Current insight into treatment of chronic rhinosinusitis: Phenotypes, endotypes, and implications for targeted therapeutics

Abstract

Chronic rhinosinusitis is characterized by persistent locoregional mucosal inflammation of the paranasal sinuses and upper airway that has substantial associated health care costs. Personalized approaches to care that incorporate use of molecular biomarkers, phenotypes, and inflammatory endotypes is a major focus of research at this time, and the concurrent rise of targeted therapeutics and biologic therapies has the potential to rapidly advance care and improve outcomes. Recent findings suggest that improved understanding of chronic rhinosinusitis phenotypic and endotypic heterogeneity, and incorporation of these characteristics into clinical care pathways, may facilitate more effective selection of surgical and/or therapeutic interventions. Ultimately, these personalized approaches have the potential to target specific inflammatory pathways, increase efficacy, reduce costs, and limit side effects. This review summarizes recent advances in the identification and characterization of chronic rhinosinusitis phenotypes, endotypes, and biomarkers and reviews potential implications for targeted therapeutics.

Keywords: Endotypes; biologics; biomarkers; cytokines; phenotypes; rhinosinusitis.

Figure 1.. Chronic Rhinosinusitis (CRS) Phenotypes and Endotypes.

CRS is a clinical syndrome characterized by chronic sinonasal mucosal inflammation, variable symptom presentation, and characteristic CT findings. Disease heterogeneity is evidenced by contrasting CT images in CRS patients with nasal polyps (left), without nasal polyps (middle) and AFRS (right). CRS patients can be grouped into phenotypes and subphenotypes based on observable characteristic features or endotypes based on distinct biological mechanisms or molecular pathways. Endotypic features can sometimes be inferred by tissue histology or type of cellular infiltrate. Abbreviations: AERD, aspirin-exacerbated respiratory disease; AFRS, allergic fungal rhinosinusitis; CCAD, central compartment atopic disease; CRSsNP, chronic rhinosinusitis without nasal polyps; CRSwNP, chronic rhinosinusitis with nasal polyps; EMRS, eosinophilic mucin rhinosinusitis.