International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40694656 The changing paradigm for cystic fibrosis in rhinology 385 385 EN A.R. Sedaghat Cincinnati, OH, USA 3331 10.4193/Rhin25.904 I would like to welcome you to the August issue of Rhinology. In the latest issue of Rhinology, you will find high quality articles spanning the entire breadth of the field of rhinology. From studies on inflammatory sinus disease to skull base pathology, from medical to surgical treatments, every reader is sure to find studies of interest and applicability to their practice. For the focus of this editorial, I highlight for the reader the article by Le Bon et al., which describes the case of a patient with cystic fibrosis (CF) and chronic rhinosinusitis (CRS) with nasal polyps in whom concomitant NSAID-exacerbated respiratory disease (NERD) was uncovered after the initiation of triple combination CFTR modulatory therapy with elexacaftor-tezacaftor-ivacaftor (ETI).

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40305840 Eosinophilic complications during dupilumab therapy for type 2 diseases: a systematic review 386 396 EN M. Lazzeroni Amsterdam Rhinology Team, Department of Otorhinolaryngology and Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands;Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy P. Kemp Amsterdam Rhinology Team, Department of Otorhinolaryngology and Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands W.J. Fokkens Amsterdam Rhinology Team, Department of Otorhinolaryngology and Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands S. Reitsma Amsterdam Rhinology Team, Department of Otorhinolaryngology and Head and Neck Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands 3290 10.4193/Rhin24.528 Background: Dupilumab shows promising results in the management of several type 2 disorders. However, it often leads to transient, early increases in blood eosinophil count (BEC). This has led to awareness of possibly associated eosinophilic complications, such as eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). Aim of the current work was to collect all eosinophilic complications reported in literature.Methodology: PubMed, Embase, Scopus, and Web of Science were systematically searched for papers reporting on eosinophilic complications of dupilumab therapy for type 2 disorders. Results: While around one million patients are treated with dupilumab globally, we identified a total of 35 reports on 53 patients. The most common complications were EGPA: 24 patients, eosinophilic pneumonia: 15, and HES: 6. Complications developed after a median of 9 (range: 0-71) weeks and the median eosinophilic count at the moment of diagnosis was 6.38x109 cells/L (IQR 3.13- 9.08). Most complications were treated with systemic corticosteroids. Of all patients, 89% discontinued dupilumab therapy and no deceased patients were reported. Conclusions: Reported eosinophilic complications during dupilumab therapy are extremely rare and mostly develop during the first months of treatment, challenging the need for (prolonged) BEC monitoring during dupilumab therapy. No patient patterns or predictors were identified.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40445119 Risk factors in patients treated with surgical drainage for rhinogenic intracranial complications: a nationwide study 397 404 EN M. Morita Department of Otolaryngologyâ€"Head and Neck Surgery, Kansai Medical University, Hirakata, Osaka, Japan K. Tarasawa Department of Health Administration and Policy, Tohoku University School of Medicine, Sendai, Miyagi, Japan H. Hidaka Department of Otolaryngologyâ€"Head and Neck Surgery, Kansai Medical University, Hirakata, Osaka, Japan Y. Yun Department of Otolaryngologyâ€"Head and Neck Surgery, Kansai Medical University, Hirakata, Osaka, Japan K. Fujimori Department of Health Administration and Policy, Tohoku University School of Medicine, Sendai, Miyagi, Japan K. Fushimi Department of Health Policy and Informatics, Institute of Science Tokyo Graduate School of Medicine, Tokyo, Japan S. Hamada Department of Otolaryngology, Kansai Medical University Kori Hospital, Neyagawa, Osaka, Japan M. Asako Department of Otolaryngology, Kansai Medical University Medical Center, Moriguchi, Osaka, Japan R. Kawachi Department of Otolaryngologyâ€"Head and Neck Surgery, Kansai Medical University, Hirakata, Osaka, Japan M. Yagi Department of Otolaryngologyâ€"Head and Neck Surgery, Kansai Medical University, Hirakata, Osaka, Japan H. Iwai Department of Otolaryngologyâ€"Head and Neck