Integrated-omics endotyping of patients with chronic rhinosinusitis with nasal polyps and their response to glucocorticoid therapy.

BACKGROUND

Integrated omics approaches provide deeper insights into disease heterogeneity, but combined host immune and nasal microbiota profiles in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly characterized.

OBJECTIVE

This study aimed to identify biologically distinct CRSwNP endotypes by integrating transcriptomic and microbiota data from nasal brushings and to assess responses to corticosteroid therapy across these endotypes.

METHODS

Baseline transcriptomic and microbiota data from the multicenter COMPASS cohort (ClinicalTrials.gov registration: NCT05598424) were integrated using similarity network fusion and hierarchical clustering. Differential gene expression and bacterial genus abundance analyses were performed to characterize each endotype. In the COMPASS cohort, patients with CRSwNP who had a bilateral nasal polyp score (NPS) ≥ 4 points were enrolled and received 4 weeks of intranasal corticosteroid (INCS) treatment. Those whose NPS remained ≥4 after INCS treatment received a 2-week course of add-on systemic corticosteroid (SCS) therapy. Response rates were compared across endotypes using χ2 or Fisher's exact tests.

RESULTS

Among 132 patients from 20 hospitals in China, four endotypes were identified: one non-type 2 inflammatory endotype (Cluster A) and three type 2 inflammatory endotypes distinguished by microbiota composition: a Corynebacterium-dominated profile (Cluster B), a Staphylococcus-dominated profile (Cluster C), and a polymicrobial profile (Cluster D). Among patients receiving add-on SCS therapy, Cluster C showed the highest observed response rate (94.1%), followed by Cluster D (72.7%), Cluster B (62.5%), and Cluster A (56.7%).

CONCLUSION

Integrated transcriptome and microbiota analysis identified four CRSwNP endotypes with distinct immune-microbial signatures and variable corticosteroid responsiveness, supporting the potential for endotype-driven precision therapy in CRSwNP.