International Forum of Allergy and Rhinology 2020-12-22

Exclusively endoscopic endonasal resection of benign orbital tumors: a systematic review and meta‐analysis

Aria Jafari, Manuela Sneidern, Ashton E. Lehmann, Sarek A. Shen, Sachie Shishido, Suzanne K. Freitag, Benjamin S. Bleier

Publication date 22-12-2020


Background The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) classification system was developed to standardize prospective outcome analysis following orbital cavernous hemangioma (OCH) resection. The goal of this study was to retroactively apply the CHEER system to all prior existing reports of endoscopic resection of primary benign orbital tumors (BOTs) to: (1) compare patient presentations, perioperative characteristics, and outcomes between OCH and other BOTs; and (2) determine whether the CHEER categorization regime could be expanded to other BOTs.
MethodsA systematic review of studies reporting exclusively endoscopic resections of OCH and other BOTs (eg, solitary fibrous tumor, schwannoma, and meningioma) was performed. Patient, tumor characteristics, and operative outcomes were recorded. All tumors with adequate reporting were retrospectively assigned a CHEER stage. Outcomes were compared using chi‐square or Fishers exact tests.
Results Ninety‐three studies met inclusion criteria, and sufficient data were available in 36 studies, comprising 105 tumors (n = 87 OCHs; n = 18 other BOTs). Baseline patient and tumor characteristics, as well as intraoperative and short‐term postoperative outcomes were not significantly different between OCHs and other BOTs. Long‐term outcomes (eg, visual deficits, diplopia, eye position, and recurrence) also did not differ when controlling for CHEER stage.
Conclusion This review represents the largest collection of outcomes data following exclusively endoscopic endonasal resection of BOTs. Short‐term and long‐term outcomes appear similar between OCHs and other BOTs. These results suggest that exclusively endoscopic resection of orbital tumors may be effective in a range of benign pathologies. Furthermore, these results support a broader application of the CHEER system to other benign primary orbital tumors.

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Nasal preparation with local anesthetic should be considered an aerosol‐generating procedure

Rana S. Dhillon, Lana V. Nguyen, Wagih Abu Rowin, Ruhi S. Humphries, Kevin Kevin, Jason D. Ward, Andrew Yule, Tuong D. Phan, David Wynne, Peter M. McNeill, Nicholas Hutchins, David A. Scott, Yi Chen Zhao

Publication date 21-12-2020


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Prophylactic antibiotics after endoscopic sinus surgery for chronic rhinosinusitis: a randomized, double‐blind, placebo‐controlled noninferiority clinical trial

Ashton E. Lehmann, Aaishah R. Raquib, Shan H. Siddiqi, Josh Meier, Marlene L. Durand, Stacey T. Gray, Eric H. Holbrook

Publication date 19-12-2020


Background Surgeons commonly prescribe prophylactic antibiotics after endoscopic sinus surgery (ESS), yet minimal data exist to support this practice. In this study we aimed to assess the impact of post‐ESS antibiotics on infection, quality of life (QOL), and endoscopic scores.
Methods This was a randomized, double‐blind, placebo‐controlled, noninferiority trial comparing amoxicillin‐clavulanate vs placebo after ESS (NCT01919411, Clinical Trials.gov). Adults (N = 77) with chronic rhinosinusitis (CRS) refractory to appropriate medical therapy who underwent ESS were randomized to antibiotics (N = 37) or placebo (N = 40) and followed clinically (mean ± standard deviation: 1.3 ± 0.3 and 8.8 ± 3.9 weeks postoperatively). At baseline and follow‐up, QOL was measured with 22‐item Sino‐Nasal Outcome Test questionnaires and Lund‐Kennedy endoscopic scores were evaluated. Outcomes were analyzed with repeated‐measures analysis of variance and analysis of covariance and z tests for proportions.
Results Placebo was noninferior to antibiotic prophylaxis with regard to postoperative SNOT‐22 scores (β = 0.18, 2‐tailed p < 0.05). There were no significant differences between the antibiotic and placebo groups in LK score trajectories over time (p = 0.63) or in postoperative infection rates (2.6% vs 2.4%, respectively; p = 0.96). The rate of diarrhea was significantly higher in the antibiotic group (24.3% vs 2.5%; relative risk = 10.8; p = 0.02).
Conclusion Although statistically underpowered, the results suggest placebo was noninferior to prophylactic antibiotics after ESS for CRS regarding postoperative sinonasal‐specific QOL. There were no significant differences in postoperative endoscopic scores or rates of infection, but the rate of diarrhea was significantly higher in the antibiotic group. These findings add to the growing evidence that routine use of prophylactic postoperative antibiotics does not improve outcomes post‐ESS and significantly increases the rate of diarrhea.

