From Airway Inflammation to Molecular Remodeling: Integrating YKL-40, MBL and Epigenetic Biomarkers in Asthma and COPD

Background: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous chronic airway disorders characterized by complex interactions among inflammation, immune dysregulation, environmental exposures, and tissue remodeling. Conventional clinical classifications based on symptoms, lung function, and exacerbation history often fail to fully capture the biological mechanisms underlying disease progression and therapeutic variability. Methods: This narrative review summarizes current evidence regarding the biological and clinical significance of YKL-40, mannose-binding lectin (MBL), and epigenetic remodeling in asthma and COPD, with particular emphasis on the inflammation–epigenetic axis and its potential role in disease phenotyping and precision medicine. Results: Available evidence suggests that YKL-40, MBL, and epigenetic signatures represent complementary biomarker layers reflecting tissue remodeling, innate immune variability, and cumulative inflammatory adaptation, respectively. Chronic inflammatory signaling, oxidative stress, and epigenetic remodeling may contribute to persistent molecular memory and phenotypic stabilization, providing a mechanistic framework for understanding disease heterogeneity and progression. Advances in multi-omics technologies, artificial intelligence, and machine learning are further supporting the development of integrated multimarker models. Conclusions: YKL-40, MBL, and epigenetic signatures should currently be considered complementary research variables rather than validated clinical tools. Their translation requires disease-specific assay standardization, prospective evaluation against prespecified outcomes, external validation, and evidence that biomarker-guided decisions improve patient care.