Surgery, Kansai Medical University, Hirakata, Osaka, Japan 3298 10.4193/Rhin25.057 Background: Data on risk factors for rhinogenic intracranial complications (RICs) including cerebral abscess have been limited. Using a nationwide database, the aim was to identify the factors related to mortality and delayed discharge. Methodology: Data of 326 patients between 2012 and 2022 were extracted from a Japanese inpatient database. The main outcome was survival at discharge. In a subgroup analysis of the 316 surviving patients, the outcome was delayed discharge. Results: The mortality rate was 3.1%. Logistic regression analyses identified intracerebral complications more than one surgical intervention and consciousness level evaluated by the Japan Coma Scale (JCS): JCS I and JCSâ�¥ II as risk factors for mortality. Concurrent interventions of intracranial and sinonasal drainage was identified as a factor associated with decreased risk. Conclusions: Although RICs are rare, with decreasing mortality due to progress in imaging and clinical strategies, they remain the most severe complications of rhinosinusitis. Subdural and/or intracerebral abscess, consciousness level at admission, and more than one surgical intervention were found to be risk factors for mortality. Conversely, concurrent interventions, intracranial and sinonasal drainage, contributed to reducing this risk.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40406956 Chronic rhinosinusitis in nasopharyngeal carcinoma patients post- IMRT: a meta-analysis 405 415 EN N.Y.M. Chua Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore W.K. Lau Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore A.L. Chui Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore C.L. Ng Department of Otolaryngology-Head and Neck Surgery, Ng Teng Fong General Hospital, Singapore D.Y. Wang Department of Otolaryngology, National University of Singapore, Singapore 3292 10.4193/Rhin25.095 BACKGROUND: Intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) can cause chronic rhinosinusitis (CRS), an underexplored side effect. This review aimed to etermine the incidence and severity of CRS in NPC patients post-IMRT. METHODS: Electronic databases (PubMed, CINAHL, Embase, Cochrane Library, Web of Science) were searched for studies published from 2000 onwards. Eligible studies assessed CRS in NPC patients post-IMRT, using validated methods per EPOS 2020 (Lund-Mackay (LM) CT scoring, Lund-Kennedy (LK) endoscopic scoring, SNOT questionnaire). Meta-analysis was conducted using SPSS and R to quantify pooled CRS incidence and severity. RESULTS: Nine studies (n=1,478) were included, revealing distinct patterns in CRS development and severity. Patients without prior sinusitis showed significantly increased likelihood of developing CRS post-IMRT, while those with prior sinusitis had reduced odds due to a ceiling effect, as CRS was already present in 100% of these patients before IMRT. Both groups showed significant increases in CRS severity pre- and post-IMRT, with the LK and LM scoring methods showing the most substantial changes. CONCLUSIONS: This review underscores the significant increases in both the incidence and severity of CRS in NPC patients post-IMRT. Clinicians should recognise the risk of CRS post-IMRT and recommend options to reduce the likelihood of CRS development.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40445072 Clinical features and outcomes of skull base osteoradionecrosis in nasopharyngeal carcinoma patients: a systematic review and meta-analysis 416 430 EN S. Ding School of Clinical Medicine, University of Cambridge, Cambridgeshire, United Kingdom C.X.Y. Liao Department of Otorhinolaryngology, The Chinese University of Hong Kong, Sha Tin, Hong Kong W.H.B. Mak Department of Otorhinolaryngology, The Chinese University of Hong Kong, Sha Tin, Hong Kong H.K. Chan Department of Otorhinolaryngology, The Chinese University of Hong Kong, Sha Tin, Hong Kong C.P.L. Chan Department of Otorhinolaryngology, The Chinese University of Hong Kong, Sha Tin, Hong Kong C.C.F. Lai Department of Otorhinolaryngology, The Chinese University of Hong Kong, Sha Tin, Hong Kong S.M.W. Chow Department of Otorhinolaryngology, The Chinese University of Hong Kong, Sha Tin, Hong Kong J.Y.K. Chan Department of Otorhinolaryngology, The Chinese University of Hong Kong, Sha Tin, Hong Kong D.C.M. Yeung Department of Otorhinolaryngology, The Chinese University of Hong Kong, Sha Tin, Hong Kong 3297 10.4193/Rhin25.522 Background: Skull base osteoradionecrosis following