Denatonium benzoate bitter taste perception in chronic rhinosinusitis subgroups

Denatonium benzoate bitter taste perception in chronic rhinosinusitis subgroups
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DOI:
10.1002/alr.22687
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发表时间:
2020-09-03
影响因子:
6.4
通讯作者:
Cohen, Noam A.
Cohen, Noam A.
中科院分区:
医学1区
文献类型:
--
作者:
Civantos, Alyssa M.;Maina, Ivy W.;Cohen, Noam A.

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慢性鼻窦炎(CRS)伴鼻息肉(CRSwNP)和CRS不伴鼻息肉(CRSsNP)以及阿司匹林加重的呼吸道疾病(AERD)具有不同程度的炎症和疾病严重程度。孤立的化学感受细胞(SCC)在鼻息肉中富集,是上呼吸道中白细胞介素25(IL-25)的主要来源,导致2型炎症,并被具有苦味的苯甲酸地那铵(DB)激活。因此,我们试图在一系列浓度下评价DB味觉,以鉴定最能区分CRS亚组与对照的1。方法CRSsNP(n = 25)、CRSwNP(n = 26)和AERD(n = 27)患者以及对照组(n = 25)以固定的随机顺序品尝6种DB浓度,在0(无强度)至12(极强度)的类别量表上评级。用和不用地那铵处理鼻窦上皮培养物,并通过流式细胞术分析IL-25。结果CRSsNP患者在所有浓度下对DB的评分均显著低于对照组: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和1.00 x 10(-7)M(allp< 0.0083)。CRSwNP患者与对照组无显著差异。在1.00 x 10(-8)M和3.16 x 10(-8)M浓度下,AERD患者对DB的评分明显高于对照组(p< 0.0083)。体外数据表明,与对照组(n = 5)相比,地那铵刺激后IL-25阳性细胞(n = 5)显著增加(p= 0.012)。结论我们的研究结果将鼻窦组织的体外DB刺激与IL-25增加联系起来,并显示CRS亚组相对于对照组的DB味觉差异,CRSsNP是低敏感的,AERD是高敏感的。我们建议浓度为3.16 x 10(-8)M,用于未来的临床实用性研究。
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.