International Forum of Allergy and Rhinology 2020-11-23

Objective sleep measures after endoscopic sinus surgery in patients with chronic rhinosinusitis

\nRyan E. Little, \nJeremiah A. Alt, \nVijay R. Ramakrishnan, \nMichael P. Platt, \nRodney J. Schlosser, \nKristina A. Storck, \nZachary M. Soler\n

Publicatie 23-11-2020


BackgroundPoor sleep quality is common in chronic rhinosinusitis (CRS). Prior studies have demonstrated improvements in patient‐reported measures of sleep quality following endoscopic sinus surgery (ESS). The purpose of this study was to evaluate the effect of ESS on objective sleep parameters and identify any associations between specific objective measures and patient characteristics, comorbidities, and patient‐reported outcome measures (PROMs).MethodsAdults with CRS undergoing ESS were prospectively enrolled from 4 centers across North America. Any subject previously diagnosed with a known primary sleep disorder was excluded. Objective sleep indices were recorded using a portable sleep diagnostic device preoperatively and postoperatively. Patient‐reported outcome instruments were completed including the Pittsburgh Sleep Quality Index (PSQI) and the 22‐item Sino‐Nasal Outcome Test (SNOT‐22).ResultsThirty‐six patients (mean age 47 years, 56% male) completed baseline and postoperative sleep studies with mean ± standard deviation (SD) follow‐up 9.6 ± 7.7 months. Mean PSQI and SNOT‐22 before and after ESS was 10.2 ± 3.9 vs 7.8 ± 4.4 (p = 0.001); and 54.6 ± 14.6 vs 28.5 ± 15.3 (p < 0.001), respectively. Total sleep time, sleep latency, and awakenings after sleep onset did not change following ESS (all p > 0.5) despite improvements in PSQI and SNOT‐22. Changes in PSQI did not correlate with comorbidities or objective sleep indices (all p > 0.1).ConclusionIn this multicenter prospective cohort, objective sleep indices were not improved following ESS for CRS despite significant improvements in patient‐reported sleep quality and CRS‐specific QOL.

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Predictors of survival outcomes in sinonasal squamous cell carcinoma: an analysis of the National Cancer Database

\nNyssa Fox Farrell, \nJess C. Mace, \nKara Y. Detwiller, \nRyan Li, \nPeter E. Andersen, \nTimothy L. Smith, \nDaniel R. Clayburgh, \nMathew Geltzeiler\n

Publicatie 23-11-2020


BackgroundSinonasal squamous cell carcinoma (SNSCC) is a rare malignancy that poses management challenges. Although surgery and chemoradiation therapy (CRT) remain therapeutic mainstays, induction chemotherapy (IC) has emerged as a useful adjunct with locally advanced disease. This study used the National Cancer Data Base (NCDB) to examine treatment outcomes for patients diagnosed with SNSCC.MethodsThe NCDB (2004‐2015) was queried for cases with SNSCC. Multivariate hazard regression modeling was used to identify significant predictors of 24‐month and 60‐month overall survival (OS) including treatment modality.ResultsA total of 3516 patients with SNSCC met inclusion criteria, including 1750 patients (49.8%) treated with surgery ± adjuvant therapy, 1352 (38.5%) treated with definitive radiotherapy (RT) or CRT, 300 (8.5%) who underwent IC followed by definitive CRT, and 114 (3.2%) who received IC followed by surgery and adjuvant therapy. Hazard modeling for confirmed treatment modality significantly associated (p < 0.001) with OS after adjustment. Patients who received surgical intervention ± adjuvant therapy had lower 24‐month and 60‐month mortality risk compared to definitive RT or CRT (hazard ratio HR ≥ 1.97; p < 0.001) or IC followed by definitive CRT (HR ≥ 1.73; p < 0.001). Compared to primary surgery ± adjuvant therapy, patients undergoing IC then surgery had similar 24‐month and 60‐month OS (p ≥ 0.672) after adjustment.ConclusionMultimodality therapy, including surgical intervention, associates with improved OS after multifactorial adjustments. IC followed by surgery associated with improved OS compared to IC, followed by CRT and CRT alone. Study results highlight the utility of surgery toward optimizing OS in patients with SNSCC and demonstrates the potential utility of IC when primary surgical management is not preferred.

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Preprints—expediting access or compromising quality?

