Comorbid Chronic Rhinosinusitis and Asthma: Shared Risk Factors and Treatment Implications-An EAACI Task Force Report

Chronic rhinosinusitis (CRS) and asthma are prevalent conditions that often coexist. These diseases share common inflammatory mechanisms, such as T-helper cell 2 (T2)-high inflammation, driven by interleukin (IL)-4, IL-5, and IL-13 cytokines. The frequent comorbidity between CRS, especially CRS with nasal polyps (CRSwNP), and asthma exacerbates disease severity, impairs quality of life, and complicates treatment. Patients with NSAID-exacerbated respiratory disease (N-ERD) represent a severe phenotype of this disease, characterized by the coexistence of CRSwNP, asthma, and NSAID hypersensitivity, which poses unique therapeutic challenges. This EAACI Task Force explores the shared risk factors, including genetic predispositions, epithelial barrier dysfunction, microbiome dysbiosis, underlying CRS, and asthma. It also evaluates current therapeutic strategies such as biologics, aspirin therapy after desensitization (ATAD), and endoscopic sinus surgery (ESS). Biologics have shown their effectiveness and safety in the treatment of asthma and CRS. Dupilumab, mepolizumab, depemokimab, and omalizumab have emerged as transformative therapies, particularly for patients with severe type 2 inflammation. Tezepelulumab is effective for both T2-high and T2-low asthma and CRSwNP. Itepekimab has shown its effect in asthma and is under investigation for CRSwNP. Omalizumab is effective in allergic asthma and CRSwNP. ATAD provides an additional disease-modifying approach for N-ERD, though patient adherence and tolerability remain critical challenges. ESS significantly improves asthma control, reduces medication use, and enhances sinonasal outcomes, particularly in severe asthma cases; however, these patients often need recurring surgeries. Despite these advances, treatment outcomes vary based on individual phenotypes and endotypes, underscoring the need for personalized approaches. The report highlights gaps in the literature, such as the lack of head-to-head trials comparing biologics, ATAD, and surgery. Future research should focus on refining treatment algorithms, identifying biomarkers for treatment selection, and assessing long-term outcomes to optimize care for patients with CRS, asthma, and N-ERD.