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Background: Bitter (T2R) and sweet (T1R) taste receptors in the airway are important in innate immune defense, and variations in taste receptor functionality in one T2R (T2R38) correlate with disease status and disease severity in chronic rhinosinusitis (CRS). Quinine is a bitter compound that is an agonist for several T2Rs also expressed on sinonasal cells, but not for T2R38. Because of this property, quinine may stimulate innate immune defense mechanisms in the airway, and functional differences in quinine perception may be reflective of disease status in CRS. Methods: Demographic and taste intensity data were collected prospectively from CRS patients and non-CRS control subjects. Sinonasal tissue from patients undergoing rhinologic surgery was also collected and grown at an air--liquid interface (ALI). Nitric oxide (NO) production and dynamic regulation of ciliary beat frequency in response to quinine stimulation were assessed in vitro. results: Quinine reliably increased ciliary beat frequency and NO production in ALI cultures in a manner consistent with T2R activation (p < 0.01). Quinine taste intensity rating was performed in 328 CRS patients and 287 control subjects demonstrating that CRS with nasal polyps (CRSwNP) patients rated quinine as significantly less intense than did control subjects. conclusion: Quinine stimulates airway innate immune defenses by increasing ciliary beat frequency and stimulating NO production in a manner fitting with T2R activation. Patient variability in quinine sensitivity is observed in taste intensity ratings, and gustatory quinine "insensitivity" is associated with CRSwNP status. Thus, taste tests for quinine may be a biomarker for CRSwNP, and topical quinine has therapeutic potential as a stimulant of innate defenses. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is a multifactorial disease with a high co‐occurrence with asthma. In this multicohort study, we tested whether single nucleotide polymorphisms (SNPs) associated with childhood asthma and rhinovirus (RV)‐associated disease are related to an increased susceptibility to adult CRS in a multicohort retrospective case‐control study. Methods: Participants at two tertiary academic rhinology centers, University of Arizona (UofA) and University of Pennsylvania (UPenn) were recruited. Cases were defined as those with physician diagnosed CRS (UofA, n = 149; UPenn, n = 250), and healthy controls were those without CRS (UofA, n = 66; UPenn, n = 275). Genomic DNA was screened for the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP. Gene dosage, or the number of combined risk alleles in a single subject was calculated. Meta‐analysis of the association between GSDMB or CDHR3 genotypes and CRS was performed and additive gene dosage effect for each population calculated using p for trend. Results: A meta‐analysis revealed a combined increased risk for CRS in subjects with the GSDMB rs7216389 SNP (odds ratio [OR] 1.40; 95% confidence interval [CI], 1.16–1.76; p = 0.004). Both the UofA (OR 1.73; 95% CI, 1.23–2.43; p = 0.002) and UPenn (OR 1.27; 95% CI, 1.02–1.58; p = 0.035) populations showed a significant positive association between the number of combined risk alleles of GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP and risk for CRS. Conclusion: Carriers of the GSDMB rs7216389 SNP and CDHR3 rs6967330 SNP are at increased susceptibility for CRS. These data suggest that therapeutic approaches to target aberrant responses to RV infection may play a role in the treatment of unified airway disease. [ABSTRACT FROM AUTHOR]

Background: Treatment of aspirin‐exacerbated respiratory disease (AERD) includes endoscopic sinus surgery (ESS) and aspirin desensitization (AD) with aspirin therapy after desensitization (ATAD). The objective of this study was to determine the rate of major complications associated with aspirin use that resulted in the discontinuation of aspirin therapy. Methods: This study was a retrospective chart review of patients with AERD who underwent ESS, AD, and ATAD at a single AERD tertiary center between July 2016 and February 2019. Complications associated with aspirin that resulted in the discontinuation of aspirin therapy were analyzed via analysis of variance and logistic regression. Results: In total, 109 AERD patients underwent ESS with subsequent AD. Ten patients (9.2%) discontinued therapy after AD, before starting ATAD. Eight patients (7.3%) discontinued therapy after starting ATAD. There were 91 patients (83.5%) with no complications throughout ATAD. Reasons for discontinuation included gastritis, upper gastrointestinal (GI) bleed, anaphylaxis, persistent sinonasal symptoms, recurrent epistaxis, asthma exacerbation, and a nummular rash. There was no significant correlation between complication rate and (1) aspirin doses (analysis of variance [ANOVA] F: 0.69; p = 0.51), (2) gender (odds ratio [OR] 0.56; 95% confidence interval [CI], 0.19 to 1.65; p = 0.30), (3) age (OR 1.04; 95% CI, 0.96 to 1.09; p = 0.06), or (4) race/ethnicity (OR 1.12; 95% CI, 0.88 to 1.44; p = 0.36). Conclusion: AD with ATAD was associated with only a 0.92% incidence of a clinically significant GI bleed, and only a 0.92% incidence of anaphylaxis. A remaining 16 patients (14.7%) discontinued aspirin therapy due to minor clinical sequelae. These findings demonstrate that the majority of AERD patients tolerate AD with ATAD without any major complications. [ABSTRACT FROM AUTHOR]

Background Antimicrobial peptides (AMPs) produced by the epithelium are important for innate immune defense. In 2001, a novel AMP dermcidin (DCD) was described with no homology to other AMPs and an expression pattern restricted to eccrine sweat glands. In contrast to other AMPs, DCD expression has not been shown to be induced under inflammatory conditions in the skin. After identifying DCD by mass spectrometry in a protein sample isolated from human nasal secretions, we sought to determine the role of DCD in innate defense of the sinonasal airway. Methods After institutional review board approval, sinonasal mucosal tissue specimens were acquired from residual clinical material obtained during sinonasal surgery and used to grow cultures in an air-liquid interface environment. After stimulation of the cultures with various bitter compounds and phosphate-buffered saline, airway surface liquid was collected, and a DCD-specific enzyme-linked immunoassay was used to quantify DCD in each sample. To localize DCD expression, ALI cultures were fixed and immunofluorescence performed against DCD, β-tubulin IV, and Muc-5A. Results Enzyme-linked immunoassay showed DCD in air-surface liquid and in clinical nasal secretion samples at concentrations comparable to eccrine sweat. There was no evidence of inducible expression with any of the tested stimulants. Confocal microscopy revealed DCD expression in sinonasal mucosal goblet cells. Conclusion This is the first report of the presence of DCD in nasal mucosa and demonstration of DCD in clinical samples of human nasal secretions at clinically relevant concentrations, which may represent a novel arm of sinonasal airway innate defense. [ABSTRACT FROM AUTHOR]