence of autoinflammatory disease in chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis and rheumatoid lung disease and suggest that the fundamental pathology of these diseases places them towards the autoinflammatory pole of the immunological disease continuum. © 2018 John Wiley & Sons Ltd.

Blue Journal Conference. Aging and Susceptibility to Lung Disease

PubMed Central

Thannickal, Victor J.; Murthy, Mahadev; Balch, William E.; Chandel, Navdeep S.; Meiners, Silke; Eickelberg, Oliver; Selman, Moisés; Pardo, Annie; White, Eric S.; Levy, Bruce D.; Busse, Paula J.; Tuder, Rubin M.; Antony, Veena B.; Sznajder, Jacob I.

2015-01-01

The aging of the population in the United States and throughout the developed world has increased morbidity and mortality attributable to lung disease, while the morbidity and mortality from other prevalent diseases has declined or remained stable. Recognizing the importance of aging in the development of lung disease, the American Thoracic Society (ATS) highlighted this topic as a core theme for the 2014 annual meeting. The relationship between aging and lung disease was discussed in several oral symposiums and poster sessions at the annual ATS meeting. In this article, we used the input gathered at the conference to develop a broad framework and perspective to stimulate basic, clinical, and translational research to understand how the aging process contributes to the onset and/or progression of lung diseases. A consistent theme that emerged from the conference was the need to apply novel, systems-based approaches to integrate a growing body of genomic, epigenomic, transcriptomic, and proteomic data and elucidate the relationship between biologic hallmarks of aging, altered lung function, and increased susceptibility to lung diseases in the older population. The challenge remains to causally link the molecular and cellular changes of aging with age-related changes in lung physiology and disease susceptibility. The purpose of this review is to stimulate further research to identify new strategies to prevent or treat age-related lung disease. PMID:25590812

Detection and classification of interstitial lung diseases and emphysema using a joint morphological-fuzzy approach

NASA Astrophysics Data System (ADS)

Chang Chien, Kuang-Che; Fetita, Catalin; Brillet, Pierre-Yves; Prêteux, Françoise; Chang, Ruey-Feng

2009-02-01

Multi-detector computed tomography (MDCT) has high accuracy and specificity on volumetrically capturing serial images of the lung. It increases the capability of computerized classification for lung tissue in medical research. This paper proposes a three-dimensional (3D) automated approach based on mathematical morphology and fuzzy logic for quantifying and classifying interstitial lung diseases (ILDs) and emphysema. The proposed methodology is composed of several stages: (1) an image multi-resolution decomposition scheme based on a 3D morphological filter is used to detect and analyze the different density patterns of the lung texture. Then, (2) for each pattern in the multi-resolution decomposition, six features are computed, for which fuzzy membership functions define a probability of association with a pathology class. Finally, (3) for each pathology class, the probabilities are combined up according to the weight assigned to each membership function and two threshold values are used to decide the final class of the pattern. The proposed approach was tested on 10 MDCT cases and the classification accuracy was: emphysema: 95%, fibrosis/honeycombing: 84% and ground glass: 97%.

Malfolded Protein Structure and Proteostasis in Lung Diseases

PubMed Central

Balch, William E.; Sznajder, Jacob I.; Budinger, Scott; Finley, Daniel; Laposky, Aaron D.; Cuervo, Ana Maria; Benjamin, Ivor J.; Barreiro, Esther; Morimoto, Richard I.; Postow, Lisa; Weissman, Allan M.; Gail, Dorothy; Banks-Schlegel, Susan; Croxton, Thomas

2014-01-01

Recent discoveries indicate that disorders of protein folding and degradation play a particularly important role in the development of lung diseases and their associated complications. The overarching purpose of the National Heart, Lung, and Blood Institute workshop on “Malformed Protein Structure and Proteostasis in Lung Diseases” was to identify mechanistic and clinical research opportunities indicated by these recent discoveries in proteostasis science that will advance our molecular understanding of lung pathobiology and facilitate the development of new diagnostic and therapeutic strategies for the prevention and treatment of lung disease. The workshop's discussion focused on identifying gaps in scientific knowledge with respect to proteostasis and lung disease, discussing new research advances and opportunities in protein folding science, and highlighting novel technologies with potential therapeutic applications for diagnosis and treatment. PMID:24033344

Acute Exacerbation in Interstitial Lung Disease

PubMed Central

Leuschner, Gabriela; Behr, Jürgen

2017-01-01

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has been defined as an acute, clinically significant deterioration that develops within less than 1 month without obvious clinical cause like fluid overload, left heart failure, or pulmonary embolism. Pathophysiologically, damage of the alveoli is the predominant feature of AE-IPF which manifests histopathologically as diffuse alveolar damage and radiologically as diffuse, bilateral ground-glass opacification on high-resolution computed tomography. A growing body of literature now focuses on acute exacerbations of interstitial lung disease (AE-ILD) other than idiopathic pulmonary fibrosis. Based on a shared pathophysiology it is generally accepted that AE-ILD can affect all patients with interstitial lung disease (ILD) but apparently occurs more frequently in patients with an underlying usual interstitial pneumonia pattern. The etiology of AE-ILD is not fully understood, but there are distinct risk factors and triggers like infection, mechanical stress, and microaspiration. In general, AE-ILD has a poor prognosis and is associated with a high mortality within 6–12 months. Although there is a lack of evidence based data, in clinical practice, AE-ILD is often treated with a high dose corticosteroid therapy and antibiotics. This article aims to provide a summary of the clinical features, diagnosis, management, and prognosis of AE-ILD as well as an update on the current developments in the field. PMID:29109947

Peripleural lung disease detection based on multi-slice CT images

NASA Astrophysics Data System (ADS)

Matsuhiro, M.; Suzuki, H.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.

2015-03-01

With the development of multi-slice CT technology, obtaining accurate 3D images of lung field in a short time become possible. To support that, a lot of image processing methods need to be developed. Detection peripleural lung disease is difficult due to its existence out of lung region, because lung extraction is often performed based on threshold processing. The proposed method uses thoracic inner region extracted by inner cavity of bone as well as air region, covers peripleural lung diseased cases such as lung nodule, calcification, pleural effusion and pleural plaque. We applied this method to 50 cases including 39 peripleural lung diseased cases. This method was able to detect 39 peripleural lung disease with 2.9 false positive per case.

Fibred confocal fluorescence microscopy in the diagnosis of interstitial lung diseases

PubMed Central

Meng, Peng; Low, Su Ying; Takano, Angela; Ng, Yuen Li; Anantham, Devanand

2016-01-01

Background Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD. Methods In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients’ final diagnoses based on multi-disciplinary consensus. Results One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24–79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001). Conclusions Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited. PMID:28149543

Pleural mesothelial cells in pleural and lung diseases

PubMed Central

Antony, Veena B.

2015-01-01

During development, the mesoderm maintains a complex relationship with the developing endoderm giving rise to the mature lung. Pleural mesothelial cells (PMCs) derived from the mesoderm play a key role during the development of the lung. The pleural mesothelium differentiates to give rise to the endothelium and smooth muscle cells via epithelial-to-mesenchymal transition (EMT). An aberrant recapitulation of such developmental pathways can play an important role in the pathogenesis of disease processes such as idiopathic pulmonary fibrosis (IPF). The PMC is the central component of the immune responses of the pleura. When exposed to noxious stimuli, it demonstrates innate immune responses such as Toll-like receptor (TLR) recognition of pathogen associated molecular patterns as well as causes the release of several cytokines to activate adaptive immune responses. Development of pleural effusions occurs due to an imbalance in the dynamic interaction between junctional proteins, n-cadherin and β-catenin, and phosphorylation of adherens junctions between PMCs, which is caused in part by vascular endothelial growth factor (VEGF) released by PMCs. PMCs play an important role in defense mechanisms against bacterial and mycobacterial pleural infections, and in pathogenesis of malignant pleural effusion, asbestos related pleural disease and malignant pleural mesothelioma. PMCs also play a key role in the resolution of inflammation, which can occur with or without fibrosis. Fibrosis occurs as a result of disordered fibrin turnover and due to the effects of cytokines such as transforming growth factor-β, platelet-derived growth factor (PDGF), and basic fibroblast growth factor; which are released by PMCs. Recent studies have demonstrated a role for PMCs in the pathogenesis of IPF suggesting their potential as a cellular biomarker of disease activity and as a possible therapeutic target. Pleural-based therapies targeting PMCs for treatment of IPF and other lung diseases need

Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

PubMed

Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

2009-06-01

Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; p<0.01) and among patients with severe motor dysfunction (90% vs. 35%; p<0.001). Although we were not able to prove a causal relationship between esophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

Women's Health and Lung Development and Disease.

PubMed

Kocurek, Emily G; Hemnes, Anna R

2016-06-01

Although the lung is not traditionally thought of as an organ affected by sex-based differences, emerging literature elucidates major differences between men and women in the development, physiology, and predilection to and outcomes in lung diseases. These differences are driven by both differences in sex hormones and differences in environmental exposures. However, in many cases the underlying etiology of these sex- and gender-based differences is unknown. This article outlines the state-of-the-art knowledge on the etiology of sex differences in lung disease, including differences in lung development and physiology, and reviews therapy recommendations that are sex based. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic hypersensitivity pneumonitis: important considerations in the work-up of this fibrotic lung disease.

PubMed

Glazer, Craig S

2015-03-01

Chronic hypersensitivity pneumonitis is increasingly recognized as an important mimic of other fibrotic lung diseases. This review will summarize recent data regarding the importance and difficulty of determining causative exposures both for accurate diagnosis and prognosis, and describe the expanded pathologic spectrum of the disease, the effects of fibrosis on prognosis and challenges in the diagnostic evaluation. Several recent publications show the potential pathologic patterns induced by chronic hypersensitivity pneumonitis are broader than the classic triad of bronchiolitis, interstitial infiltrates and granulomas. Other pathologic patterns include nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, bronchiolitis and airway centric fibrosis. Detecting a causative antigen in fibrotic hypersensitivity pneumonitis is challenging but critically important both for accurate diagnosis and improved prognosis. The prognosis in hypersensitivity pneumonitis worsens in the presence of fibrosis, but it remains significantly better than idiopathic pulmonary fibrosis. Hypersensitivity pneumonitis is increasingly recognized as an important cause of fibrotic interstitial lung disease. Hypersensitivity pneumonitis demonstrates a remarkable tendency to mimic other idiopathic interstitial pneumonias. A detailed exposure history remains a cornerstone of diagnosis and management.

Stem cell treatment for chronic lung diseases.

PubMed

Tzouvelekis, Argyris; Ntolios, Paschalis; Bouros, Demosthenes

2013-01-01

Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. In view of the current disappointing status of available pharmaceutical agents, there is an urgent need for alternative more effective therapeutic approaches that will not only help to relieve patient symptoms but will also affect the natural course of the respective disease. Regenerative medicine represents a promising option with several fruitful therapeutic applications in patients suffering from chronic lung diseases. Nevertheless, despite relative enthusiasm arising from experimental data, application of stem cell therapy in the clinical setting has been severely hampered by several safety concerns arising from the major lack of knowledge on the fate of exogenously administered stem cells within chronically injured lung as well as the mechanisms regulating the activation of resident progenitor cells. On the other hand, salient data arising from few 'brave' pilot investigations of the safety of stem cell treatment in chronic lung diseases seem promising. The main scope of this review article is to summarize the current state of knowledge regarding the application status of stem cell treatment in chronic lung diseases, address important safety and efficacy issues and present future challenges and perspectives. In this review, we argue in favor of large multicenter clinical trials setting realistic goals to assess treatment efficacy. We propose the use of biomarkers that reflect clinically inconspicuous alterations of the disease molecular phenotype before rigid conclusions can be safely drawn. Copyright © 2013 S. Karger AG, Basel.

Lung Ultrasound Pattern Is Normal during the Last Gestational Weeks: An Observational Pilot Study.

PubMed

Arbeid, Erik; Demi, Alessio; Brogi, Etrusca; Gori, Elisa; Giusto, Teresa; Soldati, Gino; Vetrugno, Luigi; Giunta, Francesco; Forfori, Francesco

2017-01-01

The normal lung ultrasound (US) pattern during a regular pregnancy has not been evaluated extensively in the current literature. Pregnancy-related changes in the respiratory tract affect maternal predisposition to several respiratory complications; consequently, it is important to differentiate between a physiologic pattern during pregnancy and a pathologic lung pattern, due to respiratory failure. The goal of our study was to assess the normal US lung pattern in women without known comorbidities in the last weeks of pregnancy. We conducted a prospective cross-sectional observational pilot study. Chest wall was examined in 8 areas, 1 scan for each area with women in supine position. One hundred fifty parturients were enrolled during the 36th-38th gestational weeks. None of the participants showed pleural effusion, pneumothorax or lung consolidation. None presented an interstitial syndrome US pattern. One hundred thirteen participants out of 150 (75%) showed A-lines in all the regions. The remaining 25% showed 1 or 2 B-lines in at least 3 regions. Only 2 participants showed 2 positive regions also. We found that, in the majority of the women examined, the lung US pattern matches the physiological pattern in non-pregnant patients. Lung US assessment is a feasible and a helpful diagnostic tool during pregnancy. © 2016 S. Karger AG, Basel.

Heritability of Lung Disease Severity in Cystic Fibrosis

PubMed Central

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

2007-01-01

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

The airway microbiota in early cystic fibrosis lung disease.

PubMed

Frayman, Katherine B; Armstrong, David S; Grimwood, Keith; Ranganathan, Sarath C

2017-11-01

Infection plays a critical role in the pathogenesis of cystic fibrosis (CF) lung disease. Over the past two decades, the application of molecular and extended culture-based techniques to microbial analysis has changed our understanding of the lungs in both health and disease. CF lung disease is a polymicrobial disorder, with obligate and facultative anaerobes recovered alongside traditional pathogens in varying proportions, with some differences observed to correlate with disease stage. While healthy lungs are not sterile, differences between the lower airway microbiota of individuals with CF and disease-controls are already apparent in childhood. Understanding the evolution of the CF airway microbiota, and its relationship with clinical treatments and outcome at each disease stage, will improve our understanding of the pathogenesis of CF lung disease and potentially inform clinical management. This review summarizes current knowledge of the early development of the respiratory microbiota in healthy children and then discusses what is known about the airway microbiota in individuals with CF, including how it evolves over time and where future research priorities lie. © 2017 Wiley Periodicals, Inc.

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.

CT in the diagnosis of interstitial lung disease

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

Bergin, C.J.; Mueller, N.L.

1985-09-01

The computed tomographic (CT) appearance of interstitial lung disease was assessed in 23 patients with known interstitial disease. These included seven patients with fibrosing alveolitis, six with silicosis, two with hypersensitivity pneumonitis, three with lymphangitic spread of tumor, two with sarcoidosis, one with rheumatoid lung disease, and two with neurofibromatosis. The CT appearance of the interstitial changes in the different disease entities was assessed. Nodules were a prominent CT feature in silicosis, sarcoidosis, and lymphangitic spread of malignancy. Distribution of nodules and associated interlobular septal thickening provided further distinguishing features in these diseases. Reticular densities were the predominant CT changemore » in fibrosing alveolitis, rheumatoid lung disease, and extrinsic allergic alveolitis. CT can be useful in the investigation of selected instances of interstitial pulmonary disease.« less

Sex Differences and Sex Steroids in Lung Health and Disease

PubMed Central

Townsend, Elizabeth A.; Miller, Virginia M.

2012-01-01

Sex differences in the biology of different organ systems and the influence of sex hormones in modulating health and disease are increasingly relevant in clinical and research areas. Although work has focused on sex differences and sex hormones in cardiovascular, musculoskeletal, and neuronal systems, there is now increasing clinical evidence for sex differences in incidence, morbidity, and mortality of lung diseases including allergic diseases (such as asthma), chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, as well as pulmonary hypertension. Whether such differences are inherent and/or whether sex steroids play a role in modulating these differences is currently under investigation. The purpose of this review is to define sex differences in lung structure/function under normal and specific disease states, with exploration of whether and how sex hormone signaling mechanisms may explain these clinical observations. Focusing on adult age groups, the review addresses the following: 1) inherent sex differences in lung anatomy and physiology; 2) the importance of certain time points in life such as puberty, pregnancy, menopause, and aging; 3) expression and signaling of sex steroid receptors under normal vs. disease states; 4) potential interplay between different sex steroids; 5) the question of whether sex steroids are beneficial or detrimental to the lung; and 6) the potential use of sex steroid signaling as biomarkers and therapeutic avenues in lung diseases. The importance of focusing on sex differences and sex steroids in the lung lies in the increasing incidence of lung diseases in women and the need to address lung diseases across the life span. PMID:22240244

[New toxicity of fotemustine: diffuse interstitial lung disease].

PubMed

Bertrand, M; Wémeau-Stervinou, L; Gauthier, S; Auffret, M; Mortier, L

2012-04-01

Fotemustine is an alkylating cytostatic drug belonging to the nitrosourea family and is used in particular in the treatment of disseminated malignant melanoma. Herein, we report a case of interstitial lung disease associated with fotemustine. An 81-year-old man treated with fotemustine for metastatic melanoma presented acute interstitial lung disease 20 days after a fourth course of fotemustine monotherapy. The condition regressed spontaneously, with the patient returning to the clinical, radiological and blood gas status that had preceded fotemustine treatment. After other potential aetiologies had been ruled out, acute fotemustine-induced lung toxicity was considered and this treatment was definitively withdrawn. Other cytostatic agents belonging to the nitrosourea family can cause similar pictures, with a number of cases of interstitial lung disease thus being ascribed to fotemustine and dacarbazine. To our knowledge, this is the first case of interstitial lung disease induced by fotemustine monotherapy. This diagnosis should be considered where respiratory signs appear in melanoma patients undergoing fotemustine treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Radiation-induced heart disease in lung cancer radiotherapy

PubMed Central

Ming, Xin; Feng, Yuanming; Yang, Chengwen; Wang, Wei; Wang, Ping; Deng, Jun

2016-01-01

Abstract Background: Radiation-induced heart disease (RIHD), which affects the patients’ prognosis with both acute and late side effects, has been published extensively in the radiotherapy of breast cancer, lymphoma and other benign diseases. Studies on RIHD in lung cancer radiotherapy, however, are less extensive and clear even though the patients with lung cancer are delivered with higher doses to the heart during radiation treatment. Methods: In this article, after extensive literature search and analysis, we reviewed the current evidence on RIHD in lung cancer patients after their radiation treatments and investigated the potential risk factors for RIHD as compared to other types of cancers. Result: Cardiac toxicity has been found highly relevant in lung cancer radiotherapy. So far, the crude incidence of cardiac complications in the lung cancer patients after radiotherapy has been up to 33%. Conclusion: The dose to the heart, the lobar location of tumor, the treatment modality, the history of heart and pulmonary disease and smoking were considered as potential risk factors for RIHD in lung cancer radiotherapy. As treatment techniques improve over the time with better prognosis for lung cancer survivors, an improved prediction model can be established to further reduce the cardiac toxicity in lung cancer radiotherapy. PMID:27741117

Discharge and aftercare in chronic lung disease of the newborn.

PubMed

Primhak, R A

2003-04-01

This article deals with the discharge planning and continuing care of babies with chronic lung disease of the newborn (CLD), especially those with a continuing oxygen requirement, with some reference to longer term outcome. The pattern of CLD has changed since early descriptions, and the most useful definition for persisting morbidity in a baby with lung disease is a continuing oxygen requirement beyond 36 weeks post-menstrual age. Long-term oxygen therapy to maintain oxygen saturation at a mean of 95% or more and prevent levels below 90% is the cornerstone of management, and with adequate oxygen therapy the excess mortality previously reported in CLD can largely be avoided. Care must be given to the method of assessing oxygen saturation: overnight monitoring using appropriate recording devices is recommended. Exposure to respiratory viruses should be minimized where possible. Metabolic requirements are increased, but if efforts are made to maintain adequate energy input the long-term outlook for catch-up growth in height is good. Respiratory morbidity is increased in early life, but this improves in later childhood, along with lung function and exercise tolerance. Although respiratory symptoms should be treated as they arise, there is no evidence for long-term benefit from any pharmacological intervention in CLD.

Electronic Nose for Identification of Lung Diseases

NASA Astrophysics Data System (ADS)

Ogorodnik, V.; Kleperis, J.; Taivans, I.; Jurka, N.; Bukovskis, M.

2008-01-01

In the paper, the authors analyze the preliminary results of testing a classical gas sensing instrument - the electronic nose (a metal oxide transistor sensor of chemical substances) in a hospital where patients with different lung diseases are treated. To reveal the correlation between the amplitudes of the sensor's responses and the patients' diagnoses, different statistical analysis methods have been used. It is shown that the lung cancer can easily be discriminated from other lung diseases if short breath sampling and analysis time (less than 1 min) is used in the test. Volatiles obtained from a breath sample of a patient with lung cancer give the major contribution to the responses of different e-nose sensors, so in these cases highly precise identification could be achieved.

The lung in rheumatoid arthritis - focus on interstitial lung disease.

PubMed

Spagnolo, Paolo; Lee, Joyce C; Sverzellati, Nicola; Rossi, Giulio; Cottin, Vincent

2018-05-27

Interstitial lung disease (ILD) is an increasingly recognized complication of rheumatoid arthritis (RA) and is associated with significant morbidity and mortality. In addition, approximately one-third of patients have subclinical disease with varying degrees of functional impairment. While risk factors for RA-ILD are well established (e.g., older age, male gender, ever smoking history and seropositivity to rheumatoid factor and anti-cyclic citrullinated peptide antibodies) little is known about optimal disease assessment, treatment and monitoring, particularly in patients with progressive disease. Patients with RA-ILD are also at high risk of infection and drug toxicity, which, along with comorbidities, complicate further treatment decision making. There are distinct histopathologic patterns of RA-ILD with different clinical phenotypes, natural history and prognosis. Of these, the usual interstitial pneumonia (UIP) subtype of RA-ILD shares a number of clinical and histopathologic features with idiopathic pulmonary fibrosis (IPF), the most common and severe of the idiopathic interstitial pneumonias, suggesting the existence of common mechanistic pathways and possibly therapeutic targets. There remain substantial gaps in our knowledge of RA-ILD. Concerted multinational effort of expert centres has the potential to elucidate the basic mechanisms underlying RA-UIP and other subtypes of RA-ILD and facilitate the development of more efficacious and safer drugs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Reflux and Lung Disease

MedlinePlus

... Serving Size vs Portion Size Healthy Snacking Bone Health Taking Multivitamins Shortness of Breath and Eating Steroids and Nutrition Proper Hydration Reflux and Lung Disease Sodium Dangers Plant-Based Diets Why Breakfast Matters No Thanks Patients & Visitors Giving ...

Patterns of Care for Lung Cancer in Radiation Oncology Departments of Turkey

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

Demiral, Ayse Nur; Alicikus, Zuemre Arican; Isil Ugur, Vahide

2008-12-01

Purpose: To determine the patterns of care for lung cancer in Turkish radiation oncology centers. Methods and Materials: Questionnaire forms from 21 of 24 (87.5%) centers that responded were evaluated. Results: The most frequent histology was non-small cell lung cancer (NSCLC) (81%). The most common postoperative radiotherapy (RT) indications were close/(+) surgical margins (95%) and presence of pN2 disease (91%). The most common indications for postoperative chemotherapy (CHT) were '{>=} IB' disease (19%) and the presence of pN2 disease (19%). In Stage IIIA potentially resectable NSCLC, the most frequent treatment approach was neoadjuvant concomitant chemoradiotherapy (CHRT) (57%). In Stage IIIAmore » unresectable and Stage IIIB disease, the most frequent approach was definitive concomitant CHRT (91%). In limited SCLC, the most common treatment approach was concomitant CHRT with cisplatin+etoposide for cycles 1-3, completion of CHT to cycles 4-6, and finally prophylactic cranial irradiation in patients with complete response (71%). Six cycles of cisplatin + etoposide CHT and palliative thoracic RT, when required, was the most commonly used treatment (81%) in extensive SCLC. Sixty-two percent of centers did not have endobronchial brachytherapy (EBB) facilities. Conclusion: There is great variation in diagnostic testing, treatment strategies, indications for postoperative RT and CHT, RT features, and EBB availability for LC cases. To establish standards, national guidelines should be prepared using a multidisciplinary approach.« less

Profiles of chronic obstructive lung disease: characteristics of stable chronic obstructive lung disease in different parts of Asia.

PubMed

Bhome, Arvind B; Brashier, Bill

2014-03-01

This review discusses the recent Asian chronic obstructive lung disease (COPD) studies that characterize stable COPD, to understand its peculiarities. Asian research has improved our understanding of COPD. Household air pollution (HAP) is as important as smoking. Smoking in Asia is varied, and noncigarette smoking exposure remains under-investigated. Prevalence studies are often questionnaire based. Spirometry-based prevalence needs study. Burden of obstructive lung disease studies are getting published. Female COPD in Asia is predominantly HAP induced. The patients are underweight, milder 'Global Initiative for Obstructive Lung Disease- class' and have compromised health-related quality of life often with depression and anxiety, but other comorbidities do occur and are getting defined.Nonsmokers' COPD is often associated with small airway thickening, less emphysema, but considerable morbidity. Asian COPD may have an eosinophilic component, but its significance is unknown. There is genetic predisposition among some Asians to COPD, and among some patients to lung cancer. The emerging pandemic of lifestyle diseases demands that metabolic and cardiovascular comorbidities in COPD need investigation. COPD in Asia is increasing and burdensome. It is affecting both sexes; is caused by HAP as much as smoking; causes poor quality of life and intense psychological burden; and is associated with unique patho-physiology, which will require research and action.

Episodes of breathlessness: types and patterns - a qualitative study exploring experiences of patients with advanced diseases.

PubMed

Simon, Steffen T; Higginson, Irene J; Benalia, Hamid; Gysels, Marjolein; Murtagh, Fliss Em; Spicer, James; Bausewein, Claudia

2013-06-01

Despite the high prevalence and impact of episodic breathlessness, information about characteristics and patterns is scarce. To explore the experience of patients with advanced disease suffering from episodic breathlessness, in order to describe types and patterns. Qualitative design using in-depth interviews with patients suffering from advanced stages of chronic heart failure, chronic obstructive pulmonary disease, lung cancer or motor neurone disease. As part of the interviews, patients were asked to draw a graph to illustrate typical patterns of breathlessness episodes. Interviews were tape-recorded, transcribed verbatim and analysed using Framework Analysis. The graphs were grouped according to their patterns. Fifty-one participants (15 chronic heart failure, 14 chronic obstructive pulmonary disease, 13 lung cancer and 9 motor neurone disease) were included (mean age 68.2 years, 30 of 51 men, mean Karnofsky 63.1, mean breathlessness intensity 3.2 of 10). Five different types of episodic breathlessness were described: triggered with normal level of breathlessness, triggered with predictable response (always related to trigger level, e.g. slight exertion causes severe breathlessness), triggered with unpredictable response (not related to trigger level), non-triggered attack-like (quick onset, often severe) and wave-like (triggered or non-triggered, gradual onset). Four patterns of episodic breathlessness could be identified based on the graphs with differences regarding onset and recovery of episodes. These did not correspond with the types of breathlessness described before. Patients with advanced disease experience clearly distinguishable types and patterns of episodic breathlessness. The understanding of these will help clinicians to tailor specific management strategies for patients who suffer from episodes of breathlessness.

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

Radiomics-based differentiation of lung disease models generated by polluted air based on X-ray computed tomography data.

PubMed

Szigeti, Krisztián; Szabó, Tibor; Korom, Csaba; Czibak, Ilona; Horváth, Ildikó; Veres, Dániel S; Gyöngyi, Zoltán; Karlinger, Kinga; Bergmann, Ralf; Pócsik, Márta; Budán, Ferenc; Máthé, Domokos

2016-02-11

Lung diseases (resulting from air pollution) require a widely accessible method for risk estimation and early diagnosis to ensure proper and responsive treatment. Radiomics-based fractal dimension analysis of X-ray computed tomography attenuation patterns in chest voxels of mice exposed to different air polluting agents was performed to model early stages of disease and establish differential diagnosis. To model different types of air pollution, BALBc/ByJ mouse groups were exposed to cigarette smoke combined with ozone, sulphur dioxide gas and a control group was established. Two weeks after exposure, the frequency distributions of image voxel attenuation data were evaluated. Specific cut-off ranges were defined to group voxels by attenuation. Cut-off ranges were binarized and their spatial pattern was associated with calculated fractal dimension, then abstracted by the fractal dimension -- cut-off range mathematical function. Nonparametric Kruskal-Wallis (KW) and Mann-Whitney post hoc (MWph) tests were used. Each cut-off range versus fractal dimension function plot was found to contain two distinctive Gaussian curves. The ratios of the Gaussian curve parameters are considerably significant and are statistically distinguishable within the three exposure groups. A new radiomics evaluation method was established based on analysis of the fractal dimension of chest X-ray computed tomography data segments. The specific attenuation patterns calculated utilizing our method may diagnose and monitor certain lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, tuberculosis or lung carcinomas.

Proceedings: Regenerative Medicine for Lung Diseases: A CIRM Workshop Report.

PubMed

Kadyk, Lisa C; DeWitt, Natalie D; Gomperts, Brigitte

2017-10-01

The mission of the California Institute of Regenerative Medicine (CIRM) is to accelerate treatments to patients with unmet medical needs. In September 2016, CIRM sponsored a workshop held at the University of California, Los Angeles, to discuss regenerative medicine approaches for treatment of lung diseases and to identify the challenges remaining for advancing such treatments to the clinic and market approval. Workshop participants discussed current preclinical and clinical approaches to regenerative medicine in the lung, as well as the biology of lung stem cells and the role of stem cells in the etiology of various lung diseases. The outcome of this effort was the recognition that whereas transient cell delivery approaches are leading the way in the clinic, recent advances in the understanding of lung stem cell biology, in vitro and in vivo disease modeling, gene editing and replacement methods, and cell engraftment approaches raise the prospect of developing cures for some lung diseases in the foreseeable future. In addition, advances in in vitro modeling using lung organoids and "lung on a chip" technology are setting the stage for high quality small molecule drug screening to develop treatments for lung diseases with complex biology. Stem Cells Translational Medicine 2017;6:1823-1828. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Unusual progression and subsequent improvement in cystic lung disease in a child with radiation-induced lung injury

PubMed Central

Wolf, Michael S.; Chadha, Ashley D.; Carroll, Clinton M.; Borinstein, Scott C.

2014-01-01

Radiation-induced lung disease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lung disease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lung disease, with subsequent improvement, is striking and has not been previously described in children. PMID:25434733

[Work capacity evaluation in nonspecific lung diseases in a polyclinic section for lung diseases and tuberculosis].

PubMed

Herlík, J; Kos, S

1991-01-01

Describing the structure of a chest clinic in a large city requirements for a high level on the field of medical assessing in patients with non-specific lung diseases are formulated. 1. It must be sure, that all patients suffering from lung diseases are referred to a pneumologist. 2. Opportunities for optimal diagnosis must be given (knowledge and experiences of physicians and nurses; medical equipments of a high technical standard). 3. A scientific-based treatment must be guaranteed. Under optimal conditions it is possible to shorten the duration of disablement and to avoid the hospitalization in some cases.

Current and new challenges in occupational lung diseases.

PubMed

De Matteis, Sara; Heederik, Dick; Burdorf, Alex; Colosio, Claudio; Cullinan, Paul; Henneberger, Paul K; Olsson, Ann; Raynal, Anne; Rooijackers, Jos; Santonen, Tiina; Sastre, Joaquin; Schlünssen, Vivi; van Tongeren, Martie; Sigsgaard, Torben

2017-12-31

Occupational lung diseases are an important public health issue and are avoidable through preventive interventions in the workplace. Up-to-date knowledge about changes in exposure to occupational hazards as a result of technological and industrial developments is essential to the design and implementation of efficient and effective workplace preventive measures. New occupational agents with unknown respiratory health effects are constantly introduced to the market and require periodic health surveillance among exposed workers to detect early signs of adverse respiratory effects. In addition, the ageing workforce, many of whom have pre-existing respiratory conditions, poses new challenges in terms of the diagnosis and management of occupational lung diseases. Primary preventive interventions aimed to reduce exposure levels in the workplace remain pivotal for elimination of the occupational lung disease burden. To achieve this goal there is still a clear need for setting standard occupational exposure limits based on transparent evidence-based methodology, in particular for carcinogens and sensitising agents that expose large working populations to risk. The present overview, focused on the occupational lung disease burden in Europe, proposes directions for all parties involved in the prevention of occupational lung disease, from researchers and occupational and respiratory health professionals to workers and employers. The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2017.

