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BackgroundBroncho-Vaxom® (OM-85 BV) is an extract of infectious respiratory bacteria that is used as an immunostimulant outside of the United States for the prevention and treatment of bronchitis and rhinosinusitis. Prior studies have shown that use of OM-85 BV is associated with reduction in frequency of respiratory infection and decreased duration of antibiotic usage. However, the effects of OM-85 BV on respiratory mucosal innate immunity are unknown.MethodsHuman sinonasal epithelial cells were grown at an air-liquid interface (ALI). Ciliary beat frequency (CBF) and nitric oxide (NO) production in response to stimulation with OM-85 BV was measured in vitro. Pharmacologic inhibitors of bitter taste receptor (T2R) signaling were used to determine if this pathway was taste-receptor-mediated.ResultsApical application of OM-85 BV resulted in an NO-mediated increase in CBF (p

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: Chronic rhinosinusitis (CRS) is a frequently observed condition in patients with immunodeficiency secondary to tumor necrosis factor alpha inhibitors (TNFαis). The histologic features of CRS caused by TNFαis have yet to be determined and may have important implications in understanding the pathophysiology of the disease process. Methods: A structured histopathology report was used to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). These structured histopathology variables were compared among patients with CRS on TNFαi (CRSαi), CRS without nasal polyps (CRSsNP) patients, and CRS with nasal polyps (CRSwNP) patients. Results: Eighteen CRSαi, 91 CRSwNP, and 113 CRSsNP patients undergoing FESS were analyzed. Compared to CRSsNP, CRSαi patients exhibited increased mucosal ulceration (16.7% vs 0.9%, p < 0.008), increased fibrosis (100% vs 34.5%, p < 0.001), and increased presence of Charcot‐Leiden crystals (16.7% vs 0%, p < 0.002). Compared to CRSwNP, CRSαi patients demonstrated increased fibrosis (100% vs 54.9%, p < 0.001), decreased presence of subepithelial edema (44.4% vs 69.2% p < 0.043), decreased eosinophil aggregates (22.2% vs 47.3% p < 0.042), and fewer eosinophils per high‐power field (44.4% vs 73.6%, p < 0.017). Conclusion: CRSαi exhibits structured histopathology more similar to CRSsNP. In the appropriate clinical context, it may be reasonable that the medical regimen for these patients be focused on a more antineutrophilic, macrolide‐based approach. This study provides insight into the inflammatory environment of patients with CRSαi and may have implications for disease management. [ABSTRACT FROM AUTHOR]

Background Off-label use of topical ophthalmologic formulations for treatment of rhinologic disease is cited in recent literature and is anecdotally prevalent among practicing otolaryngologists. Steroids, antibiotics, and other drugs designed for ocular use have subjective clinical efficacy in the nose and sinuses, but their specific effects on the ciliated epithelium are less well defined. This study examines 9 commercially available ophthalmologic drug formulations for effects on ciliary motility in sinonasal cultures, in an effort to characterize their utility as topical therapies for sinonasal diseases. Methods Ophthalmologic solutions were tested on human sinonasal cultures grown at an air-liquid interface. Baseline ciliary beat frequency (CBF) was recorded and compared with CBF changes in the 20 minutes after drug addition. Substances were categorized by degree of ciliostimulation or cilioinhibition. Results All ophthalmologic solutions tested had only moderate effects on CBF during the 20-minute experimental period, with no solutions causing overt ciliostasis. Azithromycin, neomycin, and olopatadine were slightly ciliostimulatory, whereas levofloxacin, tobramycin, dexamethasone, azelastine, and prednisolone acetate were cilioinhibitory. Ciprofloxacin elicited moderate cilioinhibition that progressed to ciliostimulation. Conclusion All solutions tested appear to have moderate effects on ciliated cell surfaces for a period of time typical of mucociliary clearance (10 to 20 minutes). Both active drugs and excipients can play a role in ciliary modulation, and specific formulations can show unique or unexpected properties. Any other individual ophthalmologic solutions to be used in a nasal drug delivery system should be tested in this manner to evaluate potential ciliary effects before clinical use. [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]