antihistamine, azelastine (AZL), reported effective in non-allergic rhinitis. (NAR), activates TRPV1 ion channels. The purpose of this study was to elucidate the ...
AB134 Abstracts
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Anti-Histaminergic Responses On TRPV1 Channels Umesh Singh1, Jonathan A. Bernstein, MD2,3, Kristin Luther1, Lauren Haar1, W. Keith Jones1; 1University of Cincinnati, Cincinnati, OH, 2 Bernstein Allergy Group, Cincinnati, OH, 3University of Cincinnati Medical Center, Cincinnati, OH. RATIONALE: Activation of sensory neurons are known to be mediated by TRPV1 ion channels which may contribute to the pathophysiology of neurogenic inflammation. Recently we demonstrated that the topical antihistamine, azelastine (AZL), reported effective in non-allergic rhinitis (NAR), activates TRPV1 ion channels. The purpose of this study was to elucidate the effect of AZL on TRPV1 signaling. METHODS: Mice neuronal cells (CATH.a) were plated on glass coverslips and incubated (378C/5%CO2 324 hrs.). After loading cells with Ca2+ specific fluorescent dye Fluo-4 AM, changes in free cytosolic Ca2+([Ca2+]i), in response to AZL 30 mM and the TRPV1 agonist, Capsaicin 1 mM (CAP) , were assessed by confocal imaging. RT-PCR for mRNA expression of protein kinases (PKA and PKC) and phospholipase C (PLC) were performed to assess for TRPV1 responses recovering from desensitization. RESULTS: Sustained pre-treatment (;15 minutes) of CATH.a cells with CAP (1 mM) or AZL (30 mM) made these cells refractory to further increase in [Ca2+]i after subsequent applications of these agents indicating desensitization of TRPV1. After allowing for TRPV1 channel recovery (;25 minutes) from the desensitized state, treatment with either CAP (1 mM) or AZL (30 mM) resulted in a significant increase in [Ca2+]i which correlated with increased mRNA expression of the phosphorylating proteins PKA, PKC and PLC associated with re-sensitization of TRPV1. CONCLUSIONS: Sustained application of either CAP or AZL desensitize TRPV1 ion channels. This data could explain the therapeutic effect of AZL in NAR thought to be caused by neurogenic inflammation.
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Allergen Exposure Affects Sinonasal Microbiota Chris Choi1, Valeriy Poroyko1, So Watanabe2, Duo Jiang1, James Lane3, Marcella DeTineo4, Fuad M. Baroody, MD, FAAAAI5, Robert M. Naclerio, MD, FAAAAI5, Jayant M. Pinto, MD5; 1Univ of Chicago, 2 Showa University, Toyko, Japan, 3University of Chicago, Chicago, IL, 4 Univ. of Chicago, 5The University of Chicago, Chicago, IL. RATIONALE: Both microbes and allergens can stimulate the nasal mucosa, potentially affecting the development of acute rhinosinusitis. We hypothesized that allergen exposure alters the sinonasal microbiome. METHODS: We performed a parallel observational study of healthy adults with SAR (grass or tree, n520) or controls (n519). Microbiota specimens were obtained by nasal endoscopy from the middle meatus and vestibule prior to and during the relevant season and analyzed by Terminal Restriction Fragment Length Polymorphism analysis. Differences in bacterial microbiota were assessed by number of distinct organisms and standard ecologic measures of bacterial diversity. RQLQ and symptom scores were recorded and nasal lavages for eosinophils were performed . RESULTS: Subjects with SAR had increased nasal symptoms in season, impaired disease-specific quality of life, and increased nasal eosinophils, with no changes in controls. During the season, subjects with SAR had a significantly greater variety of organisms in the middle meatus compared to controls (P