Imaging and imagining chronic obstructive pulmonary disease (COPD): Uruguayans draw their lungs.

PubMed

Wainwright, Megan

2017-09-11

This anthropological study investigated what people imagined chronic obstructive pulmonary disease to look like in their lungs, what may be influencing these images and how this imagery shapes embodiment. Employing graphic elicitation, in one of multiple ethnographic interviews, participants were asked to draw their lungs: "If we could look inside your chest now, what would we see?" Lung drawings and accompanying narratives and fieldnotes from 14 participants were analyzed for themes and patterns. The theme of "imaging/imagining" emerged and three distinct patterns within this theme were identified: the microscope perspective, the X-ray perspective and the reduced pulmonary capacity perspective. These patterns demonstrate how embodiment can be shaped by an integration and reinterpretation of the medical images that form part of everyday clinic visits and pulmonary rehabilitation. Medical technology and images impact patients' embodiment. Understanding this is important for rehabilitation practitioners who work in a challenging space created by potentially conflicting medical narratives: on the one hand, chronic obstructive pulmonary disease is incurable permanent damage, and on the other, improvement is possible through rehabilitation. Drawing could be integrated into pulmonary rehabilitation and may help identify perceptions of the body that could hinder the rehabilitation process. Implications for rehabilitation Drawings, when combined with interviews, can lead to a deeper and more complex understanding of patients' perspectives and embodiment. Rehabilitation practitioners should be concerned with how patients embody the medical technology and imagery they are exposed to as part of the educational component of pulmonary rehabilitation and healthcare generally. Asking patients to visualize their illness through drawing may help pulmonary rehabilitation practitioners identify perceptions of the body which could hinder the patient's ability to reap the full benefit

VEGF (Vascular Endothelial Growth Factor) and Fibrotic Lung Disease.

PubMed

Barratt, Shaney L; Flower, Victoria A; Pauling, John D; Millar, Ann B

2018-04-24

Interstitial lung disease (ILD) encompasses a group of heterogeneous diseases characterised by varying degrees of aberrant inflammation and fibrosis of the lung parenchyma. This may occur in isolation, such as in idiopathic pulmonary fibrosis (IPF) or as part of a wider disease process affecting multiple organs, such as in systemic sclerosis. Anti-Vascular Endothelial Growth Factor (anti-VEGF) therapy is one component of an existing broad-spectrum therapeutic option in IPF (nintedanib) and may become part of the emerging therapeutic strategy for other ILDs in the future. This article describes our current understanding of VEGF biology in normal lung homeostasis and how changes in its bioavailability may contribute the pathogenesis of ILD. The complexity of VEGF biology is particularly highlighted with an emphasis on the potential non-vascular, non-angiogenic roles for VEGF in the lung, in both health and disease.

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.

Fitness to fly in patients with lung disease.

PubMed

Nicholson, Trevor T; Sznajder, Jacob I

2014-12-01

Patients with chronic lung disease may have mild hypoxemia at sea level. Some of these cases may go unrecognized, and even among those who are known to be hypoxemic, some do not use supplemental oxygen. During air travel in a hypobaric hypoxic environment, compensatory pulmonary mechanisms may be inadequate in patients with lung disease despite normal sea-level oxygen requirements. In addition, compensatory cardiovascular mechanisms may be less effective in some patients who are unable to increase cardiac output. Air travel also presents an increased risk of venous thromboembolism. Patients with cystic lung disease may also be at increased risk of pneumothorax. Although overall this risk appears to be relatively low, should a pneumothorax occur, it could present a significant challenge to the patient with chronic lung disease, particularly if hypoxemia is already present. As such, a thorough assessment of patients with chronic lung disease and cardiac disease who are contemplating air travel should be performed. The duration of the planned flight, the anticipated levels of activity, comorbid illnesses, and the presence of risk factors for venous thromboembolism are important considerations. Hypobaric hypoxic challenge testing reproduces an environment most similar to that encountered during actual air travel; however, it is not widely available. Assessment for hypoxia is otherwise best performed using a normobaric hypoxic challenge test. Patients in need of supplemental oxygen need to contact the airline and request this accommodation during flight. They should also be advised on arranging portable oxygen concentrators before air travel, and a discussion of the potential risks of travel should take place.

[Strategies for lung cancer with ischemic heart disease].

PubMed

Miyamoto, Nobuhiro; Kishimoto, Koji; Suehiro, Shouichi; Oda, Teiji; Tanabe, Kazuaki

2015-04-01

For lung cancer surgery which merged ischemic heart disease to need coronary artery treatments, the strategy is demanded on the timing of each treatment. Our department conforms to American College of Chest Physicians( ACCP) guideline and treatment strategies are decided as follows. 1) If right heart load has already occurred, we choose limited surgery for lung cancer. 2) Two-stage surgery is performed with principle. Coronary artery treatment is given priority to against left main trunk disease and unstable angina. 3) Simultaneous surgery is chosen for lung cancer more than stage II or lung cancer pressing neighboring organ and vessel not to be able to wait coronary artery treatments. Since 2007, we performed 4 simultaneous surgeries and experienced 3 pneumonia cases, 1 patient died in 5 months. We must decide a strategy in consideration of progress of the lung cancer and cardiac urgency.

Best practices in the treatment of early cystic fibrosis lung disease.

PubMed

Proesmans, Marijke

2017-02-01

For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection. In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized.

Stem cell therapy: the great promise in lung disease.

PubMed

Siniscalco, Dario; Sullo, Nikol; Maione, Sabatino; Rossi, Francesco; D'Agostino, Bruno

2008-06-01

Lung injuries are leading causes of morbidity and mortality worldwide. Pulmonary diseases such as asthma or chronic obstructive pulmonary disease characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions, or idiopathic pulmonary fibrosis characterized by excessive matrix deposition and destruction of the normal lung architecture, have essentially symptomatic treatments and their management is costly to the health care system.Regeneration of tissue by stem cells from endogenous, exogenous, and even genetically modified cells is a promising novel therapy. The use of adult stem cells to help with lung regeneration and repair could be a newer technology in clinical and regenerative medicine. In fact, different studies have shown that bone marrow progenitor cells contribute to repair and remodeling of lung in animal models of progressive pulmonary hypertension.Therefore, lung stem cell biology may provide novel approaches to therapy and could represent a great promise for the future of molecular medicine. In fact, several diseases can be slowed or even blocked by stem cell transplantation.

CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease.

PubMed

Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

2015-08-01

Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4(+) granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4(+) airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease. Copyright ©ERS 2015.

Differentiation of several interstitial lung disease patterns in HRCT images using support vector machine: role of databases on performance

NASA Astrophysics Data System (ADS)

Kale, Mandar; Mukhopadhyay, Sudipta; Dash, Jatindra K.; Garg, Mandeep; Khandelwal, Niranjan

2016-03-01

Interstitial lung disease (ILD) is complicated group of pulmonary disorders. High Resolution Computed Tomography (HRCT) considered to be best imaging technique for analysis of different pulmonary disorders. HRCT findings can be categorised in several patterns viz. Consolidation, Emphysema, Ground Glass Opacity, Nodular, Normal etc. based on their texture like appearance. Clinician often find it difficult to diagnosis these pattern because of their complex nature. In such scenario computer-aided diagnosis system could help clinician to identify patterns. Several approaches had been proposed for classification of ILD patterns. This includes computation of textural feature and training /testing of classifier such as artificial neural network (ANN), support vector machine (SVM) etc. In this paper, wavelet features are calculated from two different ILD database, publically available MedGIFT ILD database and private ILD database, followed by performance evaluation of ANN and SVM classifiers in terms of average accuracy. It is found that average classification accuracy by SVM is greater than ANN where trained and tested on same database. Investigation continued further to test variation in accuracy of classifier when training and testing is performed with alternate database and training and testing of classifier with database formed by merging samples from same class from two individual databases. The average classification accuracy drops when two independent databases used for training and testing respectively. There is significant improvement in average accuracy when classifiers are trained and tested with merged database. It infers dependency of classification accuracy on training data. It is observed that SVM outperforms ANN when same database is used for training and testing.

Spectrum of high-resolution computed tomography imaging in occupational lung disease

PubMed Central

Satija, Bhawna; Kumar, Sanyal; Ojha, Umesh Chandra; Gothi, Dipti

2013-01-01

Damage to the lungs caused by dusts or fumes or noxious substances inhaled by workers in certain specific occupation is known as occupational lung disease. Recognition of occupational lung disease is especially important not only for the primary worker, but also because of the implications with regard to primary and secondary disease prevention in the exposed co-workers. Although many of the disorders can be detected on chest radiography, high-resolution computed tomography (HRCT) is superior in delineating the lung architecture and depicting pathology. The characteristic radiological features suggest the correct diagnosis in some, whereas a combination of clinical features, occupational history, and radiological findings is essential in establishing the diagnosis in others. In the presence of a history of exposure and consistent clinical features, the diagnosis of even an uncommon occupational lung disease can be suggested by the characteristic described HRCT findings. In this article, we briefly review the HRCT appearance of a wide spectrum of occupational lung diseases. PMID:24604929

Spectrum of high-resolution computed tomography imaging in occupational lung disease.

PubMed

Satija, Bhawna; Kumar, Sanyal; Ojha, Umesh Chandra; Gothi, Dipti

2013-10-01

Damage to the lungs caused by dusts or fumes or noxious substances inhaled by workers in certain specific occupation is known as occupational lung disease. Recognition of occupational lung disease is especially important not only for the primary worker, but also because of the implications with regard to primary and secondary disease prevention in the exposed co-workers. Although many of the disorders can be detected on chest radiography, high-resolution computed tomography (HRCT) is superior in delineating the lung architecture and depicting pathology. The characteristic radiological features suggest the correct diagnosis in some, whereas a combination of clinical features, occupational history, and radiological findings is essential in establishing the diagnosis in others. In the presence of a history of exposure and consistent clinical features, the diagnosis of even an uncommon occupational lung disease can be suggested by the characteristic described HRCT findings. In this article, we briefly review the HRCT appearance of a wide spectrum of occupational lung diseases.

Lung ultrasound has limited diagnostic value in rare cystic lung diseases: a cross-sectional study.

PubMed

Davidsen, Jesper Rømhild; Bendstrup, Elisabeth; Henriksen, Daniel P; Graumann, Ole; Laursen, Christian B

2017-01-01

Background : Lung ultrasound (LUS) used to identify interstitial syndrome (IS) and pleural thickening related to diffuse parenchymal lung disease (DPLD) has shown significant correlations with ground glass opacity (GGO) on high-resolution computed tomography (HRCT). However, the applicability of LUS in patients with DPLD subtypes as rare cystic lung diseases has not previously been investigated. This study aimed to observe if distinctive LUS findings could be found in patients with lymphangioleiomyomatosis (LAM), pulmonary Langerhans cell histiocytosis (PLCH), and Birt-Hogg-Dubé syndrome (BHDS). Methods : This single centre case-based cross-sectional study of patients diagnosed with LAM, PCLH and BHDS was conducted at a Danish DPLD specialist centre. Patients underwent clinical examination including LUS. LUS findings were compared to findings scored according to a modified Belmaati score on HRCT and reviewed in consensus between two pulmonologists and one radiologist. Results : Twelve patients with HRCT proven cystic lung disease were included, six with LAM, three with PLCH, two with BHDS, and one with uncharacteristic cystic lung disease. The mean age was 48.7 years (SD ± 15.8). In general all had normal LUS findings. IS could not be found in any patients despite GGO presentation on HRCT among 75% of the patients with a Belmaati in the highest category of 0.76-1.00. Pleural thickening on LUS was present in three patients, but with inconsistent findings. Conclusion : This study indicates that LUS has limited value as a diagnostic tool in patients with LAM, PLCH, and BHDS as normal LUS findings did not rule out severe cystic lung disease.

[Lung involvement in systemic connective tissue diseases].

PubMed

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

2008-09-01

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

Genetic Modification of the Lung Directed Toward Treatment of Human Disease.

PubMed

Sondhi, Dolan; Stiles, Katie M; De, Bishnu P; Crystal, Ronald G

2017-01-01

Genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. Lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy, and lung cancer, infections such as respiratory syncytial virus (RSV) and Pseudomonas, as well as pulmonary arterial hypertension, transplant rejection, and lung injury. A variety of viral and non-viral vectors have been employed to overcome the many physical barriers to gene transfer imposed by lung anatomy and natural defenses. Beyond the treatment of lung diseases, the lung has the potential to be used as a metabolic factory for generating proteins for delivery to the circulation for treatment of systemic diseases. Although much has been learned through a myriad of experiments about the development of genetic modification of the lung, more work is still needed to improve the delivery vehicles and to overcome challenges such as entry barriers, persistent expression, specific cell targeting, and circumventing host anti-vector responses.

New insights into lung diseases using hyperpolarized gas MRI.

PubMed

Flors, L; Altes, T A; Mugler, J P; de Lange, E E; Miller, G W; Mata, J F; Ruset, I C; Hersman, F W

2015-01-01

Hyperpolarized (HP) gases are a new class of contrast agents that permit to obtain high temporal and spatial resolution magnetic resonance images (MRI) of the lung airspaces. HP gas MRI has become important research tool not only for morphological and functional evaluation of normal pulmonary physiology but also for regional quantification of pathologic changes occurring in several lung diseases. The purpose of this work is to provide an introduction to MRI using HP noble gases, describing both the basic principles of the technique and the new information about lung disease provided by clinical studies with this method. The applications of the technique in normal subjects, smoking related lung disease, asthma, and cystic fibrosis are reviewed. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung disease.

PubMed

Sato, Miho; Mori, Masaaki; Nishimaki, Shigeru; An, Hiromi; Naruto, Takuya; Sugai, Toshiyuki; Shima, Yoshio; Seki, Kazuo; Yokota, Shumpei

2010-04-01

It is clear that inflammation plays an important role in developing chronic lung disease in preterm infants. The purpose of the present study is to investigate changes of serum soluble tumor necrosis factor receptor-1 levels over time in infants with chronic lung disease. The serum levels of soluble tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21 and 28 days of age in 10 infants with chronic lung disease and in 18 infants without chronic lung disease. The serum level of soluble tumor necrosis factor receptor-1 was significantly higher in infants with chronic lung disease than in infants without chronic lung disease after delivery. The differences between these two groups remained up to 28 days of age. Prenatal inflammation with persistence into postnatal inflammation may be involved in the onset of chronic lung disease.

Connective tissue diseases, multimorbidity and the ageing lung.

PubMed

Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

2016-05-01

Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. Copyright ©ERS 2016.

Differential N-Glycosylation Patterns in Lung Adenocarcinoma Tissue

PubMed Central

Ruhaak, L. Renee; Taylor, Sandra L.; Stroble, Carol; Nguyen, Uyen Thao; Parker, Evan A.; Song, Ting; Lebrilla, Carlito B.; Rom, William N.; Pass, Harvey; Kim, Kyoungmi; Kelly, Karen; Miyamoto, Suzanne

2015-01-01

To decrease the mortality of lung cancer, better screening and diagnostic tools as well as treatment options are needed. Protein glycosylation is one of the major post-translational modifications that is altered in cancer, but it is not exactly clear which glycan structures are affected. A better understanding of the glycan structures that are differentially regulated in lung tumor tissue is highly desirable and will allow us to gain greater insight into the underlying biological mechanisms of aberrant glycosylation in lung cancer. Here, we assess differential glycosylation patterns of lung tumor tissue and nonmalignant tissue at the level of individual glycan structures using nLC–chip–TOF–MS. Using tissue samples from 42 lung adenocarcinoma patients, 29 differentially expressed (FDR < 0.05) glycan structures were identified. The levels of several oligomannose type glycans were upregulated in tumor tissue. Furthermore, levels of fully galactosylated glycans, some of which were of the hybrid type and mostly without fucose, were decreased in cancerous tissue, whereas levels of non- or low-galactosylated glycans mostly with fucose were increased. To further assess the regulation of the altered glycosylation, the glycomics data was compared to publicly available gene expression data from lung adenocarcinoma tissue compared to nonmalignant lung tissue. The results are consistent with the possibility that the observed N-glycan changes have their origin in differentially expressed glycosyltransferases. These results will be used as a starting point for the further development of clinical glycan applications in the fields of imaging, drug targeting, and biomarkers for lung cancer. PMID:26322380

[Lung transplant therapy for suppurative diseases].

PubMed

de Pablo, A; López, S; Ussetti, P; Carreño, M C; Laporta, R; López García-Gallo, C; Ferreiro, M J

2005-05-01

Lung transplantation is a valid therapeutic approach for patients with bronchiectasis. The objective of the present study was to evaluate our experience with bronchiectasis patients and compare the results in patients with cystic fibrosis to results in those with bronchiectasis caused by other processes. We carried out a retrospective study of bronchiectasis patients treated by lung transplantation in order to analyze demographic, functional and microbiological characteristics before and after transplantation, and survival. From 1991 to 2002 lung transplants were performed on 171 patients, 44 of whom had suppurative lung disease (27 had cystic fibrosis and 17 had bronchiectasis caused by other processes). There were no significant differences in the demographic variables between the 2 groups. At transplantation, lung function variables showed severe bronchial obstruction (mean [SD] forced expiratory volume in 1 second of 808 [342] mL and forced vital capacity of 1,390 [611] mL) and respiratory insufficiency (PaO2 at 52 [10] mm Hg and PaCO2 at 48 [9] mm Hg). Only PaO2 was significantly lower in patients with bronchiectasis from causes other than cystic fibrosis. Airway colonization was present in 91% of the patients; Pseudomonas spp germs were detected in 64% of the cases and were multiresistant in 9%. In the early postoperative period germs were isolated in 59% of the cases, half of which involved the same germ as had been isolated before transplantation. One year after lung transplantation, 34% of the patients continued to have bronchial colonization. Survival at 1 year was 79% and at 5 years, 49%, with no significant difference between the patients with cystic fibrosis and those with other suppurative diseases, nor between the patients with and without Pseudomonas colonization. Only 2 patients had died of bacterial pneumonia at 1 month after transplantation. Although airway colonization in patients with suppurative diseases complicates postoperative management

Comparative Effectiveness Research in Lung Diseases and Sleep Disorders

PubMed Central

Lieu, Tracy A.; Au, David; Krishnan, Jerry A.; Moss, Marc; Selker, Harry; Harabin, Andrea; Connors, Alfred

2011-01-01

The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) held a workshop to develop recommendations on topics, methodologies, and resources for comparative effectiveness research (CER) that will guide clinical decision making about available treatment options for lung diseases and sleep disorders. A multidisciplinary group of experts with experience in efficacy, effectiveness, implementation, and economic research identified (a) what types of studies the domain of CER in lung diseases and sleep disorders should include, (b) the criteria and process for setting priorities, and (c) current resources for and barriers to CER in lung diseases. Key recommendations were to (1) increase efforts to engage stakeholders in developing CER questions and study designs; (2) invest in further development of databases and other infrastructure, including efficient methods for data sharing; (3) make full use of a broad range of study designs; (4) increase the appropriate use of observational designs and the support of methodologic research; (5) ensure that committees that review CER grant applications include persons with appropriate perspective and expertise; and (6) further develop the workforce for CER by supporting training opportunities that focus on the methodologic and practical skills needed. PMID:21965016

Current Status of Stem Cells and Regenerative Medicine in Lung Biology and Diseases

PubMed Central

Weiss, Daniel J.

2014-01-01

Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPD), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the 3rd leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and chronic obstructive pulmonary disease (COPD) with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been utilized to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy based clinical trials in lung diseases. PMID:23959715

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

PubMed

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

2016-01-01

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

Lung ultrasound has limited diagnostic value in rare cystic lung diseases: a cross-sectional study

PubMed Central

Davidsen, Jesper Rømhild; Bendstrup, Elisabeth; Henriksen, Daniel P.; Graumann, Ole; Laursen, Christian B.

2017-01-01

ABSTRACT Background: Lung ultrasound (LUS) used to identify interstitial syndrome (IS) and pleural thickening related to diffuse parenchymal lung disease (DPLD) has shown significant correlations with ground glass opacity (GGO) on high-resolution computed tomography (HRCT). However, the applicability of LUS in patients with DPLD subtypes as rare cystic lung diseases has not previously been investigated. This study aimed to observe if distinctive LUS findings could be found in patients with lymphangioleiomyomatosis (LAM), pulmonary Langerhans cell histiocytosis (PLCH), and Birt-Hogg-Dubé syndrome (BHDS). Methods: This single centre case-based cross-sectional study of patients diagnosed with LAM, PCLH and BHDS was conducted at a Danish DPLD specialist centre. Patients underwent clinical examination including LUS. LUS findings were compared to findings scored according to a modified Belmaati score on HRCT and reviewed in consensus between two pulmonologists and one radiologist. Results: Twelve patients with HRCT proven cystic lung disease were included, six with LAM, three with PLCH, two with BHDS, and one with uncharacteristic cystic lung disease. The mean age was 48.7 years (SD ± 15.8). In general all had normal LUS findings. IS could not be found in any patients despite GGO presentation on HRCT among 75% of the patients with a Belmaati in the highest category of 0.76–1.00. Pleural thickening on LUS was present in three patients, but with inconsistent findings. Conclusion: This study indicates that LUS has limited value as a diagnostic tool in patients with LAM, PLCH, and BHDS as normal LUS findings did not rule out severe cystic lung disease. PMID:28649310

Pathogens, patterns of pneumonia, and epidemiologic risk factors associated with respiratory disease in recently weaned cattle in Ireland.

PubMed

Murray, Gerard M; More, Simon J; Sammin, Dónal; Casey, Mìcheàl J; McElroy, Máire C; O'Neill, Rónan G; Byrne, William J; Earley, Bernadette; Clegg, Tracy A; Ball, Hywel; Bell, Colin J; Cassidy, Joseph P

2017-01-01

We examined the pathogens, morphologic patterns, and risk factors associated with bovine respiratory disease (BRD) in 136 recently weaned cattle ("weanlings"), 6-12 mo of age, that were submitted for postmortem examination to regional veterinary laboratories in Ireland. A standardized sampling protocol included routine microbiologic investigations as well as polymerase chain reaction and immunohistochemistry. Lungs with histologic lesions were categorized into 1 of 5 morphologic patterns of pneumonia. Fibrinosuppurative bronchopneumonia (49%) and interstitial pneumonia (48%) were the morphologic patterns recorded most frequently. The various morphologic patterns of pulmonary lesions suggest the involvement of variable combinations of initiating and compounding infectious agents that hindered any simple classification of the etiopathogenesis of the pneumonias. Dual infections were detected in 58% of lungs, with Mannheimia haemolytica and Histophilus somni most frequently recorded in concert. M. haemolytica (43%) was the most frequently detected respiratory pathogen; H. somni was also shown to be frequently implicated in pneumonia in this age group of cattle. Bovine parainfluenza virus 3 (BPIV-3) and Bovine respiratory syncytial virus (16% each) were the viral agents detected most frequently. Potential respiratory pathogens (particularly Pasteurella multocida, BPIV-3, and H. somni) were frequently detected (64%) in lungs that had neither gross nor histologic pulmonary lesions, raising questions regarding their role in the pathogenesis of BRD. The breadth of respiratory pathogens detected in bovine lungs by various detection methods highlights the diagnostic value of parallel analyses in respiratory disease postmortem investigation.

Genetically manipulated mouse models of lung disease: potential and pitfalls

PubMed Central

Choi, Alexander J. S.; Owen, Caroline A.; Choi, Augustine M. K.

2012-01-01

Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators. PMID:22198907

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

PubMed Central

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

2013-01-01

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

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.

Imaging of Occupational Lung Disease.

PubMed

Champlin, Jay; Edwards, Rachael; Pipavath, Sudhakar

2016-11-01

Occupational lung diseases span a variety of pulmonary disorders caused by inhalation of dusts or chemical antigens in a vocational setting. Included in these are the classic mineral pneumoconioses of silicosis, coal worker's pneumoconiosis, and asbestos-related diseases as well as many immune-mediated and airway-centric diseases, and new and emerging disorders. Although some of these have characteristic imaging appearances, a multidisciplinary approach with focus on occupational exposure history is essential to proper diagnosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Gallium scintigraphic pattern in lung CMV infections

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

Ganz, W.I.; Cohen, D.; Mallin, W.

1994-05-01

Due to extensive use of prophylactic therapy for Pneumonitis Carinii Pneumonia (PCP), Cytomegalic Viral (CMV) infection may now be the most common lung infection in AIDS patients. This study was performed to determine Gallium-67 patterns in AIDS patients with CMV. Pathology reports were reviewed in AIDS patients who had a dose of 5 to 10 mCi of Gallium-67 citrate. Analysis of images were obtained 48-72 hours later of the entire body was performed. Gallium-67 scans in 14 AIDS patients with biopsy proven CMV, were evaluated for eye, colon, adrenal, lung and renal uptake. These were compared to 40 AIDS patientsmore » without CMV. These controls had infections including PCP, Mycobacterial infections, and lymphocytic interstitial pneumonitis. 100% of CMV patients had bowel uptake greater than or equal to liver. Similar bowel activity was seen in 50% of AIDS patients without CMV. 71% had intense eye uptake which was seen in only 10% of patients without CMV. 50% of CMV patients had renal uptake compared to 5% of non-CMV cases. Adrenal uptake was suggested in 50%, however, SPECT imaging is needed for confirmation. 85% had low grade lung uptake. The low grade lung had perihilar prominence. The remaining 15% had high grade lung uptake (greater than sternum) due to superimposed PCP infection. Colon uptake is very sensitive indicator for CMV infection. However, observing eye, renal, and or adrenal uptake improved the diagnostic specificity. SPECT imaging is needed to confirm renal or adrenal abnormalities due to intense bowel activity present in 100% of cases. When high grade lung uptake is seen superimposed PCP is suggested.« less

Clinical potentials of human pluripotent stem cells in lung diseases

PubMed Central

2014-01-01

Lung possesses very limited regenerative capacity. Failure to maintain homeostasis of lung epithelial cell populations has been implicated in the development of many life-threatening pulmonary diseases leading to substantial morbidity and mortality worldwide, and currently there is no known cure for these end-stage pulmonary diseases. Embryonic stem cells (ESCs) and somatic cell-derived induced pluripotent stem cells (iPSCs) possess unlimited self-renewal capacity and great potential to differentiate to various cell types of three embryonic germ layers (ectodermal, mesodermal, and endodermal). Therapeutic use of human ESC/iPSC-derived lung progenitor cells for regeneration of injured or diseased lungs will have an enormous clinical impact. This article provides an overview of recent advances in research on pluripotent stem cells in lung tissue regeneration and discusses technical challenges that must be overcome for their clinical applications in the future. PMID:24995122

The mortality patterns of lung cancer between 1990 and 2013 in Xuanwei, China.

PubMed

Chen, Gongbo; Sun, Xin; Ren, Hongyan; Wan, Xia; Huang, Hecang; Ma, Xiangyun; Ning, Bofu; Zou, Xiaonong; Hu, Weijiang; Yang, Gonghuan

2015-11-01

To explore the variations in the mortality trends, especially death due to lung cancer, from 1990 to 2013 in Xuanwei City. Mortality data were collected in Xuanwei during the 2nd and 3rd National Retrospective Sampling Survey on Mortality and Routine Death Registration System (DRS) during 2011-2013. According to the result of the survey on under-reported deaths, mortality data from DRS during 2011-2013 were adjusted. Disease specific mortality rate, age-standardized mortality rate (ASMR) and 45Q15 were calculated in Xuanwei and compared with those in rural areas of China. During three periods, 1990-1992, 2004-2005 and 2011-2013, lung cancer contributed to 56.86%, 58.45% and 63.03% of deaths from all cancers respectively with a much higher proportion than rural areas nationally. The ASMR of lung cancer for males surged from 41.43/10(5) to 88.17/10(5) during 1990-2005 and it surged from 37.70/10(5) to 74.45/10(5) for females. Although they declined slightly during 2011-2013 (82.53/10(5) and 62.62/10(5) for males and females respectively), the ASMR of lung cancer among males in Xuanwei was three times of that in rural areas in China, and it was six times higher among females. The 45Q15 of lung cancer for males in Xuanwei was 3-5 times of that in rural areas of China and for females it was 7-9 times. The high-mortality areas of lung cancer were still located in Laibin, Longchang, Wanshui and Shuanglong Communities. High-mortality areas of lung cancer expanded to their surrounding areas and those in southeast. Although indoor air pollution caused by smoky coal has been fairly well controlled, patterns of death due to lung cancer have not obviously changed. The mortality rate of lung cancer among females was similar to that among males. Therefore, further studies should be conducted to comprehensively explore the risk factors of lung cancer in Xuanwei. Copyright © 2015. Published by Elsevier Ireland Ltd.

Profiling over 1500 lipids in induced lung sputum and the implications in studying lung diseases.

PubMed

t'Kindt, Ruben; Telenga, Eef D; Jorge, Lucie; Van Oosterhout, Antoon J M; Sandra, Pat; Ten Hacken, Nick H T; Sandra, Koen

2015-01-01

Induced lung sputum is a valuable matrix in the study of respiratory diseases. Although the methodology of sputum collection has evolved to a point where it is repeatable and responsive to inflammation, its use in molecular profiling studies is still limited. Here, an in-depth lipid profiling of induced lung sputum using high-resolution liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-Q-TOF MS) is described. An enormous complexity in lipid composition could be revealed. Over 1500 intact lipids, originating from 6 major lipid classes, have been accurately identified in 120 μL of induced sputum. By number and measured intensity, glycerophospholipids represent the largest lipid class, followed by sphingolipids, glycerolipids, fatty acyls, sterol lipids, and prenol lipids. Several prenol lipids, originating from tobacco, could be detected in the lung sputum of smokers. To illustrate the utility of the methodology in studying respiratory diseases, a comparative lipid screening was performed on lung sputum extracts in order to study the effect of Chronic Obstructive Pulmonary Disease (COPD) on the lung barrier lipidome. Results show that sphingolipid expression in induced sputum significantly differs between smokers with and without COPD.

Disruption of iron homeostasis and lung disease.

PubMed

Ghio, Andrew J

2009-07-01

As a result of a direct exchange with the external environment, the lungs are exposed to both iron and agents with a capacity to disrupt the homeostasis of this metal (e.g. particles). An increased availability of catalytically reactive iron can result from these exposures and, by generating an oxidative stress, this metal can contribute to tissue injury. By importing this Fe(3+) into cells for storage in a chemically less reactive form, the lower respiratory tract demonstrates an ability to mitigate both the oxidative stress presented by iron and its potential for tissue injury. This means that detoxification is accomplished by chemical reduction to Fe(2+) (e.g. by duodenal cytochrome b and other ferrireductases), iron import (e.g. by divalent metal transporter 1 and other transporters), and storage in ferritin. The metal can subsequently be exported from the cell (e.g. by ferroportin 1) in a less reactive state relative to that initially imported. Iron is then transported out of the lung via the mucociliary pathway or blood and lymphatic pathways to the reticuloendothelial system for long term storage. This coordinated handling of iron in the lung appears to be disrupted in several acute diseases on the lung including infections, acute respiratory distress syndrome, transfusion-related acute lung injury, and ischemia-reperfusion. Exposures to bleomycin, dusts and fibers, and paraquat similarly alter iron homeostasis in the lung to affect an oxidative stress. Finally, iron homeostasis is disrupted in numerous chronic lung diseases including pulmonary alveolar proteinosis, transplantation, cigarette smoking, and cystic fibrosis.

Autophagy in lung disease pathogenesis and therapeutics

PubMed Central

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

2015-01-01

Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy) may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics. PMID:25617802

Lung Disease Including Asthma and Adult Vaccination

MedlinePlus

... Vaccine-Preventable Adult Diseases Resources Lung Disease including Asthma and Adult Vaccination Language: English (US) Español (Spanish) ... are hospitalized, and some even die. People with asthma or COPD are at higher risk for serious ...

Lung Cancer: One Disease or Many.

