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

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 vunerable 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).

Keywords:

• chronic obstructive pulmonary disease
• epigenetics
• genetics
• immunology
• microbiota

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Smoking is an important cause or initiating factor but it is not the only driver of ongoing chronic inflammation and disease progression in chronic obstructive pulmonary disease (COPD) patients.

• The chronic exposure to cigarette smoke or other air pollutants induces non-reversible epigenetic modifications, changes in lung cellular microenvironment and epithelial dysfunction, resulting in chronic inflammation and disease progression in COPD.

• COPD patients may be stratified according to their immunological and inflammatory status, such as lung microbiota (innate immunity), autoantigen status (adaptive immunity: Th1-B-cell axis), epigenetic modifications (inflammation and structural changes) and (innate and adaptive immunity: macrophages, CD8 cells, NK cells, etc.).

• Stratification of COPD patients by the underlying drivers of disease may enable more effective and personalized treatment.

• Further analysis and identification of biomarkers to define this subpopulation of COPD patients is required to allow appropriate treatment of COPD patients.

Notes