International Rhinologic Society Rhinology 0300-0729 58 1 2020 February 1 32078669 EPOS2020: a major step forward 1 1 EN W.J. Fokkens Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, the Netherlands 2355 10.4193/Rhin20.401

International Rhinologic Society Rhinology 0300-0729 58 1 2020 February 1 31884513 Endoscopic transnasal orbital decompression for Graves 2 9 EN N. Tsetsos Department of Otorhinolaryngology-Head and Neck Surgery, 424 General Military Hospital, Thessaloniki, Greece D. Daskalakis Department of Otorhinolaryngology-Head and Neck Surgery, York Teaching Hospital, York, United Kingdom; Department of Otorhinolaryngology-Head and Neck Surgery, G. Gennimatas â€" St Demetrios Hospital, Thessaloniki, Greece D. Tzakri Department of Ophthalmology, 424 General Military Hospital, Thessaloniki, Greece S. Blioskas Department of Otorhinolaryngology-Head and Neck Surgery, Derriford Hospital, Plymouth, United Kingdom J. Goudakos Department of Otorhinolaryngology-Head and Neck Surgery, 424 General Military Hospital, Thessaloniki, Greece K. Markou 2nd Academic Otorhinolaryngology-Head and Neck Surgery Department, Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece 2226 10.4193/Rhin19.282 BACKGROUND: The aim of this study was to assess all available data regarding the efficacy of endoscopic transnasal orbital decompression for Graves' ophthalmopathy. METHODOLOGY: MEDLINE, ScienceDirect and the Cochrane Library databases as well as other sources were searched by two independent reviewers followed by extensive hand-searching for the identification of relevant studies. The primary outcome was the reduction in orbital proptosis. Secondary outcomes were the improvement in visual acuity, post-operative diplopia, and complications RESULTS: Twelve prospective and retrospective case series met the inclusion criteria. All of them demonstrated an improvement in postoperative proptosis that ranged from 2.07 mm to 8.2 mm (weighted mean improvement 5.05 mm). Improvement in visual acuity was reported in all but one study. Studies presented a wide range of results regarding pre-existing and new-onset diplopia. Apart from diplopia, a wide variety of minor and major complications were noted in ten studies, the most serious of which being 3 cases of Cerebrospinal fluid (CSF) leak presented in 2 studies. CONCLUSIONS: The present systematic review shows that endoscopic transnasal decompression safely addresses symptoms of Graves’ ophthalmopathy. However, high-quality, large-sample, controlled studies need to be performed in the future.

International Rhinologic Society Rhinology 0300-0729 58 1 2020 February 1 31671432 Dupilumab reduces opacification across all sinuses and related symptoms in patients with CRSwNP 10 17 EN Claus Bachert Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium, and Clintec, Karolinska Institute, Stockholm, Sweden S. James Zinreich Division of Neuroradiology, Department of Radiology, Johns Hopkins Hospital, Baltimore, MD, USA Peter W. Hellings Department of Otorhinolaryngology, University Hospitals Leuven, Leuven, Belgium Joaquim Mullol Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, and Rhinology Unit and Smell Clinic, Department of Otorhinolaryngo logy, Hospital Clinic, Universitat de Barcelona, CIBERES, Barcelona, Catalonia, Spain Daniel L. Hamilos Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, USA Philippe Gevaert Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium, and Clintec, Karolinska Institute, Stockholm, Sweden Robert M. Naclerio Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA Nikhil Amin Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA Vijay N. Joish Formerly employed at Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA Chunpeng Fan Sanofi, Bridgewater, NJ, USA Donghui Zhang Sanofi, Bridgewater, NJ, USA Heribert Staudinger Sanofi, Bridgewater, NJ, USA Gianluca Pirozzi Sanofi, Bridgewater, NJ, USA Neil M.H. Graham Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA Asif