PubMed

O'Brien, Timothy D; Jia, Peilin; Aldrich, Melinda C; Zhao, Zhongming

2018-06-05

Lung cancer is classified as a single entity comprised of multiple histological subtypes. But how similar are these subtypes on a genetic level? This paper aims to address this question through a concise overview of germline and somatic differences between small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma. We reveal the weak overlap found between these 3 lung cancer subtypes using published data from one of the largest germline genetic studies on lung cancer to date and somatic mutation data from Catalogue of Somatic Mutations in Cancer (COSMIC). These data indicate that these 3 subtypes share very little with each other at the genetic level. At the germline SNP level, only 24 independent SNPs from 2 chromosomes were shared across all 3 subtypes. We also demonstrate that only 30 unique cancer-specific mutations overlap the 3 subtypes from COSMIC, and that this is fewer than overlapping mutations chosen at random. Finally, we show that only 3 somatic mutational signatures are shared between these 3 subtypes. This paper highlights that these 3 lung cancer subtypes may be distinct diseases at the genetic level. In the era of precision medicine, we feel that these genomic differences will be of utmost importance in the choice of lung cancer therapy in the future. © 2018 S. Karger AG, Basel.

Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer

PubMed Central

Truong, Kimberly K.; Lam, Michael T.; Grandner, Michael A.; Sassoon, Catherine S.

2016-01-01

Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption. PMID:27104378

Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer.

PubMed

Truong, Kimberly K; Lam, Michael T; Grandner, Michael A; Sassoon, Catherine S; Malhotra, Atul

2016-07-01

Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption.

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

PubMed

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

2001-03-01

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

Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases

PubMed Central

Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

2016-01-01

Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent. PMID:27200087

Rare lung disease research: strategies for improving identification and recruitment of research participants.

PubMed

Gupta, Samir; Bayoumi, Ahmed M; Faughnan, Marie E

2011-11-01

Research in rare lung diseases faces methodologic limitations by virtue of the small number of participants available to be studied. We explored several strategies that may improve researchers' ability to identify and recruit research participants with rare lung diseases. We provide an overview of strategies based on available evidence, previously used approaches, and reasoning. First, disease detection is generally poor and may be improved through strategies targeted at primary care practitioners or directly at patients, thus increasing the pool of patients available for research studies. Next, standardization of case definitions in rare lung diseases is often lacking, hindering research recruitment efforts because of confusion over appropriate recruitment criteria. Expert consensus statements can enhance both clinical care and research recruitment by standardizing definitions. Finally, recruitment strategies using rare lung disease registries, clinical research networks, novel Internet-based direct patient recruitment approaches, and patient organizations may facilitate recruitment of patients with rare lung diseases. In summary, although several strategies for improving the identification and recruitment of research participants with rare lung diseases have been proposed, published examples are few. Objective measurement and reporting of novel recruitment methods and collaboration among researchers facing the same limitations across various rare lung diseases are required. Advancements in this area are vital to the design and performance of much-needed robust clinical studies across the spectrum of rare lung diseases.

Role of macrophage migration inhibitory factor in age-related lung disease

PubMed Central

Sauler, Maor; Bucala, Richard

2015-01-01

The prevalence of many common respiratory disorders, including pneumonia, chronic obstructive lung disease, pulmonary fibrosis, and lung cancer, increases with age. Little is known of the host factors that may predispose individuals to such diseases. Macrophage migration inhibitory factor (MIF) is a potent upstream regulator of the immune system. MIF is encoded by variant alleles that occur commonly in the population. In addition to its role as a proinflammatory cytokine, a growing body of literature demonstrates that MIF influences diverse molecular processes important for the maintenance of cellular homeostasis and may influence the incidence or clinical manifestations of a variety of chronic lung diseases. This review highlights the biological properties of MIF and its implication in age-related lung disease. PMID:25957294

Update on host-pathogen interactions in cystic fibrosis lung disease.

PubMed

Hector, Andreas; Frey, Nina; Hartl, Dominik

2016-12-01

Bacterial and fungal infections are hallmarks of cystic fibrosis (CF) lung disease. In the era of long-term inhaled antibiotics and increasing CF patient survival, new "emerging" pathogens are detected in CF airways, yet their pathophysiological disease relevance remains largely controversial and incompletely defined. As a response to chronic microbial triggers, innate immune cells, particularly neutrophils, are continuously recruited into CF airways where they combat pathogens but also cause tissue injury through release of oxidants and proteases. The coordinated interplay between host immune cell activation and pathogens is essential for the outcome of CF lung disease. Here, we provide a concise overview and update on host-pathogen interactions in CF lung disease.

Image-based diagnostic aid for interstitial lung disease with secondary data integration

NASA Astrophysics Data System (ADS)

Depeursinge, Adrien; Müller, Henning; Hidki, Asmâa; Poletti, Pierre-Alexandre; Platon, Alexandra; Geissbuhler, Antoine

2007-03-01

Interstitial lung diseases (ILDs) are a relatively heterogeneous group of around 150 illnesses with often very unspecific symptoms. The most complete imaging method for the characterisation of ILDs is the high-resolution computed tomography (HRCT) of the chest but a correct interpretation of these images is difficult even for specialists as many diseases are rare and thus little experience exists. Moreover, interpreting HRCT images requires knowledge of the context defined by clinical data of the studied case. A computerised diagnostic aid tool based on HRCT images with associated medical data to retrieve similar cases of ILDs from a dedicated database can bring quick and precious information for example for emergency radiologists. The experience from a pilot project highlighted the need for detailed database containing high-quality annotations in addition to clinical data. The state of the art is studied to identify requirements for image-based diagnostic aid for interstitial lung disease with secondary data integration. The data acquisition steps are detailed. The selection of the most relevant clinical parameters is done in collaboration with lung specialists from current literature, along with knowledge bases of computer-based diagnostic decision support systems. In order to perform high-quality annotations of the interstitial lung tissue in the HRCT images an annotation software and its own file format is implemented for DICOM images. A multimedia database is implemented to store ILD cases with clinical data and annotated image series. Cases from the University & University Hospitals of Geneva (HUG) are retrospectively and prospectively collected to populate the database. Currently, 59 cases with certified diagnosis and their clinical parameters are stored in the database as well as 254 image series of which 26 have their regions of interest annotated. The available data was used to test primary visual features for the classification of lung tissue patterns

Notch signaling in lung diseases: focus on Notch1 and Notch3

PubMed Central

Zong, Dandan; Ouyang, Ruoyun; Li, Jinhua; Chen, Yan; Chen, Ping

2016-01-01

Notch signaling is an evolutionarily conserved cell–cell communication mechanism that plays a key role in lung homeostasis, injury and repair. The loss of regulation of Notch signaling, especially Notch1 and Notch3, has recently been linked to the pathogenesis of important lung diseases, in particular, chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis, pulmonary arterial hypertension (PAH), lung cancer and lung lesions in some congenital diseases. This review focuses on recent advances related to the mechanisms and the consequences of aberrant or absent Notch1/3 activity in the initiation and progression of lung diseases. Our increasing understanding of this signaling pathway offers great hope that manipulating Notch signaling may represent a promising alternative complementary therapeutic strategy in the future. PMID:27378579

Characteristic features of tacrolimus-induced lung disease in rheumatoid arthritis patients.

PubMed

Sasaki, Takanori; Nakamura, Wataru; Inokuma, Shigeko; Matsubara, Erika

2016-02-01

This paper aims to study the background and clinical characteristics of tacrolimus (TAC)-induced lung disease. A case of a rheumatoid arthritis (RA) patient who developed TAC-induced interstitial lung disease (TAC-ILD) is reported. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) website was searched for cases of TAC-ILD and its prevalence among all cases of TAC-related adverse events. As for cases of TAC-ILD, its underlying disease, preexisting lung diseases, and fatal outcome were also searched. Literature review of TAC-ILD cases was added. A 65-year-old female RA patient with preexisting bronchiectasis developed near-fatal TAC-ILD. Amelioration of RA, ground-glass opacities in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings in this patient. A search of the PMDA website revealed the following: the prevalence of TAC-ILD was 3 % of all cases of TAC-related adverse events, 56 out of 85 RA cases (66 %), and one out of 15 other cases had a preexisting lung disease; the prevalences of fatal outcome in RA and other cases were 24 and 38 %, respectively. A few cases in the literature had preexisting ILD and developed diffuse alveolar damage. In our case, preexisting bronchiectasis, arthritis remission, newly developed ground-glass opacities (GGOs) in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings. From the search of the PMDA website, about one fourth of the cases with TAC-related lung injury had a fatal outcome, and among RA patients, two thirds had preexisting lung diseases.

Prevention of chronic lung disease

PubMed Central

Laughon, Matthew M.; Smith, P. Brian; Bose, Carl

2010-01-01

Considerable effort has been devoted to the development of strategies to reduce the incidence of chronic lung disease, including use of medications, nutritional therapies, and respiratory care practices. Unfortunately, most of these strategies have not been successful. To date, the only two treatments developed specifically to prevent CLD whose efficacy is supported by evidence from randomized, controlled trials are the parenteral administration of vitamin A and corticosteroids. Two other therapies, the use of caffeine for the treatment of apnea of prematurity and aggressive phototherapy for the treatment of hyperbilirubinemia were evaluated for the improvement of other outcomes and found to reduce CLD. Cohort studies suggest that the use of CPAP as a strategy for avoiding mechanical ventilation might also be beneficial. Other therapies reduce lung injury in animal models but do not appear to reduce CLD in humans. The benefits of the efficacious therapies have been modest, with an absolute risk reduction in the 7–11% range. Further preventive strategies are needed to reduce the burden of this disease. However, each will need to be tested in randomized, controlled trials, and the expectations of new therapies should be modest reductions of the incidence of the disease. PMID:19736053

Coxiella burnetii, a hidden pathogen in interstitial lung disease?

PubMed

Melenotte, Cléa; Izaaryene, Jalal-Jean; Gomez, Carine; Delord, Marion; Prudent, Elsa; Lepidi, Hubert; Mediannikov, Oleg; Lacoste, Marion; Djossou, Felix; Mania, Alexandre; Bernard, Noelle; Huchot, Eric; Mège, Jean-Louis; Brégeon, Fabienne; Raoult, Didier

2018-04-06

We report 7 patients with interstitial lung disease (ILD) on CT-scan reviewing. C. burnetii was diagnosed in situ in one lung biopsy performed. All patients had advanced interstitial lung fibrosis and persistent C. burnetii infection. Q fever may be a cofactor of ILD, especially in endemic areas.

The lung microbiome in health and disease.

PubMed

Moffatt, Miriam F; Cookson, William Ocm

2017-12-01

The Human Microbiome Project began 10 years ago, leading to a significant growth in understanding of the role the human microbiome plays in health and disease. In this article, we explain with an emphasis on the lung, the origins of microbiome research. We discuss how 16S rRNA gene sequencing became the first major molecular tool to examine the bacterial communities present within the human body. We highlight the pitfalls of molecular-based studies, such as false findings resulting from contamination, and the limitations of 16S rRNA gene sequencing. Knowledge about the lung microbiome has evolved from initial scepticism to the realisation that it might have a significant influence on many illnesses. We also discuss the lung microbiome in the context of disease by giving examples of important respiratory conditions. In addition, we draw attention to the challenges for metagenomic studies of respiratory samples and the importance of systematic bacterial isolation to enable host-microbiome interactions to be understood. We conclude by discussing how knowledge of the lung microbiome impacts current clinical diagnostics. © Royal College of Physicians 2017. All rights reserved.

Radiation-induced heart disease in lung cancer radiotherapy: A dosimetric update.

PubMed

Ming, Xin; Feng, Yuanming; Yang, Chengwen; Wang, Wei; Wang, Ping; Deng, Jun

2016-10-01

Radiation-induced heart disease (RIHD), which affects the patients' prognosis with both acute and late side effects, has been published extensively in the radiotherapy of breast cancer, lymphoma and other benign diseases. Studies on RIHD in lung cancer radiotherapy, however, are less extensive and clear even though the patients with lung cancer are delivered with higher doses to the heart during radiation treatment. In this article, after extensive literature search and analysis, we reviewed the current evidence on RIHD in lung cancer patients after their radiation treatments and investigated the potential risk factors for RIHD as compared to other types of cancers. Cardiac toxicity has been found highly relevant in lung cancer radiotherapy. So far, the crude incidence of cardiac complications in the lung cancer patients after radiotherapy has been up to 33%. The dose to the heart, the lobar location of tumor, the treatment modality, the history of heart and pulmonary disease and smoking were considered as potential risk factors for RIHD in lung cancer radiotherapy. As treatment techniques improve over the time with better prognosis for lung cancer survivors, an improved prediction model can be established to further reduce the cardiac toxicity in lung cancer radiotherapy.

Adult bone marrow-derived stem cells for the lung: implications for pediatric lung diseases.

PubMed

van Haaften, Timothy; Thébaud, Bernard

2006-04-01

Bronchopulmonary dysplasia (BPD) and cystic fibrosis (CF) are two common serious chronic respiratory disorders without specific treatments affecting children. BPD is characterized by an arrest in alveolar growth in premature infants requiring respiratory support. CF is the most common fatal inherited genetic disorder characterized by abnormally thick mucus secretions, recurrent infection and ultimately lung destruction. One commonality between these two diseases is the promise of utilizing stem cells therapeutically. Indeed, the use of exogenous cells to supplement the natural repair mechanisms or the possibility of genetic manipulation in vitro before administration are appealing therapeutic options for these diseases. Increasing attention has been focused on the use of adult bone marrow-derived stem cells (BMSC) to regenerate damaged organs such as the heart, the brain, and the liver. However, due to the lung's complexity as well as the low rate of cellular turnover within the lung, progress has been slower in this area compared with the skin or liver. Initial work suggests that BMSC can engraft and differentiate into a variety of lung cells, but these findings have been challenged recently. This article critically reviews the current advances on the therapeutic use of stem cells for lung regeneration.

Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis.

PubMed

DePianto, Daryle J; Chandriani, Sanjay; Abbas, Alexander R; Jia, Guiquan; N'Diaye, Elsa N; Caplazi, Patrick; Kauder, Steven E; Biswas, Sabyasachi; Karnik, Satyajit K; Ha, Connie; Modrusan, Zora; Matthay, Michael A; Kukreja, Jasleen; Collard, Harold R; Egen, Jackson G; Wolters, Paul J; Arron, Joseph R

2015-01-01

There is microscopic spatial and temporal heterogeneity of pathological changes in idiopathic pulmonary fibrosis (IPF) lung tissue, which may relate to heterogeneity in pathophysiological mediators of disease and clinical progression. We assessed relationships between gene expression patterns, pathological features, and systemic biomarkers to identify biomarkers that reflect the aggregate disease burden in patients with IPF. Gene expression microarrays (N=40 IPF; 8 controls) and immunohistochemical analyses (N=22 IPF; 8 controls) of lung biopsies. Clinical characterisation and blood biomarker levels of MMP3 and CXCL13 in a separate cohort of patients with IPF (N=80). 2940 genes were significantly differentially expressed between IPF and control samples (|fold change| >1.5, p<0.05). Two clusters of co-regulated genes related to bronchiolar epithelium or lymphoid aggregates exhibited substantial heterogeneity within the IPF population. Gene expression in bronchiolar and lymphoid clusters corresponded to the extent of bronchiolisation and lymphoid aggregates determined by immunohistochemistry in adjacent tissue sections. Elevated serum levels of MMP3, encoded in the bronchiolar cluster, and CXCL13, encoded in the lymphoid cluster, corresponded to disease severity and shortened survival time (p<10(-7) for MMP3 and p<10(-5) for CXCL13; Cox proportional hazards model). Microscopic pathological heterogeneity in IPF lung tissue corresponds to specific gene expression patterns related to bronchiolisation and lymphoid aggregates. MMP3 and CXCL13 are systemic biomarkers that reflect the aggregate burden of these pathological features across total lung tissue. These biomarkers may have clinical utility as prognostic and/or surrogate biomarkers of disease activity in interventional studies in IPF. 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.

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

PubMed

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

1982-11-01

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

Glucose Transporter-1 Distribution in Fibrotic Lung Disease

PubMed Central

Malide, Daniela; Yao, Jianhua; Nathan, Steven D.; Rosas, Ivan O.; Gahl, William A.; Moss, Joel; Gochuico, Bernadette R.

2013-01-01

Background: [18F]-2-fluoro-2-deoxyglucose (FDG)-PET scan uptake is increased in areas of fibrosis and honeycombing in patients with idiopathic pulmonary fibrosis (IPF). Glucose transporter-1 (Glut-1) is known to be the main transporter for FDG. There is a paucity of data regarding the distribution of Glut-1 and the cells responsible for FDG binding in fibrotic lung diseases. Methods: We applied immunofluorescence to localize Glut-1 in normal, IPF, and Hermansky-Pudlak syndrome (HPS) pulmonary fibrosis lung tissue specimens as well as an array of 19 different lung neoplasms. In addition, we investigated Glut-1 expression in inflammatory cells from BAL fluid (BALF) from healthy volunteers, subjects with IPF, and subjects with HPS pulmonary fibrosis. Results: In normal lung tissue, Glut-1 immunoreactivity was seen on the surface of erythrocytes. In tissue sections from fibrotic lung diseases (IPF and HPS pulmonary fibrosis), Glut-1 immunoreactivity was present on the surface of erythrocytes and inflammatory cells. BALF inflammatory cells from healthy control subjects showed no immunoreactivity; BALF cells from subjects with IPF and HPS pulmonary fibrosis showed Glut-1 immunoreactivity associated with neutrophils and alveolar macrophages. Conclusions: Glut-1 transporter expression in normal lung is limited to erythrocytes. In fibrotic lung, erythrocytes and inflammatory cells express Glut-1. Together, these data suggest that FDG-PET scan uptake in IPF could be explained by enhanced inflammatory and erythrocytes uptake due to neovascularization seen in IPF and not an upregulation of metabolic rate in pneumocytes. Thus, FDG-PET scan may detect inflammation and neovascularization in lung fibrosis. PMID:23699745

[Basic lung ultrasound. Part 2. Parenchymal diseases].

PubMed

de la Quintana Gordon, F B; Nacarino Alcorta, B; Fajardo Pérez, M

2015-01-01

In this second part, an analysis is made of the pathology of lung parenchyma. This text is structured into different sections, including the study of atelectasias, pneumonia and abscess, interstitial/alveolar or Blines patterns, and finally an analysis is made of pulmonary embolism. With this second part, the basic knowledge to develop lung ultrasound in the anesthesia department has been presented. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

A Healthy Dietary Pattern Reduces Lung Cancer Risk: A Systematic Review and Meta-Analysis.

PubMed

Sun, Yanlai; Li, Zhenxiang; Li, Jianning; Li, Zengjun; Han, Jianjun

2016-03-04

Diet and nutrients play an important role in cancer development and progress; a healthy dietary pattern has been found to be associated with several types of cancer. However, the association between a healthy eating pattern and lung cancer risk is still unclear. Therefore, we conducted a systematic review with meta-analysis to evaluate whether a healthy eating pattern might reduce lung cancer risk. We identified relevant studies from the PubMed and Embase databases up to October 2015, and the relative risks were extracted and combined by the fixed-effects model when no substantial heterogeneity was observed; otherwise, the random-effects model was employed. Subgroup and publication bias analyses were also performed. Finally, eight observational studies were included in the meta-analysis. The pooled relative risk of lung cancer for the highest vs. lowest category of healthy dietary pattern was 0.81 (95% confidence interval, CI: 0.75-0.86), and no significant heterogeneity was detected. The relative risks (RRs) for non-smokers, former smokers and current smokers were 0.89 (95% CI: 0.63-1.27), 0.74 (95% CI: 0.62-0.89) and 0.86 (95% CI: 0.79-0.93), respectively. The results remained stable in subgroup analyses by other confounders and sensitivity analysis. The results of our meta-analysis suggest that a healthy dietary pattern is associated with a lower lung cancer risk, and they provide more beneficial evidence for changing the diet pattern in the general population.

Molecular Basis of Asbestos-Induced Lung Disease

PubMed Central

Liu, Gang; Cheresh, Paul; Kamp, David W.

2013-01-01

Asbestos causes asbestosis and malignancies by molecular mechanisms that are not fully understood. The modes of action underlying asbestosis, lung cancer, and mesothelioma appear to differ depending on the fiber type, lung clearance, and genetics. After reviewing the key pathologic changes following asbestos exposure, we examine recently identified pathogenic pathways, with a focus on oxidative stress. Alveolar epithelial cell apoptosis, which is an important early event in asbestosis, is mediated by mitochondria- and p53-regulated death pathways and may be modulated by the endoplasmic reticulum. We review mitochondrial DNA (mtDNA)-damage and -repair mechanisms, focusing on 8-oxoguanine DNA glycosylase, as well as cross talk between reactive oxygen species production, mtDNA damage, p53, OGG1, and mitochondrial aconitase. These new insights into the molecular basis of asbestos-induced lung diseases may foster the development of novel therapeutic targets for managing degenerative diseases (e.g., asbestosis and idiopathic pulmonary fibrosis), tumors, and aging, for which effective management is lacking. PMID:23347351

Mechanisms Underlying HIV-Associated Noninfectious Lung Disease.

PubMed

Presti, Rachel M; Flores, Sonia C; Palmer, Brent E; Atkinson, Jeffrey J; Lesko, Catherine R; Lau, Bryan; Fontenot, Andrew P; Roman, Jesse; McDyer, John F; Twigg, Homer L

2017-11-01

Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for COPD, pulmonary hypertension, and lung cancer even in the era of combination antiretroviral therapy. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggests that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage, which predisposes PLWH to these conditions. Some of the factors that drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome toward pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

The Epidemiology and Management of Lung Diseases in Sickle Cell Disease: Lessons Learned from Acute and Chronic Lung Disease in Cystic Fibrosis.

PubMed

Willen, Shaina M; DeBaun, Michael R

2018-06-01

Although sickle cell disease and cystic fibrosis are two of the most common monogenic diseases presenting in childhood worldwide, cystic fibrosis and sickle cell disease enjoy vastly different funding and collaborative research efforts. Pulmonary complications in cystic fibrosis have well established guidelines and multidisciplinary involvement focusing on comorbidities, routine monitoring, infectious complications, nutrition, and treatment recommendations. These guidelines can provide a framework on which to build knowledge of lung disease in sickle cell disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD).

PubMed

O'Dwyer, David N; Armstrong, Michelle E; Cooke, Gordon; Dodd, Jonathan D; Veale, Douglas J; Donnelly, Seamas C

2013-10-01

Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD. © 2013.

Pulmonary hypertension in patients with interstitial lung disease.

PubMed

Karampitsakos, Theodoros; Tzouvelekis, Argyrios; Chrysikos, Serafeim; Bouros, Demosthenes; Tsangaris, Iraklis; Fares, Wassim H

2018-06-01

Interstitial lung diseases (ILDs) comprise a broad and heterogeneous group of more than two hundred diseases with common functional characteristics. Their diagnosis and management require a multidisciplinary approach. This multidisciplinary approach involves the assessment of comorbid conditions including pulmonary hypertension (PH) that exerts a dramatic impact on survival. The current World Health Organization (WHO) classification of PH encompasses many of the interstitial lung diseases into WHO Group 3, while sarcoidosis, Pulmonary Langerhans Cell Histiocytosis and lymphangioleiomyomatosis are placed into WHO Group 5 as diseases with unclear or multifactorial mechanisms. Connective tissue diseases could span any of the 5 WHO groups based on the primary phenotype into which they manifest. Interestingly, several challenging phenotypes present with features that overlap between two or more WHO PH groups. Currently, PH-specific treatment is recommended only for patients classified into WHO Group 1 PH. The lack of specific treatment for other groups, including PH in the setting of ILD, reflects the poor outcomes of these patients. Thus, identification of the optimal strategy for ILD patients with PH remains an amenable need. This review article provides a brief overview of biomarkers indicative of vascular remodeling in interstitial lung disease, summarizes the current state of knowledge regarding patients with PH and ILD and highlights future perspectives that remain to be addressed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Lung Microbiome for Clinicians. New Discoveries about Bugs in Healthy and Diseased Lungs

PubMed Central

Rom, William N.; Weiden, Michael D.

2014-01-01

Microbes are readily cultured from epithelial surfaces of the skin, mouth, and colon. In the last 10 years, culture-independent DNA-based techniques demonstrated that much more complex microbial communities reside on most epithelial surfaces; this includes the lower airways, where bacterial culture had failed to reliably demonstrate resident bacteria. Exposure to a diverse bacterial environment is important for adequate immunological development. The most common microbes found in the lower airways are also found in the upper airways. Increasing abundance of oral characteristic taxa is associated with increased inflammatory cells and exhaled nitric oxide, suggesting that the airway microbiome induces an immunological response in the lung. Furthermore, rhinovirus infection leads to outgrowth of Haemophilus in patients with chronic obstructive pulmonary disease, and human immunodeficiency virus–infected subjects have more Tropheryma whipplei in the lower airway, suggesting a bidirectional interaction in which the host immune defenses also influence the microbial niche. Quantitative and/or qualitative changes in the lung microbiome may be relevant for disease progression and exacerbations in a number of pulmonary diseases. Future investigations with longitudinal follow-up to understand the dynamics of the lung microbiome may lead to the development of new therapeutic targets. PMID:24460444

State-of-the-art MS technology applications in lung disease.

PubMed

Végvári, Ákos; Döme, Balázs

2011-12-01

Two frontline MS technologies, which have recently gained much attention, are discussed within the scope of this review. Besides a brief summary on the contemporary state of lung cancer and chronic obstructive pulmonary disease, the principles of multiple reaction monitoring and matrix assisted laser desorption ionization (MALDI) MS imaging are presented. A comprehensive overview of quantitative mass spectrometry applications is provided, covering multiple reaction monitoring assay developments for analysis of proteins (biomarkers) and low-molecular-weight compounds (drugs) with a special focus on the disease areas of lung cancer and chronic obstructive pulmonary disease. The MALDI-MS imaging applications are discussed similarly, providing references to studies conducted on lung tissues in order to localize drug compounds and protein biomarkers.

Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report.

PubMed

Ramsey, Bonnie W; Banks-Schlegel, Susan; Accurso, Frank J; Boucher, Richard C; Cutting, Garry R; Engelhardt, John F; Guggino, William B; Karp, Christopher L; Knowles, Michael R; Kolls, Jay K; LiPuma, John J; Lynch, Susan; McCray, Paul B; Rubenstein, Ronald C; Singh, Pradeep K; Sorscher, Eric; Welsh, Michael

2012-04-15

Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.

Occupational exposure to dust and lung disease among sheet metal workers.

PubMed Central

Hunting, K L; Welch, L S

1993-01-01

A previous large medical survey of active and retired sheet metal workers with 20 or more years in the trade indicated an unexpectedly high prevalence of obstructive pulmonary disease among both smokers and non-smokers. This study utilised interviews with a cross section of the previously surveyed group to explore occupational risk factors for lung disease. Four hundred and seven workers were selected from the previously surveyed group on the basis of their potential for exposure to fibreglass and asbestos. Selection was independent of health state, and excluded welders. A detailed history of occupational exposure was obtained by telephone interview for 333 of these workers. Exposure data were analysed in relation to previously collected data on chronic bronchitis, obstructive lung disease, and personal characteristics. Assessment of the effects of exposure to fibreglass as distinct from the effects of exposure to asbestos has been difficult in previous studies of construction workers. The experienced workers studied here have performed a diversity of jobs involving exposure to many different types of materials, and this enabled exposure to each dust to be evaluated separately. The risk of chronic bronchitis increased sharply by pack-years of cigarettes smoked; current smokers had a double risk compared with those who had never smoked or had stopped smoking. The occurrence of chronic bronchitis also increased with increasing duration of exposure to asbestos. Workers with a history of high intensity exposure to fibreglass had a more than doubled risk of chronic bronchitis. Obstructive lung disease, defined by results of pulmonary function tests at the medical survey, was also related to both smoking and occupational risk factors. Number of pack years smoked was the strongest predictor of obstructive lung disease. Duration of direct and indirect exposure to welding fume was also a positive predictor of obstructive lung disease. Duration of exposure to asbestos was

Frequency and number of ultrasound lung rockets (B-lines) using a regionally based lung ultrasound examination named vet BLUE (veterinary bedside lung ultrasound exam) in dogs with radiographically normal lung findings.

PubMed

Lisciandro, Gregory R; Fosgate, Geoffrey T; Fulton, Robert M

2014-01-01

Lung ultrasound is superior to lung auscultation and supine chest radiography for many respiratory conditions in human patients. Ultrasound diagnoses are based on easily learned patterns of sonographic findings and artifacts in standardized images. By applying the wet lung (ultrasound lung rockets or B-lines, representing interstitial edema) versus dry lung (A-lines with a glide sign) concept many respiratory conditions can be diagnosed or excluded. The ultrasound probe can be used as a visual stethoscope for the evaluation of human lungs because dry artifacts (A-lines with a glide sign) predominate over wet artifacts (ultrasound lung rockets or B-lines). However, the frequency and number of wet lung ultrasound artifacts in dogs with radiographically normal lungs is unknown. Thus, the primary objective was to determine the baseline frequency and number of ultrasound lung rockets in dogs without clinical signs of respiratory disease and with radiographically normal lung findings using an 8-view novel regionally based lung ultrasound examination called Vet BLUE. Frequency of ultrasound lung rockets were statistically compared based on signalment, body condition score, investigator, and reasons for radiography. Ten left-sided heart failure dogs were similarly enrolled. Overall frequency of ultrasound lung rockets was 11% (95% confidence interval, 6-19%) in dogs without respiratory disease versus 100% (95% confidence interval, 74-100%) in those with left-sided heart failure. The low frequency and number of ultrasound lung rockets observed in dogs without respiratory disease and with radiographically normal lungs suggests that Vet BLUE will be clinically useful for the identification of canine respiratory conditions. © 2014 American College of Veterinary Radiology.

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.

Lung cancer and chronic obstructive pulmonary disease: From a clinical perspective

PubMed Central

Dai, Jie; Yang, Ping; Cox, Angela; Jiang, Gening

2017-01-01

Chronic obstructive pulmonary disease (COPD) and lung cancer are devastating pulmonary diseases that commonly coexist and present a number of clinical challenges. COPD confers a higher risk for lung cancer development, but available chemopreventive measures remain rudimentary. Current studies have shown a marked benefit of cancer screening in the COPD population, although challenges remain, including the common underdiagnosis of COPD. COPD-associated lung cancer presents distinct clinical features. Treatment for lung cancer coexisting with COPD is challenging as COPD may increase postoperative morbidities and decrease survival. In this review, we outline current progress in the understanding of the clinical association between COPD and lung cancer, and suggest possible cancer prevention strategies in this patient population. PMID:28061470

Hard metal lung disease: a case series.

PubMed

Mizutani, Rafael Futoshi; Terra-Filho, Mário; Lima, Evelise; Freitas, Carolina Salim Gonçalves; Chate, Rodrigo Caruso; Kairalla, Ronaldo Adib; Carvalho-Oliveira, Regiani; Santos, Ubiratan Paula

2016-01-01

To describe diagnostic and treatment aspects of hard metal lung disease (HMLD) and to review the current literature on the topic. This was a retrospective study based on the medical records of patients treated at the Occupational Respiratory Diseases Clinic of the Instituto do Coração, in the city of São Paulo, Brazil, between 2010 and 2013. Of 320 patients treated during the study period, 5 (1.56%) were diagnosed with HMLD. All of those 5 patients were male (mean age, 42.0 ± 13.6 years; mean duration of exposure to hard metals, 11.4 ± 8.0 years). Occupational histories were taken, after which the patients underwent clinical evaluation, chest HRCT, pulmonary function tests, bronchoscopy, BAL, and lung biopsy. Restrictive lung disease was found in all subjects. The most common chest HRCT finding was ground glass opacities (in 80%). In 4 patients, BALF revealed multinucleated giant cells. In 3 patients, lung biopsy revealed giant cell interstitial pneumonia. One patient was diagnosed with desquamative interstitial pneumonia associated with cellular bronchiolitis, and another was diagnosed with a hypersensitivity pneumonitis pattern. All patients were withdrawn from exposure and treated with corticosteroid. Clinical improvement occurred in 2 patients, whereas the disease progressed in 3. Although HMLD is a rare entity, it should always be included in the differential diagnosis of respiratory dysfunction in workers with a high occupational risk of exposure to hard metal particles. A relevant history (clinical and occupational) accompanied by chest HRCT and BAL findings suggestive of the disease might be sufficient for the diagnosis. Descrever aspectos relacionados ao diagnóstico e tratamento de pacientes com doença pulmonar por metal duro (DPMD) e realizar uma revisão da literatura. Estudo retrospectivo dos prontuários médicos de pacientes atendidos no Serviço de Doenças Respiratórias Ocupacionais do Instituto do Coração, localizado na cidade de S�

Chorioamnionitis and chronic lung disease of prematurity: a path analysis of causality.

