International Forum of Allergy and Rhinology 2020-10-20

Use of Google Trends to investigate anosmia: Power and pitfalls of infodemiology

\nArthur W. Wu, \nThomas S. Higgins, \nJonathan Y. Ting, \nElisa A. Illing\n

Publicatie 20-10-2020


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Interim analysis of an open‐label randomized controlled trial evaluating nasal irrigations in non‐hospitalized patients with coronavirus disease 2019

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

Publicatie 20-10-2020


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Erratum

Publicatie 19-10-2020


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Impact of novel CFTR modulator on sinonasal quality of life in adult patients with cystic fibrosis

\nJennifer E. Douglas, \nAlyssa M. Civantos, \nTran B. Locke, \nAuddie M. Sweis, \nDenis Hadjiliadis, \nGina Hong, \nDaniel J. Dorgan, \nMichael A. Kohanski, \nJames N. Palmer, \nNithin D. Adappa\n

Publicatie 18-10-2020


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Aspirin desensitization for aspirin‐exacerbated respiratory disease in the era of biologics: Clinical perspective

\nJohn V. Bosso\n

Publicatie 18-10-2020


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Cystic fibrosis: On the cusp of cure?

\nBrent A. Senior\n

Publicatie 18-10-2020


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In reply: Aspirin desensitization for aspirin‐exacerbated respiratory disease in the era of biologics: Clinical perspective

\nJoshua M Levy, \nMerin Kuruvilla\n

Publicatie 15-10-2020


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The clinical implications of microbiome research

\nRichard Douglas\n

Publicatie 13-10-2020


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Nasal mucosal brush biopsy for cat allergy

\nWesley Davison, \nDaniel Alfonso, \nAnjile An, \nWilliam R. Reisacher\n

Publicatie 13-10-2020


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How our specialty can contribute and benefit from COVID‐19 research

\nEugene H Chang\n

Publicatie 12-10-2020


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Solitary chemosensory cells are innervated by trigeminal nerve endings and autoregulated by cholinergic receptors

\nJie Deng, \nLi Hui Tan, \nMichael A. Kohanski, \nDavid W. Kennedy, \nJohn V. Bosso, \nNithin D. Adappa, \nJames N. Palmer, \nJianbo Shi, \nNoam A. Cohen\n

Publicatie 11-10-2020


BackgroundSolitary chemosensory cells (SCCs) in the murine nasal epithelium are discrete specialized cells that respond to irritants and activate trigeminal nerve fibers through the release of acetylcholine (ACh), resulting in local neurogenic inflammation. In addition to releasing ACh, SCCs are the exclusive epithelial source of interleukin (IL)‐25. In humans, SCCs are significantly expanded in sinonasal polyps (NPs). However, the SCC‐trigeminal synapse has yet to be demonstrated in human sinonasal epithelium.MethodsImmunofluorescence for trigeminal nerve fiber markers, nicotinic ACh receptors (nChR), and SCC markers was performed in vibratome sections from polyp and healthy turbinate tissue. Quantitative polymerase chain reaction and immunofluorescence of cultured epithelial cells were used to evaluate the expansion of SCCs. Last, intracellular calcium imaging was used to demonstrate cholinergic signaling in sinonasal epithelial cells.ResultsCalcitonin gene‒related peptide (CGRP) immunostaining was used to identify cholinergic nerve endings, which were only evident in sections from the inferior turbinate and intertwined with SCCs (α‐gustducin‒positive cells). CGRP‐positive nerve endings were not identified in sections from NPs. Human SCCs expressed nChR as well as the ACh synthetic enzyme choline acetyltransferase. Live cell calcium imaging demonstrated functionally active cholinergic signaling in discrete sinonasal epithelial cells, consistent with SCCs. Finally, SCC‐specific genes were dramatically upregulated with pretreatment with IL‐13 and nicotinic agonists.ConclusionSCCs are innervated by trigeminal nerve endings in healthy turbinate tissue but not in NPs. SCCs express ACh receptors as well as choline acetyltransferase and, in the setting of a type 2 inflammatory environment, denervated SCCs dramatically expand with nicotinic stimulation.

