International Forum of Allergy and Rhinology 2020-09-11

Interim Analysis of an Open‐label Randomized Controlled Trial Evaluating Nasal Irrigations in Non‐hospitalized Patients with COVID‐19

\nKyle S. Kimura, \nMichael H. Freeman, \nBronson C Wessinger, \nVeerain Gupta, \nQuanhu Sheng, \nLi Ching Huang, \nKate Von Wahlde, \nSuman Das, \nNaweed I. Chowdhury, \nJustin H. Turner\n

Publicatie 11-09-2020


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Association of subjective olfactory dysfunction and 12‐item odor identification testing in ambulatory COVID‐19 patients

\nDivya P. Prajapati, \nBita Shahrvini, \nBridget V. MacDonald, \nKayva L. Crawford, \nMatt Lechner, \nAdam S. DeConde, \nCarol H. Yan\n

Publicatie 10-09-2020


BackgroundAcute loss of smell and taste are well‐recognized symptoms of coronavirus disease 2019 (COVID‐19), yet the correlation between self‐reported and psychophysical olfactory function remains unclear. Understanding the reliability of self‐reported smell loss in ambulatory cases can assess the utility of this screening measure.MethodsA prospective, longitudinal study evaluating patient‐reported and measured olfactory function using the validated 12‐item Brief Smell Identification Test (BSIT) was conducted on adult outpatients with COVID‐19. Patient‐reported olfaction scores using a visual analog scale (VAS) were obtained at baseline, time of COVID‐19 testing, and time of BSIT completion. Linear associations between VAS and BSIT were evaluated using Spearmans correlation coefficient and the sensitivity, specificity, and accuracy of VAS scores were calculated. Logistic regression identified characteristics associated with accurate assessment of olfactory function.ResultsA total of 81 polymerase chain reaction (PCR)‐confirmed COVID‐19 positive subjects, of whom 54 self‐reported smell loss, were prospectively recruited ≤5 days from diagnosis date between May 8, 2020, and July 8, 2020. Self‐reported smell loss had good discriminative ability in identifying abnormal BSIT (area under receiver operating curve AUC 0.82, 95% confidence interval CI, 0.71 to 0.92). A VAS <5 demonstrated sensitivity of 0.62 and specificity of 0.94 for predicting hyposmia (BSIT ≤8) with accuracy of 82.7%, whereas a VAS <9 had highest sensitivity at 0.86. Moderate bivariate linear associations were found between VAS and BSIT scores (rs = 0.59, p < 0.001).ConclusionSelf‐reported olfactory loss associated with COVID‐19 has a strong ability to predict abnormal olfactory function though the 2 measures are moderately correlated. Subjective olfactory assessment is useful in screening olfactory dysfunction at early disease time points when psychophysical testing cannot be conducted.

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Management of epistaxis secondary to extracranial anterior ethmoid artery pseudoaneurysm

\nMatthew Hill, \nNyssa Farrell, \nRohan Verma, \nJohn Ng, \nMathew Geltzeiler\n

Publicatie 10-09-2020


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Can we assess the sense of smell through a face mask?

\nBen Chen, \nQiang Wang, \nXiaomei Zhong, \nLena Heyne, \nYuping Ning, \nThomas Hummel\n

Publicatie 06-09-2020


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Denatonium benzoate bitter taste perception in chronic rhinosinusitis subgroups

\nAlyssa M. Civantos, \nIvy W. Maina, \nMonique Arnold, \nCailu Lin, \nElizabeth M. Stevens, \nLi Hui Tan, \nPatrick K. Gleeson, \nLauren R. Colquitt, \nBeverly J. Cowart, \nJohn V. Bosso, \nJames N. Palmer, \nNithin D. Adappa, \nMichael A. Kohanski, \nDanielle R. Reed, \nNoam A. Cohen\n

Publicatie 03-09-2020


BackgroundChronic 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.MethodsCRSsNP (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.ResultsCRSsNP patients rated DB as significantly less intense than did controls at all concentrations: 5.62 × 10–9M, 1.00 × 10–8M, 1.78 × 10–8M, 3.16 × 10–8M, 5.62 × 10–8M, and 1.00 × 10–7M (all p < 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 × 10–8M and 3.16 × 10–8M (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).ConclusionOur 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 × 10–8M for future study of clinical utility.

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Olfactory training: what is the evidence?

\nJustin H. Turner\n

Publicatie 03-09-2020


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Efficacy of neutral electrolyzed water in postoperative chronic rhinosinusitis patients—a pilot study

\nChristian Albert Lux, \nJames Johnston, \nKristi Biswas, \nRichard George Douglas\n

Publicatie 03-09-2020


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Interleukin 13 (IL‐13) alters hypoxia‐associated genes and upregulates CD73

\nSyed Muaz Khalil, \nIsaac Bernstein, \nHeather Kulaga, \nNaina Gour, \nNicholas Rowan, \nStephane Lajoie, \nAndrew P. Lane\n

Publicatie 01-09-2020


BackgroundInterleukin 13 (IL‐13) is a pleiotropic cytokine that has been shown to be important in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and other type 2 inflammation–related diseases. Increased IL‐13 expression can elicit several pro‐inflammatory effects, including eosinophilia, and pathology such as increased mucus secretion. Polypogenesis in chronic rhinosinusitis (CRS) can be caused by hypoxia, which can also lead to hyperpermeability of airway epithelium and epithelium‐to‐mesenchymal translation through the upregulation of hypoxia‐associated genes, such as HIF1. Whether T‐helper 2 (Th2) inflammatory cytokines, such as IL‐13, can also induce sinonasal epithelial hypoxia‐associated genes is currently unknown.MethodsHuman air‐liquid interface (ALI) sinonasal epithelial cell cultures treated with recombinant IL‐13 were analyzed by real‐time polymerase chain reaction (PCR) and flow cytometry to determine the effect on epithelial cells.ResultsWhole tissue from CRSwNP subjects showed increased HIF1A gene expression. Treatment of fully differentiated human ALI cultures with IL‐13 resulted in a concurrent increase in HIF1A and ARNT messenger RNA (mRNA) expression. However, the level of EPAS1 expression was significantly reduced. IL‐13 also had a dose‐dependent response on the expression of HIF genes and the time course experiment showed peak expression of HIF1A and ARNT at 5 to 7 days poststimulation. Remarkably, CD73 surface expression also peaked at day 5 poststimulation.ConclusionOur data suggests that IL‐13 can induce hypoxia signaling pathway genes leading to surface expression of CD73, which has an anti‐inflammatory effect.

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Complete endoscopic sinus surgery followed by aspirin desensitization is associated with decreased overall corticosteroid use

\nJohn V. Bosso, \nTran B. Locke, \nEdward C. Kuan, \nSiddhant H. Tripathi, \nKevin I. Ig‐Izevbekhai, \nLaila T. Kalaf, \nMichael A. Kohanski, \nJames N. Palmer, \nNithin D. Adappa\n

Publicatie 01-09-2020


BackgroundAspirin‐exacerbated respiratory disease (AERD) is an aggressive respiratory tract inflammatory disorder manifesting as asthma, chronic rhinosinusitis with nasal polyposis, and a respiratory sensitivity to aspirin and nonsteroidal anti‐inflammatory drugs (NSAIDs). Corticosteroids, both systemic and topical/inhaled, are used to treat inflammation of the upper and lower airways. Our objective was to examine the potential impact of complete endoscopic sinus surgery (ESS) and aspirin desensitization (AD) on short‐term and long‐term corticosteroid use.MethodsFor this pilot study, a retrospective chart review of all patients with AERD who underwent ESS followed by AD was performed. Daily prednisone use, average daily prednisone dose, and inhaled corticosteroid use were analyzed at the following time points: preoperative, postoperative/pre‐AD, and 2 to 3 months, 4 to 6 months, 7 to 12 months, and 13 to 24 months following AD.ResultsA total of 125 patients underwent ESS followed by AD. Compared to preoperatively, patients who underwent ESS and AD were less likely to be on daily prednisone at all time points and upon long‐term follow‐up (32% preoperatively vs 10% at 13 to 24 months, McNemars test = 9.00, p = 0.009). Average daily prednisone dose decreased from 10.6 ± 7.9 mg preoperatively to 3.8 ± 2.6 mg at 13 to 24 months following AD (Mann‐Whitney U; W = 122, p = 0.01). Similarly, high‐dose and medium‐dose inhaled corticosteroid use decreased from 18% to 7% and from 36% to 22% respectively (Pearsons chi‐square = 8.06, p = 0.05).ConclusionIn our AERD cohort who underwent ESS followed by AD, there was an observed decrease in overall systemic and topical/inhaled corticosteroid use. These findings can have implications for treatment given the potentially hazardous side effects of corticosteroid use.

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Surgeon cost feedback through a surgical receipt program reduces cost in sinonasal surgery

\nAmarbir S. Gill, \nRenuka K. Reddy, \nAndrea G Kulinich, \nJoanna Kim, \nMachelle D Wilson, \nJonathan Liang, \nE. Bradley Strong, \nToby O. Steele\n

Publicatie 01-09-2020


BackgroundOperating room (OR) costs are a large portion of healthcare expenses. This study evaluates the impact of a surgeon‐targeted surgical receipt cost feedback system on OR supply costs in sinonasal surgery and individual components contributing to procedural cost.MethodsItemized weekly surgical receipts detailing individual case supply costs were analyzed before and after the implementation of a non‐incentivized surgeon cost feedback system between January 2017 and June 2019. Supply cost data collected 15 months prior to intervention was compared to cost data 15 months after implementation of the weekly automated receipt dissemination to surgeons. Chi square test was used for categorical data and the Wilcoxon test was used to compare change in cost. Univariate and mediation analyses were performed to assess variables impacting cost.ResultsOf 502 sinonasal procedures analyzed, 239 were before and 264 after cost feedback implementation. There were no significant differences in age/gender, or indication for surgery. The median OR supply cost decreased from $1229.64 to $1097.22 (p = 0.02) after receipt implementation. There were effects of procedure type (p = 0.02), circulating nurse specialization (p < 0.001), steroid eluting stent (p = 0.002), and sinus drill (p < 0.001) on cost. Mediation analysis confirmed full mediation by decreasing use of steroid‐eluting stents.ConclusionSurgeon cost feedback in the form of individualized OR surgical receipts is an effective model to reduce supply cost per case in sinonasal surgery.

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Assessing tissue transcription biomarkers of chronic rhinosinusitis: a comparison of sampling methodologies

\nMichael Hoggard, \nRichard G. Douglas, \nMichael W. Taylor, \nKristi Biswas\n

Publicatie 01-09-2020


BackgroundChronic rhinosinusitis (CRS) is a spectrum of complex inflammatory conditions of the sinonasal mucosa. Identification of biomarkers that enable classification and improved delineation among CRS endotypes is of increasing interest. However, the extent to which less invasive sampling methods identify genuine tissue inflammatory patterns is not well understood. The aim of this study was to investigate mucosal swab and cytobrush sampling as less invasive proxies for tissue transcription levels of putative biomarkers of CRS.MethodsExpression levels of 21 biomarkers of interest were assessed via custom TaqMan array cards from mucosal biopsy, cytobrush, and swab samples, in 32 patients with CRS. Reported expression levels were compared between each of the 3 sample types within each patient.ResultsReported transcription levels from swab samples for IL33, MUC5AC, IL1RN, CXCL8 (IL‐8), TNF, IFNG, IL5, OSM, IL1A, and IL17C, and cytobrush levels for IL33, MUC5AC, IL5RA, IL1RN, CXCL8 (IL‐8), and IL5 were significantly different to tissue levels from matched biopsy samples.ConclusionReported expression via swab and cytobrush sampling differed from patterns observed in matched tissue for 10 of 21 and 6 of 21 markers, respectively. Non–biopsy‐based studies for these particular markers may therefore not adequately represent tissue inflammatory processes and should be interpreted with caution. Cytobrush samples largely tracked tissue patterns for the remaining target biomarkers. In these cases, cytobrush sampling appears to adequately reflect tissue patterns for several putative biomarkers of CRS, supporting their use in clinical and research settings as a less‐invasive proxy for the assessment of mucosal tissue inflammatory transcription patterns.

