Personalized Medicine in Chronic Rhinosinusitis: Treatable Traits Using Biologics for Unmet Needs

Chronic rhinosinusitis (CRS) is a prevalent airway disease, leading to health, social, and economic burdens, and substantially impairs quality of life. As CRS is heterogeneous and contains diverse pathogenesis, treatment outcomes and prognosis vary from curative to intractable. Inflammatory endotypes of CRS are divided into 3 types-type 1, type 2 and type 3-based on cytokines promoted. Tissue/blood eosinophilia seems to be the most reliable and feasible biomarker for type 2 CRS in clinical settings, although the cutoff level of eosinophilia remains to be elucidated. In East Asia, the predominant pathogenesis has changed from neutrophilic type 3 inflammation to eosinophilic type 2 inflammation over the past decades. The treatment strategy for CRS has also evolved from classical phenotype-based "reliever-controller" treatment to endotype-based "treatable traits" treatment. "Treatable traits" treatment is a personalized approach for the management of airway disease with complex and heterogeneous conditions. In CRS, traits can be grouped into sinonasal, extra-nasal and risk factor/behavioral domains. Type 2 CRS is one of the sinonasal traits, and biologics targeting immunoglobulin E, interleukin (IL)-5 and its receptor, IL-4/IL-13 receptor (IL-4/IL-13R) and thymic stromal lymphopoietin are the corresponding treatments for this trait. Proper use of these biologics can achieve high efficacy with patient satisfaction, leading to clinical remission. However, some cases show marked hypereosinophilia after the reduction or discontinuation of systemic corticosteroid or the switching of biologics from anti-IL-5/IL-5R to anti-IL-4R alpha monoclonal antibody. More precise research on CRS targeting endotype, genotype, regiotype and theratype is needed to address the unmet needs and refine the "treatable traits" treatment of CRS.