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Postoperative placement of an anti‐fibrotic poly L‐lactide electrospun fibrous membrane after sinus surgery

\nTao Zhang, \nWei Wang, \nRuoyu Cheng, \nZiying Tang, \nZhengming Chen, \nWenguo Cui, \nBijun Lian, \nHongliang Zheng, \nHaihong Tang\n

Publicatie 07-10-2020


BackgroundEndoscopic sinus surgery (ESS) is used to treat chronic rhinosinusitis. However, nasal adhesions often develop postoperatively, triggered by chronic inflammation and local fibrosis. A poly L‐lactide (PLLA) electrospun microfibrous membrane is a functional biodegradable material that can be placed on the wound surface to protect the wound and prevent adhesions.MethodsWe divided 24 rabbits randomly into 2 groups, a control operation group (group A) and an operation+PLLA placement group (group B). We investigated the anti‐fibrotic effects of the topical biomaterial after sinus surgery. We placed PLLA fibrous membranes in the sinus cavity of group B rabbits after sinus surgery, and then evaluated changes in the mucosa and in the levels of collagen fibers, interleukin 4 (IL‐4), IL‐8, tumor necrosis factor α (TNF‐α), transforming growth factor β1 (TGF‐β1), α‐smooth muscle actin (α‐SMA), and collagen I (Col I), using morphological and molecular biological methods.ResultsPLLA fibrous membranes did not inhibit the synthesis of messenger RNAs (mRNAs) encoding IL‐4, IL‐8, or TNF‐α, or the protein levels, indicating that the membrane did not have an anti‐inflammatory effect. However, the membrane inhibited the synthesis of mRNAs encoding TGF‐β1, α‐SMA, and Col I, and reduced collagen production. Thus, the nanostructured membrane inhibited fibroblast proliferation.ConclusionThe PLLA membrane had anti‐fibrotic effects, and may be used to prevent fibrosis and adhesions after ESS in human patients.

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Inflammatory features and predictors for postsurgical outcomes in patients with nasal polyps stratified by local and systemic eosinophilia

\nLi Pan, \nBo Liao, \nCui‐Lian Guo, \nJin‐Xin Liu, \nHeng Wang, \nXiao‐Bo Long, \nZheng Liu\n

Publicatie 04-10-2020


BackgroundIn this study we aimed to identify inflammatory patterns and predictors associated with clinical outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients with different blood and tissue eosinophilia.MethodsA total of 535 CRSwNP patients were enrolled, and the expression of 35 biomarkers, together with eosinophil and neutrophil counts in nasal polyps, were analyzed in a subset of 249 patients. Patients were stratified on the basis of blood (≥0.5 × 109/L) and tissue (>10%) eosinophilia. Logistic regression models were applied to identify predictors of uncontrolled disease at least 1 year after surgery. Uncontrolled disease was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020.ResultsAmong 535 patients, 38.5% showed inconsistent blood and tissue eosinophilia. In 249 CRSwNP patients, subjects with concomitant blood and tissue eosinophilia (group 1) showed marked mucosal type 2 inflammation, characterized by high levels of interleukin (IL)‐5, IL‐13, and eotaxin‐1, whereas subjects with normal blood and tissue eosinophil levels (group 4) demonstrated significant local neutrophilic inflammation with high expression of granulocyte colony‐stimulating factor and subjects with selective tissue eosinophilia (group 2) showed intermediate and mixed eosinophilic and neutrophilic inflammation. Subjects with isolated blood eosinophilia (group 3) showed low expression of vascular endothelial growth factor and IL‐10. Asthma, prior sinus surgery, and blood eosinophilia were the top 3 predictors for postsurgical uncontrolled disease. For subgroup analysis, sex in group 1, asthma in group 2, tissue IL‐10 and immunoglobulin E in group 3, and prior sinus surgery in group 4 were the strongest predictors of uncontrolled disease, respectively.ConclusionDifferent blood and tissue eosinophilia revealed distinct tissue inflammatory patterns in CRSwNP patients.