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Immunotherapy in sinonasal melanoma: treatment patterns and outcomes compared to cutaneous melanoma

\nDaniella Klebaner, \nRobert Saddawi‐Konefka, \nAndrey Finegersh, \nCarol H. Yan, \nJoseph A. Califano, \nNyall R. London, \nAdam S. Deconde, \nFarhoud Faraji\n

Publicatie 01-09-2020


BackgroundAlthough treatment with checkpoint blockade is now accepted as standard of care for cutaneous melanoma, few studies have investigated its role in sinonasal melanoma (SNM). We aimed to evaluate whether immunotherapy was associated with improved survival in SNM and to compare the effect of immunotherapy in metastatic sinonasal and cutaneous melanoma.MethodsThis was a cohort study of patients included in the United States National Cancer Database who had been diagnosed with sinonasal or cutaneous melanoma between 2012 and 2015 and had complete information regarding immunotherapy status. The primary outcome was overall survival. The influence of immunotherapy on overall survival was compared by Kaplan‐Meier and Cox proportional hazards models. Propensity score matched analyses between SNM patients who received immunotherapy and those who did not were based on clinicopathological covariates associated with survival in univariate Cox models.ResultsThe analytic cohort consisted of 704 patients with SNM, 94 of whom were treated with immunotherapy and 152,896 patients with cutaneous melanoma, 8055 of whom were treated with immunotherapy. Immunotherapy was not associated with survival in the propensity‐score matched cohort (n = 195; hazard ratio HR = 1.0; 95% confidence interval CI, 0.7 to 1.5; p = 0.88) or in adjusted Cox proportional hazards model (n = 549; HR = 1.0; 95% CI, 0.74 to 1.4; p = 0.88). Regimens including immunotherapy were associated with improved overall survival in metastatic cutaneous melanoma (HR = 0.57; 95% CI, 0.49 to 0.66; p < 0.0001), but not metastatic SNM (HR = 1.1; 95% CI, 0.67 to 1.7; p = 0.75).ConclusionCompared to current standard of care therapy, inclusion of immunotherapy as first‐line therapy was not associated with improved survival in SNM.

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Trans‐pterygomaxillary fossa sphenoidotomy can result in insufficient exposure for lateral pterygoid recess encephalocele repair

\nSean P. Chislett, \nAlexander P. Limjuco, \nAlla Y. Solyar, \nDonald C. Lanza\n

Publicatie 01-09-2020


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Commentary on: “Cranial nerve V2 and Vidian nerve trauma secondary to lateral pterygoid recess encephalocele repair”

\nWilliam E. Bolger\n

Publicatie 01-09-2020


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Reply to: Endonasal drilling may be employed safely in the COVID‐19 era

\nBenjamin S. Bleier\n

Publicatie 01-09-2020


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Management of chronic rhinosinusitis with steroid nasal irrigations: A viable nonsurgical alternative in the COVID‐19 era

\nAuddie M. Sweis, \nTran B. Locke, \nJennifer E. Douglas, \nTheodore C. Lin, \nBrian M. Sweis, \nAlyssa M. Civantos, \nDavid W. Kennedy\n

Publicatie 01-09-2020


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Reply to: Challenges in interpreting the diagnostic performance of symptoms to predict COVID‐19 status: the case of anosmia

\nLauren T. Roland, \nPatricia A. Loftus, \nJolie L. Chang\n

Publicatie 01-09-2020


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Challenges in interpreting the diagnostic performance of symptoms to predict COVID‐19 status: The case of anosmia

\nPaolo Boscolo‐Rizzo, \nDaniele Borsetto, \nClaire Hopkins, \nJerry Polesel\n

Publicatie 01-09-2020


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Endonasal drilling may be employed safely in the COVID‐19 era

\nCarl H. Snyderman, \nPaul A. Gardner\n

Publicatie 01-09-2020


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Potential pathogenesis of ageusia and anosmia in COVID‐19 patients

\nLuigi Angelo Vaira, \nGiovanni Salzano, \nAlessandro Giuseppe Fois, \nPasquale Piombino, \nGiacomo De Riu\n

Publicatie 01-09-2020


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Psychophysical tests reveal impaired olfaction but preserved gustation in COVID‐19 patients

\nConstantin A. Hintschich, \nJürgen J. Wenzel, \nThomas Hummel, \nMohammed K. Hankir, \nThomas Kühnel, \nVeronika Vielsmeier, \nChristopher Bohr\n

Publicatie 01-09-2020


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Aspirin‐exacerbated respiratory disease: personalized medical and surgical approaches

\nRodney J. Schlosser\n

Publicatie 01-09-2020


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Issue Information

Publicatie 01-09-2020


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Guidance for contemporary use of biologics in management of chronic rhinosinusitis with nasal polyps: discussion from a National Institutes of Health–sponsored workshop

\nLauren T. Roland, \nTimothy L. Smith, \nRodney J. Schlosser, \nZachary M. Soler, \nAnju T. Peters, \nTanya M. Laidlaw, \nBenjamin S. Bleier, \nVijay Ramakrishnan, \nElina Toskala, \nDavid W. Kennedy, \nAmber U. Luong\n

Publicatie 01-09-2020


BackgroundBiologic medications are emerging as options for treating chronic rhinosinusitis with nasal polyps (CRSwNP). Several questions remain regarding patient selection, indications, clinical efficacy, and cost effectiveness.MethodsIn November 2019, a group of physicians and scientists gathered to consider strategies for future studies regarding biologics. During the discussion, gaps in knowledge highlighted a need for a consensus on the present day use of biologics in polyp patients.ResultsThe goal of this guideline is to propose recommendations for the current use of biologics in CRSwNP as new evidence continues to emerge and inform practice.ConclusionWe suggest that physicians evaluate patients on an individual basis and closely monitor for improvement due to the high cost and unknown long‐term effects of biologics.

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Treatment of post‐viral olfactory dysfunction: an evidence‐based review with recommendations

\nNanki Hura, \nDeborah X. Xie, \nGarret W. Choby, \nRodney J. Schlosser, \nCinthia P. Orlov, \nStella M. Seal, \nNicholas R. Rowan\n

Publicatie 01-09-2020


BackgroundPost‐viral olfactory dysfunction (PVOD) is one of the most common causes of olfactory loss. Despite its prevalence, optimal treatment strategies remain unclear. This article provides a comprehensive review of PVOD treatment options and provides evidence‐based recommendations for their use.MethodsA systematic review of the Medline, Embase, Cochrane, Web of Science, Scopus, and Google Scholar databases was completed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Studies with defined olfactory outcomes of patients treated for PVOD following medical, surgical, acupuncture, or olfactory training interventions were included. The Clinical Practice Guideline Development Manual and Conference on Guideline Standardization (COGS) instrument recommendations were followed in accordance with a previously described, rigorous, iterative process to create an evidence‐based review with recommendations.ResultsFrom 552 initial candidate articles, 36 studies with data for 2183 patients with PVOD were ultimately included. The most common method to assess olfactory outcomes was Sniffin’ Sticks. Broad treatment categories included: olfactory training, systemic steroids, topical therapies, a variety of heterogeneous non‐steroidal oral medications, and acupuncture.ConclusionBased on the available evidence, olfactory training is a recommendation for the treatment of PVOD. The use of short‐term systemic and/or topical steroids is an option in select patients after careful consideration of potential risks of oral steroids. Though some pharmacological investigations offer promising preliminary results for systemic and topical medications alike, a paucity of high‐quality studies limits the ability to make meaningful evidence‐based recommendations for the use of these therapies for the treatment of PVOD.

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Does phenotypic expression of bitter taste receptor T2R38 show association with COVID‐19 severity?

\nHenry P. Barham, \nMohamed A. Taha, \nChristian A. Hall\n

Publicatie 27-08-2020


IntroductionSARS‐CoV‐2 has been identified as the pathogen causing the outbreak of Coronavirus Disease 2019(COVID‐19) commencing in Wuhan, China, in December 2019. Multiple reports have shown subjective loss of taste and smell as an early and hallmark symptom for COVID‐19.MethodA retrospective study was performed in our clinical practice during July 2020 on patients positive for SARS‐CoV‐2 via PCR. All patients were categorized into 3 groups (supertasters, tasters, & nontasters) via taste sensitivity to phenylthiocarbamide, thiourea, and sodium benzoate with taste strip testing. The results of the taste strip tests were correlated with clinical course.Results100 patients (mean 51 Range 24‐82 years of age; 44 44% female) were assessed. Our results showed that 21/100 (21%) were non‐tasters, 79/100 (79%) were tasters, and 0/100 (0%) were supertasters (p<0.001). 21/21 (100%) (p<0.001) of the patients requiring inpatient admission were classified as non‐tasters. 79/79 (100%) (p<0.001) of the patients who displayed mild to moderate symptoms not requiring admission were classified as tasters.ConclusionOur results show objective data that taste disturbance, specifically global loss of taste, appears to correlate with the clinical course specific to each individual because 100% of the patients requiring inpatient admission were classified as non‐tasters.This article is protected by copyright. All rights reserved

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Pepsin exposure in a non‐acidic environment upregulates mucin 5AC (MUC5AC) expression via matrix metalloproteinase 9 (MMP9)/nuclear factor κB (NF‐κB) in human airway epithelial cells

\nYoon Seok Choi, \nHyung Gyun Na, \nChang Hoon Bae, \nSi‐Youn Song, \nYong‐Dae Kim\n

Publicatie 26-08-2020


BackgroundGastric reflux (GR) is a backflow of gastric content to the aerodigestive tract. GR was previously found to be associated with inflammatory airway diseases and a potential cause of airway remodeling. Chronic exposure to gastric content may induce damage from nose to lung, because digestive enzymes and acidity are toxic to airway epithelial cells. Recently, the toxicity of pepsin in a non‐acidic environment was found to increase proinflammatory cytokines and receptors in the epithelium of the aerodigestive tract. However, the effect of pepsin in non‐acidic conditions on mucin expression has not been investigated in human airway epithelial cells. The purpose of this study was to evaluate the effect of pepsin on mucin 5AC (MUC5AC) expression in upper and lower airway epithelial cells as an important potential factor of non‐acidic GR‐related airway inflammation.MethodsIn NCI‐H292 cells and human nasal epithelial cells (HNEpCs), the effects and signaling pathways of pepsin on MUC5AC expression were examined using reverse‐transcription polymerase chain reaction (RT‐PCR), real‐time PCR, enzyme immunoassay, zymography, Western blot, and immunofluorescence staining.ResultsPepsin increased MUC5AC expression in non‐acidic condition of NCI‐H292 cells and HNEpCs. Further, pepsin activated matrix metalloproteinase 9 (MMP9) and phosphorylated nuclear factor κB (NF‐κB). Moreover, inhibitors of MMP9 and NF‐κB significantly attenuated pepsin‐induced MUC5AC expression, and the knockdown of NF‐κB by small interfering RNA (siRNA) significantly blocked pepsin‐induced MUC5AC expression in human airway epithelial cells.ConclusionThese findings suggest that pepsin increased MUC5AC expression in non‐acidic conditions via the activation of MMP9 and NF‐κB in human airway epithelial cells.

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Divergent bitter and sweet taste perception intensity in chronic rhinosinusitis patients

\nCailu Lin, \nAlyssa M. Civantos, \nMonique Arnold, \nElizabeth M. Stevens, \nBeverly J. Cowart, \nLauren R. Colquitt, \nCorrine Mansfield, \nDavid W. Kennedy, \nSteven G. Brooks, \nAlan D. Workman, \nMariel T. Blasetti, \nMichael A. Kohanski, \nLaurel Doghramji, \nJennifer E. Douglas, \nIvy W. Maina, \nJames N. Palmer, \nNithin D. Adappa, \nDanielle R. Reed, \nNoam A. Cohen\n

Publicatie 26-08-2020


BackgroundBitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that 1 of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes 1 type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses.MethodsWe examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients. CRS patients with (n = 426) and without (n = 226) nasal polyps and controls (n = 356) rated the intensity of quinine, denatonium benzoate, phenylthiocarbamide (PTC; a ligand for TAS2R38), sucrose, and salt.ResultsCRS patients rated the bitter compounds denatonium benzoate and quinine as less intense and sucrose as more intense than did controls (false discovery rate FDR <0.05) and CRS patients and controls did not differ in their ratings of salt (FDR >0.05). PTC bitter taste intensity differed between patient and control groups but were less marked than those previously reported. Though differences were statistically significant, overall effect sizes were small.ConclusionCRS patients report bitter stimuli as less intense but sweet stimuli as more intense than do control subjects. We speculate that taste responses may reflect the competence of sinonasal innate immunity mediated by taste receptor function, and thus a taste test may have potential for clinical utility in CRS patients.

