Clinical and pathophysiological roles of YKL-40 in obstructive airway diseases.

YKL-40 (chitinase-3-like protein 1) has emerged as a biomarker associated with inflammation and tissue remodeling. YKL-40 is produced by multiple cell types, including macrophages, neutrophils, and airway structural cells, and has been implicated in chronic inflammatory and remodeling processes. While the exact biological role of YKL-40 remains unclear, it has been studied in various respiratory and systemic diseases, including obstructive airway diseases. Clinical investigations in asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap have demonstrated that both serum and sputum YKL-40 levels correlate with sputum neutrophils and may reflect neutrophil-associated non-type 2 airway inflammation in these obstructive airway diseases. Specifically, serum YKL-40 levels are also associated with airflow limitation, disease severity, longitudinal lung function decline, and exacerbation risk. Sputum YKL-40 appears more closely related to symptom burden than to lung function indices. Overall, YKL-40 may represent an informative biomarker, supporting its potential clinical relevance. Future prospective studies incorporating standardized measurement and integrated biomarker approaches that combine YKL-40 with established type 2 indicators may improve inflammatory phenotyping and risk stratification, potentially supporting precision medicine strategies. In this review, we summarize the biological characteristics and clinical roles of YKL-40, with a particular focus on obstructive airway diseases.