Khan Sanofi, Chilly-Mazarin, France Leda P. Mannent Sanofi, Chilly-Mazarin, France 2190 10.4193/Rhin18.282 BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with substantial sinus opacification. In a phase 2a study (NCT01920893), dupilumab, a fully human anti-IL-4Rα monoclonal antibody, improved outcomes in CRSwNP refractory to intranasal corticosteroids. We evaluated dupilumab’s effect on sinus opacification in relation to effects on nasal polyp burden, symptoms, and health-related quality of life (HRQoL) in patients with CRSwNP. METHODOLOGY: 16-week randomized, double-blind, placebo-controlled, parallel-group study in 60 adults with CRSwNP. Patients received weekly subcutaneous dupilumab 300-mg or placebo and daily mometasone furoate nasal spray. Sinus opacification was assessed using standard and Zinreich-modified Lundâ€"Mackay (zLMK) scoring. Correlation was assessed between zLMK score and CRSwNP endpoints, including nasal polyp score (NPS), SNOT-22, daily symptom scores, and UPSIT smell-test score. RESULTS: Baseline characteristics were similar across treatment groups. Mean plus/minus SD baseline LMK scores of 18.7 plus/minus 5.5 (placebo) and 18.6 plus/minus 5.0 (dupilumab) indicated severe disease with extensive opacification involving all sinuses. Baseline LMK and LMK scores correlated with NPS severity and loss of sense of smell (daily symptoms; SNOT-22 smell/taste; loss of sense of smell [UPSIT]). At Week 16, dupilumab-treated patients had significantly improved sinus opacification measured by LMK in all individual sinuses vs placebo. Dupilumab also showed similar efficacy with zLMK, with only small differences from LMK, and correlated with SNOT22 smell/taste. The most common adverse events were nasopharyngitis, injection-site reactions, and headache. Conclusions: In patients with CRSwNP, baseline LMK showed extensive sinus opacification and correlated with symptoms, HRQoL, and hyposmia. Dupilumab treatment reduces opacification across all sinuses and related symptoms in patients with CRSwNP.

International Rhinologic Society Rhinology 0300-0729 58 1 2020 February 1 31681913 Plasma VEGF - a candidate biomarker for response to treatment with bevacizumab in HHT patients 18 24 EN D.T. Liu Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria A. Frohne Department for Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria M. Koenighofer Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria K. Frei Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria T. Lucas Department for Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria D. Riss Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria T. Parzefall Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria 2193 10.4193/Rhin19.018 BACKGROUND: Recurrent epistaxis is the principal symptom of hereditary hemorrhagic telangiectasia (HHT). Currently, there is no standard therapy for this condition. Bevacizumab (anti-VEGF) treatment has been under intense investigation but treatment effects vary greatly between individuals. There are currently no markers to predict anti-VEGF therapeutic response in HHT patients. METHODS: We evaluated plasma VEGF levels in 13 HHT patients and correlated values with i) degree of epistaxis, measured by visual analog scale (VAS), epistaxis severity score (ESS), and patient bleeding diaries ii) the prevalence of extranasal manifestations, iii) the HHT subtype and iv) the treatment response to intranasal submucosal bevacizumab. RESULTS: Plasma VEGF was elevated in all 13 HHT patients compared to reference levels and showed a moderate correlation with VAS and duration of moderate bleeding events. In patients treated with intranasal submucosal bevacizumab plasma VEGF levels showed a strong correlation with the degree of reduction of mild bleeding events and VAS. CONCLUSIONS: The role of plasma VEGF as a potential predictive biomarker for therapeutic response to bevacizumab treatment warrants further investigation in larger prospective studies.

