International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 38372674 Microbiome analyses in chronic rhinosinusitis 129 129 EN T. Smulders Amsterdam, the Netherlands S. Reitsma Amsterdam, the Netherlands C.M. van Drunen Amsterdam, the Netherlands 3160 10.4193/Rhin24.902 In this edition of Rhinology we feature the work of Connell and colleagues from Australia on chronic rhinosinusitis that describes an interesting new pipeline to characterize the bacterial composition of microbiota. We are constantly exposed to a multitude of micro-organisms in the environment and our immune system has the important task discerning and fighting off potential threats. In most people the immune system is doing its job properly and prevents anything untoward from happening. On occasion, a microbe slips by the first (innate) level of defense and we might suffer from an infection. This then activates the second layer of (the adaptive) defense tasked to clear this infection. Sometimes the immune system gets its wrong and starts a full-out defense against something harmless, and an allergy is born. The task of the immune system of doing what is right is even more difficult than it might seem at first sight. In addition to these incidental potential threats, our mucosal surfaces are lined with commensal bacteria which contributes to the complexity of our environment. This collection of bacteria or microbiome has become a major focus of research, as the composition of this microbiome seems related to the health state of the individual. Originally the relationship between the gut microbiome and the development of asthma and allergy was the main focus. In recent years, the focus has been broadened to include the microbiome of the upper and lower airways. In addition to allergy, our field has also been given more and more attention to studying the microbiome in chronic rhinosinusitis.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 37943054 Association of gustatory dysfunction and Alzheimer 130 142 EN I-Y. Kwak Department of Applied Statistics, Chung-Ang University, Heukseok-dong, Dongjak-gu, Seoul, South Korea K.S. Kim Department of Otorhinolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Heukseok-dong, Dongjak-gu, Seoul, South Korea H.J. Min Department of Otorhinolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Heukseok-dong, Dongjak-gu, Seoul, South Korea 3133 10.4193/Rhin23.235 BACKGROUND: Chemosensory dysfunction has been reported to be involved in the pathogenesis of Alzheimer’s disease (AD). Compared with olfaction, gustatory dysfunction in AD has not been evaluated in depth. We reviewed previously published studies regarding gustatory dysfunction in patients with AD compared with healthy controls. METHODS: A systematic review was conducted by searching the MEDLINE, Cochrane Library, Embase, and PubMed databases covering publications from January 2000 to February 2023. The search was performed using the keyword "Alzheimer* AND (gustatory OR taste OR gustation)." Only studies that performed gustatory function testing and compared the results between patients with AD and healthy controls were included. A random-effects meta-analysis was performed. RESULTS: Twelve articles were finally included, and various gustatory tests including taste strips, the taste disk test, taste solutions, and subjective questionnaires were applied. Overall gustatory function based on the taste strip test was significantly decreased in patients with AD compared with controls in two out of three papers. The overall gustatory function of patients with AD was significantly decreased in all studies based on the taste disk and taste solution tests. We also found that the sweet taste test showed low heterogeneity across all the included studies, and there was low publication bias. In studies using subjective questionnaires, gustatory function was not significantly different between patients with AD and healthy controls in the meta-analysis. CONCLUSIONS: Based on these studies, gustatory dysfunction diagnosed by gustatory function testing was closely related to AD. However, the results of subjective questionnaires were not significantly different between patients with AD and healthy controls in the current meta-analysis. As the number of studies and enrolled subjects was limited and unified gustatory function testing was lacking, further studies are needed to confirm this relationship.