Endotypes of COPD: their role in determining response to inhaled

Problem

The heterogeneity of COPD is reflected by its many phenotypes, combinations of disease attributes describing differences between individuals as they relate to clinical outcomes. Phenotypes may not explain the underlying disease processes of COPD. This lessens their usefulness as predictors of response to treatment. Improved understanding of the pathophysiology of COPD may come from determining the endotypes, subtypes defined by distinct functional or pathophysiological mechanisms, of the disease. The relationship between phenotypes and endotypes of COPD is poorly understood. The aim of this review is to identify the endotypes of COPD which may be predictive of treatment response to inhaled corticosteroids.

Approach

We conducted a scoping literature review to investigate the predictive value of endotypes in the treatment of COPD with inhaled corticosteroids. The definition and application of endotypes in COPD made a systematic review impractical. We searched the Pubmed index for all articles including the terms “COPD endotypes” & “COPD endotype” & “COPD endotypes and phenotypes”.

Findings

We found 32 articles which referred to COPD endotypes. 10 articles discussed the relationship between endotype and phenotype and its relevance to treatment decisions. 6 review articles described specific endotypes of COPD. Five endotypes of COPD, and their respective biomarkers, were most frequently proposed. These were the T-Helper 2 (TH2) inflammatory response endotype (serum/sputum eosinophilia, FeNO, perisotin, IgE, cytokines IL-4, IL-5, IL-13), the persistent systemic inflammation endotype (CRP, fibrinogen, cytokines IL-6, IL-8), the bacterial colonisation of the airways endotype (sputum culture), the neutrophilic endotype (cytokine IL-8) and the Alpha-1 antitrypsin deficiency endotype (α1AT genotyping). Of these, the TH2 inflammatory response endotype represents an opportunity to define a subgroup of patients with COPD who show steroid responsiveness. At present no single biomarker or combination of biomarkers has sufficient sensitivity and specificity to accurately predict response to treatment in COPD.

Consequences

Defining COPD endotypes may improve our understanding of the underlying pathophysiology of COPD and lead to more rational approaches to prescribing of inhaled corticosteroids. The lack of predictive power of current combinations of biomarkers limits their value in determining categories of treatment response. Progress in identifying reliable and accessible biomarkers of these endotypes should improve targeted treatment of COPD patients.