International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 34052840 Paving the post-covid Rhinology era with ERS! 225 225 EN P.W. Hellings Department of Otorhinolaryngology-Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium 2820 10.4193/Rhin21.903

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 34052840 Paving the post-covid Rhinology era with ERS! 225 225 EN P.W. Hellings Department of Otorhinolaryngology-Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium 2822 10.4193/Rhin21.903

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 The effect of coronaviruses on olfaction: systematic review 226 235 EN M. Zugaj Department of Otorhinolaryngology, Amsterdam University Medical Centres, location AMC, Amsterdam, The Netherlands N.S. van Ditzhuijzen Department of Otorhinolaryngology, Amsterdam University Medical Centres, location AMC, Amsterdam, The Netherlands K. Golebski Department of Respiratory Medicine, Amsterdam University Medical Centres, Location AMC, Amsterdam, The Netherlands W.J. Fokkens Department of Otorhinolaryngology, Amsterdam University Medical Centres, location AMC, Amsterdam, The Netherlands 2761 10.4193/Rhin20.610 BACKGROUND: Unlike other respiratory viruses, SARS-CoV-2 causes anosmia without sinonasal inflammation. Here we systematically review the effects of the 7 known human coronaviruses on olfaction to determine if SARS-CoV-2 distinctly affects the olfactory system. METHOD: PubMed, EMBASE, Web of Science, bioRxiv, medRxiv and DOAJ were searched for studies describing pathophysiological, immunohistochemical, cytological and clinical data. RESULTS: 49 studies were included. Common cold coronaviruses lead to sinonasal inflammation which can cause transient and chronic loss of smell. MERS-CoV entry receptors were not found in the nasal mucosa and it did not impair olfaction. SARS-CoV-1 had low affinity for its receptor ACE2, limiting olfactory effects. Anosmia is frequent in SARS-CoV-2 infections. SARS-CoV-2’s entry factors ACE2 and TMPRSS2 are expressed in the nasal respiratory epithelium and olfactory supporting cells. SARS-CoV-2 appeared to target the olfactory cleft while diffuse nasal inflammation was not observed. Damage of the olfactory epithelium was observed in animal models. Alternative receptors such as furin and neuropilin-1 and the similarity of viral proteins to odourant receptors could amplify olfactory impairment in SARS-CoV-2 infection. CONCLUSIONS: The pathophysiology of anosmia in SARS-CoV-2 infection is distinct from other coronaviruses due to preferentially targeting olfactory supporting cells. However, SARS-CoV-2 does not cause sinonasal inflammation in spite of preferred entry factor expression in the nasal respiratory epithelium. This raises doubts about the attention given to ACE2. Alternative receptors, odourant receptor mimicry and other as yet unknown mechanisms may be crucial in the pathogenesis of anosmia in SARS-CoV-2 infection. Further studies are warranted to investigate infection mechanisms beyond ACE2.

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 33647073 Intralymphatic immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta-analysis 236 244 EN M.P. Hoang Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Endoscopic Nasal and Sinus Surgery Excellent Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand; Department of Otolaryngology, Hue University of Medicine and Pharmacy, Hue University, Vietnam K. Seresirikachorn Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Endoscopic Nasal and Sinus Surgery Excellent Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand W. Chitsuthipakorn Center of Excellence in Otolaryngology Head and Neck Surgery, Rajavithi Hospital, Bangkok, Thailand; Department of Otolaryngology, College of Medicine, Rangsit University, Bangkok, Thailand K. Snidvongs Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Endoscopic Nasal and Sinus Surgery Excellent Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand 2755 10.4193/Rhin20.572 BACKGROUND: Intralymphatic immunotherapy (ILIT) is a new route of allergen-specific immunotherapy. Data confirming its effect is restricted to a small number of studies. METHODOLOGY: A systematic review with meta-analysis was conducted. The short-term (less than 24 weeks), medium-term (24-52 weeks), and long-term (more than 52 weeks) effects of ILIT in patients with allergic rhinoconjunctivitis (ARC) were assessed. The outcomes were combined symptom and medication scores (CSMS), symptoms visual analog scale (VAS), disease-specific quality of life (QOL), specific IgG4 level, specific IgE level, and adverse events. RESULTS: Eleven randomized controlled trials and 2 cohorts (483 participants) were included. Compared with placebo, short term benefits of ILIT for seasonal ARC improved CSMS, improved VAS and increased specific IgG4 level but did not change QOL or specific IgE level. Medium-term effect improved VAS. Data on the long-term benefit of ILIT remain unavailable and require longer term follow-up studies. There were no clinical benefits of ILIT for perennial ARC. ILIT was safe and well-tolerated. CONCLUSION: ILIT showed short-term benefits for seasonal ARC. The sustained effects of ILIT were inconclusive. It was well tolerated.