PubMed

Dessardo, Nada Sindičić; Mustać, Elvira; Dessardo, Sandro; Banac, Srđan; Peter, Branimir; Finderle, Aleksandar; Marić, Marinko; Haller, Herman

2012-02-01

Current evidence suggests that additional pathogenetic factors could play a role in the development of chronic lung disease of prematurity, other than mechanical ventilation and free radical injury. The introduction of the concept of "fetal inflammatory response syndrome" offers a new perspective on the pathogenesis of chronic lung disease of prematurity. New statistical approaches could be useful tools in evaluating causal relationships in the development of chronic morbidity in preterm infants. The aim of this study was to test a new statistical framework incorporating path analysis to evaluate causality between exposure to chorioamnionitis and fetal inflammatory response syndrome and the development of chronic lung disease of prematurity. We designed a prospective cohort study that included consecutively born premature infants less than 32 weeks of gestation whose placentas were collected for histological analysis. Histological chorioamnionitis, clinical data, and neonatal outcomes were related to chronic lung disease. Along with standard statistical methods, a path analysis was performed to test the relationship between histological chorioamnionitis, gestational age, mechanical ventilation, and development of chronic lung disease of prematurity. Among the newborns enrolled in the study, 69/189 (36%) had histological chorioamnionitis. Of those with histological chorioamnionitis, 28/69 (37%) were classified as having fetal inflammatory response syndrome, according to the presence of severe chorioamnionitis and funisitis. Histological chorioamnionitis was associated with a lower birth weight, shorter gestation, higher frequency of patent ductus arteriosus, greater use of surfactant, and higher frequency of chronic lung disease of prematurity. Severe chorioamnionitis and funisitis were significantly associated with lower birth weight, lower gestational age, lower Apgar score at 5 minutes, more frequent use of mechanical ventilatory support and surfactant, as well

All the “RAGE” in lung disease: The receptor for advanced glycation endproducts (RAGE) is a major mediator of pulmonary inflammatory responses

PubMed Central

Oczypok, Elizabeth A.; Perkins, Timothy N.; Oury, Tim D.

2017-01-01

SUMMARY The receptor for advanced glycation endproducts (RAGE) is a pro-inflammatory pattern recognition receptor (PRR) that has been implicated in the pathogenesis of numerous inflammatory diseases. It was discovered in 1992 on endothelial cells and was named for its ability to bind advanced glycation endproducts and promote vascular inflammation in the vessels of patients with diabetes. Further studies revealed that RAGE is most highly expressed in lung tissue and spurred numerous explorations into RAGE’s role in the lung. These studies have found that RAGE is an important mediator in allergic airway inflammation (AAI) and asthma, pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), acute lung injury, pneumonia, cystic fibrosis, and bronchopulmonary dysplasia. RAGE has not yet been targeted in the lungs of paediatric or adult clinical populations, but the development of new ways to inhibit RAGE is setting the stage for the emergence of novel therapeutic agents for patients suffering from these pulmonary conditions. PMID:28416135

Computational modeling of the obstructive lung diseases asthma and COPD

PubMed Central

2014-01-01

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

Concise review: current status of stem cells and regenerative medicine in lung biology and diseases.

PubMed

Weiss, Daniel J

2014-01-01

Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPDs), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the third leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and COPD with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been used to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy-based clinical trials in lung diseases. © AlphaMed Press.

Marijuana and lung diseases.

PubMed

Joshi, Manish; Joshi, Anita; Bartter, Thaddeus

2014-03-01

Cannabis sativa (marijuana) is used throughout the world, and its use is increasing. In much of the world, marijuana is illicit. While inhalation of smoke generated by igniting dried components of the plant is the most common way marijuana is used, there is concern over potential adverse lung effects. The purpose of this review is to highlight recent studies that explore the impact upon the respiratory system of inhaling marijuana smoke. Smoking marijuana is associated with chronic bronchitis symptoms and large airway inflammation. Occasional use of marijuana with low cumulative use is not a risk factor for the development of chronic obstructive pulmonary disease. The heavy use of marijuana alone may lead to airflow obstruction. The immuno-histopathologic and epidemiologic evidence in marijuana users suggests biological plausibility of marijuana smoking as a risk for the development of lung cancer; at present, it has been difficult to conclusively link marijuana smoking and cancer development. There is unequivocal evidence that habitual or regular marijuana smoking is not harmless. A caution against regular heavy marijuana usage is prudent. The medicinal use of marijuana is likely not harmful to lungs in low cumulative doses, but the dose limit needs to be defined. Recreational use is not the same as medicinal use and should be discouraged.

Periodontal Disease and Incident Lung Cancer Risk: A Meta-Analysis of Cohort Studies.

PubMed

Zeng, Xian-Tao; Xia, Ling-Yun; Zhang, Yong-Gang; Li, Sheng; Leng, Wei-Dong; Kwong, Joey S W

2016-10-01

Periodontal disease is linked to a number of systemic diseases such as cardiovascular diseases and diabetes mellitus. Recent evidence has suggested periodontal disease might be associated with lung cancer. However, their precise relationship is yet to be explored. Hence, this study aims to investigate the association of periodontal disease and risk of incident lung cancer using a meta-analytic approach. PubMed, Scopus, and ScienceDirect were searched up to June 10, 2015. Cohort and nested case-control studies investigating risk of lung cancer in patients with periodontal disease were included. Hazard ratios (HRs) were calculated, as were their 95% confidence intervals (CIs) using a fixed-effect inverse-variance model. Statistical heterogeneity was explored using the Q test as well as the I(2) statistic. Publication bias was assessed by visual inspection of funnel plots symmetry and Egger's test. Five cohort studies were included, involving 321,420 participants in this meta-analysis. Summary estimates based on adjusted data showed that periodontal disease was associated with a significant risk of lung cancer (HR = 1.24, 95% CI = 1.13 to 1.36; I(2) = 30%). No publication bias was detected. Subgroup analysis indicated that the association of periodontal disease and lung cancer remained significant in the female population. Evidence from cohort studies suggests that patients with periodontal disease are at increased risk of developing lung cancer.

Histological findings and lung dust analysis as the basis for occupational disease compensation in asbestos-related lung cancer in Germany.

PubMed

Feder, Inke Sabine; Theile, Anja; Tannapfel, Andrea

2018-01-15

This study has researched the significance of histologically raised findings and lung dust analyses in the context of claiming the recognition of and thus compensation for an asbestos-associated occupational disease. For this approach, all findings from the German Mesothelioma Register in 2015 that included lung dust analyses were evaluated and were compared with information on asbestos fiber exposure at work based on fiber years, and with the results of radiological findings. For 68 insured persons, recognition of an asbestos-induced lung disease according to Section 4104 of the German Ordinance on Occupational Diseases (Berufskrankheitenverordnung - BKV) could be recommended solely on the basis of the histological examinations of lung tissues and complementary lung dust analyses. Neither did the calculation of the cumulative asbestos dust exposure at work yield 25 fiber years, nor could bridge findings (e.g., plaques) be identified. In addition, the autopsies of 12 patients revealed plaques that had not been diagnosed during radiological examinations. These results show that - irrespective of the prescribed working techniques and radiological diagnosis - pathological/anatomical and histological diagnostics are often the only way for the insureds to demonstrate the causal connection between asbestos and their disease. Even after long intervals of up to 40 years post last exposure, the asbestos fibers would still be easily detectable in the lung tissues evaluated. Whenever suitable tissue is available, it should be examined for mild asbestosis with the aid of a lung dust analysis. Otherwise there is a risk that an occupational disease is wrongfully rejected. In the context of health insurance, the lung dust analysis and the resulting proof of the presence of asbestosis often constitute one option of providing evidence of an occupational disease. Int J Occup Med Environ Health 2018;31(3):293-305. This work is available in Open Access model and licensed under a CC BY

[Analysis of 2 patients with occupational hard mental lung disease].

PubMed

Ding, Bangmei; Ding, Lu; Yu, Bin; Fan, Cunhua; Han, Lei; Hu, Jinmei; Zhu, Baoli

2015-01-01

We sought to master the clinical characteristics and prognosis of hard mental lung disease, improving this disease's diagnosis and treatment quality. We recruited two suspected patients with hard mental lung disease and collected their occupational history, examination results of occupational health, and past medical records. By virtue of laboratory tests, high Kv chest radiography, CT and HRCT of chest, fiberoptic bronchoscopy and ECG examination, diagnostic report was synthesized respectively by respiratory physicians and pathologist from three different agencies. Then the report was submitted to diagnosis organizations of occupational disease, and diagnostic conclusion of occupational disease was drawn after discussion by at least three diagnosticians of occupational disease. We found that both of the two suspected patients were exposed to dusts of hard metal, and length of exposure service ranged from 8 to 9 years. Clinical manifestations were dominated by dry cough, wheezing after activities, and pathological manifestation was characteristic giant cell interstitial pneumonia. The prognosis and outcome of the disease were different. According to exact occupational exposure history, clinical manifestations, combined with the results of high Kv chest radiography, CT of chest and pathological manifestation, it can be diagnosed with hard mental lung disease.

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.

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

Social media use for occupational lung disease.

PubMed

Harber, Philip; Leroy, Gondy

2017-04-01

Social media have great impact on all aspects of life throughout the world. The utilization of social media for occupational lung disease, however, has been much more limited. This article summarizes recent literature concerning social media for occupational lung disease and identifies areas for additional use. Social media are used in six relevant areas: information dissemination, peer-to-peer communication, survey research data collection, participatory research and exposome data acquisition, assessing public concerns, and knowledge generation. There are very clear advantages for information dissemination from experts to workers and on a peer-to-peer basis, although variable credibility and accuracy concerns persist. For research, social media have been used for acquiring data posted for nonresearch purposes and for efficiently collecting information specifically for research. The benefits of efficiency, democracy, and very large data sources may counterbalance concerns about inadequate specification of recruitment strategies and limited control over data quality. The potential benefits of using social media for lung health-workplace interactions are much greater than the very limited current utilization.

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

Caveolin-1 regulates leucocyte behaviour in fibrotic lung disease.

PubMed

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

2010-06-01

Reduced caveolin-1 levels in lung fibroblasts from patients with scleroderma and the lungs of bleomycin-treated mice promote collagen overexpression and lung fibrosis. This study was undertaken to determine whether caveolin-1 is deficient in leucocytes from bleomycin-treated mice and patients with scleroderma and to examine the consequences of this deficiency and its reversal. Mice or cells received the caveolin-1 scaffolding domain (CSD) peptide to reverse the pathological effects of reduced caveolin-1 expression. In bleomycin-treated mice, the levels of caveolin-1 in leucocytes and the effect of CSD peptide on leucocyte accumulation in lung tissue were examined. To validate the results in human disease and to identify caveolin-1-regulated molecular mechanisms, monocytes and neutrophils were isolated from patients with scleroderma and control subjects and caveolin-1, extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38, CXC chemokine receptor 4 (CXCR4) and matrix metalloproteinase 9 (MMP-9) expression/activation were evaluated. These parameters were also studied in monocytes treated with cytokines or CSD peptide. Leucocyte caveolin-1 is important in lung fibrosis. In bleomycin-treated mice, caveolin-1 expression was diminished in monocytes and CSD peptide inhibited leucocyte recruitment into the lungs. These observations are relevant to human disease. Monocytes and neutrophils from patients with scleroderma contained less caveolin-1 and more activated ERK, JNK and p38 than those from control subjects. Treatment with CSD peptide reversed ERK, JNK and p38 hyperactivation. Scleroderma monocytes also overexpressed CXCR4 and MMP-9, which was inhibited by the CSD peptide. Cytokine treatment of normal monocytes caused adoption of the scleroderma phenotype (low caveolin-1, high CXCR4 and MMP-9 and signalling molecule hyperactivation). Caveolin-1 downregulation in leucocytes contributes to fibrotic lung disease, highlighting caveolin-1 as

Caveolin-1 Regulates Leukocyte Behaviour in Fibrotic Lung Disease

PubMed Central

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

2010-01-01

Objectives Reduced caveolin-1 levels in scleroderma lung fibroblasts and the lungs of bleomycin-treated mice promote collagen overexpression and lung fibrosis. We now evaluate whether caveolin-1 is deficient in leucocytes from bleomycin-treated mice and scleroderma patients and examine the consequences of this deficiency and its reversal. Methods Mice or cells received the caveolin-1 scaffolding domain (CSD) peptide to reverse the pathological effects of reduced caveolin-1 expression. In bleomycin-treated mice, we examined caveolin-1 levels in leucocytes and the effect of CSD peptide on leucocyte accumulation in lung tissue. To validate our results in human disease and identify caveolin-1-regulated molecular mechanisms, we isolated monocytes and neutrophils from scleroderma patients and control subjects and evaluated caveolin-1, ERK, JNK, p38, CXCR4, and MMP-9 expression/activation. We also studied these parameters in monocytes treated with cytokines or CSD peptide. Results Leucocyte caveolin-1 is important in lung fibrosis. In bleomycin-treated mice, caveolin-1 expression is diminished in monocytes and CSD peptide inhibits leucocyte recruitment into the lungs. These observations are relevant to human disease. Scleroderma monocytes and neutrophils contain less caveolin-1 and more activated ERK, JNK, and p38 than their normal counterparts. CSD peptide treatment reverses ERK, JNK, and p38 hyperactivation. Scleroderma monocytes also overexpress CXCR4 and MMP-9. The overexpression of CXCR4 and MMP-9 is inhibited by the CSD peptide. Cytokine treatment of normal monocytes causes adoption of the scleroderma phenotype: low caveolin-1, high CXCR4 and MMP-9, and signaling molecule hyperactivation. Conclusions Caveolin-1 downregulation in leucocytes contributes to fibrotic lung disease, highlighting caveolin-1 as a promising therapeutic target in scleroderma. PMID:20410070

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

The safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel in the treatment of non-small cell lung cancer patients with interstitial lung disease.

PubMed

Yasuda, Yuichiro; Hattori, Yoshihiro; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Urata, Yoshiko; Nogami, Munenobu; Takenaka, Daisuke; Negoro, Shunichi; Satouchi, Miyako

2018-01-01

The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

PubMed Central

Meyer, Keith C; Nathanson, Ian; Angel, Luis; Bhorade, Sangeeta M; Chan, Kevin M; Culver, Daniel; Harrod, Christopher G; Hayney, Mary S; Highland, Kristen B; Limper, Andrew H; Patrick, Herbert; Strange, Charlie; Whelan, Timothy

2012-01-01

Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. PMID:23131960

SU-F-R-31: Identification of Robust Normal Lung CT Texture Features for the Prediction of Radiation-Induced Lung Disease

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

Choi, W; Riyahi, S; Lu, W

Purpose: Normal lung CT texture features have been used for the prediction of radiation-induced lung disease (radiation pneumonitis and radiation fibrosis). For these features to be clinically useful, they need to be relatively invariant (robust) to tumor size and not correlated with normal lung volume. Methods: The free-breathing CTs of 14 lung SBRT patients were studied. Different sizes of GTVs were simulated with spheres placed at the upper lobe and lower lobe respectively in the normal lung (contralateral to tumor). 27 texture features (9 from intensity histogram, 8 from grey-level co-occurrence matrix [GLCM] and 10 from grey-level run-length matrix [GLRM])more » were extracted from [normal lung-GTV]. To measure the variability of a feature F, the relative difference D=|Fref -Fsim|/Fref*100% was calculated, where Fref was for the entire normal lung and Fsim was for [normal lung-GTV]. A feature was considered as robust if the largest non-outlier (Q3+1.5*IQR) D was less than 5%, and considered as not correlated with normal lung volume when their Pearson correlation was lower than 0.50. Results: Only 11 features were robust. All first-order intensity-histogram features (mean, max, etc.) were robust, while most higher-order features (skewness, kurtosis, etc.) were unrobust. Only two of the GLCM and four of the GLRM features were robust. Larger GTV resulted greater feature variation, this was particularly true for unrobust features. All robust features were not correlated with normal lung volume while three unrobust features showed high correlation. Excessive variations were observed in two low grey-level run features and were later identified to be from one patient with local lung diseases (atelectasis) in the normal lung. There was no dependence on GTV location. Conclusion: We identified 11 robust normal lung CT texture features that can be further examined for the prediction of radiation-induced lung disease. Interestingly, low grey-level run features

Crohn's disease-associated interstitial lung disease mimicking sarcoidosis: a case report and review of the literature.

PubMed

Thao, Choua; Lagstein, Amir; Allen, Tadashi; Dincer, Huseyin Erhan; Kim, Hyun Joo

2016-10-07

Respiratory involvement in Crohn's disease (CD) is a rare manifestation known to involve the large and small airways, lung parenchyma, and pleura. The clinical presentation is nonspecific, and diagnostic tests can mimic other pulmonary diseases, posing a diagnostic challenge and delay in treatment. We report a case of a 60-year-old female with a history of CD and psoriatic arthritis who presented with dyspnea, fever, and cough with abnormal radiological findings. Diagnostic testing revealed an elevated CD4:CD8 ratio in the bronchoalveolar lavage fluid, and cryoprobe lung biopsy results showed non-necrotizing granulomatous inflammation. We describe here the second reported case of pulmonary involvement mimicking sarcoidosis in Crohn's disease and a review of the literature on the approaches to making a diagnosis of CD-associated interstitial lung disease.

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

PubMed Central

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

2010-01-01

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

Fitness to Fly Testing in Patients with Congenital Heart and Lung Disease.

PubMed

Spoorenberg, Mandy E; van den Oord, Marieke H A H; Meeuwsen, Ted; Takken, Tim

2016-01-01

During commercial air travel passengers are exposed to a low ambient cabin pressure, comparable to altitudes of 5000 to 8000 ft (1524 to 2438 m). In healthy passengers this causes a fall in partial pressure of oxygen, which results in relative hypoxemia, usually without symptoms. Patients with congenital heart or lung disease may experience more severe hypoxemia during air travel. This systematic review provides an overview of the current literature focusing on whether it is safe for patients with congenital heart or lung disease to fly. The Pubmed database was searched and all studies carried out at an (simulated) altitude of 5000-8000 ft (1524-2438 m) for a short time period (several hours) and related to patients with congenital heart or lung disease were reviewed. Included were 11 studies. These studies examined patients with cystic fibrosis, neonatal (chronic) lung disease and congenital (a)cyanotic heart disease during a hypoxic challenge test, in a hypobaric chamber, during commercial air travel, or in the mountains. Peripheral/arterial saturation, blood gases, lung function, and/or the occurrence of symptoms were listed. Based on the current literature, it can be concluded that air travel is safe for most patients. However, those at risk of hypoxia can benefit from supplemental in-flight oxygen. Therefore, patients with congenital heart and lung disease should be evaluated carefully prior to air travel to select the patients at risk for hypoxia using the current studies and guidelines.

COPA mutations impair ER-Golgi transport causing hereditary autoimmune-mediated lung disease and arthritis

PubMed Central

Watkin, Levi B.; Jessen, Birthe; Wiszniewski, Wojciech; Vece, Timothy; Jan, Max; Sha, Youbao; Thamsen, Maike; Santos-Cortez, Regie L. P.; Lee, Kwanghyuk; Gambin, Tomasz; Forbes, Lisa; Law, Christopher S.; Stray-Petersen, Asbjørg; Cheng, Mickie H.; Mace, Emily M.; Anderson, Mark S.; Liu, Dongfang; Tang, Ling Fung; Nicholas, Sarah K.; Nahmod, Karen; Makedonas, George; Canter, Debra; Kwok, Pui-Yan; Hicks, John; Jones, Kirk D.; Penney, Samantha; Jhangiani, Shalini N.; Rosenblum, Michael D.; Dell, Sharon D.; Waterfield, Michael R.; Papa, Feroz R.; Muzny, Donna M.; Zaitlen, Noah; Leal, Suzanne M.; Gonzaga-Jauregui, Claudia; Boerwinkle, Eric; Eissa, N. Tony; Gibbs, Richard A.; Lupski, James R.; Orange, Jordan S.; Shum, Anthony K.

2015-01-01

Advances in genomics have allowed unbiased genetic studies of human disease with unexpected insights into the molecular mechanisms of cellular immunity and autoimmunity1. We performed whole exome sequencing (WES) and targeted sequencing in patients with an apparent Mendelian syndrome of autoimmune disease characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease (ILD). In five families, we identified four unique deleterious variants in the Coatomer subunit alpha (COPA) gene all located within the same functional domain. We hypothesized that mutant COPA leads to a defect in intracellular transport mediated by coat protein complex I (COPI)2–4. We show that COPA variants impair binding of proteins targeted for retrograde Golgi to ER transport and demonstrate that expression of mutant COPA leads to ER stress and the upregulation of Th17 priming cytokines. Consistent with this pattern of cytokine expression, patients demonstrated a significant skewing of CD4+ T cells toward a T helper 17 (Th17) phenotype, an effector T cell population implicated in autoimmunity5,6. Our findings uncover an unexpected molecular link between a vesicular transport protein and a syndrome of autoimmunity manifested by lung and joint disease. These findings provide a unique opportunity to understand how alterations in cellular homeostasis caused by a defect in the intracellular trafficking pathway leads to the generation of human autoimmune disease. PMID:25894502

Intravascular laser therapy in different forms of lung diseases

NASA Astrophysics Data System (ADS)

Kirillov, M. N.; Reshetnikov, V. A.; Kazhekin, O. A.; Shepelenko, A. F.

1993-06-01

The potentions of laser intravascular therapy in elimination of pyogenic and inflammatory intoxication in cases of acute pneumonia, pyo-destructive diseases (including posttraumatic diseases) of the lungs are studied clinically.

Epigenetics in asthma and other inflammatory lung diseases.

PubMed

Durham, Andrew; Chou, Pai-Chien; Kirkham, Paul; Adcock, Ian M

2010-08-01

Asthma is a chronic inflammatory disease of the airways. The causes of asthma and other inflammatory lung diseases are thought to be both environmental and heritable. Genetic studies do not adequately explain the heritability and susceptabilty to the disease, and recent evidence suggests that epigentic changes may underlie these processes. Epigenetics are heritable noncoding changes to DNA and can be influenced by environmental factors such as smoking and traffic pollution, which can cause genome-wide and gene-specific changes in DNA methylation. In addition, alterations in histone acetyltransferase/deacetylase activities can be observed in the cells of patients with lung diseases such as severe asthma and chronic obstructive pulmonary disease, and are often linked to smoking. Drugs such as glucocorticoids, which are used to control inflammation, are dependent on histone deacetylase activity, which may be important in patients with severe asthma and chronic obstructive pulmonary disease who do not respond well to glucocorticoid therapy. Future work targeting specific histone acetyltransferases/deacetylases or (de)methylases may prove to be effective future anti-inflammatory treatments for patients with treatment-unresponsive asthma.

Marijuana and Lung Disease.

PubMed

Tashkin, Donald P

2018-05-17

As marijuana smoking prevalence increases in the U.S. concern regarding its potential risks to lung health has also risen, given the general similarity in the smoke contents between marijuana and tobacco. Most studies have found a significant association between marijuana smoking and chronic bronchitis symptoms after adjustment for tobacco. While reports are mixed regarding associations between marijuana smoking and lung function, none has shown a relationship to decrements in forced expired volume in 1 sec (FEV1) and few have found a relationship to a decreased ratio of FEV1 to forced vital capacity (FVC), possibly related to an association between marijuana and an increased FVC. A few studies have found a modest reduction in specific airway conductance in relation to marijuana, probably reflecting endoscopic evidence of bronchial mucosal edema among habitual marijuana smokers. Diffusing capacity in marijuana smokers has been normal and two studies of thoracic high-resolution computed tomography (HRCT) have not shown any association of marijuana smoking with emphysema. Although bronchial biopsies from habitual marijuana smokers have shown precancerous histopathological changes, a large cohort study and a pooled analysis of six well-designed case-control studies have not found evidence of a link between marijuana smoking and lung cancer. The immunosuppressive effects of delta-9 tetrahydrocannabinol raise the possibility of an increased risk of pneumonia, but further studies are needed to evaluate this potential risk. Several cases series have demonstrated pneumothoraces/pneumomediastinum, as well as bullous lung disease, in marijuana smokers, but these associations require epidemiologic studies for firmer evidence of possible causality. Copyright © 2018. Published by Elsevier Inc.

Current Status of Gene Therapy for Inherited Lung Diseases

PubMed Central

Driskell, Ryan R.; Engelhardt, John F.

2007-01-01

Gene therapy as a treatment modality for pulmonary disorders has attracted significant interest over the past decade. Since the initiation of the first clinical trials for cystic fibrosis lung disease using recombinant adenovirus in the early 1990s, the field has encountered numerous obstacles including vector inflammation, inefficient delivery, and vector production. Despite these obstacles, enthusiasm for lung gene therapy remains high. In part, this enthusiasm is fueled through the diligence of numerous researchers whose studies continue to reveal great potential of new gene transfer vectors that demonstrate increased tropism for airway epithelia. Several newly identified serotypes of adeno-associated virus have demonstrated substantial promise in animal models and will likely surface soon in clinical trials. Furthermore, an increased understanding of vector biology has also led to the development of new technologies to enhance the efficiency and selectivity of gene delivery to the lung. Although the promise of gene therapy to the lung has yet to be realized, the recent concentrated efforts in the field that focus on the basic virology of vector development will undoubtedly reap great rewards over the next decade in treating lung diseases. PMID:12524461

The Intersection of Aging Biology and the Pathobiology of Lung Diseases: A Joint NHLBI/NIA Workshop

PubMed Central

Budinger, GR Scott; Kohanski, Ronald A; Gan, Weiniu; Kobor, Michael S; Amaral, Luis A; Armanios, Mary; Kelsey, Karl T; Pardo, Annie; Tuder, Rubin; Macian, Fernando; Chandel, Navdeep; Vaughan, Douglas; Rojas, Mauricio; Mora, Ana L; Kovacs, Elizabeth; Duncan, Steven R; Finkel, Toren; Choi, Augustine; Eickelberg, Oliver; Chen, Danica; Agusti, Alvar; Selman, Moises; Balch, William E; Busse, Paula; Lin, Anning; Morimoto, Richard; Sznajder, Jacob I; Thannickal, Victor J

2017-01-01

Abstract Death from chronic lung disease is increasing and chronic obstructive pulmonary disease has become the third leading cause of death in the United States in the past decade. Both chronic and acute lung diseases disproportionately affect elderly individuals, making it likely that these diseases will become more frequent and severe as the worldwide population ages. Chronic lung diseases are associated with substantial morbidity, frequently resulting in exercise limiting dyspnea, immobilization, and isolation. Therefore, effective strategies to prevent or treat lung disease are likely to increase healthspan as well as life span. This review summarizes the findings of a joint workshop sponsored by the NIA and NHLBI that brought together investigators focused on aging and lung biology. These investigators encouraged the use of genetic systems and aged animals in the study of lung disease and the development of integrative systems-based platforms that can dynamically incorporate data sets that describe the genomics, transcriptomics, epigenomics, metabolomics, and proteomics of the aging lung in health and disease. Further research was recommended to integrate benchmark biological hallmarks of aging in the lung with the pathobiology of acute and chronic lung diseases with divergent pathologies for which advanced age is the most important risk factor. PMID:28498894

Epidemiology of Lung Cancer

PubMed Central

Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

2013-01-01

Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

A biomechanical hypothesis for the pathophysiology of apical lung disease.

PubMed

Casha, Aaron R; Manché, Alexander; Camilleri, Liberato; Gatt, Ruben; Dudek, Krzysztof; Pace-Bardon, Michael; Gauci, Marilyn; Grima, Joseph N

2016-07-01

A hypothesis is presented suggesting that the pathogenesis of apical lung disease is due to progression of subclinical congenital apical bullae in people with low Body Mass Index (BMI), a combination present in 15% of the population, due to high pleural stress levels present in the antero-posteriorly flattened chests of these individuals. The hypothesis was tested for validity in two apical lung pathologies with widespread epidemiological literature, namely tuberculosis (TB) and primary spontaneous pneumothorax (PSP), assessing whether the hypothesis could identify high-risk populations, explain exceptional cases like apical lower lobe disease and confirm predictions. The biomechanical hypothesis can explain the high-risk factors of apical location, age, gender and low-BMI build, as well as the occurrence of disease in the apex of the lower lobe, in both TB and PSP patients. A predicted common pathogenesis for apical lung disease was confirmed by the higher-than-expected incidence of concomitant TB and PSP. Pleural stress levels depend on chest wall shape, but are highest in the apex of young males with low BMI, leading to growth of congenital bullae that can eventually limit clearance inhaled material, superinfect or burst. This hypothesis suggests that low-dose computerized tomography may be used to screen for TB eradication. This paper is the first to propose a biomechanical mechanism for all apical lung disease pathophysiology. Copyright © 2016 Elsevier Ltd. All rights reserved.

CT of chronic infiltrative lung disease: Prevalence of mediastinal lymphadenopathy

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

Niimi, Hiroshi; Kang, Eun-Young; Kwong, S.

1996-03-01

Our goal was to determine the prevalence of mediastinal lymph node enlargement at CT in patients with diffuse infiltrative lung disease. The study was retrospective and included 175 consecutive patients with diffuse infiltrative lung diseases. Diagnoses included idiopathic pulmonary fibrosis (IPF) (n = 61), usual interstitial pneumonia associated with collagen vascular disease (CVD) (n = 20), idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) (n = 22), extrinsic allergic alveolitis (EAA) (n = 17), and sarcoidosis (n = 55). Fifty-eight age-matched patients with CT of the chest performed for unrelated conditions served as controls. The presence, number, and sites of enlarged nodesmore » (short axis {ge}10 mm in diameter) were recorded. Enlarged mediastinal nodes were present in 118 of 175 patients (67%) with infiltrative lung disease and 3 of 58 controls (5%) (p < 0.001). The prevalence of enlarged nodes was 84% (46 of 55) in sarcoidosis, 67% (41 of 61) in IPF, 70% (14 of 20) in CVD, 53% (9 of 17) in EAA, and 36% (8 of 22) in BOOP. The mean number of enlarged nodes was higher in sarcoidosis (mean 3.2) than in the other infiltrative diseases (mean 1.2) (p < 0.001). Enlarged nodes were most commonly present in station 10R, followed by 7, 4R, and 5. Patients with infiltrative lung disease frequently have enlarged mediastinal lymph nodes. However, in diseases other than sarcoid, usually only one or two nodes are enlarged and their maximal short axis diameter is <15 mm. 11 refs., 2 figs., 1 tab.« less

Comparison of antemortem antimicrobial treatment regimens to antimicrobial susceptibility patterns of postmortem lung isolates from feedlot cattle with bronchopneumonia.

PubMed

Lamm, Catherine G; Love, Brenda C; Krehbiel, Clint R; Johnson, Nicholas J; Step, Douglas L

2012-03-01

A retrospective study was performed to compare the treatment regimens in feedlot cattle that died with bovine respiratory disease (BRD) to the antimicrobial susceptibility patterns of the microorganisms isolated from lungs. Forty-three cattle submitted by the Willard Sparks Beef Research Center (WSBRC) to the Oklahoma Animal Disease Diagnostic Laboratory for postmortem examination during 2007 had bronchopneumonia (acute = 16, subacute = 5, or chronic = 22). Lungs from cattle were cultured aerobically (40 cattle) and for Mycoplasma spp. (34 cattle). Susceptibility panels were performed. At least 1 BRD pathogen (Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Mycoplasma bovis, or Arcanobacterium pyogenes) was isolated from 39 cattle, and 77% (30/39) had multiple organisms recovered. Mycoplasmal infections were common (25/34) and a major component of mixed infections (24/25). The majority (60%) of the M. haemolytica, P. multocida, and H. somni isolates were resistant to tetracycline. Most of the H. somni isolates (67%) were susceptible to tilmicosin (Ti), enrofloxacin (En), ceftiofur (Ce), and florfenicol, despite extensive treatment with Ti, En, and Ce (75% of isolates were from cattle that received each antimicrobial once). Most of the M. haemolytica (65%) and P. multocida (79%) isolates were susceptible to En and Ce, despite antemortem treatment of cattle with these antimicrobials. Hence, the current study reports a discrepancy between the antemortem treatment of clinical BRD and the susceptibility patterns of the bacteria isolated from lungs postmortem. Based on these findings, factors other than antimicrobial resistance are playing a role in the death of feedlot cattle with BRD.