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 37942998 Topical anaesthesia and decongestion in rhinology 143 151 EN S. J. M. Hale Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Grafton, Auckland, New Zealand R. Kim Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Grafton, Auckland, New Zealand R. G. Douglas Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Grafton, Auckland, New Zealand 3131 10.4193/Rhin23.285 Topical anaesthesia and decongestion of the sinonasal mucosa are used commonly in rhinology practice to facilitate nasal endoscopy, as well as debridement and biopsies. Topical agents used for sinonasal anaesthesia include lignocaine, tetracaine and cocaine. Unlike lignocaine and tetracaine, cocaine also has a decongestant effect. Phenylephrine, oxymetazoline, xylometazoline or adrenaline are usually added to lignocaine and tetracaine to provide decongestion. Several studies have been performed seeking to identify the optimal nasal preparation for nasal endoscopy in the clinic setting. However, there remains no clear consensus in the literature resulting in ongoing wide variation between anaesthetic-decongestant preparations used in clinical practice. Indeed, some authors have argued that no anaesthetic is required at all for flexible nasendoscopy despite the apparent consensus that nasal instrumentation is generally uncomfortable, inferred by the persistence of ongoing research in this area. This review provides a practical summary of local anaesthetic and decongestant pharmacology as it relates to rhinologic practice and summarises the literature to date, with the goal of identifying current gaps in the literature and guiding future research efforts.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 38165666 Enhanced phylogenetic insights into the microbiome of chronic rhinosinusitis through the novel application of long read 16S rRNA gene amplicon sequencing 152 162 EN J. T. Connell Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide, South Australia, Australia; Department of Otolaryngology, Head and Neck Surgery, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia K. Yeo Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide, South Australia, Australia; G. Bouras Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide, South Australia, Australia; A. Bassiouni Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide, South Australia, Australia; Department of Otolaryngology, Head and Neck Surgery, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia K. Fenix Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide, South Australia, Australia C. Cooksley Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide, South Australia, Australia S. Vreugde Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide, South Australia, Australia P.J. Wormald Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide, South Australia, Australia; Department of Otolaryngology, Head and Neck Surgery, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia A.J. Psaltis Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide, South Australia, Australia; Department of Otolaryngology, Head and Neck Surgery, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia 3146 10.4193/Rhin23.333 INTRODUCTION: 16S rRNA next generation sequencing (NGS) has been the de facto standard of microbiome profiling. A limitation of this technology is the inability to accurately assign taxonomy to a species order. Long read 16S sequencing platforms, including Oxford Nanopore Technologies (ONT), have the potential to overcome this limitation. The paranasal sinuses are an ideal niche to apply this technology, being a low biomass environment where bacteria are implicated in disease propagation. Characterising the microbiome to a species order may offer new pathophysiological insights. METHODOLOGY: Cohort series comparing ONT and NGS biological conclusions. Swabs obtained endoscopically from the middle meatus of 61 CRSwNP patients underwent DNA extraction, amplification and dual sequencing (Illumina Miseq (NGS) and ONT GridION). Agreement, relative abundance, prevalence, and culture correlations were compared. RESULTS: Mean microbiome agreement between sequencers was 61.4%. Mean abundance correlations were strongest at a familial/genus order and declined at a species order where NGS lacked resolution. The most significant discrepancies applied to Corynebacterium and Cutibacterium, which were estimated in lower abundance by ONT. ONT accurately identified 84.2% of cultured species, which was significantly higher than NGS. CONCLUSIONS: ONT demonstrated superior resolution and culture correlations to NGS, but underestimated core sinonasal taxa. Future application and optimisation of this technology can advance our understanding of the sinonasal microenvironment.