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 33730750 Matrix metalloproteinases and chronic rhinosinusitis with nasal polyposis. Unravelling a puzzle through a systematic review 245 257 EN S. Lygeros Department of Otorhinolaryngology-Head and Neck Surgery, University of Patras, Medical School, Patras, Greece G. Danielides Department of Otorhinolaryngology-Head and Neck Surgery, University of Patras, Medical School, Patras, Greece K. Grafanaki Department of Biochemistry and Department of Dermatology School of Medicine, University of Patras, Greece M. Riga Department of Otorhinolaryngology-Head and Neck Surgery, Dammam Medical Complex, Dammam, Kingdom of Saudi Arabia 2758 10.4193/Rhin20.578 BACKGROUND: The expression of metalloproteinases (MMPs) in chronic rhinosinusitis with nasal polyposis (CRSwNP) was reviewed in order to investigate their possible use as therapeutical targets and/or biomarkers. METHODOLOGY: The differences between CRSwNP and normal controls or CRS without NP, as well as the effects of various treatments on MMPs, tissue inhibitors of MMPs (TIMPs) and MMP/TIMP ratios were considered as primary outcomes. Additional factors reported to affect MMP expression levels were noted as secondary outcomes. Data regarding inflammatory subtypes, patients’ clinical characteristics, controls, laboratory method(s) and origin of samples were also pooled. Studies on 10 or fewer patients or on specimens other than nasal and serum were excluded. RESULTS: Forty-three studies were included. Tissue sample origin, allergic rhinitis, smoking, infection, medication intake and primary or recurrent disease should be considered as confounding factors for MMP levels. MMP-1 and -7 were consistently found to be significantly higher in CRSwNP patients than controls. CRSwNP endotypes with distinctly different inflammation patterns seem to present similar MMP-related remodelling patterns. CONCLUSIONS: The existing literature has revealed several population and methodology related confounding factors and remains inconclusive regarding the roles of MMPs in CRSwNP pathophysiology and their possible clinical usefulness as biomarkers and therapeutical targets.

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 Towards a new epidemiological definition of chronic rhinitis: prevalence of nasal complaints in the general population 258 266 EN K.S. Avdeeva Department of Otorhinolaryngology, Amsterdam UMC, location Academic Medical Centre, Amsterdam, The Netherlands W.J. Fokkens Department of Otorhinolaryngology, Amsterdam UMC, location Academic Medical Centre, Amsterdam, The Netherlands S. Reitsma Department of Otorhinolaryngology, Amsterdam UMC, location Academic Medical Centre, Amsterdam, The Netherlands 2783 10.4193/Rhin20.637 Background: Chronic rhinitis (CR) is currently defined as the presence of at least two nasal symptoms for at least 1 hour per day for more than 12 weeks per year. Such definition lacks evidence-based foundation. CR patients are often divided into ‘runners’ and ‘blockers’, although the evidence supporting such subdivision is limited. The aim of the study was to define CR, to estimate its prevalence and the proportion of ‘runners’ and ‘blockers’. Methods: Cross-sectional, questionnaire-based study in a random sample of participants representing the general population of the Netherlands. Results: The questionnaire was sent to 5000 residents of the Netherlands; the response rate was 27%. CR was defined as at least 1 nasal complaint present for more than 3 weeks per year. The prevalence of CR in the general population was 40%. Participants who would have been excluded by the former CR definition were shown to have a significantly higher VAS compared to the controls. The larger part of CR group was represented by non-allergic rhinitis (NAR): 70% vs 30%. There were 25% ‘Blockers’ and 22% ‘Runners’ in the CR group, whereas more than a half of the CR group could be classified in neither of these subgroups. Conclusion: Based on our data, we suggest that the current definition of CR should be revised and propose a new definition: at least one nasal complaint present for at least 3 weeks per year; although future studies are needed to further validate the proposed definition.