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International registry of otolaryngologist–head and neck surgeons with COVID‐19

\nLeigh J Sowerby, \nKate Stephenson, \nAlexander Dickie, \nFederico A. Di Lella, \nNiall Jefferson, \nHannah North, \nR. Daniele De Siati, \nRebecca Maunsell, \nMichael Herzog, \nRaghu Nandhan, \nMarilena Trozzi, \nPuya Dehgani‐Mobaraki, \nAntoine Melkane, \nClaudio Callejas, \nHarald Miljeteig, \nDiane Smit, \nDaniel Dibildox Reynoso, \nJoao Eloi Moura, \nAnn Hermansson, \nShazia Peer, \nLisa Burnell, \nNicolas Fakhry, \nCarlos Chiesa‐Estomba, \nÖzlem Önerci Çelebi, \nSergei Karpischenko, \nSteven Sobol, \nZoukaa Sargi, \nZara M. Patel\n

Publicatie 24-08-2020


BackgroundIt has become clear that healthcare workers are at high risk, and otolaryngology has been theorized to be among the highest risk specialties for coronavirus disease 2019 (COVID‐19). The purpose of this study was to detail the international impact of COVID‐19 among otolaryngologists, and to identify instructional cases.MethodsCountry representatives of the Young Otolaryngologists–International Federation of Otolaryngologic Societies (YO‐IFOS) surveyed otolaryngologists through various channels. Nationwide surveys were distributed in 19 countries. The gray literature and social media channels were searched to identify reported deaths of otolaryngologists from COVID‐19.ResultsA total of 361 otolaryngologists were identified to have had COVID‐19, and data for 325 surgeons was available for analysis. The age range was 25 to 84 years, with one‐half under the age of 44 years. There were 24 deaths in the study period, with 83% over age 55 years. Source of infection was likely clinical activity in 175 (54%) cases. Prolonged exposure to a colleague was the source for 37 (11%) surgeons. Six instructional cases were identified where infections occurred during the performance of aerosol‐generating operations (tracheostomy, mastoidectomy, epistaxis control, dacryocystorhinostomy, and translabyrinthine resection). In 3 of these cases, multiple operating room attendees were infected, and in 2, the surgeon succumbed to complications of COVID‐19.ConclusionThe etiology of reported cases within the otolaryngology community appear to stem equally from clinical activity and community spread. Multiple procedures performed by otolaryngologists are aerosol‐generating procedures (AGPs) and great care should be taken to protect the surgical team before, during, and after these operations.

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Comment on “Investigation of topical intranasal cocaine for sinonasal procedures: a randomized, phase III clinical trial”

\nArie Francis, \nTimothy C Backus, \nMary Ann Howland, \nRobert S Hoffman\n

Publicatie 23-08-2020


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Reply to: Correspondence – International Registry of Otolaryngologist – Head and Neck Surgeons with COVID‐19

\nLeigh J. Sowerby, \nZara M. Patel\n

Publicatie 22-08-2020


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Aerosol generation with common rhinologic devices: cadaveric study conducted in a surgical suite

\nBailey LeConte, \nGarren M.I. Low, \nMartin J. Citardi, \nWilliam C. Yao, \nArturo A. Eguia, \nAmber U. Luong\n

Publicatie 19-08-2020


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Are patients with chronic rhinosinusitis with nasal polyps at a decreased risk of COVID‐19 infection?

\nFatemeh Saheb Sharif‐Askari, \nNarjes Saheb Sharif‐Askari, \nSwati Goel, \nSamer Fakhri, \nSaleh Al‐Muhsen, \nQutayba Hamid, \nRabih Halwani\n

Publicatie 19-08-2020


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Prevalence and reversibility of smell dysfunction measured psychophysically in a cohort of COVID‐19 patients

\nShima T. Moein, \nSeyed MohammadReza Hashemian, \nPayam Tabarsi, \nRichard L. Doty\n

Publicatie 19-08-2020


BackgroundConsiderable evidence suggests that smell dysfunction is common in coronavirus disease‐2019 (COVID‐19). Unfortunately, extant data on prevalence and reversibility over time are highly variable, coming mainly from self‐report surveys prone to multiple biases. Thus, validated psychophysical olfactory testing is sorely needed to establish such parameters.MethodsOne hundred severe acute respiratory syndrome‒coronavirus‐2 (SARS‐CoV‐2)‐positive patients were administered the 40‐item University of Pennsylvania Smell Identification Test (UPSIT) in the hospital near the end of the acute phase of the disease. Eighty‐two were retested 1 or 4 weeks later at home. The data were analyzed using analysis of variance and mixed‐effect regression models.ResultsInitial UPSIT scores were indicative of severe microsmia, with 96% exhibiting measurable dysfunction; 18% were anosmic. The scores improved upon retest (initial test: mean, 21.97; 95% confidence interval CI, 20.84‐23.09; retest: mean, 31.13; 95% CI, 30.16‐32.10; p < 0.0001); no patient remained anosmic. After 5 weeks from COVID‐19 symptom onset, the test scores of 63% of the retested patients were normal. However, the mean UPSIT score at that time continued to remain below that of age‐ and sex‐matched healthy controls (p < 0.001). Such scores were related to time since symptom onset, sex, and age.ConclusionSmell loss was extremely common in the acute phase of a cohort of 100 COVID‐19 patients when objectively measured. About one third of cases continued to exhibit dysfunction 6 to 8 weeks after symptom onset. These findings have direct implications for the use of olfactory testing in identifying SARS‐CoV‐2 carriers and for counseling such individuals with regard to their smell dysfunction and its reversibility.

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Use of flexible bronchoscopy in endoscopic sinus surgery for lateral frontal sinus mucoceles

\nLu Hui Png, \nHarold Hon Wei Heah, \nWee Lee Kang\n

Publicatie 19-08-2020


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Reply to: Comment on “Investigation of topical intranasal cocaine for sinonasal procedures: a randomized, phase III clinical trial”

\nJohn McGrath, \nAlexa McGrath, \nJacob Burdett, \nTom Shokri, \nJason E. Cohn\n

Publicatie 18-08-2020


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Patient‐reported sleep outcomes lack association with mucosal eosinophilia or neutrophilia in patients with chronic rhinosinusitis undergoing functional endoscopic sinus surgery

\nNyssa Fox Farrell, \nJess C. Mace, \nDavid A. Sauer, \nAndrew J. Thomas, \nMathew Geltzeiler, \nKara Y. Detwiller, \nJeremiah A. Alt, \nTimothy L. Smith\n

Publicatie 11-08-2020


BackgroundChronic rhinosinusitis (CRS) is associated with sleep dysfunction, but the underlying pathophysiology is poorly understood. The purpose of this study was to determine if mucosal eosinophilia or neutrophilia were associated with sleep dysfunction severity or altered the improvement in sleep dysfunction following functional endoscopic sinus surgery (FESS).MethodsA total of 104 patients with medically refractory CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSsNP), completed the Pittsburgh Sleep Quality Index (PSQI) before and after FESS. Anterior ethmoid mucosa was collected during FESS and densest infiltrates of eosinophilia and neutrophilia per high‐power field (HPF) were determined by microscopy. Eosinophilic (>10 eosinophils/HPF) and neutrophilic (>4 neutrophils/HPF) CRS were then compared to preoperative and postoperative PSQI measures.ResultsOf 104 study participants, 88 (85%) reported preoperative PSQI scores consistent with “poor sleep,” (PSQI total > 5). The cohort overall demonstrated significant improvement in poor sleep (65%; χ2 = 12.03; p < 0.001) 16.8 ± 5.0 months after FESS. Regardless of nasal polyposis, neither eosinophilic nor neutrophilic CRS was associated with differences in mean postoperative PSQI improvement. However, in patients with neutrophilic CRSsNP, there was a significant relationship between severity of neutrophilia and improvement in sleep latency (R = –0.798, p = 0.003) and sleep efficacy (R = –0.777, p = 0.005).ConclusionChronic inflammation has been hypothesized to play a pathophysiologic role in sleep dysfunction associated with CRS. This study suggests that in patients with medically refractory CRS, evidence of mucosal eosinophilia and neutrophilia lack strong associations with patient‐reported sleep dysfunction or improvements in sleep quality after FESS, overall. However, neutrophilia may impact sleep latency and efficacy in patients with CRSsNP.

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Sublingual immunotherapy in the United States: history and current relevance in the time of COVID‐19

\nSandra Y. Lin\n

Publicatie 11-08-2020


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International Registry of Otolaryngologist‒Head and Neck Surgeons with COVID‐19

\nJustin H. Turner\n

Publicatie 11-08-2020


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Exposure to environmental black carbon exacerbates nasal epithelial inflammation via the reactive oxygen species (ROS)–nucleotide‐binding, oligomerization domain–like receptor family, pyrin domain containing 3 (NLRP3)–caspase‐1–interleukin 1β (IL‐1β) pathway

\nYing Li, \nYuhui Ouyang, \nJian Jiao, \nZhaojun Xu, \nLuo Zhang\n

Publicatie 10-08-2020


BackgroundAllergic rhinitis(AR) is an increasing challenge to public health worldwide. Exposure to environmental black carbon (BC) is associated with increased risk of allergic rhinitis, but the molecular mechanisms underlying its toxicity have not been fully elucidated. The aims of the present study were therefore to determine the effect of BC on the expression of interleukin 1β (IL‐1β) and to investigate the mechanism underlying BC‐induced IL‐1β production in pollen‐sensitized human nasal epithelial cells (hNECs).MethodsNasal mucosal samples collected from 10 patients undergoing nasal surgery were used to isolate and culture epithelial cells as air‐liquid interface (ALI) cultures. Cultures exposed to BC ± pollen allergen for 24 hours were assessed for the presence of IL‐1β, the production of reactive oxygen species (ROS), and activation of the nucleotide‐binding, oligomerization domain–like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Furthermore, the mechanisms underlying BC ± pollen allergen–induced IL‐1β in hNECs were evaluated.ResultsExposure to BC significantly increased the production of IL‐1β and ROS and the expression of NLRP3 in hNECs, compared with control, all of which were significantly increased further by exposure to a combination of BC and pollen. Incubation of hNECs with N‐acetyl‐L‐cysteine (NAC) significantly attenuated BC ± pollen‐induced expression of ROS, NLRP3, and IL‐1β. NLRP3 and Caspase‐1 inhibitors (MCC950 and YVAD) significantly inhibited IL‐1β expression and NLRP3 activation, but not NLRP3 expression following exposure to BC ± pollen.ConclusionThese findings suggest that exposure to BC and pollen can exaggerate oxidative stress and significantly increase the expression of IL‐1β in hNECs, and that this may involve a pathway integrating ROS–NLRP3–Caspase‐1–IL‐1β signaling.

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Quality‐of‐life impact after in‐office treatment of nasal valve obstruction with a radiofrequency device: 2‐year results from a multicenter, prospective clinical trial

\nMoshe Ephrat, \nOfer Jacobowitz, \nMark Driver\n

Publicatie 09-08-2020


BackgroundInsufficiency of the nasal valve is increasingly being recognized as a cause of nasal airway obstruction. The condition is associated with many symptoms, including nasal congestion, sleep disturbance, snoring, and an overall decline in quality of life (QoL). An in‐office, minimally invasive radiofrequency treatment of the nasal valve has been associated with improved symptoms of nasal obstruction and patients’ QoL for a 6‐month period in a noncontrolled, prospective, single‐arm study. The purpose of this study was to determine whether the results achieved with radiofrequency treatment at 6 months would be sustained through 24 months.MethodsThirty‐nine adult patients from an original cohort of 49 patients with severe to extreme Nasal Obstruction Symptom Evaluation (NOSE) Scale scores and dynamic or static internal nasal valve obstruction as the primary or significant contributor to obstruction were studied. Patients received intranasal bilateral radiofrequency treatment in a clinical study with a follow‐up to 6 months, and were prospectively evaluated at 12, 18, and 24 months at 8 community‐based otolaryngology practices. The patient‐reported NOSE Scale score and 21 QoL questions were assessed.ResultsClinically significant improvement from baseline in NOSE Scale score change demonstrated at 6 months (mean, 55.9; standard deviation SD, 23.6; p < 0.0001) was maintained through 24 months (mean, 53.5; SD, 24.6; p < 0.0001). Responders (≥15‐point improvement) consisted of 92.3% of participants at 6 months and 97.2% at 24 months. Responses to the QoL questions also showed improvement in patients’ QoL.ConclusionTreatment of the nasal valve with an in‐office, transnasal temperature‐controlled radiofrequency procedure was associated with stable and lasting improvement in symptoms of nasal obstruction and QoL through 24 months in this noncontrolled, single‐arm study.

