Correlation Between Subepithelial Fibrosis and Vitamin D Deficiency in Chronic Rhinosinusitis with Nasal Polyps: Insights from Histological and Transcriptomic Analyses.

Purpose: To investigate the correlation between serum vitamin D status and clinical, histological, and gene expression profiles in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Patients and Methods: This observational study enrolled patients with CRSwNP from November 2019 to September 2021, and diagnoses were confirmed according to the 2020 European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2020). Clinical features, histopathological characteristics, and gene expression profiles were analyzed across groups with serum vitamin D deficiency status. Histopathological evaluations and mRNA sequencing were performed on a subset of nasal polyp specimens. Results: Among 101 patients with CRSwNP, a comprehensive analysis revealed no significant correlation between vitamin D deficiency and most clinical parameters or treatment prognosis, except for a notable age difference among groups with serum vitamin D-deficiency, insufficiency, and sufficiency. Histologically, a higher prevalence of subepithelial fibrosis was observed in the vitamin D-deficient group. Moreover, transcriptomic analysis demonstrated significant differences in expression profiles among the groups, with upregulated genes in the deficient group enriched in extracellular matrix components and downregulated genes related to axoneme assembly and cilium movement. Conclusion: Our findings suggest a connection between vitamin D deficiency and subepithelial fibrosis in nasal polyps, pointing to a possible involvement of vitamin D status in fibrosis-related pathological processes in CRSwNP.