Pemetrexed-related interstitial lung disease reported from post marketing surveillance (malignant pleural mesothelioma/non-small cell lung cancer).

PubMed

Tomii, Keisuke; Kato, Terufumi; Takahashi, Masashi; Noma, Satoshi; Kobashi, Yoichiro; Enatsu, Sotaro; Okubo, Sumiko; Kobayashi, Noriko; Kudoh, Shoji

2017-04-01

Interstitial lung disease (ILD) is important drug related toxicity because it commonly forced to discontinue the treatment. To characterize the prevalence and patterns of pemetrexed induced ILD, an independent ILD advisory board composed of external experts performed reassessment of ILD in two post marketing surveillance (PMS) studies for malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). ILD incidences were originally 1.6% and 2.6% in 903 MPM and 683 NSCLC patients in safety analyses, respectively. Based on the reassessment by the board, the incidence was 1.1% MPM and 1.8% NSCLC. Common possible risk factors of ILD in MPM and NSCLC patients were male gender, 60 years or older age, and pre-existing ILD. Asbestosis in MPM, and smoking history in NSCLC are also considered as risk, respectively. In terms of computed tomography (CT) pattern, 7 of 10 cases in MPM patients had acute interstitial pneumonia pattern, which four were fatal. Eight of the 12 NSCLC patients had diffuse grand glass opacity, which all had recovered. Onset of ILD in MPM varied between the first and the fifth courses of pemetrexed treatment, and the latest onset was 48 days after the last administration. For NSCLC, it was between the second and the ninth course, 7 and 56 days after the last administration. The risk of pemetrexed-related ILD is similar level as other anti-cancer drugs under clinical settings. Careful observations continuously during and at least for 2 months after the last administration of pemetrexed are advised. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Possible Significance of Bronchoalveolar Lavage Cytology at Initial Diagnosis and Follow-up of Lung Cancer].

PubMed

Grünewaldt, A; Hügel, C; Hermann, E; Wagner, T O F

2017-02-01

Bronchoalveolar lavage [BAL] is an important procedure in the diagnosis of a variety of lung diseases. While it has enormous value in the diagnostics of inflammatory parenchymal diseases, its significance in lung cancer is unclear. Keeping in mind that immune therapy (e. g. application of checkpoint inhibitors) is gaining importance in the management of lung carcinoma, it is important to know if there are typical cellular patterns in BAL of lung cancer patients. Methods  In a retrospective proof of principle-study, we analyzed 38 patients who underwent BAL at the initial diagnosis of lung cancer. Results  We observed an elevated level of CD25 lymphocytes as well as an increased expression of DR antigen, both signaling lymphocyte activation. We could not find a typical cytologic pattern of inflammatory cells in lung carcinoma patients. Sensitivity of BAL to malignant cells was rare, thus confirming earlier analysis. Conclusion  We could not demonstrate typical cellular patterns in BAL of lung cancer patients. Evaluation of specific microRNA patterns might play a supporting role in the initial diagnosis as well as follow-up of lung cancer patients. © Georg Thieme Verlag KG Stuttgart · New York.

Rheumatoid Arthritis-Associated Interstitial Lung Disease: Current Concepts.

PubMed

Brito, Yoel; Glassberg, Marilyn K; Ascherman, Dana P

2017-11-09

Among the many extra-articular complications of rheumatoid arthritis (RA), interstitial lung disease (ILD) contributes significantly to morbidity and mortality. Prevalence estimates for RA-ILD vary widely depending on the specific clinical, radiographic, and functional criteria used to establish the diagnosis. A key unresolved issue is whether early, subclinical forms of RA-ILD represent a precursor to end stage, fibrotic lung disease. Based on uncertainties surrounding the natural history of RA-ILD, incomplete understanding of underlying disease pathogenesis, and lack of controlled clinical trials, evidence-based therapeutic strategies remain largely undefined. Correlative clinico-epidemiological studies have identified key risk factors for disease progression. Complementing these findings, the identification of specific molecular and serological markers of RA-ILD has improved our understanding of disease pathogenesis and established the foundation for predictive biomarker profiling. Experience from case series and cohort studies suggests that newer biological agents such as rituximab may be viable treatment options. RA-ILD continues to have a major impact on "disease intrinsic" morbidity and mortality. Increased understanding of disease pathogenesis and the natural history of subclinical RA-ILD will promote the development of more refined therapeutic strategies.

Lung disease in a global context. A call for public health action.

PubMed

Schluger, Neil W; Koppaka, Ram

2014-03-01

As described in a recently released report of the Forum of International Respiratory Societies, four of the leading causes of death in the world are chronic obstructive pulmonary disease, acute respiratory tract infections, lung cancer, and tuberculosis. A fifth, asthma, causes enormous global morbidity. Not enough progress has been made in introducing new therapies and reducing disease burden for these illnesses in the last few decades, despite generous investments and some notable progress in biomedical research. Four external and modifiable drivers are responsible for a substantial percentage of the disease burden represented by the major lung diseases: tobacco, outdoor air pollution, household air pollution, and occupational exposures to lung toxins. Especially in low- and middle-income countries, but in highly developed economies as well, pressures for economic development and lax regulation are contributing to the continued proliferation of these drivers. Public health approaches to the most common lung diseases could have enormous effects on reducing morbidity and mortality. There must be increased advocacy from and mobilization of civil society to bring attention to the drivers of lung diseases in the world. The World Health Organization should negotiate accords similar to the Framework Convention on Tobacco Control to address air pollution and occupational exposures. Large increases in funding by government agencies and nongovernmental organizations around the world are needed to identify technologies that will reduce health risks while allowing populations to enjoy the benefits of economic development. This paradigm, focused more on public health than on individual medical treatment, has the best chance of substantial reduction in the burden of lung disease around the world in the next several years.

Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review

PubMed Central

Iqbal, Kundan; Kelly, Clive

2015-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 0.5–1% of the worldwide population. Whilst predominantly causing chronic pain and inflammation in synovial joints, it is also associated with significant extra-articular manifestations in a large proportion of patients. Among the various pulmonary manifestations, interstitial lung disease (ILD), a progressive fibrotic disease of the lung parenchyma, is the commonest and most important, contributing significantly to increased morbidity and mortality. The most frequent patterns of RA-associated ILD (RA-ILD) are usual interstitial pneumonia and nonspecific interstitial pneumonia. New insights during the past several years have highlighted the epidemiological impact of RA-ILD and have begun to identify factors contributing to its pathogenesis. Risk factors include smoking, male sex, human leukocyte antigen haplotype, rheumatoid factor and anticyclic citrullinated protein antibodies (ACPAs). Combined with clinical information, chest examination and pulmonary function testing, high-resolution computed tomography of the chest forms the basis of investigation and allows assessment of subtype and disease extent. The management of RA-ILD is a challenge. Several therapeutic agents have been suggested in the literature but as yet no large randomized controlled trials have been undertaken to guide clinical management. Therapy is further complicated by commonly prescribed drugs of proven articular benefit such as methotrexate, leflunomide (LEF) and anti-tumour necrosis factor α agents having been implicated in both ex novo occurrence and acceleration of existing ILD. Agents that offer promise include immunomodulators such as mycophenolate and rituximab as well as newly studied antifibrotic agents. In this review, we discuss the current literature to evaluate recommendations for the management of RA-ILD and discuss key gaps in our knowledge of this important disease. PMID:26622326

Lung imaging in pulmonary disease

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

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

1976-01-01

Although it has been recognized for several years that chronic obstructive pulmonary disease (COPD) can cause lung perfusion defects which may simulate pulmonary embolism, relatively little use has been made of either the radioxenon or the radioaerosol inhalation lung imaging procedures until the last few years as a means of distinguishing pulmonary embolism (P.E.) from COPD is reported. Recent experience is reported with the use of both of these procedures in comparison with pulmonary function tests for the early detection of COPD in population studies and also in P.E. suspects. Equal emphasis is given to simultaneous aerosol ventilation-perfusion (V/P) imagingmore » in the differential diagnosis of P.E. Finally, this paper is concerned with new developments in regional lung diffusion imaging following the inhalation of radioactive gases and rapidly absorbed radioaerosols. Their experimental basis is presented and their potential clinical applications in pulmonary embolism are discussed. As a result of these investigations, a functional (V/P) diagnosis of pulmonary embolism in patients may be possible in the near future with a sequential radioaerosol inhalation procedure alone.« less

Interstitial Lung Disease in India. Results of a Prospective Registry.

PubMed

Singh, Sheetu; Collins, Bridget F; Sharma, Bharat B; Joshi, Jyotsna M; Talwar, Deepak; Katiyar, Sandeep; Singh, Nishtha; Ho, Lawrence; Samaria, Jai Kumar; Bhattacharya, Parthasarathi; Gupta, Rakesh; Chaudhari, Sudhir; Singh, Tejraj; Moond, Vijay; Pipavath, Sudhakar; Ahuja, Jitesh; Chetambath, Ravindran; Ghoshal, Aloke G; Jain, Nirmal K; Devi, H J Gayathri; Kant, Surya; Koul, Parvaiz; Dhar, Raja; Swarnakar, Rajesh; Sharma, Surendra K; Roy, Dhrubajyoti J; Sarmah, Kripesh R; Jankharia, Bhavin; Schmidt, Rodney; Katiyar, Santosh K; Jindal, Arpita; Mangal, Daya K; Singh, Virendra; Raghu, Ganesh

2017-03-15

Interstitial lung disease (ILD) is a heterogeneous group of acute and chronic inflammatory and fibrotic lung diseases. Existing ILD registries have had variable findings. Little is known about the clinical profile of ILDs in India. To characterize new-onset ILDs in India by creating a prospective ILD using multidisciplinary discussion (MDD) to validate diagnoses. Adult patients of Indian origin living in India with new-onset ILD (27 centers, 19 Indian cities, March 2012-June 2015) without malignancy or infection were included. All had connective tissue disease (CTD) serologies, spirometry, and high-resolution computed tomography chest. ILD pattern was defined by high-resolution computed tomography images. Three groups independently made diagnoses after review of clinical data including that from prompted case report forms: local site investigators, ILD experts at the National Data Coordinating Center (NDCC; Jaipur, India) with MDD, and experienced ILD experts at the Center for ILD (CILD; Seattle, WA) with MDD. Cohen's κ was used to assess reliability of interobserver agreement. A total of 1,084 patients were recruited. Final diagnosis: hypersensitivity pneumonitis in 47.3% (n = 513; exposure, 48.1% air coolers), CTD-ILD in 13.9%, and idiopathic pulmonary fibrosis in 13.7%. Cohen's κ: 0.351 site investigator/CILD, 0.519 site investigator/NDCC, and 0.618 NDCC/CILD. Hypersensitivity pneumonitis was the most common new-onset ILD in India, followed by CTD-ILD and idiopathic pulmonary fibrosis; diagnoses varied between site investigators and CILD experts, emphasizing the value of MDD in ILD diagnosis. Prompted case report forms including environmental exposures in prospective registries will likely provide further insight into the etiology and management of ILD worldwide.

Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening.

PubMed

Sly, Peter D; Brennan, Siobhain; Gangell, Catherine; de Klerk, Nicholas; Murray, Conor; Mott, Lauren; Stick, Stephen M; Robinson, Philip J; Robertson, Colin F; Ranganathan, Sarath C

2009-07-15

The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis. To determine the extent of lung disease in a geographically defined population of infants with CF diagnosed after detection by NBS. Fifty-seven infants (median age, 3.6 mo) with CF underwent bronchoalveolar lavage and chest computed tomography (CT) using a three-slice inspiratory and expiratory protocol. Despite the absence of respiratory symptoms in 48 (84.2%) of infants, a substantial proportion had lung disease with bacterial infection detected in 12 (21.1%), including Staphylococcus aureus (n = 4) and Pseudomonas aeruginosa (n = 3); neutrophilic inflammation (41. 4 x 10(3) cells/ml representing 18.7% of total cell count); proinflammatory cytokines, with 44 (77.2%) having detectable IL-8; and 17 (29.8%) having detectable free neutrophil elastase activity. Inflammation was increased in those with infection and respiratory symptoms; however, the majority of those infected were asymptomatic. Radiologic evidence of structural lung disease was common, with 46 (80.7%) having an abnormal CT; 11 (18.6%) had bronchial dilatation, 27 (45.0%) had bronchial wall thickening, and 40 (66.7%) had gas trapping. On multivariate analysis, free neutrophil elastase activity was associated with structural lung disease. Most children with structural lung disease had no clinically apparent lung disease. These data support the need for full evaluation in infancy and argue for new treatment strategies, especially those targeting neutrophilic inflammation, if the promise of NBS for CF is to be realized.

Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace.

PubMed

Hecker, Louise

2018-04-01

The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation.

PubMed

Sokai, Akihiko; Handa, Tomohiro; Chen, Fengshi; Tanizawa, Kiminobu; Aoyama, Akihiro; Kubo, Takeshi; Ikezoe, Kohei; Nakatsuka, Yoshinari; Oguma, Tsuyoshi; Hirai, Toyohiro; Nagai, Sonoko; Chin, Kazuo; Date, Hiroshi; Mishima, Michiaki

2016-04-01

Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Patterns of Emphysema Heterogeneity

PubMed Central

Valipour, Arschang; Shah, Pallav L.; Gesierich, Wolfgang; Eberhardt, Ralf; Snell, Greg; Strange, Charlie; Barry, Robert; Gupta, Avina; Henne, Erik; Bandyopadhyay, Sourish; Raffy, Philippe; Yin, Youbing; Tschirren, Juerg; Herth, Felix J.F.

2016-01-01

Background Although lobar patterns of emphysema heterogeneity are indicative of optimal target sites for lung volume reduction (LVR) strategies, the presence of segmental, or sublobar, heterogeneity is often underappreciated. Objective The aim of this study was to understand lobar and segmental patterns of emphysema heterogeneity, which may more precisely indicate optimal target sites for LVR procedures. Methods Patterns of emphysema heterogeneity were evaluated in a representative cohort of 150 severe (GOLD stage III/IV) chronic obstructive pulmonary disease (COPD) patients from the COPDGene study. High-resolution computerized tomography analysis software was used to measure tissue destruction throughout the lungs to compute heterogeneity (≥ 15% difference in tissue destruction) between (inter-) and within (intra-) lobes for each patient. Emphysema tissue destruction was characterized segmentally to define patterns of heterogeneity. Results Segmental tissue destruction revealed interlobar heterogeneity in the left lung (57%) and right lung (52%). Intralobar heterogeneity was observed in at least one lobe of all patients. No patient presented true homogeneity at a segmental level. There was true homogeneity across both lungs in 3% of the cohort when defining heterogeneity as ≥ 30% difference in tissue destruction. Conclusion Many LVR technologies for treatment of emphysema have focused on interlobar heterogeneity and target an entire lobe per procedure. Our observations suggest that a high proportion of patients with emphysema are affected by interlobar as well as intralobar heterogeneity. These findings prompt the need for a segmental approach to LVR in the majority of patients to treat only the most diseased segments and preserve healthier ones. PMID:26430783

Mechanisms of physical activity limitation in chronic lung diseases.

PubMed

Vogiatzis, Ioannis; Zakynthinos, George; Andrianopoulos, Vasileios

2012-01-01

In chronic lung diseases physical activity limitation is multifactorial involving respiratory, hemodynamic, and peripheral muscle abnormalities. The mechanisms of limitation discussed in this paper relate to (i) the imbalance between ventilatory capacity and demand, (ii) the imbalance between energy demand and supply to working respiratory and peripheral muscles, and (iii) the factors that induce peripheral muscle dysfunction. In practice, intolerable exertional symptoms (i.e., dyspnea) and/or leg discomfort are the main symptoms that limit physical performance in patients with chronic lung diseases. Furthermore, the reduced capacity for physical work and the adoption of a sedentary lifestyle, in an attempt to avoid breathlessness upon physical exertion, cause profound muscle deconditioning which in turn leads to disability and loss of functional independence. Accordingly, physical inactivity is an important component of worsening the patients' quality of life and contributes importantly to poor prognosis. Identifying the factors which prevent a patient with lung disease to easily carry out activities of daily living provides a unique as well as important perspective for the choice of the appropriate therapeutic strategy.

Will chronic e-cigarette use cause lung disease?

PubMed Central

Rowell, Temperance R.

2015-01-01

Chronic tobacco smoking is a major cause of preventable morbidity and mortality worldwide. In the lung, tobacco smoking increases the risk of lung cancer, and also causes chronic obstructive pulmonary disease (COPD), which encompasses both emphysema and chronic bronchitis. E-cigarettes (E-Cigs), or electronic nicotine delivery systems, were developed over a decade ago and are designed to deliver nicotine without combusting tobacco. Although tobacco smoking has declined since the 1950s, E-Cig usage has increased, attracting both former tobacco smokers and never smokers. E-Cig liquids (e-liquids) contain nicotine in a glycerol/propylene glycol vehicle with flavorings, which are vaporized and inhaled. To date, neither E-Cig devices, nor e-liquids, are regulated by the Food and Drug Administration (FDA). The FDA has proposed a deeming rule, which aims to initiate legislation to regulate E-Cigs, but the timeline to take effect is uncertain. Proponents of E-Cigs say that they are safe and should not be regulated. Opposition is varied, with some opponents proposing that E-Cig usage will introduce a new generation to nicotine addiction, reversing the decline seen with tobacco smoking, or that E-Cigs generally may not be safe and will trigger diseases like tobacco. In this review, we shall discuss what is known about the effects of E-Cigs on the mammalian lung and isolated lung cells in vitro. We hope that collating this data will help illustrate gaps in the knowledge of this burgeoning field, directing researchers toward answering whether or not E-Cigs are capable of causing disease. PMID:26408554

Fibrocytes in the Pathogenesis of Chronic Fibrotic Lung Disease

PubMed Central

Loomis-King, Hillary; Moore, Bethany B.

2016-01-01

Fibrocytes were initially described in 1999 and since that time there has been a growing body of literature to suggest their importance in a number of chronic lung diseases. It is now well established that fibrocytes derive from the bone marrow and circulate within the peripheral blood. However, when injury occurs, fibrocytes can travel to the site of damage via chemokine-mediated recruitment. Recent studies suggest that fibrocyte numbers increase within the lung or circulation during numerous disease processes. Although fibrocytes readily differentiate into fibroblasts in vitro, whether they do so in vivo is still unknown. The variety of pro-fibrotic mediators that are secreted by fibrocytes makes it likely that they act via paracrine functions to influence the behavior of resident lung cells. This review summarizes recent insights regarding fibrocytes in asthma, scleroderma and IPF. PMID:27512347

Stem cells for the prevention of neonatal lung disease.

PubMed

O'Reilly, Megan; Thébaud, Bernard

2015-01-01

Preterm birth affects approximately 11% of all newborns worldwide and is a major risk factor for infant mortality and morbidity. A common complication of preterm birth is the chronic lung disease of prematurity called bronchopulmonary dysplasia (BPD). Due to the lack of a specific treatment for BPD, preterm infants surviving with BPD face a lifelong risk of poor lung health. The therapeutic potential of stem cells in regenerative medicine is being harnessed for many diseases, including BPD. Compelling preclinical data using stem cells to prevent/repair lung damage in animal models of experimental BPD has built the basis for its translation into the clinic in preterm infants. This review highlights the exciting translation from bench to bedside that will hopefully lead in the near future to improved pulmonary outcomes in preterm infants. © 2015 S. Karger AG, Basel.

The Intersection of Aging Biology and the Pathobiology of Lung Diseases: A Joint NHLBI/NIA Workshop.

PubMed

Budinger, G R Scott; Kohanski, Ronald A; Gan, Weiniu; Kobor, Michael S; Amaral, Luis A; Armanios, Mary; Kelsey, Karl T; Pardo, Annie; Tuder, Rubin; Macian, Fernando; Chandel, Navdeep; Vaughan, Douglas; Rojas, Mauricio; Mora, Ana L; Kovacs, Elizabeth; Duncan, Steven R; Finkel, Toren; Choi, Augustine; Eickelberg, Oliver; Chen, Danica; Agusti, Alvar; Selman, Moises; Balch, William E; Busse, Paula; Lin, Anning; Morimoto, Richard; Sznajder, Jacob I; Thannickal, Victor J

2017-10-12

Death from chronic lung disease is increasing and chronic obstructive pulmonary disease has become the third leading cause of death in the United States in the past decade. Both chronic and acute lung diseases disproportionately affect elderly individuals, making it likely that these diseases will become more frequent and severe as the worldwide population ages. Chronic lung diseases are associated with substantial morbidity, frequently resulting in exercise limiting dyspnea, immobilization, and isolation. Therefore, effective strategies to prevent or treat lung disease are likely to increase healthspan as well as life span. This review summarizes the findings of a joint workshop sponsored by the NIA and NHLBI that brought together investigators focused on aging and lung biology. These investigators encouraged the use of genetic systems and aged animals in the study of lung disease and the development of integrative systems-based platforms that can dynamically incorporate data sets that describe the genomics, transcriptomics, epigenomics, metabolomics, and proteomics of the aging lung in health and disease. Further research was recommended to integrate benchmark biological hallmarks of aging in the lung with the pathobiology of acute and chronic lung diseases with divergent pathologies for which advanced age is the most important risk factor. Published by Oxford University Press on behalf of The Gerontological Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Role of the Lung Microbiome in the Pathogenesis of Chronic Obstructive Pulmonary Disease.

PubMed

Wang, Lei; Hao, Ke; Yang, Ting; Wang, Chen

2017-09-05

The development of culture-independent techniques for microbiological analysis shows that bronchial tree is not sterile in either healthy or chronic obstructive pulmonary disease (COPD) individuals. With the advance of sequencing technologies, lung microbiome has become a new frontier for pulmonary disease research, and such advance has led to better understanding of the lung microbiome in COPD. This review aimed to summarize the recent advances in lung microbiome, its relationships with COPD, and the possible mechanisms that microbiome contributed to COPD pathogenesis. Literature search was conducted using PubMed to collect all available studies concerning lung microbiome in COPD. The search terms were "microbiome" and "chronic obstructive pulmonary disease", or "microbiome" and "lung/pulmonary". The papers in English about lung microbiome or lung microbiome in COPD were selected, and the type of articles was not limited. The lung is a complex microbial ecosystem; the microbiome in lung is a collection of viable and nonviable microbiota (bacteria, viruses, and fungi) residing in the bronchial tree and parenchymal tissues, which is important for health. The following types of respiratory samples are often used to detect the lung microbiome: sputum, bronchial aspirate, bronchoalveolar lavage, and bronchial mucosa. Disordered bacterial microbiome is participated in pathogenesis of COPD; there are also dynamic changes in microbiota during COPD exacerbations. Lung microbiome may contribute to the pathogenesis of COPD by manipulating inflammatory and/or immune process. Normal lung microbiome could be useful for prophylactic or therapeutic management in COPD, and the changes of lung microbiome could also serve as biomarkers for the evaluation of COPD.

A Review of Clinical and Imaging Findings in Eosinophilic Lung Diseases.

PubMed

Bernheim, Adam; McLoud, Theresa

2017-05-01

The purpose of this article is to review the clinical and imaging findings associated with eosinophilic lung diseases. The spectrum of eosinophilic lung diseases comprises a diverse group of pulmonary disorders that have an association with tissue or peripheral eosinophilia. These diseases have varied clinical presentations and may be associated with several other abnormalities. Characteristic imaging findings are often detected with chest radiography, and CT best shows parenchymal abnormalities. The integration of clinical, radiologic, and pathologic findings facilitates diagnosis and directs appropriate treatment.

Usual interstitial pneumonia: typical, possible, and “inconsistent” patterns

PubMed Central

Torres, Pedro Paulo Teixeira e Silva; Rabahi, Marcelo Fouad; Moreira, Maria Auxiliadora Carmo; Meirelles, Gustavo de Souza Portes; Marchiori, Edson

2017-01-01

ABSTRACT Idiopathic pulmonary fibrosis is a severe and progressive chronic fibrosing interstitial lung disease, a definitive diagnosis being established by specific combinations of clinical, radiological, and pathological findings. According to current international guidelines, HRCT plays a key role in establishing a diagnosis of usual interstitial pneumonia (UIP). Current guidelines describe three UIP patterns based on HRCT findings: a typical UIP pattern; a pattern designated “possible UIP”; and a pattern designated “inconsistent with UIP”, each pattern having important diagnostic implications. A typical UIP pattern on HRCT is highly accurate for the presence of histopathological UIP, being currently considered to be diagnostic of UIP. The remaining patterns require further diagnostic investigation. Other known causes of a UIP pattern include drug-induced interstitial lung disease, chronic hypersensitivity pneumonitis, occupational diseases (e.g., asbestosis), and connective tissue diseases, all of which should be included in the clinical differential diagnosis. Given the importance of CT studies in establishing a diagnosis and the possibility of interobserver variability, the objective of this pictorial essay was to illustrate all three UIP patterns on HRCT. PMID:29160385

Indoor air pollution from solid fuel use, chronic lung diseases and lung cancer in Harbin, Northeast China

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

Galeone, C.; Pelucchi, C.; La Vecchia, C.

In some areas of China, indoor air pollution (IAP) originating principally from the combustion of solid fuels has a relevant role in lung cancer. Most previous studies focused on the female population and only a few on both the sexes. We analyzed the relationship between IAP from solid fuel use and selected chronic lung diseases and lung cancer risk in Harbin, Northeast China, an area with a very high base line risk of lung cancer for both the sexes. We used data from a case-control study conducted between 1987 and 1990, including 218 patients with incident, histologically confirmed lung cancermore » and 436 controls admitted to the same hospitals as cases. We calculated an index of IAP from solid fuel use exposure using data on heating type, cooking fuel used, and house measurements. Cases reported more frequently than controls on exposure to coal fuel for house heating and/or cooking, and the odds ratio (OR) for ever versus never exposed was 2.19 (95% confidence interval (CI): 1.08-4.46). The ORs of lung cancer according to subsequent tertiles of IAP exposure index were 1.82 (95% CI: 1.14-2.89) and 1.99 (95% CI: 1.26-3.15) as compared with the lowest tertile. The ORs of lung cancer for participants with a history of chronic bronchitis and tuberculosis were 3.79 (95% CI: 2.38-6.02) and 3.82 (95% CI: 1.97-7.41), respectively. This study gives further support and quantification of the positive association between IAP, history of selected nonmalignant lung diseases, and lung cancer risk for both the sexes.« less

Hyperprogressive disease in patients with non-small cell lung cancer on immunotherapy.

PubMed

Kurman, Jonathan S; Murgu, Septimiu D

2018-02-01

Immunotherapy agents in metastatic non-small cell lung cancer (NSCLC) can result in improved quality of life and survival when compared with platinum-based chemotherapy. Novel response patterns such as pseudoprogression and hyperprogression, however, have been described and pose a challenge to treating physicians. Predictors of hyperprogressive disease (HPD) have not yet been identified. Evaluation and management by a multidisciplinary team involving medical and radiation oncologists, thoracic radiologists, and proceduralists is necessary to identify this subset of patients in a timely manner. Repeat biopsy distinguishes HPD from pseudoprogression and may eventually elucidate predictive biomarkers. We describe the epidemiology of these two phenomena, their diagnostic criteria, and their relevance for interventional pulmonologists.

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.

[Combined surgical intervention treatments for lung cancer and coronary heart disease patients].

PubMed

Ma, Xuchen; Zhang, Zhitai; Hu, Yansheng; Song, Feiqiang; Zhang, Shaoyan; Ou, Songlei

2012-10-01

The number of patients with both lung cancer and coronary heart disease has increased for the last ten years. The aim of this study is to analyze the outcome of the combined treatment of radical surgery and off-pump coronary artery bypass grafting (OPCABG) for patients with both lung cancer and coronary heart disease. The clinical data of 18 patients (16 males and 2 females, mean age of 66.11 years) with both lung cancer and coronary heart disease who went through combined surgical interventions between 2003 and 2012 were summarized and analyzed. The lung cancer in these patients was predominantly at stages I and II (TNM). All patients' cardio-pulmonary function was favorable. All the patients survived the operation, without any recorded death and new myocardial infarction occurrence during the perioperative period. Squamous carcinoma and adenocarcinoma were found in 10 and 8 patients, respectively. Pathological lung cancer stage was Ia in 2 cases, Ib in 8 cases, IIa in 3 cases, II b in 3 cases, and IIIa in 2 cases. The most frequently observed complications were cardiac arrhythmias, atelectasis, and pulmonary infections. The mean values of operating room time, postoperative drainage, drainage tube time, and blood transfusion were significantly different between video-assisted thoracoscopic surgery (VATS) groups and thoractomy groups. No significant differences in survival rate were found (P=0.187). The combined method of OPCABG and pulmonary resection is a safe and effective treatment for patients with both lung cancer and coronary heart disease. VATS lobectomy is beneficial for lung cancer patients because it reduces lesions.

[Lung Cancer as an Occupational Disease].

PubMed

Baur, X; Woitowitz, H-J

2016-08-01

Lung cancer is one of the most frequently encountered cancer types. According to the latest WHO data, about 10 % of this disease are due to occupational exposure to cancerogens. Asbestos is still the number one carcinogen. Further frequent causes include quarz and ionizing radiation (uranium mining). Probable causes of the disease can be identified only with the help of detailed occupational history taken by a medical specialist and qualified exposure assessment. Without clarifying the cause of the disease, there is neither a correct insurance procedure nor compensation for the victim, and furthermore, required preventive measures cannot be initiated. © Georg Thieme Verlag KG Stuttgart · New York.

Detection of gastro-oesophageal reflux disease (GORD) in patients with obstructive lung disease using exhaled breath profiling.

PubMed

Timms, Chris; Thomas, Paul S; Yates, Deborah H

2012-03-01

Gastro-oesophageal reflux disease (GORD) has been implicated in the worsening of several respiratory disorders. Current methods of diagnosis lack accuracy, are invasive and can be costly. Recently, novel methods of analysing lung pathophysiology have been developed including the use of an electronic nose and analysis of components of exhaled breath condensate (EBC). We hypothesised that these methods would distinguish patients with GORD from those without GORD in the common obstructive lung diseases and healthy controls. In a cross-sectional study, exhaled breath was analysed using the Cyranose 320 electronic nose, using principal components and canonical discriminant analyses. EBC pH and pepsin were quantified using a pH meter and an enzyme-linked immunosorbent assay, respectively. A standardized reflux disease questionnaire (RDQ) was used to assess reflux symptoms. The Cyranose 320 distinguished exhaled breath profiles of obstructive lung disease patients without GORD from obstructive lung disease patients with GORD (p = 0.023, accuracy 67.6%), asthmatic patients with reflux from asthmatics without GORD (85%, p = < 0.015, interclass M distance > 2.8), but did not produce as robust a profile for patients with COPD and COPD with GORD (p = 0.047, accuracy 64%). Patients with obstructive lung disease and GORD had significantly higher levels of EBC pepsin (9.81 ± interquartile range (IQR) 4.38 ng ml(-1)) than those without GORD (4.6 ± IQR 6.95 ng ml(-1)), as well as healthy controls (3.44 ± IQR 7.87 ng ml(-1); p = < 0.013). EBC pH was not significantly related to the presence of GORD in any group. The RDQ results correlated significantly with the presence of EBC pepsin. This pilot study has shown that exhaled breath profiling can be used for detecting GORD in obstructive lung diseases. While the electronic nose was useful in asthma, EBC pepsin was more helpful in COPD. In this study, several different confounders could potentially have affected results and larger

The emerging role of myeloid-derived suppressor cells in lung diseases.

