Correlation of mucus inflammatory proteins and olfaction in chronic rhinosinusitis

Background Chronic rhinosinusitis (CRS) is one of the most common causes of olfactory loss, but the pathophysiology underlying olfactory dysfunction in CRS has not been fully elucidated. Previous studies found correlations between olfactory cleft (OC) inflammatory cytokines/chemokines and olfaction in CRS. The purpose of this study was to evaluate the relationship between OC mucus inflammatory proteins and olfaction in a multi‐institutional cohort. Methods Adults with CRS were prospectively recruited. Demographics, comorbidities, olfactory assessment (Sniffin’ Sticks), computed tomography (CT), and OC mucus for protein analysis were collected. Statistical analysis was performed to determine associations between olfactory function, OC mucus protein concentrations, and CT opacification. Results Sixty‐two patients were enrolled in the study, with an average age of 48.2 (standard deviation, 16.2) years, and 56.5% were female and 59.7% were classified as CRS with nasal polyps (CRSwNP). Ten of 26 OC mucus proteins were significantly correlated with threshold, discrimination, and identification (TDI) scores and OC opacification. Subgroup analysis by polyp status revealed that, within the CRSwNP group, C‐C motif ligand 2 (CCL2), interleukin‐5 (IL‐5), IL‐6, IL‐13, IL‐10, IL‐9, tumor necrosis factor‐α (TNF‐α), CCL5, and CCL11 were significantly correlated with olfaction. For CRS without nasal polyps (CRSsNP), only C‐X‐C ligand 5 (CXCL5) showed a correlation. In CRSwNP, IL‐6, IL‐10, vascular endothelial growth factor‐A, and immunoglobulin E (IgE) correlated with OC opacification, whereas, in CRSsNP, only CXCL5 showed a correlation. OC mucus proteins and Lund‐Mackay score correlated only in the CRSsNP group (CXCL5, IL‐5, IL‐13, IgE). Conclusion Several OC mucus proteins have been found to correlate with olfactory function and OC opacification. The profile of OC mucus proteins differs between CRSsNP and CRSwNP subgroups, suggesting different mechanisms between groups, but further study is required.