radiotherapy for nasopharyngeal carcinoma is a potentially life-threatening complication. Assessing severity, prognosis and providing appropriate treatment for the condition can be clinically challenging. This systematic review evaluates factors associated with patient outcome. Methodology: A literature search of PubMed, Embase, MEDLINE and Cochrane databases was conducted in August 2024. Data was extracted for patients with skull base osteoradionecrosis caused by nasopharyngeal carcinoma. Results were presented by narrative synthesis or with statistical analysis. Results: 359 patients from 31 papers were included. The clivus and posterior nasopharyngeal wall were the most common subsites for osteoradionecrosis. We categorized subsites into posterior, roof and lateral areas. Subsite was not associated with ICA exposure or infection. Frequent symptoms include headache, foul odour and epistaxis. Foul odour was negatively associated with infection and epistaxis was highly associated with ICA exposure. The most common direct complication was CSF leak (18.2%), whereas the most common post-treatment complication was infection (43.8%). Carotid blowout was the most common cause of mortality (45.9%). Conclusions: Foul odour and epistaxis may predict cases of skull base osteoradionecrosis complicated by ICA exposure and infection. Further research is necessary to assess the significance of ORN subsite as a prognosticator or guide to treatment.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40465208 Multidimensional benefits of olfactory training for chronic COVID-19-related olfactory dysfunction: a systematic review and meta-analysis 431 440 EN C-H. Chen Department of Otorhinolaryngology-Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan;Department of Otolaryngology, National Yang Ming Chiao Tung University, Taipei, Taiwan;Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan;Department of Otorhinolaryngology, Kaohsiung Show Chwan Memorial Hospital, Kaohsiung, Taiwan C-F. Shih Department of Otorhinolaryngology-Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan T. Hummel Smell and Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Dresden, Germany Y-T. Chao Department of Otorhinolaryngology-Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan;Department of Otolaryngology, National Yang Ming Chiao Tung University, Taipei, Taiwan 3300 10.4193/Rhin24.355 Background: Olfactory dysfunction is commonly observed in patients with COVID-19 infection. Chronic olfactory dysfunction can have a profound effect on one’s quality of life. Olfactory training (OT) is a rehabilitation therapy, which has emerged as a viable treatment for COVID-19-related olfactory dysfunction. Our primary objective was to assess the effectiveness of OT for individuals with chronic COVID-19-related olfactory dysfunction. Methods: A search was performed on the Cochrane Library, Embase, PubMed, Scopus, and Web of Science databases from their inception through Feb 24, 2024. Eligible studies included those with sufficient information for meta-analysis pertaining to the effectiveness of OT performed for more than 8 weeks in treating chronic (duration > 16 weeks) COVID-19-related olfactory dysfunction. Results: After a systematic review of all relevant articles, 9 studies qualified for inclusion. A total of 179 patients within 7 studies had eligible Sniffin' Sticks test data. The pooled results showed significant post-OT increases in TDI score, threshold, discrimination, and identification. Two studies documented qualified UPSIT scores in 63 patients. Pooled results of all identification tests revealed significant improvement. Conclusions: OT demonstrates benefits in treating chronic COVID-19-related olfactory dysfunction, as evidenced by multidimensional evaluations. These findings suggest the involvement of both top-down and bottom-up mechanisms in the recovery process.