\nClaire Hopkins\n

Publicatie 13-11-2020


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Assessing health literacy in rhinologic patients

\nJakob L. Fischer, \nNora L. Watson, \nAnthony M. Tolisano, \nCharles A. Riley\n

Publicatie 13-11-2020


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Fungal sinusitis: a spectrum of disease

\nConnie Ma, \nMatthew W. Ryan, \nBradley F. Marple, \nAshleigh A. Halderman\n

Publicatie 13-11-2020


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Prophylactic and therapeutic topical povidone‐iodine in coronavirus disease 2019 (COVID‐19): What is the evidence?

\nCarol H. Yan, \nBenjamin S. Bleier\n

Publicatie 10-11-2020


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Evaluating inflammation in an obstruction‐based chronic rhinosinusitis model in rabbits

\nAndrea L. Schilling, \nJohn Moore, \nYalcin Kulahci, \nSteven R. Little, \nLora H. Rigatti, \nEric W. Wang, \nStella E. Lee\n

Publicatie 08-11-2020


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Tween 80 and its derivative oleic acid promote the growth of Corynebacterium accolens and inhibit Staphylococcus aureus clinical isolates

\nMartha Alemayehu Menberu, \nAndrew James Hayes, \nSha Liu, \nAlkis James Psaltis, \nPeter‐John Wormald, \nSarah Vreugde\n

Publicatie 06-11-2020


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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 05-11-2020


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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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 05-11-2020


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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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 05-11-2020


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

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

Publicatie 05-11-2020


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

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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 05-11-2020


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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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 05-11-2020


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

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

Publicatie 05-11-2020


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

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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 05-11-2020


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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 05-11-2020


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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 05-11-2020


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Olfactory training: what is the evidence?

\nJustin H. Turner\n

Publicatie 05-11-2020


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Issue Information

Publicatie 05-11-2020


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Erratum

Publicatie 05-11-2020


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The clinical effect of psychosomatic interventions on empty nose syndrome secondary to turbinate‐sparing techniques: a prospective self‐controlled study

\nPeng Tian, \nJunwu Hu, \nYun Ma, \nChao Zhou, \nXiang Liu, \nHua Dang, \nHua Zou\n

Publicatie 05-11-2020


BackgroundIndividuals affected by empty nose syndrome secondary to turbinate‐sparing techniques (ENS‐type) experience decreased productivity and lifestyle disruption owing to considerable nasal‐associated discomfort. This study aimed to evaluate the effect of psychosomatic intervention on ENS‐type.MethodsA prospective self‐controlled study was conducted, and 28 patients suffering from ENS‐type who met the diagnostic criteria for somatic symptom disorder (SSD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM‐5) received cognitive and behavioral therapy (CBT) plus antidepressants. Nasal symptom burden was evaluated using the 25‐item Sino‐Nasal Outcome Test (SNOT‐25). Somatic symptom burden, anxiety severity, and depression severity were assessed by the 25‐item Patient Health Questionnaire (PHQ‐15), the 9‐item PHQ (PHQ‐9), and the 7‐item Generalized Anxiety Disorder (GAD‐7) scale, respectively. Patient assessments were completed prior to treatment and 3 and 12 months after the intervention.ResultsThe total scores of the SNOT‐25 declined posttreatment, showing a significant difference at the 3‐month and 12‐month follow‐ups compared with the baseline scores (p < 0.001). The severity of the 5 most common subjective symptoms, including “nose is too open,” “waking up at night,” “lack of a good nights sleep,” “difficulty falling asleep,” and “reduced concentration,” declined significantly at 3 and 12 months posttreatment compared to baseline levels. Statistically significant changes in the PHQ‐15, PHQ‐9, and GAD‐7 scores were observed at 3 and 12 months posttreatment compared to baseline scores (p < 0.001).ConclusionThis study showed that some patients with ENS‐type meeting the diagnostic criteria for SSD might benefit from psychiatric treatment.

