Endo-phenotyping of COPD patients

ABSTRACT

Introduction

Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome and may comprise several different phenotypes that are driven by different molecular mechanisms (endotypes). Several different clinical, genetic, and inflammatory phenotypes of COPD have been recognized and this may lead to more precise effective therapies.

Areas covered

The different clinical phenotypes, including smoking versus nonsmoking COPD, small airway disease versus emphysema, non-exacerbators versus frequent exacerbators are discussed. Rare genetic endotypes (alpha₁-antitrypsin deficiency, telomerase polymorphisms), and inflammatory phenotypes (eosinophilic versus neutrophilic) are also recognized in stable and exacerbating patients and have implications for the choice of therapy.

Expert opinion

Clinical phenotypes have so far not proved to be very useful in selecting more personalized therapy for COPD. Even with genetic endotypes, this has not led to improved therapy. More promising is the recognition that COPD patients who have increased sputum or blood eosinophils tend to have more frequent exacerbations and inhaled corticosteroids are more effective in preventing exacerbation. Increased blood eosinophils have proved to be a useful biomarker now used to target ICS more effectively. Furthermore, COPD patients with low eosinophils are more likely to get pneumonia with ICS and to have lower airway bacterial colonization.

KEYWORDS:

• eosinophils
• exacerbations
• neutrophils

Article highlights

• Several clinical phenotypes of COPD have been described, but so far none of these have led to more effective or precise therapies.

• Two rare genetic endotypes of COPD are recognized -alpha₁-antitrypsin deficiency and telomerase polymorphisms, but this has not yet led to more precise or effective therapy.

• Inflammatory phenotypes of COPD have recently been recognized. Eosinophilic COPD patients have a better clinical response to inhaled corticosteroids and blood eosinophils are now used to direct therapy in these patients.

• Neutrophilic COPD includes patients with bacterial colonization of the lower airways and chronic bronchitis, but so far treating neutrophilic inflammation has not been very effective.

• Exacerbations have been phenotyped using different biomarkers and this may lead to the more logical use of treatments for acute exacerbations.

• Better understanding of the molecular mechanisms and multi-omic analysis of COPD may identify new endotypes in the future which can be recognised by specific biomarkers and may be treated more precisely with new or repurposed therapies.

Declaration of interest

P Barnes receives grant funding from AstraZeneca and Boehringer Ingelheim and is a scientific advisor for AstraZeneca, Boehringer Ingelheim, Novartis, Pieris, and Epi-Endo. He has revived speaking fees for AstraZeneca, Novartis, Teva, and Boehringer Ingelheim. The author has no other 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.