Denatonium-induced sinonasal bacterial killing may play a role in chronic rhinosinusitis outcomes.
Denatonium-induced sinonasal bacterial killing may play a role in chronic rhinosinusitis outcomes.
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DOI：
10.1002/alr.21949
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发表时间：
2017-07
影响因子：
6.4
通讯作者：
Cohen NA
中科院分区：
文献类型：
--
作者：
Carey RM;Workman AD;Hatten KM;Siebert AP;Brooks SG;Chen B;Adappa ND;Palmer JN;Kennedy DW;Lee RJ;Cohen NA
鼻窦苦味受体（T2 R）有助于上气道先天免疫，并与慢性鼻窦炎（CRS）的临床结果相关。鼻腔鼻窦孤立性化学感受细胞（SCC）上表达的T2 R亚群被地那铵激活，导致邻近纤毛上皮细胞中钙介导的杀菌抗菌肽（AMP）分泌。我们假设不同浓度的地那铵诱导的细菌杀灭量存在患者差异，并且差异与CRS临床结局相关。将细菌与从地那铵刺激的鼻窦气液界面（ALI）培养物收集的气道表面液体（ASL）混合后，定量细菌生长抑制。在这些人群之间比较了0.1 mM地那铵对患者ASL细菌的杀灭率和基线特征以及鼻窦手术结局。患者之间变性钠诱导的细菌杀灭程度存在差异。在CRS伴鼻息肉（CRSwNP）中，低水平地那铵刺激后细菌杀灭增加的患者接受功能性内窥镜鼻窦手术（FESS）的次数显著增加（p = 0.037），FESS后6个月22项鼻窦结局测试（SNOT-22）评分更差（p = 0.012）。在CRSwNP中，低水平地那铵刺激后的细菌杀灭与既往FESS次数和术后SNOT-22评分相关。对低水平地那铵有高反应性的患者的CRS的一些症状可能是由于气道免疫活性增加或固有疾病严重程度所致。
Sinonasal bitter taste receptors (T2Rs) contribute to upper airway innate immunity and correlate with chronic rhinosinusitis (CRS) clinical outcomes. A subset of T2Rs expressed on sinonasal solitary chemosensory cells (SCCs) are activated by denatonium, resulting in a calcium-mediated secretion of bactericidal antimicrobial peptides (AMPs) in neighboring ciliated epithelial cells. We hypothesized that there is patient variability in the amount of bacterial killing induced by different concentrations of denatonium and that the differences correlate with CRS clinical outcomes. Bacterial growth inhibition was quantified after mixing bacteria with airway surface liquid (ASL) collected from denatonium-stimulated sinonasal air-liquid interface (ALI) cultures. Patient ASL bacterial killing at 0.1 mM denatonium and baseline characteristics and sinus surgery outcomes were compared between these populations. There is variability in the degree of denatonium-induced bacterial killing between patients. In CRS with nasal polyps (CRSwNP), patients with increased bacterial killing after stimulation with low levels of denatonium undergo significantly more functional endoscopic sinus surgeries (FESSs) (p = 0.037) and have worse 6-month post-FESS 22-item Sino-Nasal Outcome Test (SNOT-22) scores (p = 0.012). Bacterial killing after stimulation with low levels of denatonium correlates with number of prior FESS and postoperative SNOT-22 scores in CRSwNP. Some symptoms of CRS in patients with hyperresponsiveness to low levels of denatonium may be due to increased airway immune activity or inherent disease severity.
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影响因子：
6.4
作者：
Adappa ND;Farquhar D;Palmer JN;Kennedy DW;Doghramji L;Morris SA;Owens D;Mansfield C;Lysenko A;Lee RJ;Cowart BJ;Reed DR;Cohen NA
通讯作者：
Cohen NA
影响因子：
15.9
作者：
Lee, Robert J.;Xiong, Guoxiang;Cohen, Noam A.
通讯作者：
Cohen, Noam A.
DOI：
10.1159/000444957
发表时间：
2016-01-01
期刊：
RHINOSINUSITIS WITH NASAL POLYPOSIS
影响因子：
--
作者：
London, Nyall R., Jr.;Reh, Douglas D.
通讯作者：
Reh, Douglas D.
影响因子：
7.2
作者：
Rom, Darren I.;Christensen, Jenna M.;Harvey, Richard J.
通讯作者：
Harvey, Richard J.
影响因子：
6.4
作者：
Barham, Henry P.;Cooper, Sarah E.;Anderson, Catherine B.;Tizzano, Marco;Kingdom, Todd T.;Finger, Tom E.;Kinnamon, Sue C.;Ramakrishnan, Vijay R.
通讯作者：
Ramakrishnan, Vijay R.