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Postoperative antibiotics: preparing for the leap of faith

Edward D. McCoul

Publication date 19-12-2020


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The cost of rhinitis in the United States: a national insurance claims analysis

Lauren T. Roland, Sarah K. Wise, Heqiong Wang, Patrick Zhang, Christina Mehta, Joshua M. Levy

Publication date 10-12-2020


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Aerosol‐scavenging isolation barrier mitigates exposure risk during endonasal procedures in coronavirus‐2019

Alan D. Workman, Benjamin S. Bleier, Tofigh Sayahi, Kerry E. Kelly, Phillip C. Song

Publication date 10-12-2020


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The 15° reverse Trendelenburg position can improve visualization without impacting cerebral oxygenation in endoscopic sinus surgery—A prospective, randomized study

Wenjing Yang, Guyan Wang, He Li, Xing Yan, Yaoyao Ren, Yue Wang, Haili Hu, Xiaoli Song, Ying Wan, Chengshuo Wang, Hongfei Lou, Qian Huang, Xiangdong Wang, Luo Zhang

Publication date 07-12-2020


Background In this study we compared intraoperative bleeding and regional cerebral oxygenation in patients with different degrees of the reverse Trendelenburg position (RTP) during endoscopic sinus surgery (ESS).
Methods In total, 120 patients with chronic rhinosinusitis treated by ESS were randomly assigned to the following 4 groups: a horizontal position (HP) group, and 5°, 10°, and 15° RTP (5‐RTP, 10‐RTP, and 15‐RTP, respectively) groups. The primary outcome was the Boezaart grading scale (BS). The cerebral oxygen saturation (ScO2), total blood loss, numerical rating scale (NRS) scores, and complications were also recorded.
Results The median BS values in the HP, 5‐RTP, 10‐RTP, and 15‐RTP groups were 2.0, 2.0, 2.1, and 1.7, respectively. Multiple pairwise comparisons of the BS showed significant differences between the 15‐RTP group and the other 3 groups (HP, 5‐RTP, and 10‐RTP). Regarding the NRS and bleeding rate, significant differences were found between the HP and 15‐RTP groups. No difference was found in ScO2 among the 4 groups, and no cerebral desaturation events occurred in any group. No complications, including vital organ (heart, brain, and kidney) dysfunction problems, were reported in this study during hospitalization.
Conclusion Compared with HP, 5‐RTP, and 10‐RTP, 15‐RTP can improve visual clarity during ESS, and ScO2 is not affected by the degree of RTP. No cerebral deoxygenation or vital organ dysfunction was observed in this study. Therefore, we recommend 15‐RTP with moderate deliberate hypotension for ESS.

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

Kosuke Akiyama, Yasushi Samukawa, Hiroshi Hoshikawa

Publication date 06-12-2020


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

Beth Osterbauer, Steven Hasday, Matthew Lin, Danieli Salinas, Thomas Keens, Jeffrey Koempel, Elisabeth H. Ference

Publication date 06-12-2020


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Systematic review of anterior congenital cephaloceles: open vs endoscopic repair

Harrison M. Thompson, Do‐Yeon Cho, Kristen O. Riley, Jessica W. Grayson, Bradford A. Woodworth

Publication date 06-12-2020


Background Anterior 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 Pub Med, 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.
Results Nonduplicated 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).
Conclusion Endoscopic repair of congenital anterior cephaloceles resulted in decreased postoperative complications and mortality compared with open approaches. ©2020 ARSAAOA, LLC.

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

Pu Li, Kai Luo, Qiuhang Zhang, Zhenlin Wang

Publication date 06-12-2020


Background Surgical 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.
Results Of 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).
Conclusion Despite its association with threshold impairment, PRST in EETS does not seem to carry an additional risk of postoperative olfactory dysfunction.