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The clinical effect of psychosomatic interventions on empty nose syndrome secondary to turbinate‐sparing techniques: A prospective self‐controlled study

\nXimena Maul, \nAndrew Thamboo\n

Publicatie 05-11-2020


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Association of bone mineral density of the anterior cranial base, obesity, and spontaneous cerebrospinal fluid rhinorrhea

"\nChristopher M. Low, \nDong Kun Kim, \nAlyssa J. Smith, \nLinda X. Yin, \nByron M. Smith, \nJanalee K. Stokken, \nErin K. OBrien, \nMichael J. Link, \nJamie J. Van Gompel, \nGarret Choby\n"

Publicatie 05-11-2020


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Topical irrigation against gravity may lead to better sinus penetration

\nKanghyun Kim, \nBradley A. Otto, \nAlexander A. Farag, \nKai Zhao\n

Publicatie 03-11-2020


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Machine learning evaluates improvement in sinus computed tomography opacification with CFTR modulator therapy

\nDaniel M. Beswick, \nStephen M. Humphries, \nConnor D. Balkissoon, \nEszter K. Vladar, \nVijay R. Ramakrishnan, \nDavid A. Lynch, \nJennifer L. Taylor‐Cousar\n

Publicatie 02-11-2020


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Effect of nasal fluticasone exhalation delivery system on Eustachian tube dysfunction

\nArthur W. Wu, \nRandall A. Ow, \nDennis M. Tang, \nJames Mirocha, \nEvan S. Walgama, \nElisa A. Illing, \nMartin L. Hopp, \nJonathan Y. Ting, \nThomas S. Higgins\n

Publicatie 02-11-2020


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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 02-11-2020


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Inflammation‐driven vascular dysregulation in chronic rhinosinusitis

\nNitish Khurana, \nAbigail Pulsipher, \nJolanta Jedrzkiewicz, \nShaelene Ashby, \nChelsea E. Pollard, \nHamidreza Ghandehari, \nJeremiah A. Alt\n

Publicatie 02-11-2020


BackgroundAltered neovascularity is typically observed in chronic inflammatory diseases with overlapping pathophysiology to that observed in chronic rhinosinusitis (CRS). However, characterization of these inflammatory‐induced vascular‐mediated changes in CRS is limited. Understanding the underlying vascular changes in CRS will allow for strategic design and development of new drug‐delivery technologies that exploit vascular permeability for increased extravasation into the target sinonasal tissues.MethodsPatients with CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) and non‐CRS controls were enrolled in this prospective, observational study. The extent of angiogenesis in tissue was characterized using immunohistochemical and multiplex gene expression analyses. Vascular permeability, interendothelial junction structures, and endothelial barrier morphology were evaluated using transmission electron microscopy.ResultsSinonasal vascularity was increased significantly in CRSsNP and CRSwNP (p < 0.05) when compared with controls, as assessed by enumerating the platelet endothelial cell adhesion molecule (PECAM‐1)‒positive blood vessels. Pro‐angiogenic gene expression, including PECAM1 and platelet‐activating factor receptor, was elevated significantly in patients with CRSwNP when compared with controls (p < 0.05). The fenestration sizes between endothelial cells (17‐280 nm) were larger in CRSwNP compared with CRSsNP (10‐33 nm) patients and controls (4‐12 nm). Global thinning of the endothelial cell lining was observed in CRS patients but not in controls.ConclusionSignificant increases in vascularity, the pro‐angiogenic gene, and protein expression and blood vessel morphogenesis were observed in CRS patients compared with controls. In addition, fenestration sizes between interendothelial junction structures were larger in CRS patients than in controls, suggesting inflammation‐driven vascular dysregulation in CRS pathology.

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The association of frailty with olfactory and gustatory dysfunction in older adults: a nationally representative sample

\nIsaac A. Bernstein, \nChristopher R. Roxbury, \nSandra Y. Lin, \nNicholas R. Rowan\n

