SUMMARY

Are eosinophils in COPD truly a marker of type 2 (T2) inflammation, or do they simply reflect underlying or misclassified asthma?

Eosinophils in COPD: Biomarker of Type 2 Inflammation or Misclassified Asthma?

The role of eosinophils in asthma is well established and has been recognised for more than a century. Early studies demonstrated that eosinophilia was closely associated with disease activity, steroid responsiveness, and exacerbation risk.^1-3

In COPD, the evidence is more complex. Population-based data from the Copenhagen General Population Study showed that elevated blood eosinophils were linked to higher exacerbation risk, supporting the idea that eosinophilia may have prognostic relevance in COPD.⁴ However, normal reference ranges published recently remind us that eosinophil counts in the general population vary widely, complicating their interpretation in COPD.⁵ Clinical trials suggest that higher eosinophil counts may predict greater benefit from inhaled corticosteroids, yet biologics targeting type 2 pathways such as IL-5, IL-4/IL-13, or IL-33 have produced mixed or negative results.^6-8 Moreover, the biology of eosinophils in COPD may not mirror that of asthma, and the concept of a distinct “eosinophilic COPD” endotype remains controversial.⁹

Diagnostic overlap: asthma or COPD?

A major challenge is the overlap between asthma and COPD. Smokers with asthma may meet inclusion criteria for COPD studies, while COPD patients with elevated eosinophils and FeNO may actually have undiagnosed asthma.¹⁰ This raises concerns that positive treatment signals in some COPD trials may be driven by misclassified asthma populations rather than a true eosinophilic COPD phenotype.

Taken together, the ERS debate on eosinophils in COPD, underscored that asthma and COPD are not interchangeable diseases. Eosinophils carry clear diagnostic and therapeutic implications in asthma, but their role in COPD is far less certain. Reliance on blood eosinophils as a single biomarker risks misclassification, and genuine precision medicine in COPD will likely require new and more reliable markers of airway biology.