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40305821 Olfactory disorder after COVID-19 vaccination 441 447 EN M. Kawabata Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan E. Mori Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan N. Yanagi Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan M. Tei Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan N. Otori Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan 3289 10.4193/Rhin23.499 This systematic review examines 16 reported cases of olfactory disorders occurring after COVID-19 vaccination. Symptoms such as anosmia, parosmia, hyposmia, ageusia, and dysgeusia appeared within one week of vaccination. Among the 16 patients (12 women, 4 men; mean age 38 years), 9 received the Pfizer mRNA vaccine, 6 received the AstraZeneca viral vector vaccine, and 1 received the Moderna mRNA vaccine. Symptoms persisted from 4 days to 18 months, with varying degrees of severity. Diagnoses were made using Sniffin’ Sticks tests and T&T olfactometry, mosty revealing mild hyposmia. Treatment included vitamin B12, multivitamins, olfactory training, Kampo formula, and, in some cases, corticosteroids. The hypothesized mechanism involves inflammatory responses triggered by spike protein interaction with the α7 nicotinic acetylcholine receptor on macrophages. Given the lack of definitive diagnostic methods, careful clinical evaluation is essential to rule out other causes such as subclinical COVID-19 infection. While olfactory disorders have been reported after vaccination, no direct causal relationship has been established.Further research is needed to clarify underlying mechanisms and contributing factors.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40388840 Effectiveness of Artificial Intelligence in detecting sinonasal pathology using clinical imaging modalities: a systematic review 448 462 EN D-P. Petsiou Department of Otolaryngology - Head and Neck Surgery, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece D. Spinos Department of Cancer and Genomics, School of Medicine, University of Birmingham, Birmingham, United Kingdom A. Martinos Department of Otolaryngology - Head and Neck Surgery, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece J. Muzaffar Department of Otolaryngology, Head and Neck Surgery, University Hospitals of Birmingham, Birmingham, United Kingdom G. Garas Surgical Innovation Centre, Department of Surgery and Cancer, Imperial College London, St. Mary’s Hospital, London, United Kingdom;Athens Medical Centre, Marousi and Psychiko Clinic, Athens, Greece C. Georgalas Department of Head, School of Medicine, University of Nicosia, Nicosia, Cyprus;Department of Head, Neck and Skull Base surgery, Hygeia Hospital, Athens, Greece 3291 10.4193/Rhin25.044 BACKGROUND: Sinonasal pathology can be complex and requires a systematic and meticulous approach. Artificial Intelligence (AI) has the potential to improve diagnostic accuracy and efficiency in sinonasal imaging, but its clinical applicability remains an area of ongoing research. This systematic review evaluates the methodologies and clinical relevance of AI in detecting sinonasal pathology through radiological imaging. METHODOLOGY: Key search terms included �artificial intelligence,� �deep learning,� �machine learning,� �neural network,� and �paranasal sinuses,�. Abstract and full-text screening was conducted using predefined inclusion and exclusion criteria. Data were extracted on study design, AI architectures used (e.g., Convolutional Neural Networks (CNN), Machine Learning classifiers), and clinical characteristics, such as imaging modality (e.g., Computed Tomography (CT), Magnetic Resonance Imaging (MRI)). RESULTS: A total of 53 studies were analyzed, with 85% retrospective, 68% single-center, and 92.5% using internal databases. CT was the most common imaging modality (60.4%), and chronic rhinosinusitis without nasal polyposis (CRSsNP) was the most studied condition (34.0%). Forty-one studies employed neural networks, with classification as the most frequent AI task (35.8%). Key performance metrics included Area Under the Curve (AUC), accuracy, sensitivity, specificity, precision, and F1-score. Quality assessment based on CONSORT-AI yielded a mean score of 16.0 ± 2. CONCLUSIONS: AI shows promise in improving sinonasal imaging interpretation. However, as existing research is predominantly retrospective and single-center, further studies are needed to evaluate AI’s generalizability and applicability. More research is also required to explore AI's role in treatment planning and post-treatment prediction for clinical integration.