International Rhinologic Society Rhinology 0300-0729 58 1 2020 February 1 31815255 EXHANCE-3: a cohort study of the exhalation delivery system with fluticasone for chronic sinusitis with or without nasal polyps 25 35 EN M.R. Sher Sher Allergy Specialist, Largo, FL, USA G.C. Steven Allergy, Asthma and Sinus Center, S.C., Greenfield, WI, USA J.L. Romett Colorado ENT and Allergy, Colorado Springs, CO, USA G. Pien Summit Medical Group, Berkeley Heights, NJ, USA K. LeBenger Summit Medical Group, Berkeley Heights, NJ, USA J.C. Messina OptiNose US Inc, Yardley, PA, USA J.L. Carothers OptiNose US Inc, Yardley, PA, USA R.A. Mahmoud OptiNose US Inc, Yardley, PA, USA P.G. Djupesland Optinose AS, Oslo, Norway 2199 10.4193/Rhin19.124 BACKGROUND: Inhaled nasal corticosteroid sprays (INS) are often inadequate to treat chronic rhinosinusitis (CRS). The exhalation delivery system with fluticasone (EDS-FLU; XHANCE®) may improve outcomes in CRS by increasing medication delivery to target superior/posterior anatomic sites. This study assessed safety and efficacy of EDS-FLU in a large population with moderate-to-severe CRS with or without nasal polyps (CRSwNP, CRSsNP). METHODS: Prospective, multicenter, 12-week, single-arm study of EDS-FLU 372 Â#181;g twice daily (BID) at 38 U.S. sites. Safety was assessed by adverse-event evaluations, nasal endoscopy, and ocular examinations. Efficacy was serially assessed by outcomes including nasal endoscopy (Lund-Kennedy Score, polyp grade), patient- and physician-reported outcomes (22-item Sinonasal Outcome Test [SNOT-22]), study-defined surgical indicator assessment, and Patient Global Impression of Change (PGIC). RESULTS: 705 comparatively refractory subjects were enrolled, 603 CRSsNP and 102 CRSwNP [moderate-to-severely symptomatic; baseline SNOT-22 ~43, high rates of prior INS use (92.3%) and/or prior surgery (27.5%)]. More than 90% reported improvement on treatment by PGIC. SNOT-22 scores improved substantially and similarly in patients with NP (-23.7) and without NP (-24.4). Among patients with baseline Lund-Kennedy edema scores >0, 33.3% (CRSwNP) and 54.8% (CRSsNP) had complete resolution of edema. In CRSwNP patients, 48% had polyp elimination in ?1 nostril, 63% had ?1-point improvement in polyp grade, mean bilateral polyp grade decreased from 2.9 to 1.6, and study-defined surgical eligibility decreased. EDS-FLU was generally well tolerated, with a safety profile similar to conventional INS sprays when used to treat CRS CONCLUSION: EDS-FLU 372 #181;g BID in the treatment of CRS with or without polyps was safe, well-tolerated, and produced substantial improvement across a broad range of both objective and subjective measures.

International Rhinologic Society Rhinology 0300-0729 58 1 2020 February 1 31671433 Correlation between extent of sinus surgery, radiographic disease, and postoperative outcomes 36 44 EN N. Ayoub Department of Otolaryngology â€" Head and Neck Surgery, Stanford University, Palo Alto, CA, United States E. Walgama Department of Otolaryngology â€" Head and Neck Surgery, Stanford University, Palo Alto, CA, United States; Department of Otolaryngology â€" Head and Neck Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States A. Thamboo Department of Otolaryngology â€" Head and Neck Surgery, Stanford University, Palo Alto, CA, United States; Department of Otolaryngology â€" Head and Neck Surgery, University of British Columbia, Vancouver, BC, Canada W. Chitsuthipakorn Center of Excellence in Otolaryngology, Head and Neck Surgery. Rajavithi Hospital, Rangsit University. Bangkok, Thailand Z.M. Patel Department of Otolaryngology â€" Head and Neck Surgery, Stanford University, Palo Alto, CA, United States J.V. Nayak Department of Otolaryngology â€" Head and Neck Surgery, Stanford University, Palo Alto, CA, United States P.H. Hwang Department of Otolaryngology â€" Head and Neck Surgery, Stanford University, Palo Alto, CA, United States 2191 10.4193/Rhin19.213 BACKGROUND: The extent of endoscopic sinus surgery (ESS) required for optimal outcomes in chronic rhinosinusitis (CRS) is undefined. We evaluated whether concordance between the extent of surgery and degree of radiographic disease influences postoperative outcomes. METHODS: 247 CRS patients who underwent ESS were retrospectively assigned a concordance score reflecting the similarity between the extent of surgery and degree of radiographic disease. 0 points were assigned when sinusotomy was performed on a diseased sinus, or no sinusotomy was performed on a nondiseased sinus; plus 1 for sinusotomy on a nondiseased sinus; and -1 for a diseased sinus left unopened. The total possible score ranged from minus 10 to plus 10. Patients were divided into 5 subgroups according to variance from complete concordance. SNOT-22 scores and revision rates were compared at 6 and 24 months. RESULTS: All five subgroups had similar preoperative SNOT-22 scores and improved at 6 months postoperatively. At 6 months postoperatively, the most conservatively operated and most extensively operated subgroups each achieved equivalent improvements in SNOT-22 as the completely concordant subgroup. At 24 months, the most extensively operated subgroup had a 12.5-point smaller improvement in SNOT-22 scores compared to the completely concordant subgroup. Multivariate analysis showed no association between concordance score and revision rate. CONCLUSIONS: Symptom improvement and revision rates after ESS do not appear to correlate with the degree of concordance between extent of surgery and radiographic disease. More extensive surgery than indicated by CT confers neither greater symptomatic improvement nor long-term detriment.