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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 04-10-2020


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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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 04-10-2020


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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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 04-10-2020


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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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 04-10-2020


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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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 04-10-2020


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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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 04-10-2020


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

\nRakesh K. Chandra\n

Publicatie 04-10-2020


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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 04-10-2020


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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 04-10-2020


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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 04-10-2020


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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 04-10-2020


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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 04-10-2020


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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 04-10-2020


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Issue Information

Publicatie 04-10-2020


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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 04-10-2020


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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Stakeholder feedback informs investigations for chronic rhinosinusitis in cystic fibrosis

\nDaniel M. Beswick, \nMilene T. Saavedra\n

Publicatie 29-09-2020


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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 29-09-2020


BackgroundSevere acute respiratory syndrome‒associated coronavirus‐2 (SARS‐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.MethodsA retrospective study was performed in our clinical practice during July 2020 on patients positive for SARS‐CoV‐2 via polymerase chain reaction. All patients were categorized into 3 groups (supertasters, tasters, and 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.ResultsA total of 100 patients (mean, 51 range, 24‐82 years of age; 44 44% women) were assessed. We found that 21 of 100 (21%) were nontasters, 79 of 100 (79%) were tasters, and 0 of 100 (0%) were supertasters (p < 0.001). Twenty‐one of 21 (100%) (p < 0.001) of the patients requiring inpatient admission were classified as nontasters. All 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 nontasters.

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

\nHalil Onder\n

Publicatie 29-09-2020


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Effect of highly effective modulator therapy on quality of life in adults with cystic fibrosis

\nEmily DiMango, \nDaniel B. Spielman, \nJonathan Overdevest, \nClaire Keating, \nSarah Fracasso Francis, \nDavid Dansky, \nDavid A. Gudis\n

Publicatie 28-09-2020


BackgroundElexacaftor/tezacaftor/ivacaftor is a highly effective modulator that improves function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, resulting in improved pulmonary function in patients with cystic fibrosis (CF). We hypothesize that improvements in lung function are associated with improvements in health‐related quality of life and sinonasal health. The aim of this study is to measure the effect of elexacaftor/tezacaftor/ivacaftor on patient‐reported sinonasal and overall quality of life, and to determine the relationship between changes in these 2 outcome measures.MethodsA prospective cohort study was conducted at an accredited adult CF care center. Participants completed the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and the Cystic Fibrosis Questionnaire–Revised (CFQ‐R), a validated patient‐reported outcome metric for CF patients, at baseline and at 3 months after initiation of elexacaftor/tezacaftor/ivacaftor.ResultsForty‐three individuals completed the study. There was significant improvement in nearly all domains of the SNOT‐22 and CFQ‐R after 3 months of therapy. SNOT‐22 improved from 34.8 to 24.4 (p = 0.000003). Mean baseline FEV‐1 improved from 65% to 76% predicted (p = 0.0000005). The greatest effect was seen in those participants previously taking modulator therapy. Linear regression between the change in SNOT‐22 individual domains and the CFQ‐R respiratory domain revealed the strongest correlation between the extranasal domain score and the respiratory domain of the CFQ‐R (R2 = 0.24).ConclusionCF patients taking elexacaftor/tezacaftor/ivacaftor experience a significant improvement in both sinonasal and health‐related quality of life.

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Adjunctive techniques to dacryocystorhinostomy: an evidence‐based review with recommendations

\nMichael Yim, \nPeter‐John Wormald, \nManon Doucet, \nAmarbir Gill, \nTodd Kingdom, \nRichard Orlandi, \nAlison Crum, \nDouglas Marx, \nJeremiah Alt\n

Publicatie 27-09-2020


BackgroundMany adjunctive techniques exist for dacryocystorhinostomy (DCR), with varying levels of supportive evidence.MethodsLiterature from PubMed, EMBASE, and Cochrane Databases was reviewed between January 1990 and January 2020 to examine evidence regarding the utility of adjunctive techniques to DCR, including mucosal flap preservation, concurrent septoplasty, stenting, topical mitomycin C (MMC), and 5‐fluorouracil (5‐FU), as well as perioperative antibiotics and steroids. Recommendations were made based on the evidence found.ResultsSeven adjunctive techniques used in DCR were examined. The literature supported concurrent septoplasty when septal deviation is present. Silicone stents are recommended for external DCR approaches. MMC use is optional in external DCR and revision cases. The literature does not support the routine use of silicone stents or MMC in primary endoscopic DCR. Mucosal flap preservation is optional, with evidence showing comparable results with or without utilization. The level of evidence is limited for topical 5‐FU, as well as perioperative antibiotic and steroid use.ConclusionRecommendations for adjunctive techniques to external and endoscopic DCR surgeries can be made based on the current literature. Higher‐level studies are needed to better optimize perioperative approaches to DCR.

