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Immunology, genetics and microbiota in the COPD pathophysiology: potential scope for patient stratification

Significance statement

Chronic obstructive pulmonary disease (COPD) is a syndrome defined by loss of lung function with smoking as an important cause or initiating factor. This paper reviews possible driver mechanisms of COPD pathogenesis beyond the initiating effects of smoking and addresses the interplay between host predisposition (genetic and epigenetic), airway mucosal immune responses and lung microbiota population dynamics. An improved understanding of these biological drivers of disease chronicity and progression provides important clues for patient stratification and the development of novel precision treatments for COPD patients.

Figure Legend: Identification of patients with an autoimmune component are likely to respond well to immunosuppressive therapies, whereas other patients might not respond to the same drugs.

Immunology genetics and microbiota in the COPD pathophysiology. Global Medical Discovery

 

 

 

 

Journal Reference

Malhotra R, Olsson H. Expert Rev Respir Med. 2015 Apr;9(2):153-9.

Translational Science, Respiratory, Inflammation and Autoimmunty iMED, AstraZeneca, Pepparedsleden 1, 43183, Mölndal, Sweden.

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by sustained inflammation of the airways, leading to destruction of lung tissue and declining pulmonary function. Although smoking is the most obvious risk factor for COPD, only about 20% of smokers develop COPD and smoking cessation does not reverse progression of COPD, indicating that while smoking is an important cause or initiating factor, it is not the only driver of ongoing chronic inflammation and disease progression in COPD patients. We hypothesize that smoking-induced changes in lung microbiota, epithelial integrity and epigenetic control of gene expression result in autoantigen induction and perturbed immune regulation in genetically vulnerable individuals. In our view, COPD patients may be stratified according to their immunological and inflammatory status related to specific changes in the lung microbiota (innate and adaptive immunity), presence of autoantigens (adaptive immunity: Th1-B-cell axis) and epigenetic modifications (inflammation and structural changes).

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