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Serum eosinophil cationic protein: a prognostic factor for early postoperative recurrence of nasal polyps

\nPin‐Ching Lu, \nTa‐Jen Lee, \nChi‐Che Huang, \nPo‐Huang Chang, \nYi‐Wei Chen, \nChia‐Hsiang Fu\n

Publicatie 06-08-2020


BackgroundThe objective of this work was to assess the efficacy of serum eosinophil cationic protein (ECP) concentration in predicting early postoperative recurrence in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).MethodsWe prospectively enrolled CRSwNP patients to receive bilateral functional endoscopic sinus surgery (FESS) and followed them for 1 year. Serum ECP level was measured within 1 week before surgery. Demographics and associated medical factors were analyzed with the surgical outcome, and nasal polyp histology was microscopically examined.ResultsOverall, 58 patients met the inclusion criteria and underwent FESS. After at least a 1‐year follow‐up period, 9 patients had postoperative recurrence, with significantly higher serum ECP levels (p = 0.030). Receiver operating characteristic curve analysis showed the optimal cutoff level of serum ECP concentration for predicting the postoperative recurrence of nasal polyps was 21.8 µg/L (p = 0.030). Regardless of atopy status and histology type, logistic regression analysis showed that a higher ECP level was the sole significant factor related to early postoperative recurrence of nasal polyps (odds ratio, 54.8; p = 0.014). Cox proportional hazard regression analysis revealed that the hazard ratio of CRSwNP patients with an ECP level of >21.8 µg/L resulting in early postoperative recurrence was 7.6 (p = 0.011).ConclusionSerum ECP appears to be a feasible predictor for early postoperative recurrence of nasal polyps. CRSwNP patients with preoperative serum ECP levels of ≥21.8 µg/L had an approximately 55‐fold increased risk of early recurrence. CRSwNP patients with higher preoperative serum ECP levels should be closely monitored within the first year after surgery.

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Conjunctivodacryocystorhinostomy (CDCR) success rates and complications in endoscopic vs non‐endoscopic approaches: a systematic review

\nNetanel Eisenbach, \nOhad Karni, \nEyal Sela, \nAchia Nemet, \nAmiel Dror, \nEinat Levy, \nYanir Kassif, \nRelli Ovadya, \nOhad Ronen, \nTal Marshak\n

Publicatie 06-08-2020


BackgroundEpiphora due to refractory bicanalicular obstructions is typically managed by conjunctivodacryocystorhinostomy (CDCR) with or without the assistance of nasal endoscopy. However, the evidence for its benefit is unclear.MethodsA systematic review of the literature on the treatment of epiphora by CDCR was performed (March 1, 2018). All studies reporting original data on patients suffering from epiphora treated with CDCR surgery were included. Primary outcomes were success and satisfaction rates. Secondary outcomes were CDCR complications. A comparison was made between the results obtained in patients undergoing CDCR with vs without assistance of nasal endoscopy.ResultsFifty‐four studies representing information on 2555 CDCR procedures were included in the systematic review. All the studies are case series, most of them retrospective. Lester Jones tube (LJT) is the most commonly used in CDCR (66.7%). The overall success rate with all studies included (n = 2555) was 88.9%; 90.8% (n = 890) in CDCR with assistance of nasal endoscope and 87.7% (n = 1575) in the non‐endoscopic approach. The overall “tube displacement” rate, the most common complication, was 24.5% (n = 2522), 20.8% (n = 1575) tube displacement in CDCR with assistance of nasal endoscope vs 26.7% (n = 1575) in the non‐endoscopic approach. Only 3 studies (5.5%) used patient‐reported outcome measures (PROMs) to evaluate epiphora improvement. Due to the low level of evidence and the high bias of the studies, a meta‐analysis was not performed.ConclusionBased on the data available in the literature, CDCR is considered an effective procedure for treating epiphora due to proximal obstruction. Controlled and qualitative studies are needed to clarify the significance of the endoscopes contribution to CDCR.

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Age as a factor in treatment of aspirin‐exacerbated respiratory disease: relationship to required aspirin maintenance dose after desensitization

\nTran B. Locke, \nAuddie M. Sweis, \nPatrick K. Gleeson, \nTheodore C. Lin, \nAlyssa M. Civantos, \nHarman S. Parhar, \nAndrew M. Corr, \nAnkur Kumar, \nMandy K. Salmon, \nMichael A. Kohanski, \nJames N. Palmer, \nJohn V. Bosso, \nNithin D. Adappa\n

Publicatie 06-08-2020


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Azithromycin and ciprofloxacin inhibit interleukin‐8 secretion without disrupting human sinonasal epithelial integrity in vitro

\nDong‐Jin Lim, \nHarrison M. Thompson, \nChristopher R. Walz, \nSamrath Ayinala, \nDaniel Skinner, \nShaoyan Zhang, \nJessica W. Grayson, \nDo‐Yeon Cho, \nBradford A. Woodworth\n

Publicatie 28-07-2020


BackgroundWe recently developed a ciprofloxacin and azithromycin sinus stent (CASS) to target recalcitrant infections in chronic rhinosinusitis (CRS). The objective of this study was to evaluate the anti‐inflammatory activity of azithromycin released from the CASS and assess the impact on the integrity and function of primary human sinonasal epithelial cells (HSNECs).MethodsPseudomonas aeruginosa lipopolysaccharide (LPS)‐stimulated HSNECs were treated with azithromycin and/or ciprofloxacin at concentrations attainable from CASS release. Interleukin‐8 (IL‐8) secretion was quantified by enzyme‐linked immunosorbent assay (ELISA). Epithelial integrity (transepithelial resistance TEER, paracellular permeability fluorescein isothiocyanate‐labeled dextran, lactate dehydrogenase LDH assays) and function (ciliary beat frequency CBF) were also evaluated.ResultsAzithromycin significantly reduced secreted IL‐8 from P. aeruginosa LPS‐stimulated HSNECs at all concentrations tested (mean ± standard deviation; control = 5.77 ± 0.39 ng/mL, azithromycin 6 μg/mL = 4.58 ± 0.40 ng/mL, azithromycin 60 µg/mL = 4.31 ± 0.06, azithromycin 180 µg/mL = 4.27 ± 0.26 ng/mL, p < 0.05). Co‐incubation with azithromycin (6 µg/mL) and ciprofloxacin (2.4 µg/mL) in LPS‐stimulated HSNECs also displayed a significant reduction in secreted IL‐8 when compared to P. aeruginosa LPS alone (co‐treatment = 4.61 ± 0.29 ng/mL, P. aeruginosa LPS = 7.35 ± 0.89 ng/mL, p < 0.01). The drugs did not negatively impact TEER, paracellular permeability, LDH release, or CBF, indicating retention of cell integrity and function.ConclusionAzithromycin decreased P. aeruginosa LPS IL‐8 production in HSNECs at drug concentrations attainable with sustained release of azithromycin from the CASS. In addition to antibacterial activity, anti‐inflammatory properties of the CASS should provide further benefit for patients with recalcitrant CRS.

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Topical nasal treatment efficacy on adult obstructive sleep apnea severity: a systematic review and meta‐analysis

\nDang‐Khoa Nguyen, \nJonathan Liang, \nMegan Durr\n

Publicatie 26-07-2020


BackgroundNasal obstruction is a common complaint in patients with sleep‐disordered breathing and obstructive sleep apnea (OSA). Although topical nasal treatments (TNTs) have been shown to reduce nasal resistance and improve nasal obstruction, there is conflicting evidence regarding the role of TNTs in adult OSA. In this systematic review and meta‐analysis we aim to evaluate the role of TNTs in adults with OSA. Data sources used included PubMed, Ovid MEDLINE, and Cochrane Central, from January 2001 to July 2019.MethodsInclusion criteria were English‐language studies containing original data on TNTs in adults (≥18 years) with OSA (apnea‐hypopnea index AHI ≥5). Exclusion criteria were case reports, studies without outcome measures, and concurrent non‐TNT treatment for OSA. Two investigators independently reviewed all articles and performed quality assessment using validated tools. Meta‐analysis and quality assessment were performed.ResultsOf the 2180 abstracts identified, 8 studies met inclusion criteria. TNTs included decongestants (4 of 8 studies), corticosteroids (3 of 8), and antihistamines (1 of 8). Outcome measures included AHI (8 of 8), respiratory distress index (RDI; 1 of 8), oxygen‐desaturation index (ODI; 3 of 8), minimum SaO2 (MinSaO2; 4 of 8), nasal resistance (4 of 8), endoscopic sinus surgery (4 of 8 studies) and standardized rhinoconjunctivitis quality of life questionnaire scores (1 of 8 studies). Qualitatively, all studies showed trends toward improving objective and subjective measures of OSA, although the significance of these improvements varied across studies. A meta‐analysis was performed in 5 studies, but TNTs did not reveal a significant change in AHI (p > 0.05).ConclusionTNTs may improve minimum oxygen saturation, ODI, RDI, and subjective/quality‐of‐life measures. Allergic patients may have more improvement in OSA measures compared with nonallergic patients. Future studies are indicated to accurately determine the efficacy of TNTs.

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Low‐dose and long‐term azithromycin significantly decreases Staphylococcus aureus in the microbiome of refractory CRS patients

\nAxel E. Renteria, \nAnastasios Maniakas, \nLeandra Endam Mfuna, \nMarc‐Henri Asmar, \nEmmanuel Gonzalez, \nMartin Desrosiers\n

Publicatie 26-07-2020


BackgroundThe sinonasal microbiome is believed to play an important role in the pathophysiology of refractory chronic rhinosinusitis (CRS). We evaluated changes in the microbiome following a 4‐month course of low‐dose azithromycin. Assessing microbiome alterations following such a treatment may help identify underlying mechanisms of this drug.MethodsA total of 48 adults with refractory CRS were enrolled in a double‐blind, randomized, placebo‐controlled trial. Patients were randomized to 250 mg of azithromycin or placebo 3 times weekly for 4 months. During this time, daily budesonide saline irrigations were continued. Sinonasal swabs were collected by endoscopically‐assisted method prior to treatment initiation and at the end of it, and sent for 16S ribosomal RNA gene sequencing. High‐resolution ANCHOR pipeline was used to infer and annotate putative species. The 2 patient groups were compared using DESeq2 differential abundance analysis.ResultsFrom initiation to the end of azithromycin treatment, patients showed a significant difference in beta diversity analysis (p = 0.0004) along with a significant decrease in 71 different operational taxonomic units (OTUs) of Staphylococcus aureus (false discovery rate FDR < 0.05) obtained from the differential abundance analysis. This was not observed in placebo‐treated patients. By the end of treatments, azithromycin‐treated patients had a significant decrease in 29 different OTUs of S. aureus (FDR < 0.05) when compared to placebo.ConclusionA 4‐month course of 250 mg of azithromycin 3 times weekly in patients with refractory CRS significantly decreases S. aureus abundance in the sinonasal microbiome. Considering the pathogenic role of S. aureus in the refractory CRS population, azithromycin may constitute an additional therapeutic option to help control this disease.

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Disease control after surgery for chronic rhinosinusitis: prospective, multi‐institutional validation of the Sinus Control Test

\nRyan E. Little, \nRodney J. Schlosser, \nTimothy L. Smith, \nKristina A. Storck, \nJeremiah A. Alt, \nDaniel M. Beswick, \nJess C. Mace, \nJose L. Mattos, \nVijay R. Ramakrishnan, \nZachary M. Soler\n

Publicatie 26-07-2020


BackgroundThe Sinus Control Test (SCT) is a 4‐question, patient‐reported questionnaire that assesses disease control in chronic rhinosinusitis (CRS). This prospective, multicenter study examines SCT outcomes following endoscopic sinus surgery (ESS), further validating its use as a control instrument for CRS.MethodsAdults with CRS undergoing ESS were prospectively enrolled from 5 centers across North America. The SCT was administered at baseline and once 6 months after surgery. Quality of life and disease burden were evaluated using the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and Lund‐Kennedy endoscopy scores. Linear regression was used to determine whether specific demographic, comorbidity, or disease severity measures were independently associated with changes in SCT scores postoperatively.ResultsA total of 218 patients, 111 females (50.9%) and 107 males (49.1%), were enrolled, with mean ± standard deviation age of 50.1 ± 15.6 years. Mean SCT score improved from 8.9 ± 3.5 to 4.3 ± 3.7 postoperatively (p < 0.001). Preoperatively, 21.6% were uncontrolled, 71.5% partially controlled, and 6.9% controlled. Postoperatively, 6.0% were uncontrolled, 42.6% partially controlled, and 51.4% controlled (p < 0.001). Change in SCT score correlated independently with change in SNOT‐22 (r = 0.500, p < 0.001) and endoscopy scores (r = 0.310, p < 0.001). Endoscopy scores did not correlate with control status among patients with CRS without nasal polyposis (CRSsNP) nor between uncontrolled and partially controlled patients. Demographics and comorbidities were not associated with changes in SCT.ConclusionImprovement in disease control following ESS as measured by the SCT correlated with improvements in SNOT‐22 and endoscopy scores. The SCT is an easily administered instrument that provides information complementary to existing patient‐reported and objective measures of disease severity.