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Systematic review of anterior congenital cephaloceles: open vs endoscopic repair

\nHarrison M. Thompson, \nDo‐Yeon Cho, \nKristen O. Riley, \nJessica W. Grayson, \nBradford A. Woodworth\n

Publicatie 27-09-2020


BackgroundAnterior cephaloceles are rare congenital malformations that have historically been corrected via open approaches. Although the advent of endoscopic endonasal surgery has provided a minimally invasive and theoretically less morbid approach to the anterior skull base, whether endoscopic approaches provide superior treatment outcomes to open techniques has yet to be elucidated. The objective of this study was to systematically review the available literature regarding presentation and outcomes of open vs endoscopic repair of congenital anterior cephaloceles.MethodsA systematic review of the PubMed, Embase, CINAHL, and Cochrane databases was performed on January 15, 2020, to identify studies from the past 50 years reporting cases of congenital anterior cephaloceles. Data on gender, age at operation, imaging modality, cephalocele location, operative approach, and intra‐ and postoperative complications were collected.ResultsNonduplicated data (153 articles) consisted of 781 patients with congenital anterior encephaloceles. Surgical outcomes were reported in 349 patients (222 open approaches, 127 endoscopic approaches), with an average age of 4.6 years. There was a 1.3:1 male‐to‐female ratio. Clinical presentation included nasal obstruction (n = 154), hypertelorism (n = 106), and cleft lip/palate (n = 100). Defects were classified as sincipital (n = 479) or basal (n = 257), with 45 patients broadly classified as anterior. The number of complications experienced per operation was 0.13 for endoscopic and 0.44 for open approaches (p < 0.0001). Mortality was significantly lower for the endoscopic group compared with patients treated with open surgery (0.008 vs 0.05, p < 0.05).ConclusionEndoscopic repair of congenital anterior cephaloceles resulted in decreased postoperative complications and mortality compared with open approaches. ©2020 ARSAAOA, LLC.

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Olfactory cleft polyposis and respiratory epithelial adenomatoid hamartoma in eosinophilic chronic rhinosinusitis

\nKosuke Akiyama, \nYasushi Samukawa, \nHiroshi Hoshikawa\n

Publicatie 27-09-2020


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Efficacy of the exhalation delivery system with fluticasone in patients who remain symptomatic on standard nasal steroid sprays

\nBrent A. Senior, \nRodney J. Schlosser, \nJohn Bosso, \nZachary M. Soler\n

Publicatie 24-09-2020


BackgroundStandard nasal steroid sprays are often first‐line treatment for chronic rhinosinusitis (CRS), but many patients remain symptomatic despite their use. The exhalation delivery system with fluticasone (EDS‐FLU) has been shown to be efficacious in mixed populations of symptomatic patients, but the question remains whether benefits would be similar in those already on traditional steroid sprays. The goal of this study was to compare EDS‐FLU treatment outcomes in patients who have previously failed nasal steroids.MethodsUsing pooled data from the NAVIGATE I and II trials, EDS‐FLU efficacy was compared in the subgroup treated with a conventional nasal steroid at trial entry (mean duration, ≈3 years) to efficacy in the overall study population. Sensitivity analyses were performed for more restrictive definitions of the subgroup changing from prior standard nasal steroids.ResultsOf 482 total subjects, 218 (45.2%) reported using standard nasal steroid sprays at entry (mean duration, 1051 days). Across multiple outcome measures, improvements for “switchers” receiving EDS‐FLU (least squares mean change from baseline vs EDS plus placebo) were comparable with improvements in the overall population. For EDS‐FLU 372 μg, comparable improvements were observed in congestion (−0.73 vs −0.62), rhinorrhea (−0.71 vs −0.57), facial pain/pressure (−0.48 vs −0.41), and sense of smell (−0.35 vs −0.30) at week 4 and 22‐item Sino‐Nasal Outcome Test (−21.01 vs −20.52), Patient Global Impression of Change, and other outcomes at week 16. Results for EDS‐FLU 186 μg were similar.ConclusionEDS‐FLU comparably improves symptoms, irrespective of whether patients are symptomatic while using conventional nasal steroids before treatment.