International Rhinologic Society Rhinology 0300-0729 58 1 2020 February 1 31287451 Impact of anterior skull base fracture on lateralized olfactory function 45 50 EN V. Gudziol Department of Otorhinolaryngology, Smell and Taste Clinic, Technische Universitat Dresden, Germany; Department of Otorhinolaryngology, Head and Neck Surgery, Municipal Hospital Dresden, Germany T. Marschke Department of Anesthesiology, Technische Universitat Dresden, Germany J. Reden Department of Otorhinolaryngology, Smell and Taste Clinic, Technische Universitat Dresden, Germany T. Hummel Department of Otorhinolaryngology, Smell and Taste Clinic, Technische Universitat Dresden, Germany 1912 10.4193/Rhin18.092 BACKGROUND: Data on the impact of anterior skull base fractures (aSBF) on lateralized olfactory function are missing. The goal of the study was to investigate olfactory function in patients with traumatic brain injury (TBI) due to aSBF separately for each side and assess the frequency of lateralized smell impairment. METHODS: Retrospective, single center study of olfactory function in 93 patients with aSBF. Olfactory function was assessed by means of the Sniffin' Sticks test battery for each side of the nose, separately. TBI severity was graded according to the Glasgow Coma Scale. Average time interval between olfactory test and trauma was 6.5 years. General olfactory function was defined as the best side out of both nostrils. RESULTS: A total of 50 patients had unilateral and 43 patients bilateral aSBF. The grade of TBI was inversely correlated with olfactory function. General olfactory function was significantly worse in patients with bilateral aSBF compared to patients with unilateral aSBF. Clinically significant side by side differences in olfactory function were found in 18 and 30% respectively for unilateral and bilateral aSBF. Grade of TBI had no significant impact on side differences. Among patients with unilateral aSBF olfactory function was not significantly different between the fractured and the non-fractured side. CONCLUSION: The severity of TBI and bilateral more than unilateral aSBF results in more impaired olfactory function. Lateralized olfactory deficits were not more frequent in any group, regardless of the fracture type and side.

