Respiratory traits and coal workers’ pneumoconiosis: Mendelian randomisation and association analysis

2020 ◽  
pp. oemed-2020-106610
Author(s):  
Ting Wang ◽  
Wenqing Sun ◽  
Hongyan Wu ◽  
Yuxin Cheng ◽  
Yan Li ◽  
...  
Keyword(s):  
Lung Function ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
Normal Lung ◽  
Mendelian Randomisation ◽  
Chronic Obstructive ◽  
Susceptibility Loci ◽  
Genetic Associations ◽  
Obstructive Pulmonary Disease

ObjectivesSusceptibility loci of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease were also significantly associated with the predisposition of coal worker’s pneumoconiosis (CWP) in recent studies. However, only a few genes and loci were targeted in previous studies.MethodsTo systematically evaluate the genetic associations between CWP and other respiratory traits, we reviewed the reported genome-wide association study loci of five respiratory traits and then conducted a Mendelian randomisation study and a two-stage genetic association study.ResultsInterestingly, we found that for each SD unit, higher lung function was associated with a 66% lower risk of CWP (OR=0.34, 95% CI: 0.15 to 0.77, p=0.010) using conventional Mendelian randomisation analysis (inverse variance weighted method). Moreover, we found susceptibility loci of interstitial lung disease (rs2609255, OR=1.29, p=1.61×10−4) and lung function (rs4651005, OR=1.39, p=1.62×10−3; rs985256, OR=0.73, p=8.24×10−4 and rs6539952, OR=1.28, p=4.32×10−4) were also significantly associated with the risk of CWP. Functional annotation showed these variants were significantly associated with the expression of FAM13A (rs2609255, p=7.4 ×10−4), ANGPTL1 (rs4651005, p=5.4 ×10−7), SPATS2L (rs985256, p=1.1 ×10−5) and RP11-463O9.9 (rs6539952, p=7.1 ×10−6) in normal lung tissues, which were related to autophagy pathway simultaneously according to enrichment analysis.ConclusionsThese results provided a deeper understanding of the genetic predisposition basis of CWP.

scholarly journals Correlation between Level of Autophagy and Amount of CD8+T Cells in Chronic Obstructive Pulmonary Disease

2020 ◽  
Author(s):  
Songming Zhuo ◽  
Hong Zhuang ◽  
Na Li ◽  
Sida Chen ◽  
Wugen Zhan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lung Function ◽  
Normal Lung ◽  
Stable Phase ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Normal Lung Function ◽  
Healthy Control ◽  
Function Group

Abstract Background: This study aimed to shed light on the correlation between the amounts of CD8+ T cells and autophagy level in COPD. Results: The objects (n = 90) were divided into three groups: COPD group (patients in the stable phase; n = 30), SN group (healthy control of smoking with normal lung function group; n = 30), and NSN groups (healthy control of non-smoking with normal lung function group; n = 30). The amounts of CD8+ (32.33 ± 4.23%), CD8+ effector (25.63 ± 8.57%) and CD8+memory (11.94 ± 5.77%) T cell in the COPD group were significantly higher those in the other two groups, while the apoptotic rate was lower in the COPD group (P < 0.05). Significant linear correlations were found of P62/GAPDH (‰) with CD8+, CD8+effector, and CD8+ memory- T cell amounts (P<0.001). Conclusions: Autophagy level is positively and linearly associated with the amounts of CD8+ T cells, suggesting that cell autophagy might be involved in COPD pathogenesis.

scholarly journals Asthma‐chronic obstructive pulmonary disease overlap: A clinical entity?

2020 ◽  
Vol 3 (1) ◽  
pp. 2-8
Author(s):  
Robert A. Wise
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Middle Age ◽  
Clinical Manifestations ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Neutrophilic Inflammation ◽  
Normal Lung Function

Asthma and COPD are easily recognizable clinical entities in their characteristic presentations. Asthma is an early-onset disorder characterized by Type 2, eosinophil-predominant, inflammation of the airways and is associated with atopy. COPD presents in middle age and is characterized by neutrophilic inflammation of the airways and is associated with cigarette smoking or biomass fuel exposure. Between exacerbations, asthma typically has normal lung function whereas COPD has incompletely reversible lung function. Approximately one in five patients with either of these disorders will show some features of both COPD and Asthma. This overlap is far more common than can be accounted for by chance concurrence of two common diseases. There are likely genetic and environmental susceptibilities to both disorders, but there is no single pathobiological mechanism that identifies all such overlap patients. Most likely there are numerous predispositions that lead to Asthma-COPD overlap that may be grounded in early childhood or even pre-natal events. Thus, Asthma-COPD overlap is best considered a family of diseases with overlapping clinical manifestations. The future elucidation of these different pathways to Asthma-COPD overlap, in conjunction with highly targeted therapies will aid clinicians in treating these patients.

scholarly journals New genetic signals for lung function highlight pathways and pleiotropy, and chronic obstructive pulmonary disease associations across multiple ancestries

2018 ◽  
Author(s):  
Nick Shrine ◽  
Anna L Guyatt ◽  
A Mesut Erzurumluoglu ◽  
Victoria E Jackson ◽  
Brian D Hobbs ◽  
...  
Keyword(s):  
Lung Function ◽  
Drug Targets ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
European Ancestry ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
A Genome ◽  
Disease Associations ◽  
Never Smokers

AbstractReduced lung function predicts mortality and is key to the diagnosis of COPD. In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, one-half of which are new. In combination these variants strongly predict COPD in deeply-phenotyped patient populations. Furthermore, the combined effect of these variants showed generalisability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

scholarly journals Expiratory reactance abnormalities in patients with expiratory dynamic airway collapse: a new application of impulse oscillometry

2018 ◽  
Vol 4 (4) ◽  
pp. 00080-2018 ◽  
Author(s):  
David I. Fielding ◽  
Justin Travers ◽  
Phan Nguyen ◽  
Michael G. Brown ◽  
Gunter Hartel ◽  
...  
Keyword(s):  
Lung Function ◽  
Regression Tree ◽  
Classification And Regression Tree ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Stepwise Logistic Regression ◽  
Impulse Oscillometry ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Normal Lung Function

Expiratory dynamic airways collapse (EDAC) is a condition that affects the central airways; it is not well characterised physiologically, with relatively few studies. We sought to characterise impulse oscillometry (IOS) features of EDAC in patients with normal spirometry. Expiratory data were hypothesised to be the most revealing. In addition, we compared IOS findings in chronic obstructive pulmonary disease (COPD) patients with and without EDAC.EDAC was identified at bronchoscopy as 75–100% expiratory closure at the carina or bilateral main bronchi. Four patient groups were compared: controls with no EDAC and normal lung function; lone EDAC with normal lung function; COPD-only patients; and COPD patients with EDAC.38 patients were studied. Mean IOS data z-scores for EDAC compared to controls showed significantly higher reactance (X) values including X at 5 Hz, resonance frequency and area under the reactance curve (AX). EDAC showed significantly greater expiratory/inspiratory differences in all IOS data compared to controls. Stepwise logistic regression showed that resonant frequency best discriminated between EDAC and normal control, whereas classification and regression tree analysis found AX ≥3.523 to be highly predictive for EDAC in cases with normal lung function (14 out of 15 cases, and none out of eight controls).These data show a new utility of IOS: detecting EDAC in patients with normal lung function.

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