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 34051075 Fire simulator exposure alters the innate epithelial response and inflammatory status in the airways of firefighters 267 276 EN T.G. Cordeiro ENT Research Lab, Department of Otorhinolaryngology and Head and Neck Surgery, Universidade Federal de São Paulo, São Paulo, Brazil J.B. do Amaral ENT Research Lab, Department of Otorhinolaryngology and Head and Neck Surgery, Universidade Federal de São Paulo, São Paulo, Brazil V. Pavão Fire Department, Escola Superior de Bombeiros â€" Polícia Militar do Estado de São Paulo, Franco da Rocha, Brazil R.G. Cardoso GRAU - Grupo de Resgate da Secretaria Estadual de Saúde de São Paulo. São Paulo, Brazil R.L. Voegels Department of Ophthalmology and Otorhinolaryngology, Universidade de São Paulo, São Paulo, Brazil P.M. Pezato ENT Research Lab, Department of Otorhinolaryngology and Head and Neck Surgery, Universidade Federal de São Paulo, São Paulo, Brazil V. Paixão ENT Research Lab, Department of Otorhinolaryngology and Head and Neck Surgery, Universidade Federal de São Paulo, São Paulo, Brazil E.B. de Almeida ENT Research Lab, Department of Otorhinolaryngology and Head and Neck Surgery, Universidade Federal de São Paulo, São Paulo, Brazil A.L.L. Bachi ENT Research Lab, Department of Otorhinolaryngology and Head and Neck Surgery, Universidade Federal de São Paulo, São Paulo, Brazil R. Pezato ENT Research Lab, Department of Otorhinolaryngology and Head and Neck Surgery, Universidade Federal de São Paulo, São Paulo, Brazil 2821 10.4193/Rhin21.002 Background: Firefighters are often exposed to high temperatures and by-products of combustion, which can compromise their health. We aimed to evaluate the effect of fire exposure in fire simulators on the airways of firefighters at different time-points. Methodology: Thirty-seven male firefighters exposed to fire simulators were evaluated in three phases: pre-exposure, at the end of the first week, and 4 weeks after. Pulmonary function by spirometry, nasal mucociliary clearance; peripheral oxygen saturation, inflammatory markers in the nasal lavage and CC16 in the sputum, nasal obstruction, and quality of life (using the questionnaires NOSE and SNOT-22) were assessed. Results: Higher levels of IL-8, IL-10, and exhaled carbon monoxide were found more in phase 2 than in phase 1. Higher CC16 levels and lower peripheral oxygen saturation were observed in phase 3 as compared to phase 1. Lower levels of IL-2 and peripheral oxygen saturation were found in phase 3 than in phase 2. Higher nasal mucociliary clearance, as well as the worst quality of life and nasal obstruction, were observed in phases 2 and 3 as compared to phase 1. Conclusions: The firefighters’ exposures to high temperatures and by-products of combustion in the fire simulators elicit an inflammatory process in the airways with impairment in the innate epithelial response of the upper airway lining. Furthermore, changes in O2 transport affected the professionals’ quality of life negatively.

