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AERD subjects demonstrated increased sensitivity to DB ( I p i < 0.01) and sucrose ( I p i < 0.01) compared with CRSsNP, while CRSsNP subjects demonstrated a reduced sensitivity to DB ( I p i < 0.05) and sucrose ( I p i < 0.05) compared with controls (Figure 1). It was anticipated that in AERD, unique genetic polymorphisms in DB-responsive T2Rs may result in upregulation of the receptors and resulting type-2 inflammation. Keywords: aspirin-exacerbated respiratory disease; bitter; chronic rhinosinusitis; gene; open array; sensory; taste EN aspirin-exacerbated respiratory disease bitter chronic rhinosinusitis gene open array sensory taste 269 272 4 02/21/23 20230301 NES 230301 INTRODUCTION Chronic rhinosinusitis (CRS), a disease of long-standing sinonasal inflammation, is divided into two phenotypes: CRS with and without nasal polyposis (CRSwNP, CRSsNP). [Extracted from the article]

Background: Patients with aspirin‐exacerbated respiratory disease (AERD) are among the most challenging rhinologic patients to treat. AERD has a complex inflammatory milieu of lipid mediators and cytokines. In this study we evaluated cytokine differences in the complex AERD environment at the mucus, epithelial, and tissue levels. Methods: Samples were acquired at the time of sinus surgery from 21 patients (seven steroid‐treated, 14 untreated) with aspirin challenge‐confirmed AERD. Three methods (sponge adsorption, epithelial brushing, tissue biopsy) were used to acquire samples from the respective sinus sampling sites (mucus, polyp epithelium, and full‐thickness polyp) of each patient. We measured and compared 16 cytokine concentrations in AERD patients with or without prednisone treatment using the Luminex platform. Results: In most sampling sites, IL‐5, IL‐6, IL‐10, IL‐13, IL‐33, CCL20, and TNF‐α were detected at higher concentrations than IFN‐γ, IL‐1β, IL‐17A, IL‐4, IL‐22, IL‐17E/IL25, and GM‐CSF. Each sampling site had a different pattern of cytokine levels, and except for IL‐5 and IL‐25 there was no correlation among sampling methods for each cytokine tested. The most notable and significant decreases in cytokines from those treated with prednisone were observed in the epithelium for IL‐5, IL‐10, IL‐33, and IFN‐γ. Conclusions: In the epithelial samples, type 2‐associated cytokines IL‐5 and IL‐33, the anti‐inflammatory cytokine IL‐10, and IFN‐γ were lower in AERD patients treated with prednisone. This work serves as a basis to assess therapeutic‐induced mucosal cytokine responses in AERD and indicates that the site of cytokine measurement is an important consideration when assessing results. [ABSTRACT FROM AUTHOR]

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 × 10–9M, 1.00 × 10–8M, 1.78 × 10–8M, 3.16 × 10–8M, 5.62 × 10–8M, and 1.00 × 10–7M (all p < 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 × 10–8M and 3.16 × 10–8M (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 × 10–8M for future study of clinical utility. [ABSTRACT FROM AUTHOR]