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

\nBenjamin Verillaud, \nVincent Bedarida, \nMarc‐Antoine Labeyrie\n

Publicatie 24-09-2020


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Superior turbinate management and olfactory outcome after endoscopic endonasal transsphenoidal surgery for pituitary adenoma: a propensity score‒matched cohort study

\nPu Li, \nKai Luo, \nQiuhang Zhang, \nZhenlin Wang\n

Publicatie 16-09-2020


BackgroundSurgical management of the superior turbinate (ST) is required to access the sella in endoscopic endonasal transsphenoidal surgery (EETS) for pituitary adenoma. Two common ST management techniques include partial resection of the ST (PRST) and intentional lateralization of the ST (ILST). Given the concentrated distribution of the olfactory nerve fibers on the medial surface of the ST, in this study we aimed to ascertain whether PRST worsens the objective olfactory outcome when compared with ILST.MethodsA retrospective, propensity score‒matched cohort study was performed at a tertiary referral center. A total of 232 adult patients undergoing EETS for pituitary adenoma were analyzed. The threshold test (STT) and the 12‐item identification test (SIT‐12) from “Sniffin’ Sticks” were administered for separate nostrils preoperatively and 6 months postoperatively.ResultsOf 232 patients, 109 had right‐sided PRST and 123 received right‐sided ILST. Propensity score matching—controlling for olfactory‐related confounding factors, including gender, age, medical comorbidities, surgical technique, and preoperative olfaction—resulted in 74 matched pairs. When comparing the 6‐month postoperative olfactory performance of the right nostril, the STT score was significantly lower in the PRST group than the ILST group (p = 0.036, η2 for effect size estimate = 0.030), but the SIT‐12 scores were similar in the 2 groups (p = 0.325). Overall, the olfactory outcomes for the right nostril did not qualitatively differ between the PRST and ILST groups (p = 0.401).ConclusionDespite its association with threshold impairment, PRST in EETS does not seem to carry an additional risk of postoperative olfactory dysfunction.

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Azithromycin in high‐risk, refractory chronic rhinosinusitus after endoscopic sinus surgery and corticosteroid irrigations: a double‐blind, randomized, placebo‐controlled trial

\nAnastasios Maniakas, \nMarc‐Henri Asmar, \nAxel Eluid Renteria, \nSmriti Nayan, \nSaud Alromaih, \nLeandra Mfuna Endam, \nJohn Sam Sampalis, \nMartin Desrosiers\n

Publicatie 15-09-2020


BackgroundRefractory chronic rhinosinusitis (CRS) remains a significant burden for patients, often leaving them with few therapeutic options that provide low‐morbidity, long‐term, and meaningful symptomatologic and endoscopic disease improvement. Macrolides have long been thought to offer both an immunomodulatory and antimicrobial effect. Our objective was to evaluate the efficacy of low‐dose, long‐term azithromycin in a carefully selected high‐risk population failing appropriate medical therapy of budesonide nasal irrigations (BNIs) and endoscopic sinus surgery (ESS).MethodsA double‐blind, randomized, placebo‐controlled trial was completed in a single tertiary‐care center assessing the addition of 250 mg azithromycin, 3 times per week for 16 weeks, in adults failing ESS and high‐volume BNIs. Associated comorbidities, as well as symptomatologic, microbiologic, and serologic values, were systematically collected.ResultsA total of 128 patients were enrolled and underwent ESS followed by BNI. At the 4‐month post‐ESS visit, 48 patients showed disease persistence and were randomized to azithromycin or placebo. Overall, azithromycin, when compared with placebo, did not show a statistically significant difference in disease clearance (54% vs 33%, respectively; p = 0.146), although patients with disease clearance who were on azithromycin showed significantly better 22‐item Sino‐Nasal Outcome Test score improvements than patients on placebo (18 vs −0.9, respectively; p = 0.046). In a subgroup analysis excluding aspirin‐exacerbated respiratory disease (AERD) patients, azithromycin significantly improved disease clearance when compared with placebo (71% vs 35%, respectively; p = 0.031), with a number needed to treat of 3 (2.8).ConclusionLow‐dose azithromycin is a therapeutic option with few side effects. Its use can show favorable clinical outcomes in this difficult‐to‐treat population, especially if patients are AERD‐negative.

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

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

Publicatie 15-09-2020


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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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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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Olfactory training: what is the evidence?

\nJustin H. Turner\n

Publicatie 03-09-2020


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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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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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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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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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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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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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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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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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