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Pulmonary arterial pressure and nasal obstruction in mouth‐breathing children: Similarities between adenotonsillar hypertrophy and allergic rhinitis

\nCarolina Maria Fontes Ferreira Nader, \nFlávio Diniz Capanema, \nLetícia Paiva Franco, \nZilda Maria Alves Meira, \nCláudia Pena Galvão, \nVinícius Malaquias Ramos, \nMariana Maciel Tinano, \nLucas Lima Torres, \nRoberto Becker Guimarães, \nHelena Maria Gonçalves Becker\n

Publicatie 26-07-2020


BackgroundUpper airway obstruction may cause pulmonary hypertension in childhood. In this study we aimed to identify a possible correlation of systolic pulmonary arterial pressure (SPAP), using Doppler echocardiography, with nasal patency (NP), as measured by rhinomanometry, in mouth‐breathing (MB) children with allergic rhinitis (AR) and adenotonsillar hypertrophy (ATH).MethodsIn this cross‐sectional study we evaluated 183 patients, from 2 to 12 years of age, at an MB referral clinic in Brazil, from December 2013 to 2017. We allocated patients to 4 etiology groups: group 1, 60 MBs with ATH; group 2, 47 MBs with AR; group 3, 43 MBs with both ATH and AR; and group 4, 33 nasal breathing control subjects. The ratio of total nasal inspiratory flow (assessed by active anterior rhinomanometry) and expected inspiratory flow adjusted for height determined the percent NP (%NP).ResultsThe median %NP was higher in controls than in the MB groups (controls, 114% 79‐147%; ATH: 65% 5‐116%; AR: 57% 23‐144%; ATH and AR: 64% 3‐120%; p < 0.001). Median SPAP was higher in the MB groups than in controls (SPAP: ATH, 26.0 20.0‐35.0 mmHg; AR, 26.0 22.0‐32.0 mmHg; ATH and AR, 26.30 20.0‐34.0 mmHg; control, 22.0 16.0‐30.0 mmHg; p < 0.001). SPAP showed a negative association with %NP (Spearmans rho = −0.24; p < 0.001).ConclusionReduced nasal airflow in MB children showed a correlation with higher levels of systolic pulmonary arterial pressure. The AR and ATH groups were similar in nasal obstruction severity and systolic pulmonary arterial pressure level distribution.

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Review of indoor aerosol generation, transport, and control in the context of COVID‐19

\nMichael A. Kohanski, \nL. James Lo, \nMichael S. Waring\n

Publicatie 24-07-2020


AbstractThe coronavirus disease‐2019 (COVID‐19) pandemic has heightened the awareness of aerosol generation by human expiratory events and their potential role in viral respiratory disease transmission. Concerns over high severe acute respiratory syndrome‒coronavirus‐2 (SARS‐CoV‐2) viral burden of mucosal surfaces has raised questions about the aerosol‐generating potential and dangers of many otorhinolaryngologic procedures. However, the risks of aerosol generation and associated viral transmission by droplet or airborne routes for many otorhinolaryngology procedures are largely unknown. Indoor aerosol and droplet viral respiratory transmission risk is influenced by 4 factors: (1) aerosol or droplet properties; (2) indoor airflow; (3) virus‐specific factors; and (4) host‐specific factors. Herein we elaborate on known aerosol vs droplet properties, indoor airflow, and aerosol‐generating events to provide context for risks of aerosol infectious transmission. We also provide simple but typically effective measures for mitigating the spread and inhalation of viral aerosols in indoor settings. Understanding principles of infectious transmission, aerosol and droplet generation, as well as concepts of indoor airflow, will assist in the integration of new data on SARS‐CoV‐2 transmission and activities that can generate aerosol to best inform on the need for escalation or de‐escalation from current societal and institutional guidelines for protection during aerosol‐generating procedures.

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In Reply: Central compartment atopic disease: the missing link in the allergy and CRSwNP saga

\nRakesh K. Chandra\n

Publicatie 24-07-2020


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Central compartment atopic disease: the missing link in the allergy and chronic rhinosinusitis with nasal polyps saga

\nJohn M. DelGaudio\n

Publicatie 23-07-2020


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Elevated mucus interleukin‐17A levels are associated with increased prior sinus surgery for chronic rhinosinusitis

\nNikita Chapurin, \nPing Li, \nRakesh K. Chandra, \nJustin H. Turner, \nNaweed I. Chowdhury\n

Publicatie 23-07-2020


BackgroundRecent advances in molecular biology have enabled the identification of potential inflammatory endotypes of chronic rhinosinusitis (CRS), with prior work suggesting differential short‐term surgical outcome trajectories based on cytokine signatures. However, there is a paucity of data assessing long‐term treatment failure and need for revision surgery based on inflammatory biomarkers.MethodsRetrospective analysis of prospectively collected cross‐sectional data from 231 patients electing surgical therapy for CRS. Intraoperative mucus specimens were quantitatively sampled for inflammatory cytokines using a multiplex flow cytometric bead assay. Univariate Spearman correlations between cytokine levels and prior number of surgeries were assessed. A stepwise adjusted multivariate Poisson regression analysis was used to model patient‐reported prior sinus surgery counts as a function of cytokine levels.ResultsSeveral cytokines (interleukin IL‐1β, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐13, IL‐17A, tumor necrosis factor α TNF‐α, interferon γ IFN‐γ, and eotaxin) demonstrated significant positive correlations with number of prior surgeries. However, only higher IL‐17A levels were independently associated with a higher number of prior sinus surgeries (β = 0.345, p = 0.0003) after adjusting for the significant covariates of age (β = 0.018, p = 0.0036), Lund‐Mackay score (β = –0.046, p = 0.02), history of aspirin‐exacerbated respiratory disease (β = 1.01, p < 0.0001) and allergic fungal rhinosinusitis (β = 1.08, p < 0.0001). Higher levels of regulated on activation, normal T‐cell expressed and secreted (RANTES) were conversely associated with a lower number of prior surgeries (β = –0.17, p = 0.048).ConclusionAn IL‐17A–predominant cytokine profile is linked to an increased number of prior sinus surgeries. Thus, type 3 inflammatory markers may indicate a particularly difficult‐to‐treat, recalcitrant CRS endotype.

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Association of spontaneous cerebrospinal fluid rhinorrhea with transverse venous sinus stenosis: a retrospective matched case‐control study

\nVincent Bedarida, \nMarc‐Antoine Labeyrie, \nMichael Eliezer, \nJean‐Pierre Saint‐Maurice, \nClément Jourdaine, \nSergios Gargalas, \nPhilippe Herman, \nEmmanuel Houdart, \nBenjamin Verillaud\n

Publicatie 23-07-2020


BackgroundA significant proportion of spontaneous cerebrospinal fluid (sCSF) leaks are associated with idiopathic intracranial hypertension (IIH). The aim of this study was to assess the association between sCSF rhinorrhea and transverse venous sinus stenosis (VSS), a feature commonly observed in IIH with a proposed role in its pathophysiology.MethodsIn this single‐center, retrospective, matched case‐control study, venous and pituitary imaging data of consecutive patients undergoing endoscopic surgery for sCSF rhinorrhea over the last 10 years were retrospectively reviewed. Measurement of the height of the pituitary gland was used to assess empty sella and VSS was quantified as the ratio between the minimal area of the transverse sinus and the cross‐sectional area of the sigmoid sinus. VSS was considered significant when it was ≥50% and bilateral. Cases were compared with 1:1 age‐ and sex‐adjusted controls explored for causes other than IIH, intracranial mass effect, or venous thrombosis.ResultsTwenty‐nine patients were included (median age 56 years, females 69%, body mass index BMI 33.8 kg/m2). Cases had a significantly lower height of the pituitary gland than controls (2.5 mm vs 6.6 mm, p < 0.001). Bilateral VSS was found in 23 of 29 cases (79%; 95% confidence interval CI, 65% to 94%) vs 3 of 29 controls (10%; 95% CI, 0% to 21%), with p < 0.001.ConclusionIn this retrospective study, sCSF leaks were strongly associated with VSS. This novel finding provides a rationale for further investigation of the role of VSS in the onset of sCSF leaks and of the potential interest in venous stenting after the surgical repair of leaks.

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Assessment of three types of intranasal nebulization devices in three‐dimensional printed models and volunteers: a pilot study

\nDong Dong, \nFangyu Cai, \nShuman Huang, \nXiaoyuan Zhu, \nJing Geng, \nJia Liu, \nLei Lv, \nYanbing Zhang, \nYulin Zhao\n

Publicatie 20-07-2020


BackgroundIntranasal nebulization is an effective treatment for chronic rhinosinusitis and allergic rhinitis; however, terminal inhalation devices have not been fully studied. We compared the sinonasal aerosol distributions and adverse effects of different inhalation units.MethodsA mask, double‐head nozzle, and single‐head nozzle were applied to atomize the methylene blue solution to 3‐dimensional printed models of the pediatric nasal cavity, adult nasal cavity with septal deviation, and postsurgical paranasal sinuses, and staining of the different sites was scored. Volunteers received nebulization of normal saline via different devices; thereafter, the adverse effects were assessed using the visual analogue scale (VAS).ResultsAfter nebulization, the staining scores for the middle turbinate and middle meatus of the pediatric and adult nasal cavity models and the score for the anterior ethmoid sinus of the sinus model with the single‐head nozzle were significantly higher than those with the mask and double‐head nozzle (all p < 0.05; η2 for effect size estimates were above 0.68). Among the 31 volunteers, the adverse effects, including nasal irritation, facial pressure/pain, ear fullness/pain, postnasal drip, and throat irritation/cough, were mild. The variations in the incidence and VAS scores of the adverse effects among the devices were not significant (all p > 0.05).ConclusionThe single‐head nozzle was the most effective device in aerosol delivery to the lateral wall of the nasal cavity and sinuses; conversely, the mask yielded limited sinonasal deposition. Intranasal nebulization was well tolerated, and the adverse effects among the devices were comparable. These findings are meaningful for selecting and developing inhalation units.

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In Reply: Navigating personal risk in rhinologic surgery during the COVID‐19 pandemic

\nAdam S. DeConde, \nCarol H. Yan, \nRobert P. DeConde\n

Publicatie 19-07-2020


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Major complications of aspirin desensitization and maintenance therapy in aspirin‐exacerbated respiratory disease

\nAuddie M. Sweis, \nTran B. Locke, \nKevin I. Ig‐Izevbekhai, \nTheodore C. Lin, \nPatrick K. Gleeson, \nAlyssa M. Civantos, \nAnkur Kumar, \nAndrew M. Corr, \nMichael A. Kohanski, \nJames N. Palmer, \nJohn V. Bosso, \nNithin D. Adappa\n

Publicatie 16-07-2020


BackgroundTreatment 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.MethodsThis 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.ResultsIn 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).ConclusionAD 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.

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Medical and surgical treatment outcomes in patients with chronic rhinosinusitis and immunodeficiency: a systematic review

\nShireen Samargandy, \nElysia Grose, \nYvonne Chan, \nEric Monteiro, \nJohn M. Lee, \nJonathan Yip\n

Publicatie 15-07-2020


BackgroundImmunodeficiency is a risk factor for recalcitrant chronic rhinosinusitis (CRS). Currently, there is no consensus on effective treatment modalities for immunodeficient CRS patients. This review aims to evaluate the existing evidence on the treatment outcomes and its limitations in patients with CRS and immunodeficiency.MethodsMEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to April 2019 for studies reporting measurable medical or surgical treatment outcomes for adult patients with CRS and underlying primary or secondary immunodeficiency.ResultsOf the 2459 articles screened, 13 studies met the inclusion criteria: 2 prospective double‐blind placebo‐controlled trials, 2 prospective case‐control studies, 2 prospective cohort studies, and 7 case series. The high degree of study heterogeneity precluded a meta‐analysis. Antibiotic monotherapy was not linked with significant improvement in clinical, radiographic, or endoscopic outcomes. Immunoglobulin replacement therapy may potentially reduce the frequency of acute or chronic sinusitis in patients with primary immunodeficiency (PID) but may not improve their sinonasal symptoms. Outcomes from endoscopic sinus surgery (ESS) were reported in 8 studies, which found that surgery was linked with improvement in symptoms, disease‐specific quality of life, endoscopy scores, and radiographic scores. The average reported ESS revision rate was 14%.ConclusionPatients with CRS and immunodeficiency likely benefit from ESS based on the available evidence. Data supporting medical therapy in this targeted population is limited overall, but there may be a potential role for immunoglobulin therapy in patients with PID and CRS.