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

Vincent Bedarida, Marc‐Antoine Labeyrie, Michael Eliezer, Jean‐Pierre Saint‐Maurice, Clément Jourdaine, Sergios Gargalas, Philippe Herman, Emmanuel Houdart, Benjamin Verillaud

Publication date 06-12-2020


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.
Methods In 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.
Results Twenty‐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.
Conclusion In 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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Postoperative placement of an anti‐fibrotic poly L‐lactide electrospun fibrous membrane after sinus surgery

Tao Zhang, Wei Wang, Ruoyu Cheng, Ziying Tang, Zhengming Chen, Wenguo Cui, Bijun Lian, Hongliang Zheng, Haihong Tang

Publication date 06-12-2020


Background Endoscopic 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.
Methods We 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.
Conclusion The PLLA membrane had anti‐fibrotic effects, and may be used to prevent fibrosis and adhesions after ESS in human patients.

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

Lifeng Li, Nyall R. London, Xiaohong Chen, Daniel M. Prevedello, Ricardo L. Carrau

Publication date 06-12-2020


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

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Endoscopic management of postradiation skull base osteoradionecrosis

Aviv Spillinger, Kelley Park, Kerolos Shenouda, Adam J Folbe

Publication date 06-12-2020


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

Kyle S. Kimura, Michael H. Freeman, Bronson C Wessinger, Veerain Gupta, Quanhu Sheng, Li Ching Huang, Kate Von Wahlde, Suman R. Das, Naweed I. Chowdhury, Justin H. Turner

Publication date 06-12-2020


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

Dong Dong, Fangyu Cai, Shuman Huang, Xiaoyuan Zhu, Jing Geng, Jia Liu, Lei Lv, Yanbing Zhang, Yulin Zhao

Publication date 06-12-2020


Background Intranasal 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).
Results After 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).
Conclusion The 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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Use of high‐fidelity 3‐dimensional–printed models for training novice residents in basic nasal endoscopic skills

Dong Dong, Wentao Liu, Shuangxia Wu, Fangyu Cai, Yue Wang, Lei Lyu, Yulin Zhao, Yanbing Zhang

Publication date 06-12-2020


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

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

Justin H. Turner

Publication date 06-12-2020


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

Leigh J Sowerby, Zara M. Patel

Publication date 06-12-2020


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Management of epistaxis secondary to extracranial anterior ethmoid artery pseudoaneurysm

Matthew Hill, Nyssa Farrell, Rohan Verma, John Ng, Mathew Geltzeiler

Publication date 06-12-2020


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

Eugene H. Chang

Publication date 06-12-2020


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

Carol H. Yan, Benjamin S. Bleier

Publication date 06-12-2020


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Issue Information

Publication date 06-12-2020


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Characterizing the complexity of frontal endoscopic sinus surgery: a multi‐institutional, prospective, observational trial

Philip G. Chen, Joshua M. Levy, Garret Choby, Kristine Smith, William C. Yao, Ashleigh Halderman, Gretchen M. Oakley, Joseph Brunworth, Jeremiah A. Alt

Publication date 04-12-2020


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Olfactory cleft mucus proteome in chronic rhinosinusitis: a case‐control pilot study

Zachary M. Soler, Rodney J. Schlosser, Jennifer K. Mulligan, Timothy L. Smith, Jess C. Mace, Vijay R. Ramakrishan, Kim Norris‐Caneda, Jennifer R. Bethard, Lauren E. Ball

