Abstract
Abstract
Background:
Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disorder of the upper respiratory tract. The bitter taste receptor T2R38, encoded by the TAS2R38 gene, is expressed in airway epithelial cells and has been implicated in mucosal chemosensory defense. However, the relationship between mucosal TAS2R38 transcript abundance and clinical and radiological measures of CRS severity remains incompletely characterized.
Objective:
To evaluate the association between mucosal TAS2R38 gene expression and clinical and radiological measures of disease severity in adults with CRS undergoing functional endoscopic sinus surgery (ESS).
Methods:
This prospective cross-sectional molecular study included 55 adult patients with medically refractory CRS undergoing ESS between April 2025 and June 2026. A total of 253 quality-controlled mucosal specimens were obtained from multiple sinonasal anatomical sites. Relative TAS2R38 mRNA expression was quantified by RT-qPCR using GAPDH as the endogenous reference. Expression was represented by Delta Cq, where lower Delta Cq indicates greater transcript abundance. Associations with preoperative SNOT-22 score, Lund-Mackay CT score, nasal polyp grade, asthma, and phenylthiocarbamide (PTC) taste phenotype were evaluated using correlation analyses, subgroup comparisons, and multivariable linear mixed-effects modeling accounting for repeated specimens within patients.
Results:
Higher preoperative SNOT-22 scores were significantly associated with lower mucosal TAS2R38 Delta Cq values (Pearson r = −0.303, P = 0.025; Spearman rho = −0.334, P = 0.013). Mean Delta Cq differed across three prespecified SNOT-22 groups (ANOVA F = 3.89, P = 0.027). In a multivariable linear mixed-effects model adjusting for age, sex, Lund-Mackay score, polyp grade, and anatomical sampling site, SNOT-22 remained associated with TAS2R38 Delta Cq (beta = −0.034, 95% CI −0.063 to −0.004; P = 0.025). No statistically significant association was detected between TAS2R38 Delta Cq and Lund-Mackay score or nasal polyp grade. PTC taste phenotype was not associated with transcript abundance (P = 0.896). Patients with asthma had numerically lower Delta Cq values, but the difference was not statistically significant (P = 0.184).
Conclusion:
Mucosal TAS2R38 transcript abundance was associated with greater patient-reported symptom burden in this surgical CRS cohort, whereas no statistically significant association was detected with radiological disease extent, nasal polyp grade, or PTC taste phenotype. These findings suggest that TAS2R38 transcription may be more closely related to the symptomatic dimension of CRS than to gross radiological disease extent. Functional and longitudinal studies are warranted.