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 33866347 Does time from previous surgery predict subsequent treatment failure in Chronic Rhinosinusitis with Nasal Polyps? 277 283 EN C. Hopkins Guy’s and St Thomas’ NHS Foundation Trust, London, UK V. Lund Royal National Throat, Nose and Ear Hospital, UCLH Foundation Trust, London, UK 2767 10.4193/Rhin21.017 Introduction: When considering the introduction of biological treatments for Chronic Rhinosinusitis with nasal polyps (CRSwNP), treatment guidelines must consider not only which patients will best respond to biologicals, but also which patients derive least benefit from current treatment pathways. Using data collected as part of the National Audit of Surgery for Chronic Rhinosinusitis and Nasal Polyps, we sought to evaluate if patients with a history of prior surgery are more likely to need a further revision operation, and whether the interval between surgery may help predict the need for further surgical intervention. Methods: In the original study, patients were prospectively and consecutively enrolled at the time of sinus surgery in multiple centres in England and Wales. Follow-up captured symptomatic outcomes and revision surgery rates at 3, 12, 36 and 60 months after surgery. Revision surgery rates 5 years after the index procedure, in patients with CRSwNP were analysed with regards to baseline demographics. Results: Complete data were available for 980 subjects, with a 5 year revision rate of 15.1%. 45.9% had a history of previous surgery before the index procedure, and this group had significantly higher rates of additional surgery compared with those undergoing their first sinus surgery (20.2% versus 9.8%). Patients with an interval of 3 years or less between their previous surgery and the index procedure had the highest rates of further surgery. In a multiple regression, time interval between previous operations was a better prediction of subsequent revision surgery than asthma. Having N-ERD was the strongest predicator of need for further surgery while more extensive surgery was associated with lower revision rates. Conclusions: Patients presenting with a symptomatic recurrence within 3 years of surgery have a high risk of treatment failure, defined as the need for further surgery. Time to failure after previous surgery may be used to help select patients who may not benefit from current treatment pathways and may be good candidates for alternative strategies, including biologicals.

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 33821291 Predictive factors for identifying macrolide responder in treating chronic rhinosinusitis 284 291 EN K. Seresirikachorn Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Endoscopic Nasal and Sinus Surgery Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand S.J. Kerr Biostatistics Excellence Centre, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand S. Aeumjaturapat Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Endoscopic Nasal and Sinus Surgery Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand S. Chusakul Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Endoscopic Nasal and Sinus Surgery Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand J. Kanjanaumporn Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Endoscopic Nasal and Sinus Surgery Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand J. Wongpiyabovorn Center of Excellence in Immunology and Immune Mediated Diseases, Division of Immunology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand K. Snidvongs Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Endoscopic Nasal and Sinus Surgery Excellence Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand 2763 10.4193/Rhin20.649 BACKGROUND: Low-dose macrolides (LDM) are anti-inflammatory agents with antineutrophilic activity, but patient selection for LDM therapy in treating chronic rhinosinusitis (CRS) is controversial. This study aimed to assess factors which predict LDM responders. METHODOLOGY: A prospective cohort study was performed. Patients with CRS received roxithromycin (150 mg) once daily for 12 weeks. Nasal secretions and serology were collected. Nine predictors for LDM response were assessed: nasal secretion IgE, nasal secretion IL-5, serum IgE, serum eosinophils, serum neutrophils, nasal polyps, asthma, allergy, and aspirin hypersensitivity, using receiver-operating curve analysis and multivariable logistic regression. Macrolide responders were those with sino-nasal outcome test-22 improvement, symptoms visual analogue scale decreased to ≤5, and no rescue medication. RESULTS: One hundred CRS patients (mean age 47.4±14.1 years, 45% male) were enrolled. Univariable logistic regression showed local total IgE less than 5.21; and serum eosinophils less than 2.2% associated with macrolide response. Multivariate models showed local total IgE maintained an independent association with macrolide response, with an ability to discriminate between responders and non-responders of 63%. Serum total IgE, nasal secretion IL-5, serum neutrophil, nasal polyp, asthma, allergy, and aspirin hypersensitivity showed no association with LDM response. CONCLUSIONS: Low total IgE level in the nasal secretion but not in the serum, predict LDM response.