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 37943027 Predictive factors of involuntary weight loss in patients with smell and taste disorders 163 171 EN D. Daskalou Rhinology-Olfactology Unit, Service of Otorhinolaryngology-Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland; The inner ear and olfaction neurosensory laboratory, University of Geneva, Faculty of Medicine, Geneva, Switzerland J.W. Hsieh Rhinology-Olfactology Unit, Service of Otorhinolaryngology-Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland; The inner ear and olfaction neurosensory laboratory, University of Geneva, Faculty of Medicine, Geneva, Switzerland M. Hugentobler Rhinology-Olfactology Unit, Service of Otorhinolaryngology-Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland S. Macario Rhinology-Olfactology Unit, Service of Otorhinolaryngology-Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland R. Sipione The inner ear and olfaction neurosensory laboratory, University of Geneva, Faculty of Medicine, Geneva, Switzerland F. Voruz Rhinology-Olfactology Unit, Service of Otorhinolaryngology-Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland G. Coppin Department of Psychology, UniDistance Suisse, Swiss Center for Affective Sciences, and Laboratory for the Study of Emotion Elicitation and Expression, Department of Psychology, University of Geneva, Switzerland J. Rimmer Department of Otolaryngology-Head and Neck Surgery, Monash Health, Department of Otolaryngology-Head and Neck Surgery, St Vincent’s Hospital Melbourne, and Department of Surgery, Monash University, Melbourne, Australia B.N. Landis Rhinology-Olfactology Unit, Service of Otorhinolaryngology-Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland; The inner ear and olfaction neurosensory laboratory, University of Geneva, Faculty of Medicine, Geneva, Switzerland 3132 10.4193/Rhin23.222 BACKGROUND: Chemosensory dysfunction (olfaction, taste, and trigeminal) affects quality of life, potentially impacting eating behaviors. We investigated which factors are associated with weight loss in patients with smell and taste disorders. METHODS: Retrospective study of consecutive adult patients seen in the smell and taste clinic during a 10-year period. Patients were asked about smell, flavor and taste impairment. Psychophysically, smell was assessed with Sniffin' Sticks, flavor with a retronasal test, and taste with Taste Strips. RESULTS: A total of 554 patients (313 females) were included with a median age of 51 years (IQR 23). Seventy-six (13.7%) reported involuntary weight loss (median 6 kg, IQR 6) due to chemosensory disorders. The odds of losing weight were 2.1 times higher when patients reported subjective changes in flavor perception. Parosmia was a significant predictor of weight loss. Patients with symptoms lasting longer than two years were less likely to present with weight loss. Post-traumatic chemosensory dysfunction was a significant predictor of losing weight. On psychophysical testing, the probability of a patient losing weight increased by 8% for every 1-unit reduction in Taste Strips score. CONCLUSION: Factors associated with weight loss were self-reported changes in flavor perception, parosmia, duration of symptoms for less than two years, head injury, and psychophysically measured low Taste Strips score. These data help to identify patients at risk of weight loss from smell or taste impairment.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 37955246 Can MRI predict olfactory loss and improvement in posttraumatic olfactory dysfunction? 172 182 EN J.W. Hsieh Rhinology-Olfactory Unit, Department of Otorhinolaryngology - Head and Neck Surgery, Geneva University Hospitals, Geneva, Switzerland; The Inner Ear and Olfaction Lab, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland V. Lenoir Division of Radiology, Department of diagnostics, Geneva University Hospitals, Geneva, Switzerland R. Sipione The Inner Ear and Olfaction Lab, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland M. Hugentobler Rhinology-Olfactory Unit, Department of Otorhinolaryngology - Head and Neck Surgery, Geneva University Hospitals, Geneva, Switzerland D. Daskalou Rhinology-Olfactory Unit, Department of Otorhinolaryngology - Head and Neck Surgery, Geneva University Hospitals, Geneva, Switzerland J.N. Lundström Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA, USA; Stockholm University Brain Imaging Centre, Stockholm University, Stockholm, Sweden P. Senn Rhinology-Olfactory Unit, Department of Otorhinolaryngology - Head and Neck Surgery, Geneva University Hospitals, Geneva, Switzerland; The Inner Ear and Olfaction Lab, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland J. Rimmer Department of Otolaryngology, Head and Neck Surgery, Monash Health, Melbourne, Australia; Department of Surgery, Monash University, Melbourne, Australia M. Becker Division of Radiology, Department of diagnostics, Geneva University Hospitals, Geneva, Switzerland B.N. Landis Rhinology-Olfactory Unit, Department of Otorhinolaryngology - Head and Neck Surgery, Geneva