Publication date 04-12-2020


Background Mechanisms of smell loss in chronic rhinosinusitis (CRS) are still unclear and likely multifactorial. Little attention has been given to olfactory cleft (OC) mucus proteins involved in odorant binding and metabolizing enzymes and their potential role in smell loss.
Methods Mucus from the OC was sampled from patients with CRS (n = 20) and controls (n = 10). Liquid chromatography and mass spectrometry were performed, followed by data processing so that protein groups could be identified, quantified, and compared. Hierarchical clustering and bioinformatic analysis were performed on significantly different proteins to explore for enrichment in known biologic pathways.
ResultsA total of 2514 proteins were found in OC mucus from all 30 subjects. Significant differences in protein abundance were found between CRS and controls, including both CRSsNP (n = 351 proteins; log2 fold change range: –3.88 to 6.71) and CRSwNP (n = 298 proteins; log2 fold change range: –4.00 to –6.13). Significant differences were found between patients with normosmia and those with dysosmia (n = 183; log2 fold change range: –3.62 to –2.16) and across groups of interest for a number of odorant binding proteins and metabolizing enzymes.
ConclusionOC mucous in CRS displays a rich and abundant array of proteins, many of which have been implicated in odorant transport and metabolization in animal studies. Significant differences in the olfactory mucus proteome were seen between CRS subtypes and controls, as well as between those with normal and abnormal olfaction. Further study should confirm these findings and explore the role individual proteins play in odorant transport and metabolization. ©2020 ARSAAOA, LLC.

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Gender‐related differences in outcomes after endoscopic sinus surgery

Michela Borrelli, Martin L. Hopp, Alexis Desales, Jonathan Y. Ting, Elisa A. Illing, Thomas S. Higgins, Arthur W. Wu

Publication date 04-12-2020


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Rhinologic disease and its impact on sleep: a systematic review

Jacob Fried, Erick Yuen, Andraia Li, Kathy Zhang, Shaun A. Nguyen, David A. Gudis, Nicholas R. Rowan, Rodney J. Schlosser

Publication date 04-12-2020


Background Rhinologic disease can be responsible for systemic symptoms affecting mood, cognition, and sleep. It is unclear whether sleep disturbance in specific rhinologic disorders (chronic rhinosinusitis CRS, rhinitis, and nasal septal deviation NSD) is an obstructive phenomenon or due to other mechanisms. In this review we examine the impact of CRS, rhinitis, and NSD on objective and subjective sleep outcome metrics and draw comparisons to normal controls and patients with known obstructive sleep apnea (OSA).
MethodsA systematic review of 4 databases (Pub Med, Scopus, Cochrane Library, and Web of Science) was performed. Studies reporting on objective (apnea‐hypopnea index AHI, respiratory disturbance index RDI, oxygen nadir) and subjective (Epworth Sleepiness Scale EpSS, Pittsburgh Sleep Quality Index PSQI, Fatigue Severity Scale FSS) sleep parameters and disease‐specific patient‐reported outcome measures (PROMs; 22‐item Sino‐Nasal Outcome Test SNOT‐22, Rhinoconjunctivitis Quality of Life Questionnaire RQLQ, Nasal Obstruction Symptom Evaluation NOSE) were included.
Results The database search yielded 1414 unique articles, of which 103 were included for analysis.
Baseline PROMs were at the high end of normal to abnormal for all 3 conditions: EpSS: CRS (9.8 ± 4.0), rhinitis (9.7 ± 4.3), and NSD (8.9 ± 4.6); and PSQI: CRS (11.0 ± 4.5), rhinitis (6.1 ± 3.7), and NSD (8.6 ± 3.5).
Objective measures demonstrated a mild to moderate OSA in the studied diseases: AHI: CRS (10.4 ± 11.5), rhinitis (8.6 ± 8.8), and NSD (13.0 ± 6.9). There were significant differences when compared with reported norms in all measured outcomes (p < 0.001).
Conclusion Sleep quality is impacted by rhinologic (CRS, rhinitis, NSD) disease. There is likely a mild obstructive component contributing to poor sleep, but other contributing factors may be involved.

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Impact of clinical practice guidelines: trends in antibiotic prescriptions for acute rhinosinusitis

Mark A. Arnold, Brian Nicholas

Publication date 04-12-2020


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Establishment and characterization of an inverted papilloma–associated sinonasal squamous cell carcinoma cell line

Wade Swenson, Kimberly A. Miller, Beverly Wuertz, W. Nicholas Jungbauer, Frank G. Ondrey

Publication date 30-11-2020


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Inferior meatus augmentation procedure (IMAP) normalizes nasal airflow patterns in empty nose syndrome patients via computational fluid dynamics (CFD) modeling