PubMed

Kolahian, Saeed; Öz, Hasan Halit; Zhou, Benyuan; Griessinger, Christoph M; Rieber, Nikolaus; Hartl, Dominik

2016-03-01

Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterised by their potential to control T-cell responses and to dampen inflammation. While the role of MDSCs in cancer has been studied in depth, our understanding of their relevance for infectious and inflammatory disease conditions has just begun to evolve. Recent studies highlight an emerging and complex role for MDSCs in pulmonary diseases. In this review, we discuss the potential contribution of MDSCs as biomarkers and therapeutic targets in lung diseases, particularly lung cancer, tuberculosis, chronic obstructive pulmonary disease, asthma and cystic fibrosis. Copyright ©ERS 2016.

Processing of CT images for analysis of diffuse lung disease in the lung tissue research consortium

NASA Astrophysics Data System (ADS)

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

2008-03-01

The goal of Lung Tissue Resource Consortium (LTRC) is to improve the management of diffuse lung diseases through a better understanding of the biology of Chronic Obstructive Pulmonary Disease (COPD) and fibrotic interstitial lung disease (ILD) including Idiopathic Pulmonary Fibrosis (IPF). Participants are subjected to a battery of tests including tissue biopsies, physiologic testing, clinical history reporting, and CT scanning of the chest. The LTRC is a repository from which investigators can request tissue specimens and test results as well as semi-quantitative radiology reports, pathology reports, and automated quantitative image analysis results from the CT scan data performed by the LTRC core laboratories. The LTRC Radiology Core Laboratory (RCL), in conjunction with the Biomedical Imaging Resource (BIR), has developed novel processing methods for comprehensive characterization of pulmonary processes on volumetric high-resolution CT scans to quantify how these diseases manifest in radiographic images. Specifically, the RCL has implemented a semi-automated method for segmenting the anatomical regions of the lungs and airways. In these anatomic regions, automated quantification of pathologic features of disease including emphysema volumes and tissue classification are performed using both threshold techniques and advanced texture measures to determine the extent and location of emphysema, ground glass opacities, "honeycombing" (HC) and "irregular linear" or "reticular" pulmonary infiltrates and normal lung. Wall thickness measurements of the trachea, and its branches to the 3 rd and limited 4 th order are also computed. The methods for processing, segmentation and quantification are described. The results are reviewed and verified by an expert radiologist following processing and stored in the public LTRC database for use by pulmonary researchers. To date, over 1200 CT scans have been processed by the RCL and the LTRC project is on target for recruitment of the

Spontaneous Chitin Accumulation in Airways and Age-Related Fibrotic Lung Disease.

PubMed

Van Dyken, Steven J; Liang, Hong-Erh; Naikawadi, Ram P; Woodruff, Prescott G; Wolters, Paul J; Erle, David J; Locksley, Richard M

2017-04-20

The environmentally widespread polysaccharide chitin is degraded and recycled by ubiquitous bacterial and fungal chitinases. Although vertebrates express active chitinases from evolutionarily conserved loci, their role in mammalian physiology is unclear. We show that distinct lung epithelial cells secrete acidic mammalian chitinase (AMCase), which is required for airway chitinase activity. AMCase-deficient mice exhibit premature morbidity and mortality, concomitant with accumulation of environmentally derived chitin polymers in the airways and expression of pro-fibrotic cytokines. Over time, these mice develop spontaneous pulmonary fibrosis, which is ameliorated by restoration of lung chitinase activity by genetic or therapeutic approaches. AMCase-deficient epithelial cells express fibrosis-associated gene sets linked with cell stress pathways. Mice with lung fibrosis due to telomere dysfunction and humans with interstitial lung disease also accumulate excess chitin polymers in their airways. These data suggest that altered chitin clearance could exacerbate fibrogenic pathways in the setting of lung diseases characterized by epithelial cell dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

[Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].

PubMed

Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio

2014-09-15

Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Patterns of Heart Attacks

DTIC Science & Technology

2010-06-01

episode of the flu and because of these misdiagnoses , some cardiologists believe that the signs and symptoms of a heart attack are often missed [25...pattern. Coronary Artery Disease Chest Pain Diabetes Lung Cancer Anemias Atrial Fibrillation Hyperlipidemia Metabolic Disorders .1 Bucket 3: Spectral...8217Urologic disease, Male genital disease, Breast disease,Female genital disease ’Complications of pregnancy, Obstetric labor complication, Puerperal

Personalized biomarkers to monitor disease progression in advanced non-small-cell lung cancer patients treated with icotinib.

PubMed

Song, Gaoguang; Liu, Yujie; Wang, Yanying; Ren, Guanjun; Guo, Shuai; Ren, Junling; Zhang, Li; Li, Zhili

2015-02-02

Disease-specific humoral immune response-related protein complexes in blood are associated with disease progression. Thirty-one patients with stage IIIB and IV non-small-cell lung cancer (NSCLC) were administered with oral dose of icotinib hydrochloride (150 mg twice daily or 125 mg 3 times daily) for a 28-continuous-day cycle until diseases progressed or unacceptable toxicity occurred. The levels of immunoinflammation-related protein complexes (IIRPCs) in a series of plasma samples from 31 NSCLC patients treated with icotinib hydrochloride were determined by an optimized native polyacrylamide gel electrophoresis. Three characteristic patterns of the IIRPCs, named as patterns a, b, and c, respectively, were detected in plasma samples from 31 patients. Prior to the treatment, there were 18 patients in pattern a consisting of 5 IIRPCs, 9 in pattern b consisting of six IIRPCs, and 4 in pattern c without the IIRPCs. The levels of the IIRPCs in 27 patients were quantified. Our results indicate that the time length of humoral immune and inflammation response (TLHIIR) was closely associated with disease progression, and the median TLHIIR was 22.0 weeks, 95% confidence interval: 16.2 to 33.0 weeks, with a lead time of median 11 weeks relative to clinical imaging evidence confirmed by computed tomography or magnetic resonance imaging (the median progression-free survival, 34.0 weeks, 95% confidence interval: 27.9 to 49.0 weeks). The complex relationships between humoral immune response, acquired resistance, and disease progression existed. Personalized IIRPCs could be indicators to monitor the disease progression. Copyright © 2014 Elsevier B.V. All rights reserved.

Lung disease and coal mining: what pulmonologists need to know.

PubMed

Go, Leonard H T; Krefft, Silpa D; Cohen, Robert A; Rose, Cecile S

2016-03-01

Coal mine workers are at risk for a range of chronic respiratory diseases including coal workers' pneumoconiosis, diffuse dust-related fibrosis, and chronic obstructive pulmonary disease. The purpose of this review is to describe coal mining processes and associated exposures to inform the diagnostic evaluation of miners with respiratory symptoms. Although rates of coal workers' pneumoconiosis declined after regulations were enacted in the 1970s, more recent data shows a reversal in this downward trend. Rapidly progressive pneumoconiosis with progressive massive fibrosis (complicated coal workers' pneumoconiosis) is being observed with increased frequency in United States coal miners, with histologic findings of silicosis and mixed-dust pneumoconiosis. There is increasing evidence of decline in lung function in individuals with pneumoconiosis. Multiple recent cohort studies suggest increased risk of lung cancer in coal miners. A detailed understanding of coal mining methods and processes allows clinicians to better evaluate and confirm chronic lung diseases caused by inhalational hazards in the mine atmosphere.

Trace metals in fluids lining the respiratory system of patients with idiopathic pulmonary fibrosis and diffuse lung diseases.

PubMed

Bargagli, Elena; Lavorini, Federico; Pistolesi, Massimo; Rosi, Elisabetta; Prasse, Antje; Rota, Emilia; Voltolini, Luca

2017-07-01

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an undefined etiopathogenesis. Oxidative stress contributes to alveolar injury and fibrosis development and, because transition metals are essential to the functioning of most proteins involved in redox reactions, a better knowledge of metal concentrations and metabolism in the respiratory system of IPF patients may provide a valuable complementary approach to prevent and manage a disease which is often misdiagnosed or diagnosed in later stages. The present review summarizes and discusses literature data on the elemental composition of bronchoalveolar lavage (BAL), induced sputum and exhaled breath condensate (EBC) from patients affected by IPF and healthy subjects. Available data are scanty and the lack of consistent methods for the collection and analysis of lung and airways lining fluids makes it difficult to compare the results of different studies. However, the elemental composition of BAL samples from IPF patients seems to have a specific profile that can be distinguished from that of patients with other interstitial lung diseases (ILD) or control subjects. Suggestions are given towards standard sampling and analytical procedures of BAL samples, in the aim to assess typical element concentration patterns and their potential role as biomarkers of IPF. Copyright © 2017 Elsevier GmbH. All rights reserved.

Chronic obstructive pulmonary disease: quantitative and visual ventilation pattern analysis at xenon ventilation CT performed by using a dual-energy technique.

PubMed

Park, Eun-Ah; Goo, Jin Mo; Park, Sang Joon; Lee, Hyun Ju; Lee, Chang Hyun; Park, Chang Min; Yoo, Chul-Gyu; Kim, Jong Hyo

2010-09-01

To evaluate the potential of xenon ventilation computed tomography (CT) in the quantitative and visual analysis of chronic obstructive pulmonary disease (COPD). This study was approved by the institutional review board. After informed consent was obtained, 32 patients with COPD underwent CT performed before the administration of xenon, two-phase xenon ventilation CT with wash-in (WI) and wash-out (WO) periods, and pulmonary function testing (PFT). For quantitative analysis, results of PFT were compared with attenuation parameters from prexenon images and xenon parameters from xenon-enhanced images in the following three areas at each phase: whole lung, lung with normal attenuation, and low-attenuating lung (LAL). For visual analysis, ventilation patterns were categorized according to the pattern of xenon attenuation in the area of structural abnormalities compared with that in the normal-looking background on a per-lobe basis: pattern A consisted of isoattenuation or high attenuation in the WI period and isoattenuation in the WO period; pattern B, isoattenuation or high attenuation in the WI period and high attenuation in the WO period; pattern C, low attenuation in both the WI and WO periods; and pattern D, low attenuation in the WI period and isoattenuation or high attenuation in the WO period. Among various attenuation and xenon parameters, xenon parameters of the LAL in the WO period showed the best inverse correlation with results of PFT (P < .0001). At visual analysis, while emphysema (which affected 99 lobes) commonly showed pattern A or B, airway diseases such as obstructive bronchiolitis (n = 5) and bronchiectasis (n = 2) and areas with a mucus plug (n = 1) or centrilobular nodules (n = 5) showed pattern D or C. WI and WO xenon ventilation CT is feasible for the simultaneous regional evaluation of structural and ventilation abnormalities both quantitatively and qualitatively in patients with COPD. (c) RSNA, 2010.

Management of Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)

PubMed Central

Silver, Katherine Culp

2015-01-01

Although scleroderma-associated interstitial lung disease (SSc-ILD) is a significant contributor to both morbidity and mortality, its pathogenesis is largely unclear. Pulmonary function tests (PFTs) and high resolution CT (HRCT) scanning continue to be the most effective tools to screen for lung involvement and to monitor for disease progression. More research and better biomarkers are needed to identify patients most at risk for developing SSc-ILD as well as to recognize which of these patients will progress to more severe disease. While immunosuppression remains the mainstay of treatment, anti-fibrotic agents may offer new avenues of treatment for patients with SSc-ILD in the future. PMID:26210128

Spatiotemporal Aeration and Lung Injury Patterns Are Influenced by the First Inflation Strategy at Birth.

PubMed

Tingay, David G; Rajapaksa, Anushi; Zonneveld, C Elroy; Black, Don; Perkins, Elizabeth J; Adler, Andy; Grychtol, Bartłomiej; Lavizzari, Anna; Frerichs, Inéz; Zahra, Valerie A; Davis, Peter G

2016-02-01

Ineffective aeration during the first inflations at birth creates regional aeration and ventilation defects, initiating injurious pathways. This study aimed to compare a sustained first inflation at birth or dynamic end-expiratory supported recruitment during tidal inflations against ventilation without intentional recruitment on gas exchange, lung mechanics, spatiotemporal regional aeration and tidal ventilation, and regional lung injury in preterm lambs. Lambs (127 ± 2 d gestation), instrumented at birth, were ventilated for 60 minutes from birth with either lung-protective positive pressure ventilation (control) or as per control after either an initial 30 seconds of 40 cm H2O sustained inflation (SI) or an initial stepwise end-expiratory pressure recruitment maneuver during tidal inflations (duration 180 s; open lung ventilation [OLV]). At study completion, molecular markers of lung injury were analyzed. The initial use of an OLV maneuver, but not SI, at birth resulted in improved lung compliance, oxygenation, end-expiratory lung volume, and reduced ventilatory needs compared with control, persisting throughout the study. These changes were due to more uniform inter- and intrasubject gravity-dependent spatiotemporal patterns of aeration (measured using electrical impedance tomography). Spatial distribution of tidal ventilation was more stable after either recruitment maneuver. All strategies caused regional lung injury patterns that mirrored associated regional volume states. Irrespective of strategy, spatiotemporal volume loss was consistently associated with up-regulation of early growth response-1 expression. Our results show that mechanical and molecular consequences of lung aeration at birth are not simply related to rapidity of fluid clearance; they are also related to spatiotemporal pressure-volume interactions within the lung during inflation and deflation.

Will chronic e-cigarette use cause lung disease?

PubMed

Rowell, Temperance R; Tarran, Robert

2015-12-15

Chronic tobacco smoking is a major cause of preventable morbidity and mortality worldwide. In the lung, tobacco smoking increases the risk of lung cancer, and also causes chronic obstructive pulmonary disease (COPD), which encompasses both emphysema and chronic bronchitis. E-cigarettes (E-Cigs), or electronic nicotine delivery systems, were developed over a decade ago and are designed to deliver nicotine without combusting tobacco. Although tobacco smoking has declined since the 1950s, E-Cig usage has increased, attracting both former tobacco smokers and never smokers. E-Cig liquids (e-liquids) contain nicotine in a glycerol/propylene glycol vehicle with flavorings, which are vaporized and inhaled. To date, neither E-Cig devices, nor e-liquids, are regulated by the Food and Drug Administration (FDA). The FDA has proposed a deeming rule, which aims to initiate legislation to regulate E-Cigs, but the timeline to take effect is uncertain. Proponents of E-Cigs say that they are safe and should not be regulated. Opposition is varied, with some opponents proposing that E-Cig usage will introduce a new generation to nicotine addiction, reversing the decline seen with tobacco smoking, or that E-Cigs generally may not be safe and will trigger diseases like tobacco. In this review, we shall discuss what is known about the effects of E-Cigs on the mammalian lung and isolated lung cells in vitro. We hope that collating this data will help illustrate gaps in the knowledge of this burgeoning field, directing researchers toward answering whether or not E-Cigs are capable of causing disease. Copyright © 2015 the American Physiological Society.

Interstitial lung disease induced by alectinib (CH5424802/RO5424802).

PubMed

Ikeda, Satoshi; Yoshioka, Hiroshige; Arita, Machiko; Sakai, Takahiro; Sone, Naoyuki; Nishiyama, Akihiro; Niwa, Takashi; Hotta, Machiko; Tanaka, Tomohiro; Ishida, Tadashi

2015-02-01

A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lung disease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lung disease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Coexistence of Chronic Bronchitis in Chronic Obstructive Lung Disease.

PubMed

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

2018-05-12

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

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.

Chest ultrasonography in health surveillance of asbestos-related lung diseases.

PubMed

Smargiassi, Andrea; Pasciuto, Giuliana; Pedicelli, Ilaria; Lo Greco, Erminia; Calvello, Mariarosaria; Inchingolo, Riccardo; Schifino, Gioacchino; Capoluongo, Patrizio; Patriciello, Pasquale; Manno, Maurizio; Cirillo, Alfonso; Corbo, Giuseppe Maria; Soldati, Gino; Iavicoli, Ivo

2017-06-01

Exposure to asbestos fibers can lead to different lung diseases, such as pleural thickening and effusion, asbestosis, mesothelioma, and lung cancer. These diseases are expected to peak in the next few years. The aim of the study was to validate ultrasonography (US) as a diagnostic tool in the management of lung diseases in subjects with a history of occupational exposure to asbestos. Fifty-nine retired male workers previously exposed to asbestos were enrolled in the study. Chest US was performed in all the subjects. The US operator was blinded to earlier performed computed tomography (CT) scan reports and images. The sonographic pathological findings were pleural thickening (with or without calcifications), peripheral lung consolidation, and focal sonographic interstitial syndrome and diffuse pneumogenic sonographic interstitial syndrome (pulmonary asbestosis). Significant US findings were recorded, stored, and subsequently compared with CT scans. With some patients falling into more than one category, on CT scan, pleural thickening was reported in 33 cases (56%, 26 with calcifications), focal interstitial peripheral alterations in 23 (39%), asbestosis in 6 (10%), and peripheral lung consolidation in 13 cases (22%). Comparing each pathological condition to CT scan reports, US findings had high levels of sensitivity, specificity, positive, and negative predictive values. US did not prove effective for the detection of central lung nodules or diaphragmatic pleural thickenings. Chest US was considered to be the best technique to detect minimal pleural effusions (six subjects, 10%). Chest US might be considered an additional tool to follow up subjects occupationally exposed to asbestos who have already undergone CT scan examination and whose pathology is detectable by US as well.

Automating the expert consensus paradigm for robust lung tissue classification

NASA Astrophysics Data System (ADS)

Rajagopalan, Srinivasan; Karwoski, Ronald A.; Raghunath, Sushravya; Bartholmai, Brian J.; Robb, Richard A.

2012-03-01

Clinicians confirm the efficacy of dynamic multidisciplinary interactions in diagnosing Lung disease/wellness from CT scans. However, routine clinical practice cannot readily accomodate such interactions. Current schemes for automating lung tissue classification are based on a single elusive disease differentiating metric; this undermines their reliability in routine diagnosis. We propose a computational workflow that uses a collection (#: 15) of probability density functions (pdf)-based similarity metrics to automatically cluster pattern-specific (#patterns: 5) volumes of interest (#VOI: 976) extracted from the lung CT scans of 14 patients. The resultant clusters are refined for intra-partition compactness and subsequently aggregated into a super cluster using a cluster ensemble technique. The super clusters were validated against the consensus agreement of four clinical experts. The aggregations correlated strongly with expert consensus. By effectively mimicking the expertise of physicians, the proposed workflow could make automation of lung tissue classification a clinical reality.

Lung Ultrasonography in the Evaluation of Interstitial Lung Disease in Systemic Connective Tissue Diseases: Criteria and Severity of Pulmonary Fibrosis - Analysis of 52 Patients.

PubMed

Buda, N; Piskunowicz, M; Porzezińska, M; Kosiak, W; Zdrojewski, Z

2016-08-01

Patients with a diagnosed systemic connective tissue disease require regular monitoring from the point of view of interstitial lung disease. The main aim of this work is a description of the criteria for pulmonary fibrosis and the degree of the severity of the fibrosis during the course of interstitial lung disease through the TLU (transthoracic lung ultrasound). 52 patients with diagnosed diffuse interstitial lung disease were qualified for this research, together with 50 volunteers in the control group. The patients in both groups were over 18 years of age and were of both sexes. The results of the TLU of the patients underwent statistical analysis and were compared to High-Resolution Computed Tomography (HRCT) results. As a consequence of the statistical analysis, we defined our own criteria for pulmonary fibrosis in TLU: irregularity of the pleura line, tightening of the pleura line, the fragmentary nature of the pleura line, blurring of the pleura line, thickening of the pleura line, artifacts of line B ≤ 3 and ≥ 4, artifacts of Am line and subpleural consolidations < 5 mm. As a result of the conducted research, a scale of severity of pulmonary fibrosis in TLU was devised (UFI - Ultrasound Fibrosis Index), enabling a division to be made into mild, moderate and severe cases. Transthoracic Lung Ultrasonography (TLU) gives a new outlook on the diagnostic possibilities, non-invasive and devoid of ionising radiation, of pulmonary fibrosis. This research work has allowed to discover two new ultrasound symptoms of pulmonary fibrosis (blurred pleural line and Am lines). © Georg Thieme Verlag KG Stuttgart · New York.

Cannabis-induced bullous lung disease leading to pneumothorax: Case report and literature review.

PubMed

Mishra, Rashmi; Patel, Ravi; Khaja, Misbahuddin

2017-05-01

Marijuana use has been increasing in the United States among college students and young adults. Marijuana use has been associated with bullous lung disease which can lead to pneumothorax. There are other recreational drugs like methylphenidate, cocaine and heroin which have been associated with pneumothorax. We present a case of a 30-year-old man with spontaneous pneumothorax associated with marijuana use. The patient had no medical conditions and presented to the emergency room with chest pain. The physical examination revealed decreased breath sound on the right side of the chest. Bed side ultrasound of chest showed stratosphere sign, absent lung sliding; consistent with right-sided pneumothorax. The patient underwent placement of a chest tube. Computed tomography chest scans performed on day two also showed bullous lung disease in the right lung. Serial x-rays of the chest showed re-expansion of the lung. Despite the beneficial effects of Marijuana there are deleterious effects which are emphasized here. This case highlights the need for further studies to establish the relationship between marijuana use and lung diseases in the absence of nicotine use.

Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice.

PubMed

Crosby, Jeff R; Zhao, Chenguang; Jiang, Chong; Bai, Dong; Katz, Melanie; Greenlee, Sarah; Kawabe, Hiroshi; McCaleb, Michael; Rotin, Daniela; Guo, Shuling; Monia, Brett P

2017-11-01

Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease. We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease. The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA. Aerosol delivered ENaC ASO down-regulated mucus marker expression and ameliorated goblet cell metaplasia, inflammation, and airway hyper-responsiveness. Lack of systemic activity of ASOs delivered via the aerosol route ensures the safety of this approach. Our results demonstrate that antisense inhibition of ENaC in airway epithelial cells could be an effective and safe approach for the prevention and reversal of lung symptoms in CF and potentially other inflammatory diseases of the lung. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Pre-existing Pulmonary Diseases and Survival in Patients With Stage-dependent Lung Adenocarcinoma

PubMed Central

Jian, Zhi-Hong; Huang, Jing-Yang; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Liang, Yu-Chiu; Wu, Ming-Fang; Liaw, Yung-Po

2016-01-01

Abstract Asthma, chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB) are common lung diseases associated with lung cancer mortality. This study evaluated sex disparities in pre-existing pulmonary diseases and stage-dependent lung adenocarcinoma survival. Patients newly diagnosed with lung adenocarcinoma between 2003 and 2008 were identified using the National Health Insurance Research Database and Cancer Registry. Cases with lung adenocarcinoma were followed until the end of 2010. Survival curves were estimated by the Kaplan–Meier method. Cox proportional-hazard regression was used to calculate the hazard ratio (HR) of pre-existing asthma, COPD, and/or TB, and to estimate all-cause mortality risk in patients with different stages of lung adenocarcinoma. A total of 14,518 cases were identified with lung adenocarcinoma. Specifically, among men, the HRs for TB were 1.69 (95% confidence interval [CI], 1.10–2.58), 1.48 (95% CI, 1.14–1.93), and 1.27 (95% CI, 1.08–1.49) for individuals with stage I + II, III, and IV diseases, respectively. The HRs for asthma were 1.41 (95% CI, 1.00–1.99) in women with stage I + II and 1.14 (95% CI, 1.04–1.26) in men with stage IV disease. For pulmonary disease combinations in men, the HRs were 1.45 (95% CI, 1.12–1.89) for asthma + COPD + TB, 1.35 (95% CI, 1.12–1.63) for COPD + TB, 1.28 (95% CI, 1.01–1.63) for TB, and 1.15 (95%CI, 1.04–1.27) for asthma + COPD, respectively. For women with stage I + II disease, the HR was 6.94 (95% CI, 2.72–17.71) for asthma + COPD + TB. Coexistence of pre-existing pulmonary diseases increased mortality risk in men with adenocarcinoma. TB is at elevated risk of mortality among men with different stages of adenocarcinoma. Asthmatic women with early-stage adenocarcinoma had increased risk of mortality. PMID:26962806

Occupational lung diseases and the mining industry in Mongolia

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

Lkhasuren, O.; Takahashi, K.; Dash-Onolt, L.

Mining production has accounted for around 50% of the gross industrial product in Mongolia since 1998. Dust-induced chronic bronchitis and pneumoconiosis currently account for the largest relative share (67.8%) of occupational diseases in Mongolia, and cases are increasing annually. In 1967-2004, medically diagnosed cases of occupational diseases in Mongolia numbered 7,600. Of these, 5,154 were confirmed cases of dust-induced chronic bronchitis and pneumoconiosis. Lung diseases and other mining-sector health risks pose major challenges for Mongolia. Gold and coal mines, both formal and informal, contribute significantly to economic growth, but the prevalence of occupational lung diseases is high and access tomore » health care is limited. Rapid implementation of an effective national program of silicosis elimination and pneumoconiosis reduction is critical to ensure the health and safety of workers in this important sector of the Mongolian economy.« less

Microbiome in the pathogenesis of cystic fibrosis and lung transplant-related disease.

PubMed

Cribbs, Sushma K; Beck, James M

2017-01-01

Significant advances in culture-independent methods have expanded our knowledge about the diversity of the lung microbial environment. Complex microorganisms and microbial communities can now be identified in the distal airways in a variety of respiratory diseases, including cystic fibrosis (CF) and the posttransplantation lung. Although there are significant methodologic concerns about sampling the lung microbiome, several studies have now shown that the microbiome of the lower respiratory tract is distinct from the upper airway. CF is a disease characterized by chronic airway infections that lead to significant morbidity and mortality. Traditional culture-dependent methods have identified a select group of pathogens that cause exacerbations in CF, but studies using bacterial 16S rRNA gene-based microarrays have shown that the CF microbiome is an intricate and dynamic bacterial ecosystem, which influences both host immune health and disease pathogenesis. These microbial communities can shift with external influences, including antibiotic exposure. In addition, there have been a number of studies suggesting a link between the gut microbiome and respiratory health in CF. Compared with CF, there is significantly less knowledge about the microbiome of the transplanted lung. Risk factors for bronchiolitis obliterans syndrome, one of the leading causes of death, include microbial infections. Lung transplant patients have a unique lung microbiome that is different than the pretransplanted microbiome and changes with time. Understanding the host-pathogen interactions in these diseases may suggest targeted therapies and improve long-term survival in these patients. Published by Elsevier Inc.

Nutritional state and lung disease in cystic fibrosis.

PubMed

Bakker, W

1992-10-01

The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the severity and progress of the pulmonary involvement associated with the disease. Many data support the view that malnutrition and deterioration of lung function are closely interrelated and interdependent, with each affecting the other, leading to a spiral decline in both. The occurrence of malnutrition appears to be associated with poor lung function and poor survival, and conversely prevention of malnutrition appears to be associated with better lung function and improved survival. Nutritional intervention may lead to an improvement in body weight, lung function and exercise tolerance, provided that the intervention is combined with exercise training in order to increase both respiratory and other muscle mass. These improvements can be preserved when patients have the stamina to continue with a high-energy, high-fat diet and daily exercise training at home.

The Lung Microbiome in Moderate and Severe Chronic Obstructive Pulmonary Disease

PubMed Central

Pragman, Alexa A.; Kim, Hyeun Bum; Reilly, Cavan S.; Wendt, Christine; Isaacson, Richard E.

2012-01-01

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora. Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients. The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid. Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats. Our results showed a significant increase in microbial diversity with the development of COPD. The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria. Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity. However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators. Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples. PMID:23071781

[Lung transplantation.].

PubMed

Guðmundsson, G

2000-09-01

Lung transplantation is an option in the treatment of end stage lung diseases, excluding lung cancer, that lead to short life expectancy and poor quality of life. Now they are mostly limited by shortage of donor organs and longterm complications. They are used for various lung diseases such as pulmonary vascular diseases, fibrosing diseases, chronic obstructive pulmonary diseases and diseases that cause chronic infections. Depending on the indication it is possible to perform heart and lung transplantation, single lung or double lung transplantation.Indications, contraindications, surgical methods, immunosuppression, complications and outcomes will be discussed. Survival is not as good as for other solid organ transplantation. Measurement of pulmonary function and quality of life improve with lung transplantation. Bronchiolitis obliterans is the most common complication and is the most limiting factor. A few Icelanders have undergone lung transplantation, most of them in Gothenburg, Sweden. The future of lung transplantation depends on limiting the incidence of bronchiolitis obliterans and finding more organ donors.

Persistent activation of an innate immune axis translates respiratory viral infection into chronic lung disease

PubMed Central

Kim, Edy Y.; Battaile, John T.; Patel, Anand C.; You, Yingjian; Agapov, Eugene; Grayson, Mitchell H.; Benoit, Loralyn A.; Byers, Derek E.; Alevy, Yael; Tucker, Jennifer; Swanson, Suzanne; Tidwell, Rose; Tyner, Jeffrey W.; Morton, Jeffrey D.; Castro, Mario; Polineni, Deepika; Patterson, G. Alexander; Schwendener, Reto A.; Allard, John D.; Peltz, Gary; Holtzman, Michael J.

2008-01-01

To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of a chronic lung disease that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after infection with a common type of respiratory virus is cleared to trace levels of noninfectious virus. Unexpectedly, the chronic inflammatory disease arises independently of an adaptive immune response and is driven by IL-13 produced by macrophages stimulated by CD1d-dependent TCR-invariant NKT cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a novel NKT cell-macrophage innate immune axis. PMID:18488036

Spectrum of high resolution computed tomography findings in occupational lung disease: experience in a tertiary care institute.

PubMed

Bhawna, Satija; Ojha, U C; Kumar, Sanyal; Gupta, Rajiv; Gothi, Dipti; Pal, R S

2013-01-01

To study the spectrum of high resolution computed tomography (HRCT) findings in occupational lung disease in industrial workers and to assess the utility of International classification of HRCT for occupational and environmental respiratory diseases (ICHOERD). Retrospective analysis of radiological data (radiographs and computed tomography chest scans) gathered over a period of 3 years (January 2010- December 2012) of industrial workers in an organised sector who presented with respiratory complaints. The HRCT findings were evaluated using ICHOERD. There were 5 females and 114 males in the study, with a mean age of 49 years. These workers were exposed to different harmful agents including silica, asbestos, cotton dust, metal dust, iron oxide, organic dust, rubber fumes, plastic fumes, acid fumes, and oil fumes. There were 10 smokers in the study. The radiograph of chest was normal in 53 patients. 46% of these normal patients (21.8% of total) demonstrated positive findings on HRCT. When the radiograph was abnormal, HRCT provided more accurate information and excluded the other diagnosis. The HRCT findings were appropriately described using the ICHOERD. Bronchiectasis was the most common finding (44.5%) with mild central cylindrical bronchiectasis as the most common pattern. Pleural thickening was seen in 41 patients (34.5%). Enlarged hilar or mediastinal lymphnodes were seen in 10 patients (8.4%) with egg-shell calcification in 1 patient exposed to silica. Bronchogenic carcinoma was seen in 1 patient exposed to asbestos. Occupational lung disease is a common work related condition in industrial workers even in the organized sector. Though chest radiograph is the primary diagnostic tool, HRCT is the undisputed Gold Standard for evaluation of these patients. Despite the disadvantage of radiation exposure, low dose CT may serve as an important tool for screening and surveillance. The ICHOERD is a powerful and reliable tool not only for diagnosis, but also for

Lung Cancer and Chronic Obstructive Pulmonary Disease: Needs and Opportunities for Integrated Research

PubMed Central

Szabo, Eva; Croxton, Thomas L.; Shapiro, Steven D.; Dubinett, Steven M.