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An internally validated diagnostic tool for acute invasive fungal sinusitis

"\nLinda X. Yin, \nAviv Spillinger, \nKatherine A. Lees, \nKent R. Bailey, \nGarret Choby, \nErin K. OBrien, \nJanalee K. Stokken\n"

Publicatie 15-07-2020


BackgroundAcute invasive fungal sinusitis (AIFS) is a potentially life‐threatening diagnosis in immunocompromised patients. Identifying patients who could benefit from evaluation and intervention can be challenging for referring providers and otolaryngologists alike. We aimed to develop and validate an accessible diagnostic tool to estimate the probability of AIFS.MethodsRetrospective chart review from 1999 to 2017 identified all patients evaluated for possible AIFS at a tertiary care center. AIFS was diagnosed by pathologic confirmation of fungal tissue angioinvasion. Stepwise selection and univariate logistic regression were used to screen risk factors for a multivariable predictive model. Model performance was assessed using Tukeys goodness‐of‐fit test and the area under the receiver operator characteristic curve (AUC). Model coefficients were internally validated using bootstrapping with 1000 iterations.ResultsA total of 283 patients (244 negative controls, 39 with AIFS) were included. Risk factors in our final diagnostic model included: fever ≥38°C (log‐odds ratio LOR 1.72; 95% CI, 0.53 to 2.90), unilateral facial swelling, pain, or erythema (LOR 2.84; 95% CI, 1.46 to 4.23), involvement of the orbit or pterygopalatine fossa on imaging (LOR 3.02; 95% CI, 1.78 to 4.26), and mucosal necrosis seen on endoscopy (LOR 5.52; 95% CI, 3.81 to 7.24), with p < 0.01 for all factors. The model had adequate goodness of fit (p > 0.05) and discrimination (AUC = 0.96).ConclusionWe present an internally validated diagnostic tool to stratify the risk for AIFS. The estimated risk may help determine which patients can be observed with serial nasal endoscopy, which ones could be biopsied, and which ones would benefit from immediate surgical intervention.

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Suction mitigation of airborne particulate generated during sinonasal drilling and cautery

\nAlan D. Workman, \nRoy Xiao, \nAllen Feng, \nShekhar K. Gadkaree, \nAlicia M. Quesnel, \nBenjamin S. Bleier, \nGeorge A. Scangas\n

Publicatie 15-07-2020


BackgroundCoronavirus disease 2019 (COVID‐19) has significantly impacted endonasal surgery, and recent experimentation has demonstrated that sinonasal drilling and cautery have significant propensity for airborne particulate generation immediately adjacent to the surgical field. In the present investigation, we assessed nasopharyngeal suctioning as a mitigation strategy to decrease particulate spread during simulated endonasal surgical activity.MethodsAirborne particulate generation in the 1‐µm to 10‐µm range was quantified with an optical particle sizer in real‐time during cadaveric‐simulated anterior and posterior endonasal drilling and cautery conditions. To test suction mitigation, experiments were performed both with and without a rigid suction placed in the contralateral nostril, terminating in the nasopharynx.ResultsBoth anterior (medial maxillary wall and nasal septum) and posterior (sphenoid rostrum) drilling produced significant particulate generation in the 1‐µm to 10‐µm range throughout the duration of drilling (p < 0.001) without the use of suction, whereas nasopharyngeal suction use eliminated the detection of generated airborne particulate. A similar effect was seen with nasal cautery, with significant particle generation (p < 0.001) that was reduced to undetectable levels with the use of nasopharyngeal suction.ConclusionThe use of nasopharyngeal suctioning via the contralateral nostril minimizes airborne particulate spread during simulated sinonasal drilling and cautery. In the era of COVID‐19, this technique offers an immediately available measure that may increase surgical safety.

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Preprocedural COVID‐19 screening: Do rhinologic patients carry a unique risk burden for false‐negative results?

\nBenjamin S. Bleier, \nKevin C. Welch\n

Publicatie 15-07-2020


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Comparison of bacterial maxillary sinus cultures between odontogenic sinusitis and chronic rhinosinusitis

\nAbdulkader Yassin‐Kassab, \nPallavi Bhargava, \nRobert J. Tibbetts, \nZachary H. Griggs, \nEdward I. Peterson, \nJohn R. Craig\n

Publicatie 12-07-2020


BackgroundBacterial odontogenic sinusitis (ODS) is distinct from other forms of rhinosinusitis. Diagnosing ODS can be challenging because of nonspecific clinical presentations and underrepresentation in the literature. The purpose of this study was to compare maxillary sinus bacterial cultures between patients with ODS and chronic rhinosinusitis (CRS), to determine whether certain bacteria are associated with ODS.MethodsThis was a retrospective case‐control study of 276 consecutive patients from August 2015 to August 2019 who underwent endoscopic sinus surgery (ESS) for bacterial ODS, CRS without nasal polyps (CRSsNP), or CRS with nasal polyps (CRSwNP). When present, pus was sterilely cultured from maxillary sinuses after maxillary antrostomy, and aerobic and anaerobic cultures were immediately sent for processing. Demographics and culture results were compared between ODS and CRS patients, and then separately between ODS and CRSsNP, and ODS and CRSwNP. ODS culture results were also compared between different dental pathologies (endodontic vs oroantral fistula).ResultsThe following bacteria were significantly more likely in ODS compared to CRS: mixed anaerobes, Fusobacterium spp., Eikenella corrodens, Streptococcus intermedius, Streptococcus anginosus, and Streptococcus constellatus. Staphylococcus aureus and Pseudomonas aeruginosa were inversely related to ODS. There were no significant differences in cultures between the different dental pathologies.ConclusionCertain bacteria were more likely to be associated with ODS compared to CRS when purulence was cultured from the maxillary sinus. Physicians should evaluate for an odontogenic source of sinusitis when these ODS‐associated bacteria are identified in maxillary sinus cultures.

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Quantitative determination of the optimal temporoparietal fascia flap necessary to repair skull‐base defects

\nAlan Siu, \nSanjeet V. Rangarajan, \nMindy R. Rabinowitz, \nAdam Luginbuhl, \nRyan A. Rimmer, \nChandala Chitguppi, \nChristopher Farrell, \nGurston G. Nyquist, \nMarc R. Rosen, \nJames J. Evans\n

Publicatie 07-07-2020


BackgroundThe ability to reconstruct large cranial base defects has greatly improved with the development of pedicled vascularized flaps. The temporoparietal fascia flap (TPFF) is a viable alternative to the Hadad‐Bassagasteguy nasoseptal flap for large ventral skull‐base defects. This study aims to characterize the size of the TPFF necessary for optimal ventral skull‐base reconstruction.MethodsEleven formaldehyde‐fixed cadaveric heads were used to harvest TPFF of varying heights on each side (total = 22). TPFF was passed through the pterygomaxillary fissure (PMF) to the ventral skull base to assess its coverage. For a subgroup of 12 sides, the TPFF was trimmed to determine the minimum height necessary for coverage.ResultsThe TPFF height was (mean ± standard deviation SD) 14.72 ± 1.02 cm (range, 12.5 to 16.5 cm) and width was 8.43 ± 1.05 cm (range, 6 to 10.5 cm). The distance from the TPFF pedicle through the PMF was 5.8 ± 0.5 cm (range, 5 to 6.5 cm). All TPFF flaps provided complete ipsilateral coverage of clival defects, and all but 1 covered the entire clivus. All TPFF flaps, when rotated anteriorly, provided coverage up to the cribriform plate. The minimum TPFF height necessary for complete coverage of cribriform defects and ventral defects up to the planum sphenoidale was 12 cm. TPFF height for specimens with and without complete ventral skull‐base coverage was significantly different (p < 0.0001).ConclusionThe TPFF is a versatile alternative to the nasoseptal flap and a height of at least 12 cm can provide enough coverage for all ventral skull base defects.

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Double‐blinded randomized prospective trial of intranasal capsaicin treatment for nonallergic rhinitis

\nDenna Zebda, \nZi Yang Jiang, \nMicah M. Gibson, \nChauchau Pham, \nSorour Ahmadi, \nSamuel Floren, \nWilliam C. Yao, \nMartin J. Citardi, \nAmber U. Luong\n

Publicatie 07-07-2020


BackgroundNonallergic rhinitis (NAR) is currently a diagnosis of exclusion with an unclear pathophysiologic mechanism and limited treatment options. In patients diagnosed with NAR based on symptoms, negative skin testing and positive optical rhinometry (ORM), the studys objective was to evaluate the therapeutic action of intranasal capsaicin in the management of rhinitic symptoms and the effect on ORM readings.MethodsPatients with a history of NAR underwent screening by a diagnostic intranasal capsaicin challenge with ORM and skin‐prick testing. Twenty‐two NAR patients were enrolled and randomized to either treatment with 0.1mM capsaicin (n = 11) or placebo (n = 11). Treatment consisted of 5 consecutive intranasal applications separated by 1 hour with follow‐up at 4 and 12 weeks. At each visit, subjects underwent intranasal capsaicin challenge with ORM reading and a visual analog scale scoring of rhinitis symptoms.ResultsTreatment with intranasal capsaicin resulted in a median change with improvement in total symptom score (TSS) of –5 from baseline vs an increase of 2 with placebo at 4 weeks, which remained significantly different between the groups at 12 weeks (p = 0.03). At 12 weeks posttreatment, 60% of the intervention group vs 80% of placebo‐treated patients still met objective criteria for NAR by ORM.ConclusionUsing ORM in the objective diagnosis of NAR, this trial showed that intranasal 0.1mM capsaicin not only improved rhinitic symptoms but also objectively reduced nasal reactivity and nasal congestion with a 40% responder rate at 12 weeks as noted by ORM.

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Machine learning of biomarkers and clinical observation to predict eosinophilic chronic rhinosinusitis: a pilot study

\nRyan M. Thorwarth, \nDerek W. Scott, \nDevyani Lal, \nMichael J. Marino\n

Publicatie 07-07-2020


BackgroundSubtyping chronic rhinosinusitis (CRS) by tissue eosinophilia has prognostic and therapeutic implications, and is difficult to predict using peripheral eosinophil counts or polyp status alone. The objective of this study was to test machine learning for prediction of eosinophilic CRS (eCRS).MethodsInput variables were defined as peripheral eosinophil count, urinary leukotriene E4 (uLTE4) level, and polyp status. The output was diagnosis of eCRS, defined as tissue eosinophil count >10 per high‐power field. Patients undergoing surgery for CRS were retrospectively reviewed for complete datasets. Univariate analysis was performed for each input as a predictor of eCRS. Logistic regression and artificial neural network (ANN) machine learning models were developed using random and surgeon‐specific training/test datasets.ResultsA total of 80 patients met inclusion criteria. In univariate analysis, area under the receiver operator characteristic curve (AUC) for peripheral eosinophil count and uLTE4 were 0.738 (95% confidence interval CI, 0.616 to 0.840) and 0.728 (95% CI, 0.605 to 0.822), respectively. Presence of polyps was 94.1% sensitive, but 51.7% specific. Logistic regression models using random and surgeon specific datasets resulted in AUC of 0.882 (95% CI, 0.665 to 0.970) and 0.945 (95% CI, 0.755 to 0.995), respectively. ANN models resulted in AUC of 0.918 (95% CI, 0.756 to 0.975) and 0.956 (95% CI, 0.828 to 0.999) using random and surgeon‐specific datasets, respectively. Model comparison of logistic regression and ANN was not statistically different. All machine learning models had AUC greater than univariate analyses (all p < 0.003).ConclusionMachine learning of 3 clinical inputs has the potential to predict eCRS with high sensitivity and specificity in this patient population. Prospective investigation using larger and more diverse populations is warranted.

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The role of preoperative blood eosinophil counts in distinguishing chronic rhinosinusitis with nasal polyps phenotypes

\nBing Zhong, \nTian Yuan, \nJintao Du, \nKaisen Tan, \nQintai Yang, \nFeng Liu, \nYafeng Liu, \nLuo Ba, \nShixi Liu\n

Publicatie 07-07-2020


BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a common heterogenous disease in the patients with chronic airway diseases. This study investigated the role of blood eosinophil count (BEC) in the classification of CRSwNP and its recurrence in eosinophilic CRSwNP.MethodsSixty‐five patients who underwent nasal endoscopic resection of CRSwNP were recruited and divided into eosinophilic CRSwNP and non‐eosinophilic CRSwNP groups based on the levels (10% cutoff) of eosinophil infiltration as indicated by hematoxylin and eosin (H&E) staining.ResultsWe recruited 30 patients in the eosinophilic CRSwNP group and 35 patients in the non‐eosinophilic CRSwNP group. The outcome of preoperative visual analogue scale (VAS) score, preoperative Lund‐Mackay score, and preoperative Lund‐Kennedy score between the 2 groups were comparable. The level of BEC in the eosinophilic CRSwNP group was significantly higher than that of non‐eosinophilic CRSwNP group (0.79 ± 0.27 × 109/L vs 0.30 ± 0.22 × 109/L; p < 0.001). We observed a statistical significance in the number of H&E eosinophils (29.11 ± 2.93 vs 3.17 ± 0.51; p < 0.001) and CRSwNP phenotypes (eosinophilic/non‐eosinophilic, 28/3 vs 2/32; p < 0.001) when the cutoff value of BEC was set at 0.39 × 109/L. The disease‐free recurrence (DFR) was found to be statistically significant when the cutoff value of BEC was 0.73 × 109/L in eosinophilic CRSwNP (p = 0.009).ConclusionResults indicate that BEC may be capable of distinguishing CRSwNP phenotypes as well as predicting polyp recurrence in eosinophilic CRSwNP. Given the relatively small sample size, further studies will be necessary to confirm a role for BEC as a systemic biomarker in CRSwNP.

