Disease phenotyping in chronic obstructive pulmonary disease: the neutrophilic endotype

Despite decades of scientific attention, chronic obstructive pulmonary disease (COPD) remains a major cause of both morbidity and mortality worldwide with strikingly few effective drug classes available. This may be in part because COPD is actually a syndrome composed of distinct diseases with varying pathophysiology (endotypes), and therapies have not been designed to target the causal pathological processes specific to an endotype.

Recent work has begun to clarify the nature of these endotypes and characterize them. One promising field focuses on the central role of the neutrophil and the tripeptide matrikine proline-glycine-proline (PGP) in a subset of COPD patients. Two drugs with mechanisms of action novel to the COPD therapeutic arena (azithromycin and roflumilast) have been shown to reduce acute exacerbations of COPD. Intriguingly, recent evidence has linked both of these agents to modulation of the PGP/neutrophil pathway in concert with this exacerbation reduction, suggesting that a neutrophilic endotype is present and amenable to pharmacological targeting.

Further work characterizing COPD endotypes, including this neutrophilic endotype, will be important as we strive to understand the mechanistic roots of this disease in the hope of creating more effective therapies.