Jennifer Malik, Sachi Dholakia, Barak M. Spector, Angela Yang, Dayoung Kim, Nicole A. Borchard, Andrew Thamboo, Kai Zhao, Jayakar V. Nayak

Publication date 29-11-2020


Background Empty nose syndrome (ENS) is a controversial upper airway disorder most commonly associated with tissue loss from the inferior turbinates. The inferior meatus augmentation procedure (IMAP) has been shown to effectively reduce ENS symptoms in a durable manner, but the precise mechanisms that may govern this symptomatic improvement remain unknown.
Methods Five patients with ENS who underwent bilateral IMAP via submucosal costal cartilage implant were assessed. Pre‐implant and 6 months post‐implant computed tomography (CT) imaging for each ENS patient was analyzed in a blinded fashion using computational fluid dynamics (CFD) modeling to investigate intrapatient changes in airflow parameters.
Results Following surgery, ENS patients have significantly improved symptoms as indexed by Empty Nose Syndrome 6‐Item Questionnaire (ENS6Q) scoring (pre‐implant: 14.00 ± 4.06 mean ± standard deviation; 95% confidence interval CI, 10.44 to 17.56; post‐implant: 4.8 ± 2.77; 95% CI, 2.37 to 7.23; Cohens d = 2.64; p = 0.02). Using CFD, a significant shift in nasal airflow patterns was observed, where airflow deviates away from the middle meatus upon hitting the implant (pre‐implant: 67.13% ± 11.14%; 95% CI, 60.22% to 74.04%; post‐implant: 46.18% ± 12.81%; 95% CI, 38.23% to 54.12%; d = 1.74; p < 0.05) toward the inferior meatus (pre‐implant: 30.55% ± 11.29%; 95% CI, 23.55% to 37.55%; post‐implant: 42.59% ± 9.60%; 95% CI, 36.63 to 48.54%; d = 1.14; p < 0.05). No significant changes were found in nasal resistance (pre‐implant: 0.102 ± 0.015; 95% CI, 0.092 to 0.112 Pa*s/mL; post‐implant: 0.105 ± 0.041; 95% CI, 0.081 to 0.130 Pa*s/mL). In addition, the improvement of ENS6Q scoring significantly correlated with percent reduction in aberrant airflow through the middle meatus (R2 = 0.60, p = 0.04).
Conclusion This study supports our prior working hypothesis that disordered vectors of nasal airflow congregate in the middle meatus contribute to ENS symptoms, not nasal resistance. Moreover, these data illuminate a paradoxical, but consistent, restoration of nasal airflow to the inferior meatus following the replacement of turbinate tissue volume in the inferior meatus via IMAP surgery, potentially due to the Coandă effect.

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Convolutional neural network algorithms for computed tomography scans of chronic rhinosinusitis subtypes

David A. Gudis

Publication date 26-11-2020


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International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Richard R. Orlandi, Todd T. Kingdom, Timothy L. Smith, Benjamin Bleier, Adam DeConde, Amber Luong, David M. Poetker, Zachary Soler, Kevin C. Welch, Sarah K. Wise, Nithin Adappa, Jeremiah A. Alt, Wilma Terezinha Anselmo‐Lima, Claus Bachert, Fuad M. Baroody, Pete S. Batra, Manuel Bernal‐Sprekelsen, Daniel Beswick, Neil Bhattacharyya, Rakesh K. Chandra, Eugene Chang, Alexander Chiu, Naweed Chowdhury, Martin J Citardi, Noam A. Cohen, David B. Conley, John DelGaudio, Martin Desrosiers, Richard Douglas, Jean Anderson Eloy, Wytske J. Fokkens, Stacey T. Gray, David A. Gudis, Daniel L. Hamilos, Joseph K. Han, Richard Harvey, Peter Hellings, Eric H. Holbrook, Claire Hopkins, Peter Hwang, Amin R. Javer, Rong‐San Jiang, David Kennedy, Robert Kern, Tanya Laidlaw, Devyani Lal, Andrew Lane, Heung‐Man Lee, Jivianne T. Lee, Joshua M. Levy, Sandra Y. Lin, Valerie Lund, Kevin C. McMains, Ralph Metson, Joaquim Mullol, Robert Naclerio, Gretchen Oakley, Nobuyoshi Otori, James N. Palmer, Sanjay R. Parikh, Desiderio Passali, Zara Patel, Anju Peters, Carl Philpott, Alkis J. Psaltis, Vijay R. Ramakrishnan, Murugappan Ramanathan, Hwan‐Jung Roh, Luke Rudmik, Raymond Sacks, Rodney J. Schlosser, Ahmad R. Sedaghat, Brent A. Senior, Raj Sindwani, Kristine Smith, Kornkiat Snidvongs, Michael Stewart, Jeffrey Suh, Bruce K. Tan, Justin H. Turner, Cornelis M Drunen, Richard Voegels, De Yun Wang, Bradford A. Woodworth, Peter‐John Wormald, Erin D. Wright, Carol Yan, Luo Zhang, Bing Zhou