University Hospitals, Geneva, Switzerland; The Inner Ear and Olfaction Lab, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland 3134 10.4193/Rhin23.246 BACKGROUND: Although most patients with post-traumatic olfactory dysfunction (PTOD) undergo MRI, there is no consensus about its diagnostic or prognostic value. The aims were: 1) to classify the extent of post-traumatic neurodegeneration; 2) to determine its relationship with chemosensory dysfunction (smell, taste, trigeminal); and 3) to establish whether MRI can predict olfactory improvement. METHODOLOGY: We conducted a retrospective cohort study based on a series of 56 patients with PTOD. All patients underwent validated psychophysical tests of their smell, taste, and trigeminal functions, otorhinolaryngologic evaluation, and MRI. An experienced radiologist blinded to patient data evaluated 40 chemosensory-relevant brain regions according to a four-point scale (0=no lesion to 3=large lesion). Follow up data after 4 years (on average) were available in 46 patients. RESULTS:The cluster analysis showed 4 brain lesion patterns that differed in lesion localization and severity. They are associated with diagnostic categories: anosmia, hyposmia and normosmia. Two clusters were highly specific for anosmia (100% specificity)and could accurately predict this condition (100% positive predictive value). No clusters were associated with trigeminal or taste dysfunction. Regarding improvement, 72.7% of patients in the cluster with mild lesions experienced subjective and measurable olfactory improvement whereas this was only the case in 21.7-37.5% of patients with larger lesions. The odds of subjective smell improvement were 5.9 times higher in patients within the milder cluster compared to larger ones. CONCLUSIONS: The analysis of brain lesions in PTOD allows corroboration of smell test results and prediction of subjective and measurable improvement.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 38009582 Evidence for a role of metformin in preventing olfactory dysfunction among older adults 183 191 EN S. Assi Cochlear Center for Hearing and Public Health, Johns Hopkins University, Baltimore, MD, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA V. Vohra Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA W. Zhang Cochlear Center for Hearing and Public Health, Johns Hopkins University, Baltimore, MD, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA N.S. Reed Cochlear Center for Hearing and Public Health, Johns Hopkins University, Baltimore, MD, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA A. P. Lane Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA M. Ramanathan Jr. Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA N.R. Rowan Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3138 10.4193/Rhin23.250 BACKGROUND: Olfactory dysfunction (OD) is increasingly recognized as a hallmark of unhealthy aging and is intimately associated with mortality, but therapies remain elusive. Recognizing the increased prevalence of OD in individuals with diabetes, and the potential anti-aging effects of metformin, we studied the association of metformin use with OD. METHODS: Cross-temporal study of participants from Waves 2 (2010-11) and 3 (2015-16) of the National Social Life, Health, and Aging Project (NSHAP), a nationally representative cohort study of community-dwelling older adults. We included participants with diabetes who had complete data on olfaction and relevant covariates at Wave 2 and were not lost to follow-up at Wave 3. Olfactory identification (OI), the ability to identify the odorant, and olfactory sensitivity (OS), the ability to detect the presence of an odorant, were tested. Weighted multivariable logistic regression was used to study the association between metformin use at Wave 2 (baseline) and odds of having impaired OI/OS at Wave 3, adjusted for age, sex, race/ethnicity, education, smoking, BMI, HbA1c, years since diabetes diagnosis, and insulin use. RESULTS: Among 228 participants with diabetes (mean age=70 years, 53% female, 21% Black), 112 (49%) used metformin at baseline. Relative to nonusers, users had 58% lower odds of impaired OI and 67% lower odds of impaired OS at Wave 3. Among participants with normal baseline OS (N=62), users had 97% lower odds of impaired OS at Wave 3. CONCLUSIONS: Metformin use is associated with lower odds of OD among individuals with diabetes, suggesting a potential protective effect on olfaction. Future work including a larger sample and additional information on metformin use is needed to establish whether these findings are independent of diabetic control.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 37942939 Can serum IgE or blood eosinophil count predict postoperative oral corticosteroid response in chronic rhinosinusitis with nasal polyps? 