From clinical phenotypes to cellular mechanisms: a precision medicine framework for COPD

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.