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 33315021 Increased risk of chronic otitis media in chronic rhinosinusitis patients: a longitudinal follow-up study using a national health screening cohort 292 300 EN S.K. Kim epartment of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Dongtan, Korea M-W. Park Department of Otorhinolaryngology-Head and Neck Surgery, Kangdong Sacred Hospital, Seoul, Korea C. Min Hallym Data Science Laboratory, Hallym University College of Medicine, Anyang, Korea; Graduate School of Public Health, Seoul National University, Seoul, Korea I-S. Park Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Dongtan, Korea B. Park Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Anyang, Korea S-H. Byun Department of Oral and Maxillofacial Surgery, Dentistry, Hallym University College of Medicine, Anyang, Korea H.G. Choi Hallym Data Science Laboratory, Hallym University College of Medicine, Anyang, Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Anyang, Korea S.J. Hong Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Dongtan, Korea 2725 10.4193/Rhin20.363 BACKGROUND: Chronic rhinosinusitis (CRS) and chronic otitis media (COM) share pathophysiological mechanisms such as bacterial infection, biofilm, and persistence of the obstruction state of ventilation routes. However, only a few studies have investigated the relationship between these two diseases nationwide and in the general population. The purpose of this study was to determine whether the incidence of COM in patients with CRS differed from that of a matched control from the national health screening cohort. METHODS: Data from the Korean Health Insurance Review and Assessment Service-National Patient Samples were collected from 2002 to 2015. Participants who were treated ≥2 times and underwent head and neck computed tomography evaluation were selected. A 1:4 matched CRS group (n=8,057) and a control group (n=32,228) were selected. The control group included participants who were never treated with the ICD-10 code J32 from 2002 to 2015. The CRS group included CRS patients with/without nasal polyps. RESULTS: The incidence of COM was significantly higher in the CRS group than in the control group. In a subgroup analysis, the incidence of COM in all age groups and in men and women was significantly higher in the CRS group than in the control group. More, CRS increased the risk of COM. CONCLUSIONS: A significant association was observed between CRS and COM. This indicates that CRS patients have a high risk of developing COM.

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 33847325 Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP 301 311 EN M. Desrosiers Centre de recherche du Centre hospitalier de l’Universite de Montreal (CRCHUM), Montreal, QC, Canada L.P. Mannent Sanofi, Chilly-Mazarin, France N. Amin Regeneron Pharmaceuticals, Inc. Tarrytown, NY, USA G.W. Canonica Regeneron Pharmaceuticals, Inc. Tarrytown, NY, USA P.W. Hellings University Hospitals Leuven, Leuven, Belgium P. Gevaert Ghent University, Ghent, Belgium J. Mullol Hospital Clínic, IDIBAPS, Universitat de Barcelona, CIBERES, Barcelona, Catalonia, Spain S.E. Lee University of Pittsburgh Medical Center, Pittsburgh, PA, USA S. Fujieda University of Fukui, Fukui, Japan J.K. Han Eastern Virginia Medical School, Norfolk, VA, USA C. Hopkins Guy’s and St Thomas’ Hospitals, London, UK W. Fokkens Academic Medical Center, Amsterdam, Netherlands R. Jankowski University Hospital of Nancy, University of Lorraine, Nancy, France S.H. Cho University of South Florida, Tampa, FL, USA X. Mao Sanofi, Bridgewater, NJ, USA M. Zhang Sanofi, Bridgewater, NJ, USA M.S. Rice Sanofi, Cambridge, MA, USA A.H. Khan Sanofi, Chilly-Mazarin, France S. Kamat Regeneron Pharmaceuticals, Inc. Tarrytown, NY, USA N. Patel Sanofi, Bridgewater, NJ, USA N.M.H. Graham Regeneron Pharmaceuticals, Inc. Tarrytown, NY, USA M. Ruddy Regeneron Pharmaceuticals, Inc. Tarrytown, NY, USA C. Bachert Ghent University, Ghent, Belgium; Karolinska Institutet, Stockholm, Sweden; Sun Yat-sen University, First Affiliated Hospital, Guangzhou, China 2765 10.4193/Rhin20.415 BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery. METHODOLOGY: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153). RESULTS: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test. CONCLUSIONS: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery.

