From Sinuses to Bronchi: Molecular Endotypes and Therapeutic Convergence in CRS-Asthma Comorbidity

Chronic rhinosinusitis (CRS) and asthma represent interrelated inflammatory disorders within the unified airway continuum, sharing overlapping molecular and immunologic mechanisms, clinical features, and therapeutic responses. Epidemiological studies indicate a high prevalence of CRS-asthma comorbidity, which is associated with increased disease severity, healthcare utilization, and impaired quality of life compared with either condition alone. Advances in airway immunology have established type 2 (T2) inflammation, characterized by epithelial barrier dysfunction, eosinophilic infiltration, and cytokine signaling via interleukin (IL)-4, IL-5, IL-13, thymic stromal lymphopoietin (TSLP), and IL-33, as a central pathogenic axis across both upper and lower airways. Non-type 2 (non-T2) endotypes contribute to disease heterogeneity and treatment resistance. This review synthesizes current evidence on shared molecular endotypes, emerging biomarkers, and clinical consequences of CRS-asthma comorbidity, with particular emphasis on biologic therapies targeting immunoglobulin E (IgE), IL-5, and multi-omics profiling and artificial intelligence-assisted analytics, in refining disease stratification, predicting therapeutic response, and guiding integrated treatment strategies. Finally, we highlight key research gaps and propose future directions toward endotype-driven, unified airway care aimed at improved long-term outcomes for patients with CRS-asthma comorbidity.