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From clinical phenotypes to cellular mechanisms: a precision medicine framework for COPD
Jianjun Wu1, Xiaomeng Cheng1, Fangyuan Yu1
1Respiratory Department, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China.
Frontiers in Immunology
|June 8, 2026
Summary
This review proposes a cellular phenotype classification for chronic obstructive pulmonary disease (COPD) to guide precision therapies. This approach aims to improve COPD management by targeting specific inflammatory mechanisms rather than just symptoms.
Area of Science:
- Pulmonology
- Immunology
- Pharmacology
Background:
- Chronic obstructive pulmonary disease (COPD) is a heterogeneous, progressive lung disease.
- Current management relies on symptoms and pulmonary function tests, which have limitations in aligning with individual pathological mechanisms and are resource-intensive.
- A gap exists between clinical presentation and underlying disease mechanisms in COPD.
Purpose of the Study:
- To systematically map cellular inflammatory phenotypes in COPD to targeted therapies.
- To highlight the potential of mechanistic, cell-based classifications for improving COPD management.
- To propose a framework for precision interventions in COPD.
Main Methods:
- Critical examination of the evolution from clinical to cellular phenotyping in COPD.
- Systematic mapping of cellular inflammatory phenotypes (neutrophilic, eosinophilic, lymphocytic, macrophage, mixed granulocytic) to targeted therapies.
- Validation of the proposed cellular phenotype classification in multinational cohorts.
Main Results:
- A validated cellular phenotype classification for COPD is presented: neutrophilic (>60% sputum neutrophils), eosinophilic (≥3% eosinophils), lymphocytic, macrophage, and mixed granulocytic.
- Specific targeted therapies are identified for neutrophilic (CXCR1/2 pathway or neutrophil elastase inhibition) and eosinophilic (anti-IL-5/IL-13 biologics or Th2 blockade) phenotypes.
- A four-tiered diagnostic pathway (biomarker screening, multi-omics validation, consensus assignment, dynamic therapy escalation) is proposed.
Conclusions:
- The proposed cellular phenotyping approach shifts COPD management from symptom control to pathogenesis modification.
- This framework enables precision interventions based on underlying inflammatory mechanisms.
- Challenges remain in translating cellular phenotypes into routine clinical practice, requiring further research.
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