Biomarkers for chronic obstructive pulmonary disease (COPD) with type-2 inflammation.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung disease traditionally characterized by neutrophilic inflammation. However, a distinct type-2 (T2) inflammatory endotype is present in 20% to 40% of patients. This review examines the pathophysiology and clinical consequences of T2 inflammation in COPD, focusing on established and emerging biomarkers to identify this treatable trait and guide targeted therapies. Orchestrated by TH2 cells and innate lymphoid cells, T2 inflammation involves the signature cytokines interleukin (IL)-4, IL-5, and IL-13, which drive eosinophilic tissue infiltration, mucus hypersecretion, airway hyperreactivity, and accelerated remodeling. These processes are correlated with an increased exacerbation risk and a more rapid decline in lung function. Blood eosinophil count is the most validated and accessible biomarker, with established thresholds guiding the use of inhaled corticosteroids and biologics. Fractional exhaled nitric oxide and serum IgE offer complementary predictive value, and combining biomarkers may enhance the identification of responders to specific targeted agents. Clinical trials of biologics, such as dupilumab and mepolizumab, have validated the therapeutic potential of targeting T2 pathways in selected populations, although variable success with other agents highlights unique aspects of COPD pathophysiology and persistent knowledge gaps. Precision medicine, informed by a nuanced interpretation of reliable T2 biomarkers, is crucial for optimizing outcomes in this significant patient subgroup.