Epigenetics in chronic rhinosinusitis.

PURPOSE OF REVIEW: Increasing evidence suggests that epigenetic regulation plays a central role in chronic rhinosinusitis pathogenesis, heterogeneity, and treatment response. This review summarizes current knowledge of epigenetics in CRS pathogenesis, their role in endotype differentiation, and potential as diagnostic and therapeutic targets. RECENT FINDINGS: Distinct epigenetic signatures have been identified across CRS subtypes. Hypermethylation of TSLP and differential regulation of FZD5, IL8, and EMT-related genes distinguish eosinophilic CRSwNP from other phenotypes. Specific microRNAs (miR-941, miR-21, miR-125b, miR-155) correlate with disease severity, tissue eosinophilia, and corticosteroid responsiveness, highlighting their utility as noninvasive biomarkers. Experimental data suggest that targeting DNMTs or HDACs may reverse pathogenic remodeling. Emerging therapeutic approaches - such as biologics modulating epigenetically controlled cytokines (e.g. tezepelumab) and engineered extracellular vesicle-based miRNA delivery - illustrate translational promise. SUMMARY: Epigenetic mechanisms critically influence CRS pathogenesis and clinical variability. Their modulation offers novel opportunities for biomarker discovery, disease stratification, and personalized therapy. Future research should focus on standardizing epigenetic profiling methodologies, validating candidate biomarkers in diverse populations, and integrating multiomics and single-cell approaches to uncover cell-specific regulatory networks. These advances may enable precision medicine in CRS, bridging the gap between molecular mechanisms and targeted clinical management.