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 33847326 Trigeminal impairment in treatment-refractory chronic nasal obstruction 312 318 EN C. Migneault-Bouchard Department of Anatomy, Universite du Quebec a Trois-Rivieres (UQTR), Trois-Rivieres, QC, Canada F.J.M. Boselie Head and Neck Surgery Unit, Department of Otorhinolaryngology â€" Head and Neck Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland M. Hugentobler Rhinology-Olfactology Unit, Department of Otorhinolaryngology â€" Head and Neck Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland B.N. Landis Rhinology-Olfactology Unit, Department of Otorhinolaryngology â€" Head and Neck Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland J. Frasnelli Department of Anatomy, Universite du Quebec a Trois-Rivieres (UQTR), Trois-Rivieres, QC, Canada; Research Center of the Sacre-Coeur Hospital, Montreal, QC, Canada 2766 10.4193/Rhin20.510 BACKGROUND: Patients with anatomically unexplained, chronic nasal obstruction (CNO) that is refractory to medical treatment pose a challenge for clinicians. A surgical solution, addressing mechanical obstacles, is unsuited for these patients. CNO may result from disrupted airflow perception due to activation of the intranasal trigeminal system; therefore, aim of this study is to evaluate if intranasal trigeminal function of these CNO patients is decreased. METHODS: In this retrospective cross-sectional study, we compared 143 CNO patients and 58 healthy volunteers, between 18 to 80 years old. We assessed nasal patency by means of rhinomanometry (RM) and measured susceptibility of intranasal trigeminal system by the trigeminal lateralization task (TLT). RESULTS: TLT scores were significantly lower in CNO patients compared to controls (p less than 0.001), but RM scores were not different between groups. Accordingly, TLT allowed to identify CNO patients with an accuracy of the area under the curve (AUC) of 0.78, while the value for RM was at chance (AUC=0.47). CNO patients showed normal reaction to vasoconstrictive agents with significantly lower RM values after Xylomethazoline application. CONCLUSION: Results suggest that reported nasal obstruction in CNO patients without any obvious anatomical obstacle and resistant to medical treatment may be linked to decreased perception of nasal airflow rather than physical obstruction. In this sub-set of CNO patients, trigeminal testing more adequately reflects the reported obstruction than nasal resistance assessment does. In future studies, the relation of the trigeminal status and the subjective sensation of nasal obstruction needs to be addressed with validated patient rated outcome measures (PROMs).

