Denatonium Benzoate Bitter Taste Perception In Chronic Rhinosinusitis Subgroups

Background Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), and aspirin-exacerbated respiratory disease (AERD) have varying levels of inflammation and disease severity. Solitary chemosensory cells (SCCs) are enriched in nasal polyps, are the primary source of interleukin 25 (IL-25) in upper airways, leading to type 2 inflammation, and are activated by bitter-tasting denatonium benzoate (DB). Thus, we sought to evaluate DB taste perception at a range of concentrations in order to identify 1 that most differentiates CRS subgroups from controls. Methods CRSsNP (n = 25), CRSwNP (n = 26), and AERD (n = 27) patients as well as controls (n = 25) tasted 6 DB concentrations in a fixed, random order, rating on a category scale of 0 (no intensity) to 12 (extremely intense). Sinonasal epithelial cultures were treated with and without denatonium and analyzed for IL-25 via flow cytometry. Results CRSsNP patients rated DB as significantly less intense than did controls at all concentrations: 5.62 x 10(-9)M, 1.00 x 10(-8)M, 1.78 x 10(-8)M, 3.16 x 10(-8)M, 5.62 x 10(-8)M, and 1.00 x 10(-7)M (allp< 0.0083). CRSwNP patients did not show significant differences from controls. AERD patients rated DB as significantly more intense than did controls at concentrations of 1.00 x 10(-8)M and 3.16 x 10(-8)M (p< 0.0083). In vitro data demonstrated significant increase in IL-25-positive cells after denatonium stimulation (n = 5), compared to control (n = 5) (p= 0.012). Conclusion Our findings link in vitro DB stimulation of sinonasal tissue with increased IL-25 and show differential DB taste perception in CRS subgroups relative to the control group, with CRSsNP being hyposensitive and AERD being hypersensitive. We propose a concentration of 3.16 x 10(-8)M for future study of clinical utility.