Publication date 24-11-2020


Abstract Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document.
Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary.
Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided.
Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS.
This article is protected by copyright. All rights reserved

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

Ryan E. Little, Jeremiah A. Alt, Vijay R. Ramakrishnan, Michael P. Platt, Rodney J. Schlosser, Kristina A. Storck, Zachary M. Soler

Publication date 23-11-2020


Background Poor 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).
Methods Adults 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).
Results Thirty‐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).
Conclusion In 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

Nyssa Fox Farrell, Jess C. Mace, Kara Y. Detwiller, Ryan Li, Peter E. Andersen, Timothy L. Smith, Daniel R. Clayburgh, Mathew Geltzeiler

Publication date 23-11-2020


Background Sinonasal 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.
Methods The 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.
Conclusion Multimodality 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?

Claire Hopkins

Publication date 13-11-2020


Pubmed PDF Web

Assessing health literacy in rhinologic patients

Jakob L. Fischer, Nora L. Watson, Anthony M. Tolisano, Charles A. Riley

Publication date 13-11-2020


Pubmed PDF Web

Fungal sinusitis: a spectrum of disease

Connie Ma, Matthew W. Ryan, Bradley F. Marple, Ashleigh A. Halderman

Publication date 13-11-2020


Pubmed PDF Web

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

Andrea L. Schilling, John Moore, Yalcin Kulahci, Steven R. Little, Lora H. Rigatti, Eric W. Wang, Stella E. Lee

Publication date 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

Martha Alemayehu Menberu, Andrew James Hayes, Sha Liu, Alkis James Psaltis, Peter‐John Wormald, Sarah Vreugde

Publication date 06-11-2020


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

Peng Tian, Junwu Hu, Yun Ma, Chao Zhou, Xiang Liu, Hua Dang, Hua Zou

Publication date 05-11-2020


Background Individuals 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.
Results The 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).
Conclusion This 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

Ximena Maul, Andrew Thamboo

Publication date 05-11-2020


Pubmed PDF Web

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

"Christopher M. Low, Dong Kun Kim, Alyssa J. Smith, Linda X. Yin, Byron M. Smith, Janalee K. Stokken, Erin K. OBrien, Michael J. Link, Jamie J. Van Gompel, Garret Choby"

Publication date 05-11-2020


Pubmed PDF Web

Topical irrigation against gravity may lead to better sinus penetration

Kanghyun Kim, Bradley A. Otto, Alexander A. Farag, Kai Zhao

Publication date 03-11-2020


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

Daniel M. Beswick, Stephen M. Humphries, Connor D. Balkissoon, Eszter K. Vladar, Vijay R. Ramakrishnan, David A. Lynch, Jennifer L. Taylor‐Cousar

Publication date 02-11-2020


Pubmed PDF Web

Effect of nasal fluticasone exhalation delivery system on Eustachian tube dysfunction

Arthur W. Wu, Randall A. Ow, Dennis M. Tang, James Mirocha, Evan S. Walgama, Elisa A. Illing, Martin L. Hopp, Jonathan Y. Ting, Thomas S. Higgins

Publication date 02-11-2020


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

Arthur W. Wu, Thomas S. Higgins, Jonathan Y. Ting, Elisa A. Illing

Publication date 02-11-2020


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Inflammation‐driven vascular dysregulation in chronic rhinosinusitis