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Lipopolysaccharide regulates thymic stromal lymphopoietin expression via TLR4/MAPK/Akt/NF‐κB‒signaling pathways in nasal fibroblasts: differential inhibitory effects of macrolide and corticosteroid

\nJu‐Hyung Kang, \nHyun‐Woo Yang, \nJoo‐Hoo Park, \nJae‐Min Shin, \nTae‐Hoon Kim, \nSeung Hoon Lee, \nHeung‐Man Lee, \nIl‐Ho Park\n

Publicatie 05-07-2020


BackgroundChronic rhinosinusitis (CRS) is an inflammatory disease of the sinonasal mucosa. Thymic stromal lymphopoietin (TSLP) is associated with T‐helper 2 (Th2) response and induced by pathogen, allergen, toll‐like receptor (TLR) ligands, and cytokines. Fibroblasts are known to be modulators of wound‐healing, from inflammation to tissue remodeling. We examined effect of lipopolysaccharide (LPS) on TSLP production and the underlying mechanisms. We aimed to determine whether the effects of commonly used medications in CRS, namely corticosteroids, and macrolides, are related to LPS‐induced TSLP in nasal fibroblasts.MethodsFibroblasts were isolated from inferior turbinate tissues of CRS patients. TSLP and TLR4 expressions were determined by reverse transcript‒polymerase chain reaction (RT‐PCR), Western blot, enzyme‐linked immunoassay, and immunofluorescence staining. Mitogen‐activated protein kinase (MAPK), protein kinase B (Akt), and nuclear factor‐kappaB (NF‐κB) phosphorylation was determined by Western blot and/or luciferase assay.ResultsLPS increased TSLP expression in a dose‐ and time‐dependent manner. LPS antagonist and corticosteroids inhibited TLR4 expression in LPS‐stimulated fibroblasts. LPS‐RS, macrolides, corticosteroids, and specific inhibitors suppressed LPS‐induced alterations. Ex vivo culture showed similar results.ConclusionLPS induces TSLP production via the TLR4, MAPK, Akt, and NF‐κB pathways. The effects of corticosteroids and macrolides are related to LPS‐induced TSLP expression. We explored new treatment modalities targeting LPS‐induced TSLP production that could replace the currently used corticosteroid and macrolides for treatment of CRS.

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Period2 gene regulates diurnal changes of nasal symptoms in an allergic rhinitis mouse model

\nFeng‐Li Cheng, \nYun‐Fang An, \nZhuo‐Qin Han, \nChao Li, \nZe‐Qing Li, \nPing‐Chang Yang, \nChang‐Qing Zhao\n

Publicatie 01-07-2020


BackgroundAllergic rhinitis (AR) symptoms exhibit prominent 24‐hour variations associated with the biological clock. Although endogenous glucocorticoids synchronize circadian oscillator in the nasal mucosa, the precise mechanism of AR remains unclear. Therefore, using a mouse model, we investigated the association between circadian‐clock genes and AR symptoms at various time‐points.MethodsBased on the rhythmic secretion of corticosterone levels, we chose 2 time‐points, ZT4 (10:00 AM) and ZT16 (10:00 PM), to observe dynamic changes of nasal symptoms, immunologic responses, and circadian‐clock gene period (Per) expressions.ResultsIn the AR group, nasal symptom scores at ZT4 were significantly higher than at ZT16, with a greater increase in eosinophils, mast cells, and total immunoglobulin E levels at ZT4. The scores had a negative correlation with fluctuation of corticosterone levels. T‐helper 1 (Th1) cell counts and interferon‐γ levels decreased significantly at ZT4 compared with ZT16 in the AR group, whereas Th2 cells; Th17 cells; and interleukin (IL)‐4, ‐13, and ‐17A levels increased significantly at ZT4 compared with ZT16. Furthermore, Per2 gene expression levels were attenuated at ZT4 and elevated at ZT16, but correlated negatively with Th2 and Th17 responses associated with Gata3 and Rorγt expression levels that were enhanced at ZT4 and reduced at ZT16 in the AR group.ConclusionOur results suggest that the Per2 gene may influence diurnal variations of AR symptom severity, partially through its possible anti‐inflammatory effect on the circadian regulation of GATA3 and RORγt levels in immune cells. This further demonstrates the neural‐immune‐endocrinal mechanism of circadian rhythm in AR and sheds new light on chronotherapeutic approaches to AR.

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Specific sublingual immunotherapy in children with perennial rhinitis: a systemic review and meta‐analysis

\nLiang Chen, \nLijuan Lei, \nYinghuang Cai, \nTianlin Li\n

Publicatie 25-06-2020


BackgroundAllergic rhinitis (AR) is a major public health problem and is increasing worldwide. AR affects childrens learning efficiency, sleep quality, and other major aspects of life. Sublingual immunotherapy (SLIT) is effective and safe for children with seasonal AR, but for children with perennial allergic rhinitis (PAR) caused by house dust mites (HDM), its effectiveness and safety is less convincing.MethodsMedical literature databases up to 2019 were searched for published and unpublished pieces of evidence. Studies were individually screened by 2 reviewers against the eligibility criteria. Primary outcomes were total nasal symptoms scores (TNSS) and total medication scores (TMS). The secondary outcomes were total ocular symptoms scores and adverse events (AEs). Random effect models and fixed‐effect models were used to calculate the standard mean difference (SMD) and risk ratio (RR), respectively.ResultsWe identified 3772 abstracts, of which only 16 studies met our established criteria. SLIT significantly reduced TNSS (SMD –1.73; 95% CI, –2.62 to –0.84; p = 0.0001) and TMS (SMD –1.21; 95% CI, –1.75 to –0.67; p < 0.00001). Compared with children taking placebo, children taking SLIT were 1.08 (95% CI, 1 to 1.17; p = 0.05), 1.15 (95% CI, 0.87 to 1.51; p = 0.32), and 1.68 (95% CI, 0.68 to 4.11; p = 0.26) times more likely to develop mild, moderate, and severe AEs, respectively.ConclusionHDM SLIT can effectively alleviate TNSS and TMS in children with PAR, but care should be taken to avoid harm due to possible adverse drug reactions.

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Characterization and implications of the lingual process of the sphenoid bone: a cadaveric and radiographic study

\nLifeng Li, \nNyall R. London, \nXiaohong Chen, \nDaniel M. Prevedello, \nRicardo L. Carrau\n

Publicatie 24-06-2020


BackgroundThe surgical significance of the lingual process of the sphenoid bone (LPSB) has not been sufficiently addressed. The purpose of this study was to describe the anatomical details of the LPSB in relation to the quadrangular space. Moreover, the incidence of the LPSB and its correlation with the pneumatization of the sphenoid sinus and the development of the lateral recess of the sphenoid sinus (LRSS) were also evaluated.MethodsA dissection and exposure of the LPSB and the quadrangular space was performed on 10 cadaveric specimens (20 sides). The incidence, length, and height of the LPSB were also assessed on computed tomography (CT) images (60 patients, 120 sides). The association between the presence of the LPSB with the pneumatization type of the sphenoid sinus and the presence of a LRSS was evaluated.ResultsIn a cadaveric model, the LPSB, in association with the petrolingual ligament extending from the LPSB to the petrous apex, was identified on 7 sides (35%). The LPSB was continuous with the mandibular strut. The overall incidence of a LPSB was 48.33% on CT images, and the average length and height of the LPSB was (mean ± standard deviation) 5.30 ± 1.44 mm and 6.51 ± 1.32 mm, respectively. A significant correlation was identified between presence of the LPSB with the pneumatization type of the sphenoid sinus (p = 0.004) but no correlation was identified with the presence of the LRSS (p = 0.071).ConclusionThe LPSB and the petrolingual ligament are useful landmarks for procedures in the quadrangular space and Meckels cave. However, the LPSB is not consistently present.

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The microbiome of pediatric patients with chronic rhinosinusitis

\nAmanda L. Stapleton, \nAmber D. Shaffer, \nAlison Morris, \nKelvin Li, \nAdam Fitch, \nBarbara A. Methé\n

Publicatie 22-06-2020


BackgroundThis study aimed to compare the microbiota of pediatric patients with chronic rhinosinusitis (CRS) who are undergoing adenoidectomy to treat their disease with that of healthy control patients.MethodsPatients undergoing adenoidectomy‐only for obstructive sleep apnea (n = 50) and CRS (n = 37) were recruited. Preoperative 22‐item Sino‐Nasal Outcome Test (SNOT‐22) or Sinus and Nasal Quality of Life Survey (SN‐5) were collected. Each patient had samples collected from their nasopharynx (adenoid bed) and nasal cavity (sinus) at the onset of surgery. 16S ribosomal ribonucleic acid (rRNA) gene sequencing was subsequently performed to obtain per sample taxonomic abundances. Statistical analyses included permutational multivariate analysis of variance (PERMANOVA), alpha (within sample) diversity measures, and changes in taxonomic abundance.ResultsMoraxella was the most abundant organism. Nasopharyngeal swabs demonstrated higher alpha diversity compared to the nasal cavity. The diversity was not different based on CRS vs obstructive history. There was an increase in diversity with increasing age, and eczema contributed to a greater difference in diversity between the nasopharynx and nasal cavity. Diversity was not affected by adenoid size; however, use of nasal steroids, inhaled steroids, and antihistamines influenced diversity in both the nasopharynx and nasal cavity. Nasopharyngeal samples were higher in relative abundance for Fusobacterium, Prevotella, Porphyromonas, and Campylobacter compared to the nasal cavity.ConclusionThe nasopharynx and nasal cavity differed in both microbiota composition and diversity. In contrast, no significant difference in composition or diversity were found in CRS vs control patients. Ecological changes in the nasopharyngeal and sinus site may contribute to the etiology for adenoid hypertrophy in both healthy controls and CRS patients.

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Ethmoid‐to‐maxillary opacification ratio: a predictor of postoperative olfaction and outcomes in nasal polyposis?

\nDaniel M. Beswick, \nTimothy L. Smith, \nJess C. Mace, \nJeremiah A. Alt, \nNyssa F. Farrell, \nVijay R. Ramakrishnan, \nRodney J. Schlosser, \nZachary M. Soler\n

Publicatie 18-06-2020


BackgroundInflammatory profiles for patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) vary between North American and Asian populations. An elevated ethmoid‐to‐maxillary (E/M) opacification ratio on preoperative imaging is associated with certain postoperative outcomes in Asian populations and populations that are non‒type 2 dominant. In this study we explore this factor in North American/type 2‒based populations.MethodsAdult patients (n = 165) from a North American population with CRSwNP who underwent endoscopic sinus surgery (ESS) were prospectively enrolled into an observational, multi‐institutional study. The 22‐item Sino‐Nasal Outcome Test (SNOT‐22), Brief Smell Identification Test (BSIT), and Lund‐Kennedy (LK) endoscopic scores were obtained pre‐ and postoperatively. Patients were stratified according to increasing E/M ratios based on Lund‐Mackay (LM) scores.ResultsOn average, significant within‐subject postoperative improvement was found in all patients for SNOT‐22 total and domain scores, and also BSIT results (p ≤ 0.019). Preoperatively, elevated E/M ratio correlated with worse BSIT scores (r = −0.343, p < 0.001). Postoperatively, elevated E/M ratio correlated with BSIT improvement (r = 0.284, p = 0.002), but did not correlate with SNOT‐22 improvement or polyp recurrence. An elevated E/M ratio was associated with greater likelihood of reporting a minimal clinically important difference in BSIT scores (χ2 = 9.96, p = 0.041).ConclusionElevated E/M ratios were found to associated with worse baseline olfaction and an increased likelihood of achieving a clinically meaningful postoperative improvement in olfaction in this North American population with CRSwNP. Elevated E/M ratios did not predict postoperative changes in SNOT‐22 measures or polyp recurrence. This suggests that prognostic factors may vary according to geography and generalized inflammatory profiles (type 2 vs non‒type 2) in patients with CRS.