2009-01-01

Lung cancer and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality in the United States and worldwide. They share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by the incidence of these diseases in only a fraction of smokers. The presence of COPD increases the risk of lung cancer up to 4.5-fold. To investigate commonalities in disease mechanisms and perspectives for disease chemoprevention, the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) held a workshop. The participants identified four research objectives: 1) clarify common epidemiological characteristics of lung cancer and COPD; 2) identify shared genetic and epigenetic risk factors; 3) identify and validate biomarkers, molecular signatures, and imaging-derived measurements of each disease; and 4) determine common and disparate pathogenetic mechanisms. These objectives should be reached via four research approaches: 1) identify, publicize, and enable the evaluation and analysis of existing datasets and repositories of biospecimens; 2) obtain phenotypic and outcome data and biospecimens from large studies of subjects with and/or at risk for COPD and lung cancer; 3) develop and use animal and other preclinical models to investigate pathogenetic links between the diseases; and 4) conduct early-phase clinical trials of potential chemopreventive agents. To foster much needed research interactions, two final recommendations were made by the participants: 1) incorporate baseline phenotyping and outcome measures for both diseases in future longitudinal studies of each disease and 2) expand collaborative efforts between the NCI and NHLBI. PMID:19351920

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

PubMed

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

2016-07-01

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

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

PubMed Central

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

2015-01-01

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

Lung respiratory rhythm and pattern generation in the bullfrog: role of neurokinin-1 and mu-opioid receptors.

PubMed

Davies, B L; Brundage, C M; Harris, M B; Taylor, B E

2009-07-01

Location of the lung respiratory rhythm generator (RRG) in the bullfrog brainstem was investigated by examining neurokinin-1 and mu-opioid receptor (NK1R, muOR) colocalization by immunohistochemistry and characterizing the role of these receptors in lung rhythm and episodic pattern generation. NK1R and muOR occurred in brainstems from all developmental stages. In juvenile bullfrogs a distinct area of colocalization was coincident with high-intensity fluorescent labeling of muOR; high-intensity labeling of muOR was not distinctly and consistently localized in tadpole brainstems. NK1R labeling intensity did not change with development. Similarity in colocalization is consistent with similarity in responses to substance P (SP, NK1R agonist) and DAMGO (muOR agonist) when bath applied to bullfrog brainstems of different developmental stages. In early stage tadpoles and juvenile bullfrogs, SP increased and DAMGO decreased lung burst frequency. In juvenile bullfrogs, SP increased lung burst frequency, episode frequency, but decreased number of lung bursts per episode and lung burst duration. In contrast, DAMGO decreased lung burst frequency and burst cycle frequency, episode frequency, and number of lung bursts per episode but increased all other lung burst parameters. Based on these results, we hypothesize that NK1R and muOR colocalization together with a metamorphosis-related increase in muOR intensity marks the location of the lung RRG but not necessarily the lung episodic pattern generator.

Serum LDL cholesterol concentration and lipoprotein electrophoresis pattern in patients with small cell lung cancer.

PubMed

Siemianowicz, K; Gminski, J; Stajszczyk, M; Wojakowski, W; Goss, M; Machalski, M; Telega, A; Brulinski, K; Magiera-Molendowska, H

2000-01-01

Epidemiological studies show that people with low level of total cholesterol have a greater risk of death due to cancer, predominantly lung cancer. The aim of our study was to evaluate serum level of LDL cholesterol and lipoprotein electrophoresis pattern in patients with small cell lung cancer and their dependence on clinical stage of the neoplasm. The studied group consisted of 34 patients with newly diagnosed small cell lung cancer and 39 healthy controls. Fasting level of LDL cholesterol was analyzed and lipoprotein electrophoresis was performed. There were no statistically significant differences of evaluated serum lipid parameters between lung cancer patients and controls, and between the clinical stages of small cell lung cancer.

Noninfectious interstitial lung disease during infliximab therapy: Case report and literature review

PubMed Central

Caccaro, Roberta; Savarino, Edoardo; D’Incà, Renata; Sturniolo, Giacomo Carlo

2013-01-01

Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases. However, lung toxicity can be induced by conventional medications used to maintain remission, and similar evidence is also emerging for biologics. We present the case of a young woman affected by colonic Crohn’s disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and adalimumab. She was referred to our clinic with a severe relapse and was treated with infliximab, an anti-tumor necrosis factor α (TNF-α) antibody, to induce remission. After an initial benefit, with decreases in bowel movements, rectal bleeding and C-reactive protein levels, she experienced shortness of breath after the 5th infusion. Noninfectious interstitial lung disease was diagnosed. Both mesalamine and infliximab were discontinued, and steroids were introduced with slow but progressive improvement of symptoms, radiology and functional tests. This represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung alterations. Given the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases, this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy. PMID:23983443

Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential.

PubMed

Vij, Neeraj

2011-09-01

The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions are airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hypersecretion in these diseases, which are further induced by infection or components of cigarette smoke. Controlling chronic inflammation is at the root of treatments such as corticosteroids, antibiotics or other available drugs, which pose the challenge of sustained delivery of drugs to target cells or tissues. In spite of the wide application of nano-based drug delivery systems, very few are tested to date. Targeted nanoparticle-mediated sustained drug delivery is required to control inflammatory cell chemotaxis, fibrosis, protease-mediated chronic emphysema and/or chronic lung obstruction in COPD. Moreover, targeted epithelial delivery is indispensable for correcting the underlying defects in CF and targeted inflammatory cell delivery for controlling other chronic inflammatory lung diseases. We propose that the design and development of nano-based targeted theranostic vehicles with therapeutic, imaging and airway-defense penetrating capability, will be invaluable for treating chronic obstructive lung diseases. This paper discusses a novel nano-theranostic strategy that we are currently evaluating to treat the underlying cause of CF and COPD lung disease.

Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer.

PubMed

Matsumoto, Yoshiya; Kawaguchi, Tomoya; Yamamoto, Norio; Sawa, Kenji; Yoshimoto, Naoki; Suzumura, Tomohiro; Watanabe, Tetsuya; Mitsuoka, Shigeki; Asai, Kazuhisa; Kimura, Tatsuo; Yoshimura, Naruo; Kuwae, Yuko; Hirata, Kazuto

2017-09-01

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib.

High-resolution computed tomography findings of pulmonary tuberculosis in lung transplant recipients.

PubMed

Giacomelli, Irai Luis; Schuhmacher Neto, Roberto; Nin, Carlos Schuller; Cassano, Priscilla de Souza; Pereira, Marisa; Moreira, José da Silva; Nascimento, Douglas Zaione; Hochhegger, Bruno

2017-01-01

Respiratory infections constitute a major cause of morbidity and mortality in solid organ transplant recipients. The incidence of pulmonary tuberculosis is high among such patients. On imaging, tuberculosis has various presentations. Greater understanding of those presentations could reduce the impact of the disease by facilitating early diagnosis. Therefore, we attempted to describe the HRCT patterns of pulmonary tuberculosis in lung transplant recipients. From two hospitals in southern Brazil, we collected the following data on lung transplant recipients who developed pulmonary tuberculosis: gender; age; symptoms; the lung disease that led to transplantation; HRCT pattern; distribution of findings; time from transplantation to pulmonary tuberculosis; and mortality rate. The HRCT findings were classified as miliary nodules; cavitation and centrilobular nodules with a tree-in-bud pattern; ground-glass attenuation with consolidation; mediastinal lymph node enlargement; or pleural effusion. We evaluated 402 lung transplant recipients, 19 of whom developed pulmonary tuberculosis after transplantation. Among those 19 patients, the most common HRCT patterns were ground-glass attenuation with consolidation (in 42%); cavitation and centrilobular nodules with a tree-in-bud pattern (in 31.5%); and mediastinal lymph node enlargement (in 15.7%). Among the patients with cavitation and centrilobular nodules with a tree-in-bud pattern, the distribution was within the upper lobes in 66.6%. No pleural effusion was observed. Despite treatment, one-year mortality was 47.3%. The predominant HRCT pattern was ground-glass attenuation with consolidation, followed by cavitation and centrilobular nodules with a tree-in-bud pattern. These findings are similar to those reported for immunocompetent patients with pulmonary tuberculosis and considerably different from those reported for AIDS patients with the same disease.

Hyperprogressive disease in patients with non-small cell lung cancer on immunotherapy

PubMed Central

Kurman, Jonathan S.

2018-01-01

Immunotherapy agents in metastatic non-small cell lung cancer (NSCLC) can result in improved quality of life and survival when compared with platinum-based chemotherapy. Novel response patterns such as pseudoprogression and hyperprogression, however, have been described and pose a challenge to treating physicians. Predictors of hyperprogressive disease (HPD) have not yet been identified. Evaluation and management by a multidisciplinary team involving medical and radiation oncologists, thoracic radiologists, and proceduralists is necessary to identify this subset of patients in a timely manner. Repeat biopsy distinguishes HPD from pseudoprogression and may eventually elucidate predictive biomarkers. We describe the epidemiology of these two phenomena, their diagnostic criteria, and their relevance for interventional pulmonologists. PMID:29607190

Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib.

PubMed

Yamamoto, Yuzo; Okamoto, Isamu; Otsubo, Kohei; Iwama, Eiji; Hamada, Naoki; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi

2015-10-01

Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was therefore diagnosed with interstitial lung disease induced by alectinib. Her CT findings and respiratory condition improved after steroid pulse therapy. As far as we are aware, this is the first reported case of alectinib-induced severe interstitial lung disease (ILD). We should be aware of the possibility of such a severe adverse event and should therefore carefully monitor patients treated with this drug.

Myofibroblasts in interstitial lung diseases show diverse electron microscopic and invasive features.

PubMed

Karvonen, Henna M; Lehtonen, Siri T; Sormunen, Raija T; Harju, Terttu H; Lappi-Blanco, Elisa; Bloigu, Risto S; Kaarteenaho, Riitta L

2012-09-01

The characteristic features of myofibroblasts in various lung disorders are poorly understood. We have evaluated the ultrastructure and invasive capacities of myofibroblasts cultured from small volumes of diagnostic bronchoalveolar lavage (BAL) fluid samples from patients with different types of lung diseases. Cells were cultured from samples of BAL fluid collected from 51 patients that had undergone bronchoscopy and BAL for diagnostic purposes. The cells were visualized by transmission electron microscopy and immunoelectron microscopy to achieve ultrastructural localization of alpha-smooth muscle actin (α-SMA) and fibronectin. The levels of α-SMA protein and mRNA and fibronectin mRNA were measured by western blot and quantitative real-time reverse transcriptase polymerase chain reaction. The invasive capacities of the cells were evaluated. The cultured cells were either fibroblasts or myofibroblasts. The structure of the fibronexus, and the amounts of intracellular actin, extracellular fibronectin and cell junctions of myofibroblasts varied in different diseases. In electron and immunoelectron microscopy, cells cultured from interstitial lung diseases (ILDs) expressed more actin filaments and α-SMA than normal lung. The invasive capacity of the cells obtained from patients with idiopathic pulmonary fibrosis was higher than that from patients with other type of ILDs. Cells expressing more actin filaments had a higher invasion capacity. It is concluded that electron and immunoelectron microscopic studies of myofibroblasts can reveal differential features in various diseases. An analysis of myofibroblasts cultured from diagnostic BAL fluid samples may represent a new kind of tool for diagnostics and research into lung diseases.

Th17/Treg immunoregulation and implications in treatment of sulfur mustard gas-induced lung diseases.

PubMed

Iman, Maryam; Rezaei, Ramazan; Azimzadeh Jamalkandi, Sadegh; Shariati, Parvin; Kheradmand, Farrah; Salimian, Jafar

2017-12-01

Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL -17A) expressing CD4 + T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung. Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017. Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance.

Elemental analysis of occupational and environmental lung diseases by electron probe microanalyzer with wavelength dispersive spectrometer.

PubMed

Takada, Toshinori; Moriyama, Hiroshi; Suzuki, Eiichi

2014-01-01

Occupational and environmental lung diseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lung diseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lung disease is an occupational interstitial lung disease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lung diseases. Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Patterns of lung cancer mortality in 23 countries: application of the age-period-cohort model.

PubMed

Liaw, Yung-Po; Huang, Yi-Chia; Lien, Guang-Wen

2005-03-05

Smoking habits do not seem to be the main explanation of the epidemiological characteristics of female lung cancer mortality in Asian countries. However, Asian countries are often excluded from studies of geographical differences in trends for lung cancer mortality. We thus examined lung cancer trends from 1971 to 1995 among men and women for 23 countries, including four in Asia. International and national data were used to analyze lung cancer mortality from 1971 to 1995 in both sexes. Age-standardized mortality rates (ASMR) were analyzed in five consecutive five-year periods and for each five-year age group in the age range 30 to 79. The age-period-cohort (APC) model was used to estimate the period effect (adjusted for age and cohort effects) for mortality from lung cancer. The sex ratio of the ASMR for lung cancer was lower in Asian countries, while the sex ratio of smoking prevalence was higher in Asian countries. The mean values of the sex ratio of the ASMR from lung cancer in Taiwan, Hong Kong, Singapore, and Japan for the five 5-year period were 2.10, 2.39, 3.07, and 3.55, respectively. These values not only remained quite constant over each five-year period, but were also lower than seen in the western countries. The period effect, for lung cancer mortality as derived for the 23 countries from the APC model, could be classified into seven patterns. Period effects for both men and women in 23 countries, as derived using the APC model, could be classified into seven patterns. Four Asian countries have a relatively low sex ratio in lung cancer mortality and a relatively high sex ratio in smoking prevalence. Factors other than smoking might be important, especially for women in Asian countries.

Patterns of lung cancer mortality in 23 countries: Application of the Age-Period-Cohort model

PubMed Central

Liaw, Yung-Po; Huang, Yi-Chia; Lien, Guang-Wen

2005-01-01

Background Smoking habits do not seem to be the main explanation of the epidemiological characteristics of female lung cancer mortality in Asian countries. However, Asian countries are often excluded from studies of geographical differences in trends for lung cancer mortality. We thus examined lung cancer trends from 1971 to 1995 among men and women for 23 countries, including four in Asia. Methods International and national data were used to analyze lung cancer mortality from 1971 to 1995 in both sexes. Age-standardized mortality rates (ASMR) were analyzed in five consecutive five-year periods and for each five-year age group in the age range 30 to 79. The age-period-cohort (APC) model was used to estimate the period effect (adjusted for age and cohort effects) for mortality from lung cancer. Results The sex ratio of the ASMR for lung cancer was lower in Asian countries, while the sex ratio of smoking prevalence was higher in Asian countries. The mean values of the sex ratio of the ASMR from lung cancer in Taiwan, Hong Kong, Singapore, and Japan for the five 5-year period were 2.10, 2.39, 3.07, and 3.55, respectively. These values not only remained quite constant over each five-year period, but were also lower than seen in the western countries. The period effect, for lung cancer mortality as derived for the 23 countries from the APC model, could be classified into seven patterns. Conclusion Period effects for both men and women in 23 countries, as derived using the APC model, could be classified into seven patterns. Four Asian countries have a relatively low sex ratio in lung cancer mortality and a relatively high sex ratio in smoking prevalence. Factors other than smoking might be important, especially for women in Asian countries. PMID:15748289

Female Sex and Gender in Lung/Sleep Health and Disease: Increased Understanding of Basic Biological, Pathophysiological and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease.

PubMed

Han, MeiLan K; Arteaga-Solis, Emilio; Blenis, John; Bourjeily, Ghada; Clegg, Deborah J; DeMeo, Dawn; Duffy, Jeanne; Gaston, Ben; Heller, Nicola M; Hemnes, Anna; Henske, Elizabeth Petri; Jain, Raksha; Lahm, Tim; Lancaster, Lisa H; Lee, Joyce; Legato, Marianne J; McKee, Sherry; Mehra, Reena; Morris, Alison; Prakash, Y S; Stampfli, Martin R; Gopal-Srivastava, Rashmi; Laposky, Aaron D; Punturieri, Antonello; Reineck, Lora; Tigno, Xenia; Clayton, Janine

2018-05-10

Female sex/gender is an under-characterized variable in studies related to lung development and disease. Notwithstanding, many aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. These may manifest as differential gene expression or peculiar organ development. Some conditions are more prevalent in women, such as asthma and insomnia, or in the case of LAM, are seen almost exclusively in women. In other diseases, presentation differs such as the higher frequency of exacerbations experienced by women with COPD or greater cardiac morbidity among women with sleep disordered breathing. Recent advances in -omics and behavioral science provide an opportunity to specifically address sex-based differences and explore research needs and opportunities that will elucidate biochemical pathways, thus enabling more targeted/personalized therapies. To explore the status of and opportunities for research in this area, the National Heart, Lung, and Blood Institute (NHLBI), in partnership with the National Institutes of Health (NIH) Office of Research on Women's Health (ORWH) and the Office of Rare Diseases Research (ORDR), convened a workshop of investigators in Bethesda, (MD) on September 18-19, 2017. At the workshop the participants reviewed the current understanding of the biological, behavioral, and clinical implications of female sex and gender on lung and sleep health and disease, and formulated recommendations that address research gaps, with a view of achieving better health outcomes through more precise management of female patients with non-neoplastic lung disease were proposed. This report summarizes those discussions.

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

PubMed Central

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

2016-01-01

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

Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer

PubMed Central

Matsumoto, Yoshiya; Kawaguchi, Tomoya; Yamamoto, Norio; Sawa, Kenji; Yoshimoto, Naoki; Suzumura, Tomohiro; Watanabe, Tetsuya; Mitsuoka, Shigeki; Asai, Kazuhisa; Kimura, Tatsuo; Yoshimura, Naruo; Kuwae, Yuko; Hirata, Kazuto

2017-01-01

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib. PMID:28794368

Diagnosis and management of chronic lung disease in deployed military personnel.

PubMed

Morris, Michael J; Lucero, Pedro F; Zanders, Thomas B; Zacher, Lisa L

2013-08-01

Military personnel are a unique group of individuals referred to the pulmonary physician for evaluation. Despite accession standards that limit entrance into the military for individuals with various pre-existing lung diseases, the most common disorders found in the general population such as asthma and chronic obstructive pulmonary disease remain frequently diagnosed. Military personnel generally tend to be a more physically fit population who are required to exercise on a regular basis and as such may have earlier presentations of disease than their civilian counterparts. Exertional dyspnea is a common complaint; establishing a diagnosis may be challenging given the subtle nature of symptoms and lack of specificity with pulmonary function testing. The conflicts over the past 10 years in Iraq and Afghanistan have also given rise to new challenges for deployed military. Various respiratory hazards in the deployed environment include suspended geologic dusts, burn pits, vehicle exhaust emissions, industrial air pollution, and isolated exposure incidents and may give rise to both acute respiratory symptoms and chronic lung disease. In the evaluation of deployed military personnel, establishing the presence of actual pulmonary disease and the relationship of existing disease to deployment is an ongoing issue to both military and civilian physicians. This paper reviews the current evidence for chronic lung disease in the deployed military population and addresses any differences in diagnosis and management.

Randomised Vitamin E Supplementation and Risk of Chronic Lung Disease in the Women’s Health Study

PubMed Central

Agler, Anne H.; Kurth, Tobias; Gaziano, J. Michael; Buring, Julie E.; Cassano, Patricia A.

2011-01-01

Background The oxidant/antioxidant balance in lung tissue is hypothesised to contribute to chronic obstructive pulmonary disease (COPD) risk. Observational studies consistently report higher antioxidant status associated with lower COPD risk, but few randomised studies have been reported. Methods A post-hoc analysis of 38,597 women without chronic lung disease at baseline was conducted in the Women’s Health Study (WHS) to test the effect of vitamin E on risk of incident chronic lung disease. The WHS was a randomised, double-blind, placebo-controlled, factorial trial of vitamin E (600 IU every other day) and aspirin (100 mg every other day) in female health professionals aged ≥45. Using Cox proportional hazards models, the effect of randomised vitamin E assignment on self-reported, physician-diagnosed chronic lung disease was evaluated. Results During 10 years of follow-up (376,710 person-years), 760 first occurrences of chronic lung disease were reported in the vitamin E arm compared to 846 in the placebo arm (Hazard Ratio [HR] 0.90; 95% confidence interval [CI] 0.81–0.99; p=0.029). This 10% reduction in the risk of incident chronic lung disease was not modified by cigarette smoking, age, randomised aspirin assignment, multivitamin use, or dietary vitamin E intake (minimum P for interaction = 0.19). Current cigarette smoking was a strong predictor of chronic lung disease risk (HR 4.17; 95% CI 3.70–4.70; versus never smokers). Conclusions In this large, randomised trial, assignment to 600 IU of vitamin E led to a 10% reduction in the risk of chronic lung disease in women. PMID:21257986

The Role of the Microbiome in Exacerbations of Chronic Lung Diseases

PubMed Central

Dickson, Robert P.; Martinez, Fernando J.; Huffnagle, Gary B.

2014-01-01

Summary Culture-independent microbiological techniques have revealed a previously unappreciated complexity to the bacterial microbiome of the respiratory tract, forcing reconsideration of the interactions between host, bacteria and the pathogenesis of exacerbations of chronic lung disease. The composition of the lung microbiome is determined by microbial immigration, elimination, and the relative growth rates of its members; all of these change dramatically in chronic lung disease and further during exacerbations. Exacerbations lack key features of bacterial infections, including increased bacterial burden and decreased community diversity. We propose instead that exacerbations are occasions of respiratory dysbiosis: a disordered respiratory microbial ecosystem with negative effects on host biology. Respiratory dysbiosis provokes a dysregulated host immune response, which in turn alters microbial growth conditions in patient airways, further promoting dysbiosis and perpetuating a coupled cycle of inflammation and disordered microbiota. Differences in baseline respiratory microbiota may help explain the “frequent-exacerbator” phenotype observed across multiple disease states, and may provide novel targets for therapeutic intervention. PMID:25152271

The role of worker education in preventing occupational lung disease.

PubMed

Kaufman, J D; Rosenstock, L

1991-01-01

Training and education of workers in order to prevent occupational lung diseases represent a challenge to employers, unions, clinicians, and other interested groups. Programs attempting to meet this need range from simple programs in respiratory protection fundamentals and smoking cessation to programs that teach workers to understand and demand their right to a safe and healthful workplace. Support for educational programs has come from diverse sources, including government, labor, business, and independent organizations. In some cases nonprofit organizations have developed innovative programs, but it is important that the burden of preventing occupational lung disease through education not be carried by charitable organizations alone. The role of the clinician in this effort is to educate workers at every opportunity regarding lung hazards and to use early evidence of respiratory damage as a lever to increase the worker's understanding of his or her role in health protection.

Cell Therapy for Lung Diseases. Report from an NIH–NHLBI Workshop, November 13–14, 2012

PubMed Central

Matthay, Michael A.; Anversa, Piero; Bhattacharya, Jahar; Burnett, Bruce K.; Chapman, Harold A.; Hare, Joshua M.; Hei, Derek J.; Hoffman, Andrew M.; Kourembanas, Stella; McKenna, David H.; Ortiz, Luis A.; Ott, Harald C.; Tente, William; Thébaud, Bernard; Trapnell, Bruce C.; Weiss, Daniel J.; Yuan, Jason X.-J.

2013-01-01

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened the Cell Therapy for Lung Disease Working Group on November 13–14, 2012, to review and formulate recommendations for future research directions. The workshop brought together investigators studying basic mechanisms and the roles of cell therapy in preclinical models of lung injury and pulmonary vascular disease, with clinical trial experts in cell therapy for cardiovascular diseases and experts from the NHLBI Production Assistance for Cell Therapy program. The purpose of the workshop was to discuss the current status of basic investigations in lung cell therapy, to identify some of the scientific gaps in current knowledge regarding the potential roles and mechanisms of cell therapy in the treatment of lung diseases, and to develop recommendations to the NHLBI and the research community on scientific priorities and practical steps that would lead to first-in-human trials of lung cell therapy. PMID:23713908

Lung adenocarcinoma mimicking pulmonary fibrosis-a case report.

PubMed

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

2016-09-13

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

Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease.

PubMed

Popowicz, Natalia; Wood, Jamie; Tai, Anna; Morey, Sue; Mulrennan, Siobhain

2017-05-01

Safety-data for lumacaftor/ivacaftor (LUM/IVA) combination therapy in patients with severe lung disease (percent predicted forced expiratory volume in 1s [ppFEV 1 ] <40) remain limited. We report immediate post-dose respiratory-related adverse events in 12 patients with severe cystic fibrosis (CF) lung disease (median [IQR] ppFEV 1 : 34 [31-36]) prescribed LUM/IVA. All patients experienced a decline in ppFEV 1 from baseline at 2-hours (median [IQR] relative change: -19 [-21 to -11]%, p<0.001) that persisted at 24-hours but recovered in most patients at 1-month. No pre- and post-differences in bronchodilator response were observed. Ten (83.3%) patients reported non-severe respiratory-related adverse events within 24-hours of LUM/IVA initiation. At 1-month, eight (67%) patients had persistent symptoms and six (50%) were treated for a pulmonary exacerbation. Our results highlight that LUM/IVA respiratory-related adverse events are common in patients with a ppFEV 1 <40. We recommend close assessment of adverse events. Further studies are required to evaluate the efficacy of LUM/IVA in patients with severe lung disease. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease.

PubMed

Neves, Joana; Leitz, Dominik; Kraut, Simone; Brandenberger, Christina; Agrawal, Raman; Weissmann, Norbert; Mühlfeld, Christian; Mall, Marcus A; Altamura, Sandro; Muckenthaler, Martina U

2017-06-01

Emerging evidence suggests that pulmonary iron accumulation is implicated in a spectrum of chronic lung diseases. However, the mechanism(s) involved in pulmonary iron deposition and its role in the in vivo pathogenesis of lung diseases remains unknown. Here we show that a point mutation in the murine ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1 C326S ), increases iron levels in alveolar macrophages, epithelial cells lining the conducting airways and lung parenchyma, and in vascular smooth muscle cells. Pulmonary iron overload is associated with oxidative stress, restrictive lung disease with decreased total lung capacity and reduced blood oxygen saturation in homozygous Slc40a1 C326S/C326S mice compared to wild-type controls. These findings implicate iron in lung pathology, which is so far not considered a classical iron-related disorder. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Gene Editing and Genetic Lung Disease. Basic Research Meets Therapeutic Application.

PubMed

Alapati, Deepthi; Morrisey, Edward E

2017-03-01

Although our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis, and alpha-1 antitrypsin deficiency is extensive, treatment options are lacking. Because the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intratracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene-editing technology is a promising approach to repairing or inactivating disease-causing mutations. Recent reports have provided proof of concept by using CRISPR/Cas9 to successfully repair or inactivate mutations in animal models of monogenic human diseases. Potential pulmonary applications of CRISPR/Cas9 gene editing include gene correction of monogenic diseases in pre- or postnatal lungs and ex vivo gene editing of patient-specific airway stem cells followed by autologous cell transplant. Strategies to enhance gene-editing efficiency and eliminate off-target effects by targeting pulmonary stem/progenitor cells and the assessment of short-term and long-term effects of gene editing are important considerations as the field advances. If methods continue to advance rapidly, CRISPR/Cas9-mediated gene editing may provide a novel opportunity to correct monogenic diseases of the respiratory system.

Pathologic and Radiologic Correlation of Adult Cystic Lung Disease: A Comprehensive Review

PubMed Central

Parimi, Vamsi; Taddonio, Michale; Kane, Joshua Robert; Yeldandi, Anjana

2017-01-01

The presence of pulmonary parenchymal cysts on computed tomography (CT) imaging presents a significant diagnostic challenge. The diverse range of possible etiologies can usually be differentiated based on the clinical setting and radiologic features. In fact, the advent of high-resolution CT has facilitated making a diagnosis solely on analysis of CT image patterns, thus averting the need for a biopsy. While it is possible to make a fairly specific diagnosis during early stages of disease evolution by its characteristic radiological presentation, distinct features may progress to temporally converge into relatively nonspecific radiologic presentations sometimes necessitating histological examination to make a diagnosis. The aim of this review study is to provide both the pathologist and the radiologist with an overview of the diseases most commonly associated with cystic lung lesions primarily in adults by illustration and description of pathologic and radiologic features of each entity. Brief descriptions and characteristic radiologic features of the various disease entities are included and illustrative examples are provided for the common majority of them. In this article, we also classify pulmonary cystic disease with an emphasis on the pathophysiology behind cyst formation in an attempt to elucidate the characteristics of similar cystic appearances seen in various disease entities. PMID:28270943

An Ultrasound Surface Wave Technique for Assessing Skin and Lung Diseases.

PubMed

Zhang, Xiaoming; Zhou, Boran; Kalra, Sanjay; Bartholmai, Brian; Greenleaf, James; Osborn, Thomas

2018-02-01

Systemic sclerosis (SSc) is a multi-organ connective tissue disease characterized by immune dysregulation and organ fibrosis. Severe organ involvement, especially of the skin and lung, is the cause of morbidity and mortality in SSc. Interstitial lung disease (ILD) includes multiple lung disorders in which the lung tissue is fibrotic and stiffened. The purpose of this study was to translate ultrasound surface wave elastography (USWE) for assessing patients with SSc and/or ILD via measuring surface wave speeds of both skin and superficial lung tissue. Forty-one patients with both SSc and ILD and 30 healthy patients were enrolled in this study. An external harmonic vibration was used to generate the wave propagation on the skin or lung. Three excitation frequencies of 100, 150 and 200 Hz were used. An ultrasound probe was used to measure the wave propagation in the tissue non-invasively. Surface wave speeds were measured on the forearm and upper arm of both left and right arm, as well as the upper and lower lungs, through six intercostal spaces of patients and healthy patients. Viscoelasticity of the skin was calculated by the wave speed dispersion with frequency using the Voigt model. The magnitudes of surface wave speed and viscoelasticity of patients' skin were significantly higher than those of healthy patients (p <0.0001) for each location and each frequency. The surface wave speeds of patients' lung were significantly higher than those of healthy patients (p <0.0001) for each location and each frequency. USWE is a non-invasive and non-ionizing technique for measuring both skin and lung surface wave speed and may be useful for quantitative assessment of SSc and/or ILD. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Interstitial lung disease in an adult with Fanconi anemia: Clues to the pathogenesis

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

Rubinstein, W.S.; Wenger, S.L.; Hoffman, R.M.

1997-03-31

We have studied a 38-year-old man with a prior diagnosis of Holt-Oram syndrome, who presented with diabetes mellitus. He had recently taken prednisone for idiopathic interstitial lung disease and trimethoprim-sulfamethoxazole for sinusitis. Thrombocytopenia progressed to pancytopenia. The patient had skeletal, cardiac, renal, cutaneous, endocrine, hepatic, neurologic, and hematologic manifestations of Fanconi anemia (FA). Chest radiographs showed increased interstitial markings at age 25, dyspnea began in his late 20s, and he stopped smoking at age 32. At age 38, computerized tomography showed bilateral upper lobe fibrosis, lower lobe honeycombing, and bronchiectasis. Pulmonary function tests, compromised at age 29, showed a moderatelymore » severe obstructive and restrictive pattern by age 38. Serum alpha-1 antitrypsin level was 224 (normal 85-213) mg/dL and PI phenotype was M1. Karyotype was 46,X-Y with a marked increase in chromosome aberrations induced in vitro by diepoxybutane. The early onset and degree of pulmonary disease in this patient cannot be fully explained by environmental or known genetic causes. The International Fanconi Anemia Registry (IFAR) contains no example of a similar pulmonary presentation. Gene-environment (ecogenetic) interactions in FA seem evident in the final phenotype. The pathogenic mechanism of lung involvement in FA may relate to oxidative injury and cytokine anomalies. 49 refs., 2 figs., 1 tab.« less

Interstitial lung disease due to fumes from heat-cutting polymer rope.

PubMed

Sharman, P; Wood-Baker, R

2013-09-01

Interstitial lung disease (ILD) due to inhalation of fume/smoke from heating or burning of synthetic polymers has not been reported previously. A fish farm worker developed ILD after cutting rope (polypropylene and nylon) for about 2 hours per day over an extended period using an electrically heated 'knife'. This process produced fume/smoke that entered the workers breathing zone. No other likely cause was identified. This case suggests that exposure to airborne contaminants generated by the heating or burning of synthetic polymers has the potential to cause serious lung disease.

Pulmonary hypertension in chronic obstructive pulmonary disease and interstitial lung diseases.