Publicatie 01-11-2020


BackgroundOlfaction and gustation are associated with age‐related decline. Deficits in these chemosenses have been associated with significant comorbidities. Meanwhile, frailty, defined as a reduced physiological reserve, is well correlated with mortality and worse health outcomes. We sought to analyze a nationally representative patient population to determine the association between chemosensory dysfunction and frailty.MethodsCross‐sectional analysis of U.S. National Health and Nutrition Examination Survey (NHANES) 2013‐2014 was performed, using multivariate logistic regression to examine the association between chemosensory dysfunction and frailty in adults aged ≥40 years (n = 3547). Self‐reported olfactory dysfunction (sOD) and gustatory dysfunction (sGD), and measured olfactory dysfunction (mOD) and gustatory dysfunction (mGD) were assessed for all participants. Frailty was operationalized using a 39‐item frailty index (FI) and stratified into 4 groups using validated cutoffs.ResultsParticipants with sOD and mOD had significantly higher mean FI scores (sOD: 0.18 vs 0.13, p < 0.001; mOD: 0.20 vs 0.14, p < 0.001), whereas subjects with sGD, but not mGD, had higher mean FI scores (sGD: 0.21 vs 0.13, p < 0.001; mGD: 0.14 vs 0.14, p = 0.953). Multivariate logistic regression demonstrated frail participants had significantly greater odds of sGD (odds ratio OR 4.11; 95% confidence interval CI, 3.46 to 4.88), sOD (OR 2.35; 95% CI, 1.98 to 2.78), and mOD (OR 1.58; 95% CI, 1.22 to 2.05), but not mGD (OR 1.21; 95% CI, 0.91 to 1.61). This association was strongest in the frailest group.ConclusionSelf‐reported chemosensory dysfunction and mOD are independently associated with measures of frailty, suggesting a novel method to assess or predict frailty.

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Endoscopic management of postradiation skull base osteoradionecrosis

\nAviv Spillinger, \nKelley Park, \nKerolos Shenouda, \nAdam J Folbe\n

Publicatie 01-11-2020


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

\nEugene H. Chang\n

Publicatie 27-10-2020


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IFAR reviewers: best of 2020

\nTimothy L. Smith\n

Publicatie 27-10-2020


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International Consensus Statement: Spontaneous Cerebrospinal Fluid Rhinorrhea

\nChristos Georgalas, \nAmanda Oostra, \nShahzada Ahmed, \nPaolo Castelnuovo, \nIacopo Dallan, \nWouter Furth, \nRichard J. Harvey, \nPhilippe Herman, \nDimitrios Kombogiorgas, \nDavide Locatelli, \nCem Meco, \nJim N. Palmer, \nOtavio Piltcher, \nAnshul M. Sama, \nHesham Saleh, \nRaj Sindwani, \nThibaut Van Zele, \nBradford A. Woodworth\n

Publicatie 25-10-2020


BackgroundThe association between spontaneous cerebrospinal fluid (CSF) leak/rhinorrhea and idiopathic intracranial hypertension (IIH) has been increasingly recognized over the last years. However, considerable variability of opinion regarding the assessment, investigations, and management of patients with spontaneous CSF rhinorrhea remains.MethodsA consensus group was formed from experts from Europe, Asia, Australia, South and North America. Following literature review and open discussions with members of the panel, a set of 61 statements was produced. A modified Delphi method was used to refine expert opinion with 3 rounds of questionnaires and a consensus group meeting in Santo‐Rhino meeting in September 2019.ResultsFifty statements (82% of total) on spontaneous CSF leak and IIH reached consensus. In 38 of 50 statements, the median response was 7 (strongly agree) and in the 12 remaining statements the median response was 6 (agree). Eleven statements were excluded because they did not reach consensus and one new statement was added during SantoRhino meeting. The final statements refer to patient history and clinical examination ("History taking should include presence of headache, tinnitus and visual defects"), investigations (role of Thin Slice Computed Tomography and CISS/FLAIR sequences in Magnetic Resonance Imaging), principles of management (watchful waiting or measures to reduce ICP are supplementary but cannot subsitute surgical closure), surgical technique, intraoperative, early postoperative and long term management.ConclusionWe present fifty consensus statements on the diagnosis, investigation, and management of spontaneous CSF rhinorrhea based on the currently available evidence and expert opinion. Although by no means comprehensive and final, we believe they can contribute to the standardization of clinical practice. Early diagnosis, prompt surgical closure of the defect, assesment for and treatment of potentially co‐existing idiopathic intracranial hypertension in a comprehensive multidisciplinary approach are essential in order to successfully manage spontaneous CSF rhinorrhea, reduce associated morbidity and prevent recurrence.

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Health and social effects of the COVID‐19 pandemic on patients with cystic fibrosis

\nBeth Osterbauer, \nSteven Hasday, \nMatthew Lin, \nDanieli Salinas, \nThomas Keens, \nJeffrey Koempel, \nElisabeth H. Ference\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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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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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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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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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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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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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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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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Comment on “Investigation of topical intranasal cocaine for sinonasal procedures: a randomized, phase III clinical trial”

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

Publicatie 23-08-2020


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Reply to: 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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