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Surgical outcomes in aspirin‐exacerbated respiratory disease without aspirin desensitization

\nElysia Grose, \nDaniel J. Lee, \nJonathan Yip, \nJustin Cottrell, \nJenna Sykes, \nJason K. Lee, \nJohn M. Lee\n

Publicatie 18-06-2020


BackgroundAspirin‐exacerbated respiratory disease (AERD) represents a severe endotype of chronic rhinosinusitis with nasal polyposis. Although aspirin desensitization (AD) has emerged as an effective therapeutic option, the natural history of AERD without AD remains unclear.MethodsA retrospective review was conducted of AERD patients who underwent endoscopic sinus surgery (ESS) without AD between 2010 and 2019. The primary outcomes were revision surgery rate and time to revision surgery. Secondary outcomes included changes in 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores and Lund‐Kennedy endoscopy scores (LKES). A subgroup analysis was performed for patients on monoclonal antibody therapy (MAT).ResultsOf 141 patients, 37 (26.2%) underwent revision ESS with a median time to revision of 3.3 (interquartile range IQR, 2.2‐4.9) years. The probability of remaining free of revision surgery at 1, 3, and 5 years was: 98.2% (95% confidence interval CI, 95.7‐100.0%), 78.8% (95% CI, 70.2‐88.4%), and 44.8% (95% CI, 32.4‐62.1%), respectively. SNOT‐22 scores decreased by 34 (IQR, 18‐52) points at 6 months and 27 (IQR, 20‐46) points at 1 year postoperatively. In the revision cohort, the decrease in SNOT‐22 score was not sustained at 1 year postoperatively. No difference was found in time to revision compared with those without MAT (p = 0.23).ConclusionA significant proportion of AERD patients benefit from ESS and medical therapy alone without AD. This study presents preliminary results on the impact of MAT on surgical outcomes as it is limited by the small sample size. Further research on the use of MAT in AERD is needed.

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Targeted 595‐gene genomic profiling demonstrates low tumor mutational burden in olfactory neuroblastoma

\nJacob Friedman, \nJane K. Schumacher, \nPete Papagiannopoulos, \nSamer Al‐Khudari, \nBobby A. Tajudeen, \nPete S. Batra\n

Publicatie 18-06-2020


BackgroundOlfactory neuroblastoma (ONB) is a rare skull‐base malignancy associated with delayed local recurrence. Treatment options in recurrent disease are few and unreliable. We undertook analysis of the ONB exome and immune environment in order to identify potential future immunotherapy treatment options.MethodsRetrospective chart review and next‐generation targeted 595‐gene genomic profiling was performed on a cohort of 14 ONB cases utilizing Tempus proprietary DNA and RNA sequencing technology. Tempus analysis provided a measurement of tumor mutational burden (TMB) and composition of the immune cell infiltrate present in tumor samples. Clinically relevant genomic alterations and associated targeted therapies were identified using cancer.gov and clinicaltrials.gov. TMB was tested by univariate analysis against clinical stage, pathologic grade, recurrence risk, and immune cell infiltration.ResultsThe mean age for the subjects was 50 years (range, 13 to 76 years) with a male:female ratio of 1:1. TMB for ONB samples ranged from 1.3 to 9.6 mutations/megabase (Mb) with mean of 3.8 mutations/Mb. Univariate analysis showed no association between TMB and tumor stage, pathologic grade, risk of recurrence, or immune cell infiltration. Genomic profile revealed that 6 of 13 tumors had genetic alterations with targeted therapies in clinical trials, whereas 1 tumor demonstrated KRAS Q61R mutation with U.S. Food and Drug Administration (FDA)‐approved targeted therapies.ConclusionTMB is a novel biomarker guiding the classification of neoplasms in the emerging era of immunotherapy. The characterization of ONB as a low‐TMB pathology contributes to the overall taxonomy of all cancers and suggests limited utility of immunotherapy treatment.

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Volumetric assessment of paranasal sinus opacification on computed tomography can be automated using a convolutional neural network

\nStephen M. Humphries, \nJuan Pablo Centeno, \nAleena M. Notary, \nJustin Gerow, \nGiuseppe Cicchetti, \nRohit K. Katial, \nDaniel M. Beswick, \nVijay R. Ramakrishnan, \nRafeul Alam, \nDavid A. Lynch\n

Publicatie 15-06-2020


BackgroundComputed tomography (CT) plays a key role in evaluation of paranasal sinus inflammation, but improved, and standardized, objective assessment is needed. Computerized volumetric analysis has benefits over visual scoring, but typically relies on manual image segmentation, which is difficult and time‐consuming, limiting practical applicability. We hypothesized that a convolutional neural network (CNN) algorithm could perform automatic, volumetric segmentation of the paranasal sinuses on CT, enabling efficient, objective measurement of sinus opacification. In this study we performed initial clinical testing of a CNN for fully automatic quantitation of paranasal sinus opacification in the diagnostic workup of patients with chronic upper and lower airway disease.MethodsSinus CT scans were collected on 690 patients who underwent imaging as part of multidisciplinary clinical workup at a tertiary care respiratory hospital between April 2016 and November 2017. A CNN was trained to perform automatic segmentation using a subset of CTs (n = 180) that were segmented manually. A nonoverlapping set (n = 510) was used for testing. CNN opacification scores were compared with Lund‐MacKay (LM) visual scores, pulmonary function test results, and other clinical variables using Spearman correlation and linear regression.ResultsCNN scores were correlated with LM scores (rho = 0.82, p < 0.001) and with forced expiratory volume in 1 second (FEV1) percent predicted (rho = −0.21, p < 0.001), FEV1/forced vital capacity ratio (rho = −0.27, p < 0.001), immunoglobulin E (rho = 0.20, p < 0.001), eosinophil count (rho = 0.28, p < 0.001), and exhaled nitric oxide (rho = 0.40, p < 0.001).ConclusionSegmentation of the paranasal sinuses on CT can be automated using a CNN, providing truly objective, volumetric quantitation of sinonasal inflammation.

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Chronic rhinosinusitis: assessment of changes in nociceptive neurons

\nStijn Bogaert, \nKoen Van Crombruggen, \nGabriele Holtappels, \nNatalie De Ruyck, \nNicole Suchonos, \nJonas Jae‐Hyun Park, \nClaus Bachert\n

Publicatie 07-06-2020


BackgroundPain is a major symptom of chronic rhinosinusitis (CRS). It is mainly associated with CRS without nasal polyps (CRSsNP) and has a major impact in the decision to move on to surgery. Patients with CRS with nasal polyps (CRSwNP) are characterized by trigeminal hypoesthesia and suffer from less pain. The aim of this study was to investigate whether CRS induces alterations in the peripheral nociceptive neurons, mainly focusing on quantitative changes.MethodsSinus mucosa and inferior turbinate (IT) samples were obtained from patients with CRS, and IT tissue of healthy patients served as controls. Reverse transcription quantitative polymerase chain reaction (RT‐qPCR) was performed for neuronal markers including CNTNAP2, FAM19A1, GFRA2, NEFH, NTRK1, PLXNC1, RET, SCN10A, SCN11A, TRPV1, and PGP 9.5; enzyme‐linked immunosorbent assay (ELISA) was performed for KCNK18, SCN10A, MRGPRD, and MAP2. For PGP 9.5, immunohistochemistry was additionally used to analyze tissue slides.ResultsWe included 35 patients with CRSsNP, 47 patients with CRSwNP, and 18 control patients. No differences in expression of the neuronal markers were observed between CRSsNP, CRSwNP, and controls. SCN10A was the only marker exclusively expressed on nociceptive neurons in sinus tissue. No histological difference in nerve fibers was observed between sinus mucosa of both phenotypes.ConclusionOur results indicate that the nociceptive nerve density in CRSwNP is not lower than in CRSsNP, as was assumed previously. The nociceptive neurons in sinonasal mucosa cannot be classified into subtypes due to the lack of specificity of the respective marker genes. Our findings question the generally accepted claim that nasal polyp tissue does not contain any nerves.

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Use of high‐fidelity 3‐dimensional–printed models for training novice residents in basic nasal endoscopic skills

\nDong Dong, \nWentao Liu, \nShuangxia Wu, \nFangyu Cai, \nYue Wang, \nLei Lyu, \nYulin Zhao, \nYanbing Zhang\n

Publicatie 07-06-2020


BackgroundThe use of 3‐dimensional (3D)–printed models is promising in nasal endoscopic technique training. Here, we aimed to develop postsurgical simulants for use in conjunction with 3D‐printed nasal models and to assess their usefulness in helping residents transfer basic endoscopic skills acquired during simulation training to clinical situations.MethodsThe secretion simulant was prepared via a crosslinked reaction between sodium alginate and acrylamide, whereas the packing simulant was prepared using a superabsorbent polymer. After the simulants’ fidelity and utility were evaluated by 5 rhinologists using a 5‐point Likert scale, 46 novice residents were trained using the 3D‐printed nasal models and postsurgical simulants for 2 weeks. A checklist and Global Rating Scale (GRS) were used to assess their performances before and after training, and the time to finish each task was also recorded. Following training, the qualified trainees operated on real patients and were reevaluated.ResultsThe simulants’ similarity and usefulness scored ≥4.0, and the training cost was 28 CNY ($4 USD) per session. Following training, the checklist and GRS scores increased, and the operation time decreased (all p < 0.05). There were no statistical differences between the trainees’ performances on the models with the simulants and on patients (all p > 0.05).ConclusionThe low‐cost simulated secretion and dressing are safe to use. The application of the simulants in conjunction with that of 3D‐printed nasal models in a simulated task setting can help residents in transferring endoscopic skills acquired during simulation teaching to real patients.

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In vitro safety evaluation of a povidone‐iodine solution applied to human nasal epithelial cells

\nMahnaz Ramezanpour, \nJason L.P. Smith, \nAlkis J. Psaltis, \nPeter J. Wormald, \nSarah Vreugde\n

Publicatie 07-06-2020


BackgroundNasal topical treatments can provide an effective method of disease control for patients suffering from chronic rhinosinusitis (CRS). However, some frequently used formulations lack adequate evaluation on their safety. This study investigated the effect of 0.5% povidone‐iodine (Nasodine) on the sinonasal epithelial barrier and ciliated human nasal epithelial cells (HNECs) in vitro.MethodsNasodine was applied to air‐liquid interface (ALI) cultures of primary HNECs from CRS patients. Epithelial barrier structure was assessed by measuring the transepithelial electrical resistance (TEER), paracellular permeability, and immunolocalization of the zona occludens‐1 (ZO‐1) tight junction protein. Toxicity and ciliary beat frequency (CBF) were also studied.ResultsNasodine was not toxic and did not have detrimental effects on the paracellular permeability or CBF. Nasodine did not show a significant reduction in TEER with a 5‐minute exposure; however, with a 30‐minute exposure there was a significant reduction in TEER at 1 hour and at 4 hours after exposure.ConclusionApplication of Nasodine to HNEC‐ALI cultures in vitro for up to 30 minutes was not toxic and did not affect the paracellular permeability or CBF.

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The use of balloon dilation in revision sinus surgery

\nDavid W. Jang, \nDerek D. Cyr, \nKristine Schulz, \nRichard Scher, \nPhil Ryan, \nRalph Abi Hachem, \nDavid L. Witsell\n

Publicatie 29-05-2020


BackgroundRecent studies have demonstrated a dramatic increase in the use of balloon sinus dilation (BSD) in the United States. However, the use of BSD specifically in revision sinus surgery has not been investigated. This study addresses the question of how BSD is utilized as a tool in revision sinus surgery.MethodsData from MarketScan (Truven Health) over a 5‐year period (2012‐2016) were analyzed. Patients who underwent a sinus procedure with a minimum of 2 years of follow‐up were included.ResultsA total of 62,304 patients met inclusion criteria; 6847 (10.99%) underwent revision. Age >55 years, the South geographical region, and medical comorbidities increased the odds of revision on multivariate analysis. For patients undergoing revision, BSD was used 11%, 21%, and 13% of the time for revisions of the maxillary, frontal, and sphenoid sinuses, respectively. For a sinus that underwent revision after an initial BSD, a repeat BSD was done close to 40% of the time.ConclusionBSD is used frequently in the revision setting, especially for the frontal sinus and for patients who had already undergone an initial BSD. Our findings highlight the prevalent role of BSD in revision surgery and the need to evaluate such practices.

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