PubMed

Weitzenblum, Emmanuel; Chaouat, Ari; Canuet, Matthieu; Kessler, Romain

2009-08-01

Pulmonary hypertension (PH) is a common complication of chronic respiratory diseases and particularly of chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD). Owing to its frequency COPD is by far the most common cause of PH. It is generally a mild to moderate PH, pulmonary artery mean pressure (PAP) usually ranging between 20 and 25 mm Hg, but PH may worsen during exercise, sleep, and particularly during exacerbations of the disease. These acute increases in PAP may lead to the development of right heart failure. A small proportion of COPD patients may present "disproportionate" PH defined by a resting PAP >35 to 40 mm Hg. The prognosis is particularly poor in these patients. PH is relatively frequent in advanced ILD and particularly in idiopathic pulmonary fibrosis. As in COPD the diagnosis is suggested by Doppler echocardiography, but the confirmation still requires right heart catheterization. As in COPD, functional (alveolar hypoxia) and morphological factors (vascular remodeling, destruction of the pulmonary parenchyma) explain the elevation of pulmonary vascular resistance that leads to PH. Also as in COPD PH is most often mild to moderate. In ILD the presence of PH predicts a poor prognosis. The treatment of PH relies on long-term oxygen therapy. "New" vasodilator drugs have rarely been used in COPD and ILD patients exhibiting severe PH. In advanced ILD the presence of PH is a supplemental argument for considering lung transplantation.

Chronic obstructive pulmonary disease among lung cancer-free smokers: The importance of healthy controls.

PubMed

Karpman, Michelle D; Eldridge, Ronald; Follis, Jack L; Etzel, Carol J; Shete, Sanjay; El-Zein, Randa A

2018-01-01

The prevalence of chronic obstructive pulmonary disease (COPD) in smokers enrolled as "healthy" controls in studies is 10-50%. The COPD status of ideal smoker populations for lung cancer case-control studies should be checked via spirometry; however, this is often not feasible, because no medical indications exist for asymptomatic smokers to undergo spirometry prior to study enrollment. Therefore, there is an unmet need for robust, cost effective assays for identifying undiagnosed lung disease among asymptomatic smokers. Such assays would help excluding unhealthy smokers from lung cancer case-control studies. We used the cytokinesis-blocked micronucleus (CBMN) assay (a measure of genetic instability) to identify undiagnosed lung disease among asymptomatic smokers. We used a convenience population from an on-going lung cancer case-control study including smokers with lung cancer (n = 454), smoker controls (n = 797), and a self-reported COPD (n = 200) contingent within the smoker controls. Significant differences for all CBMN endpoints were observed when comparing lung cancer to All controls (which included COPD) and Healthy controls (with no COPD). The risk ratio (RR) was increased in the COPD group vs. Healthy controls for nuclear buds (RR 1.28, 95% confidence interval 1.01-1.62), and marginally increased for micronuclei (RR 1.06, 0.98-1.89) and nucleoplasmic bridges (RR 1.07, 0.97-1.15). These findings highlight the importance of using truly healthy controls in studies geared toward assessment of lung cancer risk. Using genetic instability biomarkers would facilitate the identification of smokers susceptible to tobacco smoke carcinogens and therefore predisposed to either disease. Copyright © 2017 The Japanese Respiratory Society. All rights reserved.

A three-dimensional model of human lung development and disease from pluripotent stem cells.

PubMed

Chen, Ya-Wen; Huang, Sarah Xuelian; de Carvalho, Ana Luisa Rodrigues Toste; Ho, Siu-Hong; Islam, Mohammad Naimul; Volpi, Stefano; Notarangelo, Luigi D; Ciancanelli, Michael; Casanova, Jean-Laurent; Bhattacharya, Jahar; Liang, Alice F; Palermo, Laura M; Porotto, Matteo; Moscona, Anne; Snoeck, Hans-Willem

2017-05-01

Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation. Infection in vitro with respiratory syncytial virus, which causes small airway obstruction and bronchiolitis in infants, led to swelling, detachment and shedding of infected cells into the organoid lumens, similar to what has been observed in human lungs. Introduction of mutation in HPS1, which causes an early-onset form of intractable pulmonary fibrosis, led to accumulation of extracellular matrix and mesenchymal cells, suggesting the potential use of this model to recapitulate fibrotic lung disease in vitro. LBOs therefore recapitulate lung development and may provide a useful tool to model lung disease.

A three-dimensional model of human lung development and disease from pluripotent stem cells

PubMed Central

Chen, Ya-Wen; Huang, Sarah Xuelian; de Carvalho, Ana Luisa Rodrigues Toste; Ho, Siu-Hong; Islam, Mohammad Naimul; Volpi, Stefano; Notarangelo, Luigi D; Ciancanelli, Michael; Casanova, Jean-Laurent; Bhattacharya, Jahar; Liang, Alice F.; Palermo, Laura M; Porotto, Matteo; Moscona, Anne; Snoeck, Hans-Willem

2017-01-01

Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modeling, drug discovery and regenerative medicine1. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation. Infection in vitro with respiratory syncytial virus, which causes small airway obstruction and bronchiolitis in infants2, led to swelling, detachment and shedding of infected cells into the organoid lumens, similar to what has been observed in human lungs3. Introduction of mutation in HPS1, which causes an early-onset form of intractable pulmonary fibrosis4,5, led to accumulation of extracellular matrix and mesenchymal cells, suggesting the potential use of this model to recapitulate fibrotic lung disease in vitro. LBOs therefore recapitulate lung development and may provide a useful tool to model lung disease. PMID:28436965

Radical Radiation Therapy After Lung-Sparing Surgery for Malignant Pleural Mesothelioma: Survival, Pattern of Failure, and Prognostic Factors

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

Minatel, Emilio; Trovo, Marco, E-mail: marcotrovo33@hotmail.com; Bearz, Alessandra

Purpose: To prospectively assess the survival, patterns of failure, and prognostic factors in a large cohort of patients with malignant pleural mesothelioma who had undergone a novel trimodal therapeutic approach, including lung-sparing surgery, chemotherapy, and subsequent treatment with high doses of intensity modulated radiation therapy (IMRT) to the whole hemithorax. Methods and Materials: The analysis was conducted on the data from 69 patients. Of the 69 patients, 35 underwent extended pleurectomy/decortication (P/D), with resection of the entire pleura, along with portions of the pericardium and diaphragm and 34, partial pleurectomy, defined as partial removal of parietal or visceral pleura formore » diagnostic purposes, leaving gross tumor behind in all cases. All patients received cisplatin/pemetrexed chemotherapy. Postoperative IMRT was delivered to the entire hemithorax, excluding the intact lung. The IMRT dose was 50 Gy in 25 fractions. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Results: The median follow-up duration was 19 months. No difference was seen in overall survival and locoregional control between the extended P/D group and the partial pleurectomy group. The 2-year overall survival was 65% and 58% in the extended P/D and partial pleurectomy groups, respectively (P=.94). Locoregional control at 2 years was 65% and 64% in the extended P/D and partial pleurectomy groups, respectively (P=.75). The predominant pattern of failure was distant: 19 patients (27.5%) developed distant metastases as the first site of relapse. Gross residual disease after surgery was significantly associated with overall survival (hazard ratio 3.45). One fatal pneumonitis was reported; 14 cases (20%) of grade 2 to 3 pneumonitis were documented. Conclusions: Radical IMRT after lung-sparing surgery and chemotherapy for malignant pleural mesothelioma leads to promising survival results

Breath analysis system for early detection of lung diseases based on multi-sensor array

NASA Astrophysics Data System (ADS)

Jeon, Jin-Young; Yu, Joon-Boo; Shin, Jeong-Suk; Byun, Hyung-Gi; Lim, Jeong-Ok

2013-05-01

Expiratory breath contains various VOCs(Volatile Organic Compounds) produced from the human. When a certain disease exists, the exhalation has specific VOCs which may be generated from diseases. Many researchers have been actively working to find different types of biomarkers which are characteristic for particular diseases. Research regarding the identification of specific diseases from exhalation is still in progress. The aim of this research is to implement early detection of lung disease such as lung cancer and COPD(Chronic Obstructive Pulmonary Disease), which was nominated on the 6th of domestic death rate in 2010, based on multi-sensor array system. The system has been used to acquire sampled expiratory gases data and PCA(Principle Component Analysis) technique was applied to analyze signals from multi-sensor array. Throughout the experimental trials, a clearly distinguishable difference between lung disease patients and healthy controls was found from the measurement and analysis of their respective expiratory gases.

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

PubMed

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

2015-11-01

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

Transbronchial Lung Cryobiopsy and Video-assisted Thoracoscopic Lung Biopsy in the Diagnosis of Diffuse Parenchymal Lung Disease. A Meta-analysis of Diagnostic Test Accuracy.

PubMed

Iftikhar, Imran H; Alghothani, Lana; Sardi, Alejandro; Berkowitz, David; Musani, Ali I

2017-07-01

Transbronchial lung cryobiopsy is increasingly being used for the assessment of diffuse parenchymal lung diseases. Several studies have shown larger biopsy samples and higher yields compared with conventional transbronchial biopsies. However, the higher risk of bleeding and other complications has raised concerns for widespread use of this modality. To study the diagnostic accuracy and safety profile of transbronchial lung cryobiopsy and compare with video-assisted thoracoscopic surgery (VATS) by reviewing available evidence from the literature. Medline and PubMed were searched from inception until December 2016. Data on diagnostic performance were abstracted by constructing two-by-two contingency tables for each study. Data on a priori selected safety outcomes were collected. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of transbronchial lung cryobiopsy were 83.7% (76.9-88.8%), 87% (85-89%), and 57% (40-73%), respectively. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of VATS were 92.7% (87.6-95.8%), 91.0% (89-92%), and 58% (31-81%), respectively. The incidence of grade 2 (moderate to severe) endobronchial bleeding after transbronchial lung cryobiopsy and of post-procedural pneumothorax was 4.9% (2.2-10.7%) and 9.5% (5.9-14.9%), respectively. Although the diagnostic test accuracy measures of transbronchial lung cryobiopsy lag behind those of VATS, with an acceptable safety profile and potential cost savings, the former could be considered as an alternative in the evaluation of patients with diffuse parenchymal lung diseases.

[Lung cancer and rheumatoid arthritis. An interdisciplinary challenge].

PubMed

Rubbert-Roth, A; Zander, T; Kneitz, C; Baerwald, C; Wirtz, H; Witt, C

2016-02-01

Lung cancer is a frequently occurring disease, particularly in the elderly; however, within the last 10 years the pharmaceutical treatment of lung cancer has been significantly improved. Due to a better understanding of the pathophysiological events and the identification of molecular subgroups of lung tumors, new therapeutic drugs have been developed that significantly prolong survival of patients with the respective molecular pattern. In particular immunotherapeutic agents, such as programmed death-ligand 1 (PD-L1) and programmed death 1 (PD1) antibodies have shown promising clinical results in a subgroup of lung cancer patients. Due to the high incidence of both lung cancer and rheumatic diseases they often occur together, which necessitates an interdisciplinary management. The success of improved therapy of lung cancer has led to a greater focus on the treatment of comorbidities; however, interventions into the immune system by immune checkpoint inhibitors can lead to new challenges when an autoimmune disease is simultaneously present. The possibility of an effective screening for lung cancer in the future also presents the prospect of an improvement in mortality, which raises the question of the optimal monitoring of patients with rheumatoid arthritis (RA) under immunosuppressive therapy. The aim of this review is to discuss the interaction between lung cancer and RA with respect to the currently available data.

Systemic inflammation in chronic obstructive pulmonary disease and lung cancer: common driver of pulmonary cachexia?

PubMed

Ceelen, Judith J M; Langen, Ramon C J; Schols, Annemie M W J

2014-12-01

In this article, a putative role of systemic inflammation as a driver of pulmonary cachexia induced by either chronic obstructive pulmonary disease or nonsmall cell lung cancer is reviewed. Gaps in current translational research approaches are discussed and alternative strategies are proposed to provide new insights. Activation of the ubiquitin proteasome system has generally been considered a cause of pulmonary cachexia, but current animal models lack specificity and evidence is lacking in nonsmall cell lung cancer and conflicting in chronic obstructive pulmonary disease patients. Recent studies have shown activation of the autophagy-lysosome pathway in both nonsmall cell lung cancer and chronic obstructive pulmonary disease. Myonuclear loss, as a consequence of increased apoptotic events in myofibers, has been suggested in cancer-cachexia-associated muscle atrophy. Plasma transfer on myotube cultures can be used to detect early inflammatory signals in patients and presence of atrophy-inducing activity within the circulation. Comparative clinical research between nonsmall cell lung cancer and chronic obstructive pulmonary disease in different disease stages is useful to unravel disease-specific versus common denominators of pulmonary cachexia.

Cryptogenic Organizing Pneumonia With Lung Nodules Secondary to Pulmonary Manifestation of Crohn Disease.

PubMed

Zaman, Taufiq; Watson, Joseph; Zaman, Mohammad

2017-01-01

Crohn disease is an immune-mediated inflammatory condition with gastrointestinal and extraintestinal manifestations in patients. Pulmonary involvement of Crohn disease is one manifestation. There have been case reports which have shown Crohn disease and lung nodules which were noted to be histopathological as cryptogenic organizing pneumonia (COP). In our case, a 22-year-old woman with Crohn disease was seen with complaints of chest pain and cough. Computed tomographic scan of chest showed multiple bilateral lung nodules, for which biopsy was done, which showed COP. The case study is followed by a deeper discussion of COP and the extraintestinal manifestation seen in inflammatory bowel disease.

Clinical significance of mycobacterial genotyping in Mycobacterium avium lung disease in Korea.

PubMed

Kim, S-Y; Lee, S-T; Jeong, B-H; Jeon, K; Kim, J-W; Shin, S J; Koh, W-J

2012-10-01

A recent study in Japan found that mycobacterial genotyping was associated with disease progression and susceptibility to certain drugs in Mycobacterium avium lung disease. However, it is not known whether this association is true in other populations. To investigate the association between mycobacterial genotype, clinical characteristics and the progression of M. avium lung disease in Korean patients. A total of 102 M. avium clinical isolates were genotyped using M. avium tandem repeats-variable number of tandem repeats (MATR-VNTR). MATR-VNTR typing demonstrated a high discriminatory power and genetic diversity for molecular epidemiological studies of M. avium. In the phylogenetic tree, the M. avium clinical isolates were divided into three major clusters: A, B and C. Cluster A was observed most frequently (64/102, 63%), whereas cluster C was found in a minor proportion of the isolates (8/102, 8%). However, there was no association between the clinical characteristics, disease progression and drug susceptibility and the phylogenetic tree based on VNTR genotyping. MATR-VNTR genotyping may be useful for epidemiological studies of M. avium lung disease; however, no association was found between the specific VNTR genotypes of M. avium and the clinical characteristics of Korean patients.

Histopathological Findings Associated With Gastroesophageal Reflux Disease and Aspiration After Lung Transplantation: Initial Brazilian Single-Center Experience.

PubMed

Carraro, R M; Nascimento, E C T; Szachnowicz, S; Camargo, P C L B; Campos, S V; Afonso, J E; Samano, M N; Pêgo-Fernandes, P M; Dolhnikoff, M; Teixeiraa, R H O B; Costa, A N

2017-05-01

Gastro-esophageal reflux disease (GERD) and broncho-aspiration (BA) are known to increase the risk for chronic lung allograft dysfunction (CLAD). However, specific lung injury mechanisms are not clearly known. The objective of the study was to describe histopathological findings in surveillance lung transbronchial biopsies that can be correlated with episodes of BA in the lung allograft. This retrospective analysis of surveillance transbronchial biopsies was performed in lung transplant recipients, with available data of broncho-alveolar fluid (cultures and cytology), lung function parameters, and esophageal functional tests. Were analyzed 11 patients, divided into 3 groups: (1) GERD group: 4 patients with GERD and CLAD diagnosis; (2) control group: 2 patients without GERD or CLAD; and (3) BA group: 5 patients with foreign material in lung biopsies. A histopathological pattern of neutrophilic bronchitis (NB) was present in 4 of 4 cases in the GERD group and in 1 of 5 cases in the BA group in 2 or more biopsy samples; culture samples were all negative; the 5 NB-positive patients developed CLAD and died (3/5) or needed re-transplantation (2/5). The other 3 patients in the BA group had GERD without NB or CLAD. Both patients in the control group had transient NB in biopsies with positive cultures but remained free of CLAD. Surveillance transbronchial biopsies may provide useful information other than the evaluation of acute cellular rejection and can help to identify high-risk patients for allograft dysfunction related to gastro-esophageal reflux. Copyright © 2017 Elsevier Inc. All rights reserved.

Hierarchical Bayesian modeling of spatio-temporal patterns of lung cancer incidence risk in Georgia, USA: 2000-2007

NASA Astrophysics Data System (ADS)

Yin, Ping; Mu, Lan; Madden, Marguerite; Vena, John E.

2014-10-01

Lung cancer is the second most commonly diagnosed cancer in both men and women in Georgia, USA. However, the spatio-temporal patterns of lung cancer risk in Georgia have not been fully studied. Hierarchical Bayesian models are used here to explore the spatio-temporal patterns of lung cancer incidence risk by race and gender in Georgia for the period of 2000-2007. With the census tract level as the spatial scale and the 2-year period aggregation as the temporal scale, we compare a total of seven Bayesian spatio-temporal models including two under a separate modeling framework and five under a joint modeling framework. One joint model outperforms others based on the deviance information criterion. Results show that the northwest region of Georgia has consistently high lung cancer incidence risk for all population groups during the study period. In addition, there are inverse relationships between the socioeconomic status and the lung cancer incidence risk among all Georgian population groups, and the relationships in males are stronger than those in females. By mapping more reliable variations in lung cancer incidence risk at a relatively fine spatio-temporal scale for different Georgian population groups, our study aims to better support healthcare performance assessment, etiological hypothesis generation, and health policy making.

Lichenoid exanthema mimicking graft-versus-host disease associated with obstructive lung disease in a non-transplanted patient.

PubMed

Eberle, Franziska Carola; Holland, Angelique; Hörster, Stefan; Vogelmeier, Claus; Hertl, Michael

2010-01-01

Lichenoid graft-versus-host disease (GVHD) is commonly observed in patients who have received donor lymphocyte infusions or allogeneic bone marrow transplantation (BMT). Here we report a striking case of lichenoid GVH-like exanthema in a young woman without any history of blood transfusions or BMT. A polymorphous, multiforme-like exanthema was observed after systemic antibiotic therapy of bronchitis and was initially diagnosed as drug eruption. Later on, disseminated lichenoid papules were noticed on the trunk and extremities with all histologic and clinical characteristics of lichenoid GVHD. Cutaneous GVH-like disease developed, as did obstructive lung disease. Pulmonary as well as skin disease were both refractory to various immunosuppressive therapies. The immune pathogenesis that caused the skin and lung disease in this patient remains unclear. Multiple pregnancies with two abortions with the potential induction of microchimerism may play a role in the disease pathogenesis.

Accumulation of BDCA1⁺ dendritic cells in interstitial fibrotic lung diseases and Th2-high asthma.

PubMed

Greer, Alexandra M; Matthay, Michael A; Kukreja, Jasleen; Bhakta, Nirav R; Nguyen, Christine P; Wolters, Paul J; Woodruff, Prescott G; Fahy, John V; Shin, Jeoung-Sook

2014-01-01

Dendritic cells (DCs) significantly contribute to the pathology of several mouse lung disease models. However, little is known of the contribution of DCs to human lung diseases. In this study, we examined infiltration with BDCA1⁺ DCs of human lungs in patients with interstitial lung diseases or asthma. Using flow cytometry, we found that these DCs increased by 5∼6 fold in the lungs of patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis, which are both characterized by extensive fibrosis in parenchyma. The same DC subset also significantly increased in the lung parenchyma of patients with chronic obstructive pulmonary disease, although the degree of increase was relatively modest. By employing immunofluorescence microscopy using FcεRI and MHCII as the specific markers for BDCA1⁺ DCs, we found that the numbers of BDCA1⁺ DCs also significantly increased in the airway epithelium of Th2 inflammation-associated asthma. These findings suggest a potential contribution of BDCA1⁺ DCs in human lung diseases associated with interstitial fibrosis or Th2 airway inflammation.

Nutrient intake and nutrient patterns and risk of lung cancer among heavy smokers: results from the COSMOS screening study with annual low-dose CT.

PubMed

Gnagnarella, Patrizia; Maisonneuve, Patrick; Bellomi, Massimo; Rampinelli, Cristiano; Bertolotti, Raffaella; Spaggiari, Lorenzo; Palli, Domenico; Veronesi, Giulia

2013-06-01

The role of nutrients in lung cancer aetiology remains controversial and has never been evaluated in the context of screening. Our aim was to investigate the role of single nutrients and nutrient patterns in the aetiology of lung cancer in heavy smokers. Asymptomatic heavy smokers (≥20 pack-years) were invited to undergo annual low-dose computed tomography. We assessed diet using a self-administered food frequency questionnaire and collected information on multivitamin supplement use. We performed principal component analysis identifying four nutrient patterns and used Cox proportional Hazards regression to assess the association between nutrients and nutrients patterns and lung cancer risk. During a mean follow-up of 5.7 years, 178 of 4,336 participants were diagnosed with lung cancer by screening. We found a significant risk reduction of lung cancer with increasing vegetable fat consumption (HR for highest vs. lowest quartile = 0.50, 95% CI = 0.31-0.80; P-trend = 0.02). Participants classified in the high "vitamins and fiber" pattern score had a significant risk reduction of lung cancer (HR = 0.57; 95% CI = 0.36-0.90, P-trend = 0.01). Among heavy smokers enrolled in a screening trial, high vegetable fat intake and adherence to the "vitamin and fiber" nutrient pattern were associated with reduced lung cancer incidence.

Role of gastroesophageal reflux disease in lung transplantation

PubMed Central

Hathorn, Kelly E; Chan, Walter W; Lo, Wai-Kit

2017-01-01

Lung transplantation is one of the highest risk solid organ transplant modalities. Recent studies have demonstrated a relationship between gastroesophageal reflux disease (GERD) and lung transplant outcomes, including acute and chronic rejection. The aim of this review is to discuss the pathophysiology, evaluation, and management of GERD in lung transplantation, as informed by the most recent publications in the field. The pathophysiology of reflux-induced lung injury includes the effects of aspiration and local immunomodulation in the development of pulmonary decline and histologic rejection, as reflective of allograft injury. Modalities of reflux and esophageal assessment, including ambulatory pH testing, impedance, and esophageal manometry, are discussed, as well as timing of these evaluations relative to transplantation. Finally, antireflux treatments are reviewed, including medical acid suppression and surgical fundoplication, as well as the safety, efficacy, and timing of such treatments relative to transplantation. Our review of the data supports an association between GERD and allograft injury, encouraging a strategy of early diagnosis and aggressive reflux management in lung transplant recipients to improve transplant outcomes. Further studies are needed to explore additional objective measures of reflux and aspiration, better compare medical and surgical antireflux treatment options, extend follow-up times to capture longer-term clinical outcomes, and investigate newer interventions including minimally invasive surgery and advanced endoscopic techniques. PMID:28507913

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 surgery - discharge

MedlinePlus

... Read More Bronchiectasis Chronic obstructive pulmonary disease Lung cancer Lung cancer - non-small cell Lung cancer - small cell ... team. Related MedlinePlus Health Topics COPD Emphysema Lung Cancer Lung Diseases Pleural Disorders Browse the Encyclopedia A.D. ...

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

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

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

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

[Pulmonary hypertension in interstitial lung diseases: diagnostic and therapeutic approach in 2011?].

PubMed

Cottin, Vincent; Kiakouama, Lize; Traclet, Julie; Cordier, Jean-François

2011-04-01

Pulmonary hypertension is frequent in late-stage idiopathic pulmonary fibrosis, and is associated with a shorter survival. It should be suspected in case of dyspnea or hypoxemia disproportionate with the degree of parenchymal lung disease. It is particularly frequent in patients with the syndrome of combined pulmonary fibrosis and emphysema, and associated with a short survival (median survival less than 1 year). Pulmonary hypertension associated with chronic infiltrative lung diseases can be detected by echocardiography and must be confirmed by right-sided heart catheterization, especially to rule out post-capillary pulmonary hypertension frequent in this context. Management is mainly palliative and based on supplemental nasal oxygen. Therapy specific for pulmonary arterial hypertension, poorly evaluated in pulmonary hypertension associated with infiltrative lung diseases, is occasionally proposed to patients with disproportionate pulmonary hypertension (mean PAP > 35 mmHg), with often limited efficacy, and requiring careful follow-up (risk of increased hypoxemia) and invasive evaluation. Pulmonary transplantation should be considered in the absence of contra-indication.

Assessment of CF lung disease using motion corrected PROPELLER MRI: a comparison with CT.

PubMed

Ciet, Pierluigi; Serra, Goffredo; Bertolo, Silvia; Spronk, Sandra; Ros, Mirco; Fraioli, Francesco; Quattrucci, Serena; Assael, M Baroukh; Catalano, Carlo; Pomerri, Fabio; Tiddens, Harm A W M; Morana, Giovanni

2016-03-01

To date, PROPELLER MRI, a breathing-motion-insensitive technique, has not been assessed for cystic fibrosis (CF) lung disease. We compared this technique to CT for assessing CF lung disease in children and adults. Thirty-eight stable CF patients (median 21 years, range 6-51 years, 22 female) underwent MRI and CT on the same day. Study protocol included respiratory-triggered PROPELLER MRI and volumetric CT end-inspiratory and -expiratory acquisitions. Two observers scored the images using the CF-MRI and CF-CT systems. Scores were compared with intra-class correlation coefficient (ICC) and Bland-Altman plots. The sensitivity and specificity of MRI versus CT were calculated. MRI sensitivity for detecting severe CF bronchiectasis was 0.33 (CI 0.09-0.57), while specificity was 100% (CI 0.88-1). ICCs for bronchiectasis and trapped air were as follows: MRI-bronchiectasis (0.79); CT-bronchiectasis (0.85); MRI-trapped air (0.51); CT-trapped air (0.87). Bland-Altman plots showed an MRI tendency to overestimate the severity of bronchiectasis in mild CF disease and underestimate bronchiectasis in severe disease. Motion correction in PROPELLER MRI does not improve assessment of CF lung disease compared to CT. However, the good inter- and intra-observer agreement and the high specificity suggest that MRI might play a role in the short-term follow-up of CF lung disease (i.e. pulmonary exacerbations). PROPELLER MRI does not match CT sensitivity to assess CF lung disease. PROPELLER MRI has lower sensitivity than CT to detect severe bronchiectasis. PROPELLER MRI has good to very good intra- and inter-observer variability. PROPELLER MRI can be used for short-term follow-up studies in CF.

Airway mucus, inflammation and remodeling: emerging links in the pathogenesis of chronic lung diseases.

PubMed

Zhou-Suckow, Zhe; Duerr, Julia; Hagner, Matthias; Agrawal, Raman; Mall, Marcus A

2017-03-01

Airway mucus obstruction is a hallmark of many chronic lung diseases including rare genetic disorders such as cystic fibrosis (CF) and primary ciliary dyskinesia, as well as common lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), which have emerged as a leading cause of morbidity and mortality worldwide. However, the role of excess airway mucus in the in vivo pathogenesis of these diseases remains poorly understood. The generation of mice with airway-specific overexpression of epithelial Na + channels (ENaC), exhibiting airway surface dehydration (mucus hyperconcentration), impaired mucociliary clearance (MCC) and mucus plugging, led to a model of muco-obstructive lung disease that shares key features of CF and COPD. In this review, we summarize recent progress in the understanding of causes of impaired MCC and in vivo consequences of airway mucus obstruction that can be inferred from studies in βENaC-overexpressing mice. These studies confirm that mucus hyperconcentration on airway surfaces plays a critical role in the pathophysiology of impaired MCC, mucus adhesion and airway plugging that cause airflow obstruction and provide a nidus for bacterial infection. In addition, these studies support the emerging concept that excess airway mucus per se, probably via several mechanisms including hypoxic epithelial necrosis, retention of inhaled irritants or allergens, and potential immunomodulatory effects, is a potent trigger of chronic airway inflammation and associated lung damage, even in the absence of bacterial infection. Finally, these studies suggest that improvement of mucus clearance may be a promising therapeutic strategy for a spectrum of muco-obstructive lung diseases.

Lung Transplantation in Gaucher Disease: A Learning Lesson in Trying to Avoid Both Scylla and Charybdis.

PubMed

de Boer, Geertje M; van Dussen, Laura; van den Toorn, Leon M; den Bakker, Michael A; Hoek, Rogier A S; Hesselink, Dennis A; Hollak, Carla E M; van Hal, Peter Th W

2016-01-01

Gaucher disease (GD), a lysosomal storage disorder, may result in end-stage lung disease. We report successful bilateral lung transplantation in a 49-year-old woman with GD complicated by severe pulmonary hypertension and fibrotic changes in the lungs. Before receiving the lung transplant, the patient was undergoing both enzyme replacement therapy (imiglucerase) and triple pulmonary hypertension treatment (epoprostenol, bosentan, and sildenafil). She had a history of splenectomy, severe bone disease, and renal involvement, all of which were related to GD and considered as relative contraindications for a lung transplantation. In the literature, lung transplantation has been suggested for severe pulmonary involvement in GD but has been reported only once in a child. To our knowledge, until now, no successful procedure has been reported in adults, and no reports deal with the severe potential posttransplantation complications specifically related to GD. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Perception of climate change in patients with chronic lung disease

PubMed Central

Götschke, Jeremias; Mertsch, Pontus; Bischof, Michael; Kneidinger, Nikolaus; Matthes, Sandhya; Renner, Ellen D.; Schultz, Konrad; Traidl-Hoffmann, Claudia; Duchna, Hans-Werner; Behr, Jürgen; Schmude, Jürgen; Huber, Rudolf M.

2017-01-01

Background Climate change affects human health. The respective consequences are predicted to increase in the future. Patients with chronic lung disease are particularly vulnerable to the involved environmental alterations. However, their subjective perception and reactions to these alterations remain unknown. Methods In this pilot study, we surveyed 172 adult patients who underwent pulmonary rehabilitation and 832 adult tourists without lung disease in the alpine region about their perception of being affected by climate change and their potential reaction to specific consequences. The patients’ survey also contained the COPD Assessment Test (CAT) to rate the severity of symptoms. Results Most of the patients stated asthma (73.8%), COPD (9.3%) or both (11.0%) as underlying disease while 5.8% suffered from other chronic lung diseases. Patients and tourists feel equally affected by current climate change in general, while allergic subjects in both groups feel significantly more affected (p = 0.04). The severity of symptoms assessed by CAT correlates with the degree of feeling affected (p<0.01). The main disturbing consequences for patients are decreased air quality, increasing numbers of ticks and mosquitos and a rising risk for allergy and extreme weather events such as thunderstroms, while tourists are less disturbed by these factors. Increasing number of heat-days is of little concern to both groups. Conclusion Overall patients are more sensitive to health-related consequences of climate change. Yet, the hazard of heat-days seems underestimated and awareness should be raised. PMID:29045479

Perception of climate change in patients with chronic lung disease.

PubMed

Götschke, Jeremias; Mertsch, Pontus; Bischof, Michael; Kneidinger, Nikolaus; Matthes, Sandhya; Renner, Ellen D; Schultz, Konrad; Traidl-Hoffmann, Claudia; Duchna, Hans-Werner; Behr, Jürgen; Schmude, Jürgen; Huber, Rudolf M; Milger, Katrin

2017-01-01

Climate change affects human health. The respective consequences are predicted to increase in the future. Patients with chronic lung disease are particularly vulnerable to the involved environmental alterations. However, their subjective perception and reactions to these alterations remain unknown. In this pilot study, we surveyed 172 adult patients who underwent pulmonary rehabilitation and 832 adult tourists without lung disease in the alpine region about their perception of being affected by climate change and their potential reaction to specific consequences. The patients' survey also contained the COPD Assessment Test (CAT) to rate the severity of symptoms. Most of the patients stated asthma (73.8%), COPD (9.3%) or both (11.0%) as underlying disease while 5.8% suffered from other chronic lung diseases. Patients and tourists feel equally affected by current climate change in general, while allergic subjects in both groups feel significantly more affected (p = 0.04). The severity of symptoms assessed by CAT correlates with the degree of feeling affected (p<0.01). The main disturbing consequences for patients are decreased air quality, increasing numbers of ticks and mosquitos and a rising risk for allergy and extreme weather events such as thunderstroms, while tourists are less disturbed by these factors. Increasing number of heat-days is of little concern to both groups. Overall patients are more sensitive to health-related consequences of climate change. Yet, the hazard of heat-days seems underestimated and awareness should be raised.

Lung disease in indigenous children.