192 201 EN K-H. Shen Department of Otolaryngology Head and Neck Surgery, Mackay Memorial Hospital, Taipei, Taiwan; Department of Otolaryngology Head and Neck Surgery, Mackay Memorial Hospital, Taitung, Taiwan J-Y. Jiang Department of Otolaryngology Head and Neck Surgery, Mackay Memorial Hospital, Taipei, Taiwan P-Y. Hsu Department of Otolaryngology Head and Neck Surgery, Mackay Memorial Hospital, Taipei, Taiwan J. C-Y. Lai Department of Otolaryngology Head and Neck Surgery, Mackay Memorial Hospital, Taipei, Taiwan; MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taitung, Taiwan W-H. Huang Department of Otolaryngology Head and Neck Surgery, Mackay Memorial Hospital, Taipei, Taiwan P-S. Wu MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Department of Pathology, Mackay Memorial Hospital, Taipei City, Taiwan Y-P. Wang Department of Otolaryngology Head and Neck Surgery, Mackay Memorial Hospital, Taipei, Taiwan; School of Medicine, Mackay Medical College, New Taipei City, Taiwan; Department of Audiology and Speech Language Pathology, Mackay Medical College, New Taipei City, Taiwan 3130 10.4193/Rhin23.124 BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterised by inflammatory mucosa and polyp formation in the paranasal sinuses. The study's primary objective was to evaluate the outcomes of postoperative oral corticosteroid (OCS) in treating patients with bilateral CRSwNP. The secondary objective was to determine whether preoperative serum IgE levels (sIgE)and/or blood eosinophil count (BEC) correlate with postoperative outcomes following OCS use. METHODS: Patients with bilateral CRSwNP (n=236) who underwent endoscopic sinus surgery (ESS) were randomly assigned to receive 15 mg OCS twice daily or a placebo for 2 weeks. We investigated the treatment effects based on the subjective visual analogue scale (VAS), Sino-Nasal Outcome Test 22 (SNOT-22), and objective Lund-Kennedy Endoscopy Score (LKES) over 6 months; subgroups were stratified preoperatively as follows: sIgE <150 IU/mL, sIgE&gt;=150 IU/mL, BEC <0.39x10(9) cells/L, and BEC&gt;=0.39x10(9) cells/L. RESULTS: A total of 193 participants completed the study up to the 6-month follow-up; no apparent linear relationship was noted between sIgE and BEC. No significant differences in scores were noted upon assessment of the VAS, SNOT-22, and LKES among the follow-up timepoints in the primary analysis. However, in the primary or subgroup analyses with sIgE or BEC, significant differences in the longitudinal scores of sleep dysfunction were observed at the 1-month follow-up. CONCLUSION: Postoperative OCS did not significantly affect bilateral CRSwNP outcomes. sIgE levels and BEC may not be surrogate predictive biomarkers to assess the role of postoperative OCS use. OCS may increase the risk of transient sleep disturbance.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 37999634 Hypereosinophilia during dupilumab treatment in patients with chronic rhinosinusitis with nasal polyps 202 207 EN P. Kemp Department of Otorhinolaryngology, Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands R.J.L. van der Lans Department of Otorhinolaryngology, Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands J.J. Otten Department of Otorhinolaryngology, Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands G.F.J.P.M. Adriaensen Department of Otorhinolaryngology, Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands L.B.L. Benoist Department of Otorhinolaryngology, Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands M.E. Cornet Department of Otorhinolaryngology, Alrijne Hospital, Leiden, The Netherlands D.R. Hoven Department of Otorhinolaryngology, Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands B. Rinia Department of Otorhinolaryngology, Isala Hospital, Zwolle, The Netherlands V. Verkest Department of Otorhinolaryngology, GZA Hospital Sint-Vincentius, Antwerp, Belgium W.J. Fokkens Department of Otorhinolaryngology, Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands S. Reitsma Department of Otorhinolaryngology, Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands 3137 10.4193/Rhin23.357 BACKGROUND: Increased blood eosinophil count (BEC) is common in patients under dupilumab treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). This study investigated the prevalence and consequences of hypereosinophilia and to help define patients at risk. METHODS: Real-life, prospective observational cohort study of patients treated with dupilumab for severe CRSwNP. Eligible patients were adult and biological-naïve (N=334). All BEC values at baseline and during treatment were reported. Patients with a follow-up of ≥ 1 year were included to define patients at risk for