Nitish Khurana, Abigail Pulsipher, Jolanta Jedrzkiewicz, Shaelene Ashby, Chelsea E. Pollard, Hamidreza Ghandehari, Jeremiah A. Alt

Publication date 02-11-2020


Background Altered 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.
Methods Patients 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.
Results Sinonasal 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.
Conclusion Significant 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

Isaac A. Bernstein, Christopher R. Roxbury, Sandra Y. Lin, Nicholas R. Rowan

Publication date 01-11-2020


Background Olfaction 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.
Methods Cross‐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.
Results Participants 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.
Conclusion Self‐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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IFAR reviewers: best of 2020

Timothy L. Smith

Publication date 27-10-2020


Pubmed PDF Web

International Consensus Statement: Spontaneous Cerebrospinal Fluid Rhinorrhea

Christos Georgalas, Amanda Oostra, Shahzada Ahmed, Paolo Castelnuovo, Iacopo Dallan, Wouter Furth, Richard J. Harvey, Philippe Herman, Dimitrios Kombogiorgas, Davide Locatelli, Cem Meco, Jim N. Palmer, Otavio Piltcher, Anshul M. Sama, Hesham Saleh, Raj Sindwani, Thibaut Van Zele, Bradford A. Woodworth

Publication date 25-10-2020


Background The 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.
Results Fifty 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 Santo Rhino 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.
Conclusion We 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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Impact of novel CFTR modulator on sinonasal quality of life in adult patients with cystic fibrosis

Jennifer E. Douglas, Alyssa M. Civantos, Tran B. Locke, Auddie M. Sweis, Denis Hadjiliadis, Gina Hong, Daniel J. Dorgan, Michael A. Kohanski, James N. Palmer, Nithin D. Adappa

Publication date 18-10-2020


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

John V. Bosso

Publication date 18-10-2020


Pubmed PDF Web

Cystic fibrosis: On the cusp of cure?

Brent A. Senior

Publication date 18-10-2020


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

Joshua M Levy, Merin Kuruvilla

Publication date 15-10-2020


Pubmed PDF Web

The clinical implications of microbiome research

Richard Douglas

Publication date 13-10-2020


Pubmed PDF Web

Nasal mucosal brush biopsy for cat allergy

Wesley Davison, Daniel Alfonso, Anjile An, William R. Reisacher

Publication date 13-10-2020


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

Jie Deng, Li Hui Tan, Michael A. Kohanski, David W. Kennedy, John V. Bosso, Nithin D. Adappa, James N. Palmer, Jianbo Shi, Noam A. Cohen

Publication date 11-10-2020


Background Solitary 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.
Methods Immunofluorescence for trigeminal nerve fiber markers, nicotinic ACh receptors (n ChR), 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.
Results Calcitonin 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 n ChR 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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Inflammatory features and predictors for postsurgical outcomes in patients with nasal polyps stratified by local and systemic eosinophilia

Li Pan, Bo Liao, Cui‐Lian Guo, Jin‐Xin Liu, Heng Wang, Xiao‐Bo Long, Zheng Liu

Publication date 04-10-2020


Background In 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.
Results Among 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.
Conclusion Different 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

Daniel M. Beswick, Milene T. Saavedra

Publication date 29-09-2020


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

Halil Onder

Publication date 29-09-2020


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

Emily DiMango, Daniel B. Spielman, Jonathan Overdevest, Claire Keating, Sarah Fracasso Francis, David Dansky, David A. Gudis

Publication date 28-09-2020


Background Elexacaftor/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.
Results Forty‐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

Michael Yim, Peter‐John Wormald, Manon Doucet, Amarbir Gill, Todd Kingdom, Richard Orlandi, Alison Crum, Douglas Marx, Jeremiah Alt

Publication date 27-09-2020


Background Many adjunctive techniques exist for dacryocystorhinostomy (DCR), with varying levels of supportive evidence.
Methods Literature from Pub Med, 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.
Results Seven 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.
Conclusion Recommendations 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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Efficacy of the exhalation delivery system with fluticasone in patients who remain symptomatic on standard nasal steroid sprays

Brent A. Senior, Rodney J. Schlosser, John Bosso, Zachary M. Soler

Publication date 24-09-2020


Background Standard 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.
Methods Using 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.
Results Of 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

