COPD guideline proposes cellular phenotype classification for targeted therapy

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Frontiers in Medicine Published May 21, 2026 Medically reviewed May 21, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider this guideline as a conceptual framework for COPD phenotype-guided therapy, noting substantial practice challenges.

This is a guideline review that proposes a framework for classifying chronic obstructive pulmonary disease (COPD) by cellular phenotype, including neutrophilic, eosinophilic, lymphocytic, macrophage, and mixed granulocytic types. The scope is to shift COPD management from symptom control to pathogenesis modification using targeted therapies such as CXCR1/2 pathway inhibitors, neutrophil elastase inhibitors, anti-interleukin-5 biologics, anti-interleukin-13 biologics, and Th2 blockers.

The authors synthesize that this approach provides a framework for precision interventions. They contrast this with traditional management based on clinical symptoms and pulmonary function tests. No pooled effect sizes or specific trial results are reported, as this is a guideline and not a primary study.

The review notes substantial challenges remain in translating cellular phenotypes into routine practice. Limitations include the lack of reported sample sizes, follow-up periods, or safety data. The authors do not report specific adverse events, serious adverse events, discontinuations, or tolerability findings.

Practice relevance is framed as providing a path toward precision medicine in COPD. However, the evidence is early and the framework is not yet validated for routine use. Clinicians should interpret this as a conceptual guide rather than a prescriptive protocol.

Study Details

Study typeGuideline

EvidenceLevel 5

PublishedMay 2026

View Original Abstract ↓

Chronic obstructive pulmonary disease (COPD) is a persistent, often progressive lung disease with a highly heterogeneous patient population. Its management has traditionally relied on clinical symptoms and pulmonary function tests. However, this approach has limitations due to a poor alignment between the clinical symptoms and underlying individual pathological mechanisms, as well as a heavy reliance on chest imaging, restricting its wide application in resource-limited settings. This review aimed to bridge the gap between clinical presentation and underlying mechanisms by systematically mapping cellular inflammatory phenotypes to targeted therapies. We critically examined the evolution from clinical to cellular phenotyping, highlighting the potential of mechanistic, cell-based classifications to improve COPD management. The proposed cellular phenotype classification—neutrophilic (>60% sputum neutrophils), eosinophilic (≥3% eosinophils), lymphocytic, macrophage, and mixed granulocytic—has been validated in multinational cohorts and provides a framework for precision interventions: inhibiting the CXCR1/2 pathway or neutrophil elastase for the neutrophilic phenotype, and anti-interleukin-5/interleukin-13 biologics or Th2 blockade for the eosinophilic phenotype. We propose a four-tiered diagnostic pathway comprising biomarker screening, multi-omics validation, consensus assignment, and dynamic therapy escalation. This approach shifts COPD management from symptom control to pathogenesis modification. However, substantial challenges remain in translating cellular phenotypes into routine practice, warranting further research.