hypereosinophilia by comparing baseline BEC values (N=218). Furthermore, clinical characteristics and therapeutic consequences for patients with BEC ≥ 3.0 were noted. RESULTS: Hypereosinophilia developed in a minority of patients, with a peak at week 12 (16.2% with BEC ≥ 1.5, and 1.7% ≥ 3.0) in cross-sectional analysis. BEC ≥ 1.5 developed in 28.9% and BEC ≥ 3.0 in 4.6% of cases with a minimal 1-year follow-up. Baseline BEC was significantly higher for patients developing BEC ≥ 1.5 and BEC ≥3.0, with an optimal cut-off point of 0.96 to predict developing BEC ≥ 3.0. CONCLUSIONS: Blood eosinophil count (BEC) ≥ 1.5 is transient and usually abates with no therapeutic interventions and BEC ≥ 3.0 is rare. Hypereosinophilic syndrome did not occur and switching to a different biological was rarely employed. A baseline BEC of ≥1.0 can be a reason for extra caution.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 38073582 Aetiology of cerebrospinal fluid rhinorrhoea in a Dutch retrospective cohort from two tertiary referral centres 208 215 EN W.B. de Jong Department of Otorhinolaryngology and head/neck surgery, Amsterdam University Medical Centers, location AMC, University of Amsterdam, the Netherlands; Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC, Rotterdam, the Netherlands J. Hoogmoed Department of Neurosurgery, Amsterdam University Medical Centers, location AMC, University of Amsterdam, the Netherlands G.F.J.P.M. Adriaensen Department of Otorhinolaryngology and head/neck surgery, Amsterdam University Medical Centers, location AMC, University of Amsterdam, the Netherlands A.P. Nagtegaal Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC, Rotterdam, the Netherlands S. Reitsma Department of Otorhinolaryngology and head/neck surgery, Amsterdam University Medical Centers, location AMC, University of Amsterdam, the Netherlands 3142 10.4193/Rhin23.158 BACKGROUND: Cerebrospinal fluid (CSF) rhinorrhoea has different aetiologies, with spontaneous leaks related to female gender and obesity. Limited data is available on patient characteristics and surgical outcomes across different aetiologies of CSF leaks in relatively non-obese populations. METHODS: Retrospective cohort study from two tertiary referral centres including adult patients that underwent surgical closure of a CSF leak, divided into four aetiologies: traumatic, iatrogenic, secondary to structural intracranial pathology (SIP), and spontaneous. Data included patient characteristics, presenting symptoms, preoperative radiologic findings, intracranial pressure (ICP) and surgical outcomes. RESULTS: 72 patients were included: 9 traumatic, 15 iatrogenic, 4 SIP and 44 spontaneous leaks. Primary surgical success was 79%, rising to 93% with reinterventions. Spontaneous leak cases displayed highest female proportion and BMI. A meningo(-encephalo)cele was present in 33 patients and was associated with surgical failure and previous meningitis. No significant differences were observed between different aetiologies regarding patient characteristics, presenting symptoms, or surgical success rates. CONCLUSIONS: Even in a relatively non-obese population, the majority of CSF leaks is spontaneous and associated with female gender and obesity. Otherwise, no differences exist across aetiologies regarding patient characteristics, presenting symptoms or surgical success.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 37983015 Skin Prick Automated Test device offers more reliable allergy test results compared to a manual skin prick test 216 222 EN S.F. Seys Hippo Dx, Aarschot, Belgium K. Roux Department of Otorhinolaryngology-Head and Neck Surgery, UZ Leuven, Leuven, Belgium C. Claes Department of Otorhinolaryngology-Head and Neck Surgery, UZ Leuven, Leuven, Belgium L. Van Cappellen Department of Otorhinolaryngology-Head and Neck Surgery, UZ Leuven, Leuven, Belgium L. Werpin Department of Otorhinolaryngology-Head and Neck Surgery, UZ Leuven, Leuven, Belgium D. Loeckx Hippo Dx, Aarschot, Belgium H. Sebrechts Department of Otorhinolaryngology, AZ Herentals, Herentals, Belgium S. Gorris Hippo Dx, Aarschot, Belgium; Department of Otorhinolaryngology, AZ Herentals, Herentals, Belgium L. Van Gerven Department of Otorhinolaryngology-Head and Neck Surgery, UZ Leuven, Leuven, Belgium; Laboratory of Experimental Otorhinolaryngology, Department of Neurosciences, KU Leuven, Belgium; Allergy and Clinical Immunology Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium 3136 10.4193/Rhin23.330 BACKGROUND: The skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of inhalant allergy. A novel device, SPAT or Skin Prick Automated Test, that enables more standardized allergy testing has been developed. Previous research has shown reduced intra-subject variability of