Benjamin Verillaud, Vincent Bedarida, Marc‐Antoine Labeyrie

Publication date 24-09-2020


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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

Anastasios Maniakas, Marc‐Henri Asmar, Axel Eluid Renteria, Smriti Nayan, Saud Alromaih, Leandra Mfuna Endam, John Sam Sampalis, Martin Desrosiers

Publication date 15-09-2020


Background Refractory 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).
Conclusion Low‐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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Denatonium benzoate bitter taste perception in chronic rhinosinusitis subgroups

Alyssa M. Civantos, Ivy W. Maina, Monique Arnold, Cailu Lin, Elizabeth M. Stevens, Li Hui Tan, Patrick K. Gleeson, Lauren R. Colquitt, Beverly J. Cowart, John V. Bosso, James N. Palmer, Nithin D. Adappa, Michael A. Kohanski, Danielle R. Reed, Noam A. Cohen

Publication date 03-09-2020


Background Chronic 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).
Conclusion Our 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

Christian Albert Lux, James Johnston, Kristi Biswas, Richard George Douglas

Publication date 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

Yoon Seok Choi, Hyung Gyun Na, Chang Hoon Bae, Si‐Youn Song, Yong‐Dae Kim

Publication date 26-08-2020


Background Gastric 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.
Methods In NCI‐H292 cells and human nasal epithelial cells (HNEp Cs), 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.
Results Pepsin increased MUC5AC expression in non‐acidic condition of NCI‐H292 cells and HNEp Cs. 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.
Conclusion These 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

Cailu Lin, Alyssa M. Civantos, Monique Arnold, Elizabeth M. Stevens, Beverly J. Cowart, Lauren R. Colquitt, Corrine Mansfield, David W. Kennedy, Steven G. Brooks, Alan D. Workman, Mariel T. Blasetti, Michael A. Kohanski, Laurel Doghramji, Jennifer E. Douglas, Ivy W. Maina, James N. Palmer, Nithin D. Adappa, Danielle R. Reed, Noam A. Cohen

Publication date 26-08-2020


Background Bitter 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.
Methods We 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”

Arie Francis, Timothy C Backus, Mary Ann Howland, Robert S Hoffman

Publication date 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”

John McGrath, Alexa McGrath, Jacob Burdett, Tom Shokri, Jason E. Cohn

Publication date 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

Nyssa Fox Farrell, Jess C. Mace, David A. Sauer, Andrew J. Thomas, Mathew Geltzeiler, Kara Y. Detwiller, Jeremiah A. Alt, Timothy L. Smith

Publication date 11-08-2020


Background Chronic 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.
Results Of 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).
Conclusion Chronic 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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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

Ying Li, Yuhui Ouyang, Jian Jiao, Zhaojun Xu, Luo Zhang

Publication date 10-08-2020


Background Allergic 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).
Methods Nasal 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.
Results Exposure 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.
Conclusion These 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

Moshe Ephrat, Ofer Jacobowitz, Mark Driver

Publication date 09-08-2020


Background Insufficiency 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.
Methods Thirty‐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.
Results Clinically 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.
Conclusion Treatment 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

Pin‐Ching Lu, Ta‐Jen Lee, Chi‐Che Huang, Po‐Huang Chang, Yi‐Wei Chen, Chia‐Hsiang Fu

Publication date 06-08-2020


Background The 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).
Methods We 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.
Results Overall, 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).
Conclusion Serum 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

Netanel Eisenbach, Ohad Karni, Eyal Sela, Achia Nemet, Amiel Dror, Einat Levy, Yanir Kassif, Relli Ovadya, Ohad Ronen, Tal Marshak

Publication date 06-08-2020


Background Epiphora 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.
Results Fifty‐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.
Conclusion Based 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

Dong‐Jin Lim, Harrison M. Thompson, Christopher R. Walz, Samrath Ayinala, Daniel Skinner, Shaoyan Zhang, Jessica W. Grayson, Do‐Yeon Cho, Bradford A. Woodworth

Publication date 28-07-2020


Background We 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).
Methods Pseudomonas 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.
Results Azithromycin 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.
Conclusion Azithromycin 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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