Toward precision medicine in COPD: phenotypes, endotypes, biomarkers, and treatable traits.

Abstract

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder characterized by diverse clinical manifestations, pathophysiological mechanisms, and therapeutic responses. This review explores the evolving landscape of precision medicine in COPD management, with particular emphasis on optimizing patient care through the integration of phenotypes, endotypes, biomarkers, and treatable traits. Phenotypic classification based on observable clinical and radiographic features has facilitated the identification of distinct subgroups such as "emphysema-dominant" or "frequent-exacerbator" subtypes. Emerging research, however, increasingly emphasizes endotypes-disease subcategories defined by unique biological mechanisms including neutrophilic inflammation, eosinophilic airway involvement, or α₁ antitrypsin deficiency-which may demonstrate superior predictive value for therapeutic responses. Biomarkers encompassing blood eosinophil counts, serum C-reactive protein, and sputum transcriptomics are progressively being implemented for patient stratification and guidance of targeted therapies, including inhaled corticosteroids or biologics. Furthermore, the "treatable traits" framework enhances personalized management by addressing modifiable factors beyond airflow limitation, such as comorbidities, psychosocial determinants, and exacerbation triggers. Despite these advancements, persistent challenges remain in biomarker validation, standardization of phenotypic definitions, and clinical translation of research findings. Future directions involve early detection of pre-COPD states and treatable traits, integration of multi-omics data, machine learning-driven dynamic phenotyping, and pragmatic clinical trials evaluating precision-guided interventions. By aligning pathobiological mechanisms with targeted therapies, precision medicine holds promise for transforming COPD care from reactive management to proactive, individualized therapeutic paradigms.