Search

Background: Bitter (T2R) and sweet (T1R) taste receptors in the airway are important in innate immune defense, and variations in taste receptor functionality in one T2R (T2R38) correlate with disease status and disease severity in chronic rhinosinusitis (CRS). Quinine is a bitter compound that is an agonist for several T2Rs also expressed on sinonasal cells, but not for T2R38. Because of this property, quinine may stimulate innate immune defense mechanisms in the airway, and functional differences in quinine perception may be reflective of disease status in CRS. Methods: Demographic and taste intensity data were collected prospectively from CRS patients and non-CRS control subjects. Sinonasal tissue from patients undergoing rhinologic surgery was also collected and grown at an air--liquid interface (ALI). Nitric oxide (NO) production and dynamic regulation of ciliary beat frequency in response to quinine stimulation were assessed in vitro. results: Quinine reliably increased ciliary beat frequency and NO production in ALI cultures in a manner consistent with T2R activation (p < 0.01). Quinine taste intensity rating was performed in 328 CRS patients and 287 control subjects demonstrating that CRS with nasal polyps (CRSwNP) patients rated quinine as significantly less intense than did control subjects. conclusion: Quinine stimulates airway innate immune defenses by increasing ciliary beat frequency and stimulating NO production in a manner fitting with T2R activation. Patient variability in quinine sensitivity is observed in taste intensity ratings, and gustatory quinine "insensitivity" is associated with CRSwNP status. Thus, taste tests for quinine may be a biomarker for CRSwNP, and topical quinine has therapeutic potential as a stimulant of innate defenses. [ABSTRACT FROM AUTHOR]

Background: Bitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that 1 of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes 1 type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses. Methods: We examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients. CRS patients with (n = 426) and without (n = 226) nasal polyps and controls (n = 356) rated the intensity of quinine, denatonium benzoate, phenylthiocarbamide (PTC; a ligand for TAS2R38), sucrose, and salt. Results: CRS patients rated the bitter compounds denatonium benzoate and quinine as less intense and sucrose as more intense than did controls (false discovery rate [FDR] <0.05) and CRS patients and controls did not differ in their ratings of salt (FDR >0.05). PTC bitter taste intensity differed between patient and control groups but were less marked than those previously reported. Though differences were statistically significant, overall effect sizes were small. Conclusion: CRS patients report bitter stimuli as less intense but sweet stimuli as more intense than do control subjects. We speculate that taste responses may reflect the competence of sinonasal innate immunity mediated by taste receptor function, and thus a taste test may have potential for clinical utility in CRS patients. [ABSTRACT FROM AUTHOR]

Background Sinonasal biofilms have been demonstrated in specimens collected from chronic rhinosinusitis (CRS) patients. Mounting evidence suggests that biofilms contribute to therapeutically recalcitrant CRS. Recently, the bitter taste receptor T2R38 has been implicated in the regulation of the sinonasal mucosal innate immune response. TAS2R38 gene polymorphisms affect receptor functionality and contribute to variations seen in sinonasal innate defense as well as taste perception reflected in gustatory sensitivity to the bitter compound phenylthiocarbamide (PTC). In a population of CRS patients with active infection or inflammation, we sought to determine if a correlation between T2R38 phenotype and in vitro biofilm formation existed. Methods Endoscopically guided sinonasal swabs were obtained prospectively from CRS (±polyp) patients with evidence of persistent inflammation or mucopurulence. In vitro biofilm formation was assessed with a modified Calgary Biofilm Detection Assay. Patients' phenotypic (functional) expression of the bitter taste receptor T2R38 was evaluated with a taste test including the compound PTC. Linear regression was used to determine the level of significance between mean in vitro biofilm formation levels and mean PTC taste test intensity ratings across CRS patients. Results Sinonasal swabs were obtained from 59 patients, with 42 of the 59 samples demonstrating in vitro biofilm formation. Analysis revealed an inverse linear association between in vitro biofilm formation and PTC taste intensity ratings ( p = 0.019) for all patients. This association was exclusively driven by nonpolypoid CRS patients ( p = 0.0026). Conclusion In vitro biofilm formation from sinonasal clinical isolates is inversely correlated with PTC taste sensitivity in nonpolypoid CRS patients. [ABSTRACT FROM AUTHOR]

Background Besides sensorineural factors, conductive impediments likely contribute to olfactory losses in chronic rhinosinusitis (CRS) patients, yet no conclusive evidence exists. We aimed to examine possible conductive factors using computational fluid dynamics (CFD) models. Methods A total of 29 CRS patients were assessed via odorant detection thresholds (ODTs), rhinomanometry (nasal resistance [NR]), acoustic rhinometry (minimum-cross-sectional area [MCA]) and computed tomography (CT) staging. CFD simulations of nasal airflow and odorant absorption to olfactory region were carried out based on individual CTs. Biopsies of olfactory epithelium (OE) were collected, cryosectioned, stained, and scored for erosion. Results Significant correlations to ODTs were found for 3 variables: odor absorption in the olfactory region ( r = −0.60, p < 0.01), MCA ( r = −0.40, p < 0.05), and CT staging ( r = 0.42, p < 0.05). However, significant findings were limited to ODTs of the highly soluble l-carvone. Multiple regression analysis revealed that these variables combined, with the addition of NR, can account for 65% of the total variance in ODTs. CT staging correlated significantly with OE erosion ( r = 0.77, p < 0.01) and can replace the latter in the regression with comparable outcomes. Partial correlations suggest the contributions of both conductive and sensorineural variables are more prominent if adjusted for the effects of the other. Olfactory loss and inflammatory factors have strong bilateral involvement, whereas conductive factors are independent between sides. As validation, CFD-simulated NRs significantly correlated with rhinomanometrically assessed NRs ( r = 0.60, p < 0.01). Conclusion Both conductive and sensorineural mechanisms can contribute to olfactory losses in CRS. CFD modeling provides critical guidance in understanding the role of conductive impediments in olfactory dysfunction in CRS. [ABSTRACT FROM AUTHOR]