Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes

Objective: Chronic rhinosinusitis (CRS) is a heterogeneous disorder with distinct pathophysiologic mechanisms. Based on transcription factor expression and cytokine production patterns in different innate lymphoid cell (ILC) types, in parallel with those of adaptive CD4⁺ T-helper (T_H) cells and CD8⁺ cytotoxic T (Tc) cells, new perspectives on endotypes of patients are emerging for the immune response deviation into type 1 (orchestrated by ILC1s and Tc1, and T_H1 cells), type 2 (characterized by ILC2s and Tc2 and T_H2 cells), and type 3 (mediated by ILC3s and Tc17 and T_H17 cells). In addition, cluster analysis has been applied to endotyping of CRS in recent years, which has provided additional novel insights into CRS pathogenesis. This review assessed pathologic mechanisms of CRS based on type 1, 2, and 3 immune responses and how they inform us to begin to understand CRS endotypes. This review also assessed recent cluster analysis studies of CRS endotypes. The impact of endotype on therapeutic management of CRS also is summarized.

Data sources: Review of published literature.

Study selections: Relevant literature concerning CRS endotypes and possible underlying mechanisms was obtained from a PubMed search and summarized.

Results and conclusion: CRS with and without nasal polyps are composed of distinct endotypes with distinct deviated immune responses, pathogenic mechanisms, and different responses to medical and surgical treatment. An endotype of CRS with prominent type 2 immune responses is the best-studied endotype and generally can benefit from treatment with steroids and specific type 2 disrupting biologics.