International Rhinologic Society Rhinology 0300-0729 58 1 2020 February 1 31475696 Assessment of craniofacial hyperhidrosis and flushing by sphenopalatine blockade - a randomized trial 51 58 EN E. Lehrer Rhinology and Skull Base Unit, Department of Otorhinolaryngology, Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Institut d Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain A. Nogues Rhinology and Skull Base Unit, Department of Otorhinolaryngology, Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Institut d Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain F. Jaume Department of Otorhinolaryngology, Hospital Comarcal d’Inca, Mallorca, Spain J. Mullol Rhinology and Skull Base Unit, Department of Otorhinolaryngology, Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Institut d Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES), Barcelona, Catalonia, Spain I. Alobid Rhinology and Skull Base Unit, Department of Otorhinolaryngology, Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain; Institut d Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES), Barcelona, Catalonia, Spain; Unidad Alergo Rino, Centro Medico Teknon, Barcelona, Catalonia, Spain 1951 10.4193/Rhin19.119 BACKGROUND: Craniofacial hyperhidrosis (CFH) and flushing express nervous system autonomic dysfunction. Available reference treatments lack good compliance. The study objective was to investigate variations of CFH/flushing after two methods of sphenopalatine ganglion (SPG) blockade. METHODOLOGY: CFH patients (n=25) were randomized in a ratio of 1:3 in two groups; 1) endoscopic application of topical lidocaine over SPG (TL; n=7); 2) endoscopic injection of lidocaine in the SPG (IL; n=18). CFH, flushing, rhinorrhoea, nasal obstruction, and smell detection were scored by Visual Analogue Scale (VAS). Nasal endoscopy, acoustic rhinometry, mucociliary transport test, smell/taste test, Schirmer test, Short Form-12, Chronic Skin Diseases Questionnaire, and Skin Satisfaction Questionnaire were also performed at visit 0, 1, 3 and 6 months. RESULTS: At baseline, groups reported similar CFH VAS (TL: 89.3 plus or minus 17.5mm; IL: 85.7 plus or minus 22.1mm) or flushing VAS (TL: 52.7 plus or minus 30mm; IL: 59 plus or minus 33.8mm). After 6 months, the least squares mean of CFH VAS in IL was -38.1 (-47.3 to -28.9) compared to TL 1.9 (-12.2 to 15.9). However, flushing VAS did not improve. Any rhinological measure nor quality of life test showed significant changes. One patient presented controlled epistaxis intraoperatively during IL. CONCLUSIONS: This preliminary study shows the sphenopalatine blockade injection as a safe procedure. Patients with CFH or flushing had significant improvement after lidocaine injection which lasted 6 months. Due to the small sample and the lack of objective measures more studies are needed.

International Rhinologic Society Rhinology 0300-0729 58 1 2020 February 1 31448805 Pathological changes from the originating to the peripheral sites of Sinonasal Inverted Papilloma are the underlying mechanisms of preoperative MRI-tumor origin prediction 59 65 EN S. Ma Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China M. Xian Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China B. Yang Department of Radiology, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China G. Fang Department of Otolaryngology Head and Neck Surgery, Beijing DiTan Hospital, Capital Medical University, Beijing, PR China H. Lou Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China W. Yu Department of Radiology, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China X. Wang Beijing Key Laboratory of nasal diseases, Beijing Institute of Otolaryngology, Beijing, PR China; Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China J. Xian Department of Radiology, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China X. Song Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China E. Fan Beijing Key Laboratory of nasal diseases, Beijing Institute of Otolaryngology, Beijing, PR China Y. Li Beijing Key Laboratory of nasal diseases, Beijing Institute of Otolaryngology, Beijing, PR China L. Zhang Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China; Department of Radiology, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China; Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China C. Wang Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China 1950 10.4193/Rhin19.131 BACKGROUND: Our previous study showed that convoluted cerebriform pattern (CCP)-based reverse tracing method in preoperative magnetic resonance imaging (MRI) is a reliable tool in predicting originating site of sinonasal inverted papilloma (SNIP). This study aimed to determine the underlying pathological mechanism of the preoperative MRI-CCP reverse tracing method by assessing the histopathological changes from the origin to the peripheral sites of SNIP. METHODOLOGY: The originating site of SNIP was predicted by preoperative MRI in 30 consecutive patients suspected to have primary SNIP. Samples of SNIP originating and peripheral sites were processed by pathological staining for evaluation of stroma score, micro-vessel density (MVD), and tight junction proteins (claudin-5, zonula occludens (ZO)-1 and occludin) expression. RESULTS: The originating site of SNIP was accurately predicted by preoperative MRI in all patients. Stroma scores, and MVD were significantly greater in the periphery of SNIP than in the originating site. In contrast, Claudin-5 expression in micro-vessels was greater at the originating site than the periphery. CONCLUSIONS: More edematous stroma and intensive micro-vessels with defective tight junction in periphery of SNIP result in more contrast agent diffusing and CCP that can only be observed at the periphery of SNIP on T2 and contrast-enhanced T1 weighted MR images, which may be the mechanisms underlying the CCP reverse tracing method.