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 33904535 Ciliary function and sinonasal mucosal cytology in pediatric patients with chronic rhinosinusitis during a year after functional endoscopic sinus surgery 319 327 EN S. Alekseenko Saint-Petersburg Research Institute of Ear, Throat, Nose and Speech, St. Petersburg, Russia; I.I. Mechnikov North-Western State Medical University, St. Petersburg, Russia; K.A. Raukhfus Childrens City Multidisciplinary Clinical Center for High Medical Technologies, St. Petersburg, Russia S. Karpischenko Saint-Petersburg Research Institute of Ear, Throat, Nose and Speech, St. Petersburg, Russia; K.A. Raukhfus Childrens City Multidisciplinary Clinical Center for High Medical Technologies, St. Petersburg, Russia; First Pavlov State Medical University of Saint Petersburg, St. Petersburg, Russia S. Artyushkin I.I. Mechnikov North-Western State Medical University, St. Petersburg, Russia S. Barashkova K.A. Raukhfus Childrens City Multidisciplinary Clinical Center for High Medical Technologies, St. Petersburg, Russia; National Center of morphological diagnostic, St. Petersburg, Russia I. Anikin Saint-Petersburg Research Institute of Ear, Throat, Nose and Speech, St. Petersburg, Russia; K.A. Raukhfus Childrens City Multidisciplinary Clinical Center for High Medical Technologies, St. Petersburg, Russia 2782 10.4193/Rhin20.642 Background: The objective of the study is evaluation of ciliary function and mucosal cytology after endoscopic sinus surgery in children with chronic rhinosinusitis (CRS). Methodology: A total of 132 children with CRS who underwent endoscopic sinus surgery, as well as 15 healthy controls were involved in the study. In this follow-up study patients were examined preoperatively, as well as 3, 6, 9, and 12 months after endoscopic sinus surgery. Assessment of ciliary function and sinonasal mucosal cytology was performed using high-speed videomicroscopy. Lund-Kennedy, Lund-Mackay, and sinonasal outcome test 20 (SNOT20) scores were also evaluated. Results: Total SNOT-20, Lund-Mackay, and Lund-Kennedy values significantly decreased after sinus surgery. In contrast, ciliary function and mucosal cytology only tended to improve after 6 months. 9 months after surgery the number of ciliated cells, ciliary beat frequency, cell viability, and ciliary length were significantly higher than preoperatively. The most significant improvement of ciliary function and cell height was observed 12 months after operation, whereas epithelial dystrophy and neutrophil infiltration were significantly reduced. Conclusions: Substantial improvement was observed only in a year after surgery, whereas 0 to 3 months after the surgery ciliary function was severely impaired thus predisposing to recurrent sinusitis or other complications.

International Rhinologic Society Rhinology 0300-0729 59 3 2021 6 1 Mucin 5AC is significantly upregulated in exosomes from the nasal lavage fluid and may promote the expression of COX-2, VEGF and MMP-9: an implication in nasal polyp pathogenesis 328 336 EN L.-F. Wang Department of Otolaryngology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan C.-H. Lee Department of Pharmacology, School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan S.-S. Liang Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan C.-C. Hung Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan Y.-R. Wu Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan C.-Y. Chien Department of Otolaryngology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan C.-H. Lee National Yujing Senior Vocational School of Technology and Commerce, Tainan, Taiwan J.Y.-F. Chen Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan 2760 10.4193/Rhin20.564 BACKGROUND: Exosomes are critical mediators of intercellular communication and could be involved in many human diseases; however, little is known about the role of exosomes in nasal polyps (NP). METHODS: Exosomes in nasal lavage fluids (NLF) were isolated by ultracentrifugation. Exosome identity was validated by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and specific exosomal markers. The exosome proteome was revealed by LC-MS/MS, and the expression of the candidate exosomal protein, mucin 5AC, was confirmed by Western blot analysis and immunohistochemistry (IHC). Cellular uptake of the exosomes was monitored by fluorescence confocal microscopy and the ensuing effects on COX-2, VEGF and MMP-2/MMP-9 were determined by Western blotting, ELISA and gelatin zymography, respectively. RESULTS: Mass spectrometry analysis and subsequent verification by Western blotting identified that mucin 5AC was significantly upregulated in exosomes from NLFs of NP patients. Moreover, the expression of mucin 5AC was increased in the tissue specimens of the NP patients. Functional assays suggest that the mucin 5 AC-enriched exosomes could be effectively taken up by chronic rhinosinusitis without NP (CRSsNP)-derived fibroblasts, the control cells, resulting in a significant increase in the expression of COX-2, VEGF and MMP-9. CONCLUSIONS: Mucin 5AC, the major airway mucin, cannot only be carried and transferred by nasal exosomes, but may also promote tissue remodeling and angiogenesis and thus could be a potential therapeutic target of NP.