histamine wheals by SPAT. OBJECTIVE: This study aimed to evaluate within-test agreement (% of patients with consistent test results) to detect sensitization to common inhalant allergens when a SPT is executed automated by SPAT or by manual SPT (SPMT) procedure. METHODS: The 110 volunteers prospectively enrolled underwent both SPAT and SPMT with 3 pricks of house dust mite, timothy grass and birch, 2 pricks of histamine and 1 prick of glycerol. The proportion of consistent (3x positive â€" 3 x negative) and inconsistent (2x positive/negative â€" 1x positive/negative) test results were analysed. Results: The proportion of inconsistent test results was significantly lower in the SPAT compared to the SPMT group. The delta histamine to control pricks was significantly higher in SPAT compared to SPMT group. Coefficient of variation was lower in SPAT compared to SPMT for house dust mite, timothy grass, birch pollen. Visual analogue scale for discomfort was significantly lower in SPAT compared to SPMT group. CONCLUSION: SPAT showed a 34% reduction in the number of inconsistent test results compared to manual SPT with common inhalant allergens. Patient experience is significantly improved when an allergy test is performed by SPAT compared to a manual SPT.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 38010118 Comparative investigation of transport and deposition of nebulized particles in nasal airways following various middle turbinectomy 223 235 EN R. Ma Department of Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China L. Tian School of Engineering, Mechanical and Automotive, RMIT University, Bundoora, VIC, Australia Y. Wang Department of Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China S. Sun Zhejiang Cuize Pharmatech Co., Ltd, China J. Zhang Department of Medical Imaging Department, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China M. Lou Department of Otolaryngology Head and Neck Surgery, Shaanxi Provincial People’s Hospital, Xi’an, China Z. Hu Department of Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China M. Gong Department of Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China F. Yang Department of Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China G. Zheng Department of Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China J. Dong Institute for Sustainable Industries and Liveable Cities, Victoria University, Melbourne, Australia; First Year College, Victoria University, Footscray Park Campus, Footscray, Australia Y. Zhang Department of Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China 3141 10.4193/Rhin23.265 BACKGROUND: Topical intranasal medication is required following functional endoscopic sinus surgery (FESS). The optimal particle size of transnasal nebulization aimed at the sinonasal cavities is not conclusive. The current study aims to evaluate the effect of particle size and various surgery scope of middle turbinectomy (MT) on post-full FESS drug delivery to the sinonasal cavities. METHODS: Sinonasal reconstructions were performed from post-full FESS CT scans in 6 chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Four additional models representing alternative surgery scopes of MT were established from each post-FESS reconstruction for simulation data comparison. Airflow and particle deposition of nebulized delivery were simulated via computational fluid dynamics (CFD) and validated through in vitro experiments. The optimal particle sizes reaching a deposition of at least 75% of the maximum in the targeted regions were identified. RESULTS: The drug deposition rate onto the targeted regions increased following MT, with the greatest deposition following posterior MT (P-MT). Droplets in the range of 18-26 μm reached a deposition of larger than 75% of the maximum onto the targeted regions. Drug delivery rate in the sinonasal cavities varied significantly among individuals and across different types of MT with varying surgical scopes. CONCLUSIONS: This study is the first to investigate the effect of various surgery scope on drug delivery by transnasal nebulization to the sinonasal cavities. The findings strongly affirm the vast potential of transnasal nebulization as an effective post-FESS treatment option. Moreover, it emphasizes that the drug delivery process via atomizers to the nasal cavity and paranasal sinuses is highly sensitive to the particle size.