International Rhinologic Society Rhinology 0300-0729 58 1 2020 February 1 31680128 Fipronil upregulates inflammatory cytokines and MUC5AC expression in human nasal epithelial cells 66 73 EN S. Kwak Department of Medical Science, College of Medicine, Graduate School of Yeungnam University, Daegu, Republic of Korea; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea Y.S. Choi Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea H.G. Na Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea C.H. Bae Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea S.-Y. Song Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea Y.-D. Kim Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea; Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Republic of Korea 2192 10.4193/Rhin19.172 BACKGROUND: Airway inflammation and excessive mucin production are pathophysiological characteristics of airway diseases. Fipronil, a pesticide, is being extensively used in agriculture and veterinary medicine worldwide. However, this compound impairs immune function in non-target organisms. The present study aimed to evaluate the effect of fipronil on pro-inflammatory cytokine and mucus production and signalling pathways in human primary nasal METHODOLOGY: The effect of fipronil on pro-inflammatory cytokine and MUC5AC expression and the signalling pathway of fipronil were investigated using real-time PCR, enzyme immunoassays, immunofluorescence, and immunoblot analysis with specific inhibitors and small interfering RNA. RESULTS: Fipronil treatment increased pro-inflammatory cytokine interleukin (IL)-1beta, IL-6, IL-8, and MUC5AC expression in human primary nasal epithelial cells. It also induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) mitogenactivated protein kinase (MAPK), p38 MAPK, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). MAPK and NF-kB inhibitor treatment significantly inhibited increases in IL-1beta, IL-6, IL-8, and MUC5AC expression. Ex vivo data confirmed that fipronil-induced MUC5AC expression occurs through ERK1/2, p38, and NF-kB signalling pathways in nasal inferior turbinate tissue. CONCLUSIONS: Fipronil induced pro-inflammatory cytokine IL-1beta, IL-6, IL-8, and MUC5AC expression via ERK1/2 MAPK, p38 MAPK, and NF-kB in human primary nasal epithelial cells.

International Rhinologic Society Rhinology 0300-0729 58 1 2020 February 1 31710049 Stathmin and EGFR correlates to HPV status and clinical outcome in sinonasal inverted papilloma 74 79 EN A. Elliot Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institutet, Stockholm, Sweden A. Nasman Department of Oncology-Pathology, Department of Clinical Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden M. Westman Department of Medicine Solna, Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden L. Hammarstedt-Nordenvall Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institutet, Stockholm, Sweden P. Stjarne Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institutet, Stockholm, Sweden L. Marklund Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institutet, Stockholm, Sweden 2195 10.4193/Rhin19.078 BACKGROUND: Inverted papilloma (IP) is a locally destructive benign tumour of the sinonasal mucosa with a tendency for malignant transformation. Stathmin and epidermal growth factor receptor (EGFR) are important markers in cancer prognosis. Here we investigate if expression of stathmin and EGFR correlate to dysplasia, recurrence and HPV in IP. METHODS: 98 patients with IP diagnosed 2000-2010 were analyzed for stathmin and EGFR by immunohistochemistry (IHC) and HPV by polymerase chain reaction assay (PCR). RESULTS: All IPs expressed stathmin while its expression was absent or weak in normal mucosa. Dysplasia was present in 26,7% of IPs with high stathmin expression while only 7.4% of IPs with low stathmin expression showed dysplasia. Stathmin positive IPs showed a trend towards earlier recurrences. 57.1% of IP expressed EGFR but no significant association was seen between EGFR-positivity and recurrence or dysplasia. EGFR was expressed by 91.7% of the HPV-positive IPs compared to 52,3% of the HPV negative IPs. CONCLUSIONS: EGFR expression is significantly higher in HPV positive IP. Stathmin is expressed by all IP tumour cells. Stathmin was also associated with dysplasia and a trend towards a correlation between stathmin positivity and recurrence was found. Stathmin and EGFR might therefore be considered therapeutic targets.