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 38085113 Impaired local Vitamin D3 metabolism contributes to IL-36g overproduction in epithelial cells in chronic rhinosinusitis with nasal polyps 236 249 EN Q. Xiao Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China H. Wang Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China J. Song Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China Z-Y. Qin Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China L. Pan Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China B. Liao Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China Y-K. Deng Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China J. Ma Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China J-X. Liu Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China J. Hu Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China P. Gao Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA R.P. Schleimer Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Z. Liu Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, P.R. China 3144 10.4193/RhinRhin23.123 BACKGROUND: Vitamin D (VD) possesses immunomodulatory properties, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains poorly studied. Herein, we aim to explore the regulation and function of VD3 in CRSwNP. METHODS: 25-hydroxyvitamin D3 (25VD3) levels in serum and tissue lysates were detected by ELISA. The expression of VD receptor (VDR) and cytochrome P450 family 27 subfamily B member 1 (CYP27B1), the enzyme that converts 25VD3 to the active 1,25-hydroxyvitamin D3 (1,25VD3), and their expression regulation in human nasal epithelial cells (HNECs) were studied by RT-PCR, western blotting, immunofluorescence, and flow cytometry. RNA sequencing was performed to identify genes regulated by 1,25VD3 in HNECs. HNECs and polyp tissue explants were treated with 1,25VD3, 25VD3, and dexamethasone. RESULTS: 25VD3 levels in serum and nasal tissue lysates were decreased in patients with eosinophilic and noneosinophilic CRSwNP than control subjects. The expression of VDR and CYP27B1 were reduced in eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells. VDR and CYP27B1 expression in HNECs were downregulated by interferon γ and poly (I:C). Polyp-derived epithelial cells demonstrated an impaired ability to convert 25VD3 to 1,25VD3 than control tissues. 1,25VD3 and 25VD3 suppressed IL-36γ production in HNECs and polyp tissues, and the effect of 25VD3 was abolished by siCYP27B1 treatment. Tissue 25VD3 levels negatively correlated with IL-36γ expression and neutrophilic inflammation in CRSwNP. CONCLUSION: Reduced systemic 25VD3 level, local 1,25VD3 generation and VDR expression result in impaired VD3 signaling activation in nasal epithelial cells, thereby exaggerating IL-36γ production and neutrophilic inflammation in CRSwNP.

International Rhinologic Society Rhinology 0300-0729 62 2 2024 4 1 38165680 MicroRNA-150-5P regulates Th1/Th2 cytokines expression levels by targeting EGR2 in allergic rhinitis 250 256 EN H. Jian Department of Otorhinolaryngology, the Third Affiliated Hospital of ZunYi Medical University/First People’s Hospital of Zunyi 563002, China H. Feng Department of Otorhinolaryngology, the Third Affiliated Hospital of ZunYi Medical University/First People’s Hospital of Zunyi 563002, China L. Zhu Department of Otorhinolaryngology, the Third Affiliated Hospital of ZunYi Medical University/First People’s Hospital of Zunyi 563002, China X. Li Department of Otorhinolaryngology, the Third Affiliated Hospital of ZunYi Medical University/First People’s Hospital of Zunyi 563002, China Z. Ma Department of Otorhinolaryngology, the Third Affiliated Hospital of ZunYi Medical University/First People’s Hospital of Zunyi 563002, China 3147 10.4193/Rhin23.223 BACKGROUND: MiR-150-5p is one of the miRNAs in the expression profile of miRNAs, and in many previous studies, it has been shown that miR-150-5p may play an important role in peripheral blood dendritic cells (DCs) of allergic rhinitis (AR) patients. We sought to investigate the role and mechanism of miR-150-5p in regulating DC function by modulating EGR2 and influencing T cell derivation to promote AR development. METHODS: The expression of miR-150-5p and EGR2 in AR patients was examined by real-time quantitative polymerase chain reaction (qRT-PCR), the expression of IL-4 cytokines in the supernatant of AR patients was tested by enzyme-linked immunosorbent assay (ELISA), and the expression of eosinophils in the supernatant of AR patients was measured by HE staining. The expression of EGR2 was detected by immunohistochemistry and fluorescent m-immunohistochemistry. RESULTS: MiR-150-5p expression was up-regulated and EGR2 expression was down-regulated in peripheral blood DCs from AR patients. miR-150-5p upregulated DCs, which promoted T-cell differentiation. miR-150-5p further regulated EGR2, which suppressed DCs and caused alteration of T-cell differentiation, in turn triggering the occurrence of AR. CONCLUSION: MiR-150-5p and its target gene EGR2 are involved in the development of AR, and DCs foster T-cell differentiation in peripheral blood of AR patients.