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40720945 The use of fascia lata can minimize olfactory damage in endoscopic endonasal skull base surgery 463 469 EN Y. Wu Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, China Y. Xue Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, China M. Zheng Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, China H. Wu Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, China Y. Zhang Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, China Q. Cai Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, China T. Zhao Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, China 3306 10.4193/Rhin24.522 Objective: The purpose of this study was to compare the impact of using fascia lata versus a nasoseptal flap for skull base repair on olfactory function following endoscopic endonasal skull base surgery. Methods: Patients who underwent the endoscopic endonasal transsphenoidal approach (EETA) or the extended endoscopic endonasal transsphenoidal approach (EEETA) were included in this study. The study included 80 patients who underwent skull base defect repair using fascia lata, while the control group consisted of 160 patients who underwent skull base defect repair using a nasoseptal flap. Preoperative demographic data, skull base repair techniques, postoperative sinonasal symptoms and the incidence of cerebrospinal fluid (CSF) leakage were compared between the two groups. Results: Olfactory dysfunction was significantly worse at 3, 6 and12 months after surgery than before surgery in the nasoseptal flap repair group, although olfactory function partially recovered at 12 months after surgery. Additionally, we found that non-validated visual analogue scale (VAS, 0â€"100 mm) and validated cross-cultural smell identification test (CC-SIT) and the butanol threshold test (BTT) olfactory impairment at 12 months after surgery were significantly worse in the nasoseptal flap repair group than in the fascia lata repair group. Furthermore, no significant difference in the incidence of CSF leakage was noted between the two groups. Conclusions: For endoscopic endonasal surgery, the use of a nasoseptal flap for skull base repair can cause severe olfactory impairment. The use of fascia lata for skull base repair can be considered an alternative method to minimize damage to olfactory function.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40305767 The 4 item Concise Aging adults Smell Test (4CAST) to screen for olfactory-related comorbidities 470 476 EN R.J. Schlosser Department of Otolaryngology â€" Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA M.J. Gregoski Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA M.A. Eckert Department of Otolaryngology â€" Head and Neck Surgery, Columbia University, New York, NY, USA A. Benitez Department of Neurology, Medical University of South Carolina, Charleston, SC, USA Z.M. Soler Department of Otolaryngology â€" Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA 3288 10.4193/Rhin24.541 BACKGROUND: Olfactory dysfunction (OD) is associated with numerous comorbidities, including cognitive decline and depression. Age-related OD is one of the most common causes of smell loss, but it is often underrecognized. In previous research the 4 item Concise Aging adults Smell Test (4CAST) accurately predicted psychophysical olfactory function in over 80% of older adults. This study examined the relationship of 4CAST to olfactory-related comorbidities. METHODS: A community-based cohort of adults over 50 years of age completed the 4CAST. Its association with olfactory-related comorbidities was assessed using: 1) National Institutes of Health Toolbox -Cognition Battery; 2) Questionnaire for Olfactory Disorders-Negative Statements (QOD-NS); 3) Patient Health Questionnaire 9 (PHQ9); 4) DeJong Giervald (DJG) social isolation scale; and 5) Mini-Nutritional Assessment (MNA). RESULTS: Participants who failed the 4CAST had worse median scores for all measures of fluid cognition, QOD-NS, and PHQ9. Of participants who failed the 4CAST, 24-39% had cognition scores suggestive of possible cognitive impairment. Participant’s 4CAST results did not differ in crystallized cognition (Picture Vocabulary Test), total DJG and MNA scores. CONCLUSION: The 4CAST is a quick screening instrument that may indicate psychophysical OD in older adults and identify olfactory-related comorbidities (i.e. cognitive decline, depression) that may merit further in-depth assessments.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40278843 Olfactory training using nasal inserts is more effective due to increased adherence 477 485 EN A.L. Winter Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden S. Henecke Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden;Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden E. Thunell Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden M. Swartz Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden J. Martinsen Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden P. Sahlstrand Johnson Skåne University Hospital, Department of Oto-Rhino-Laryngology, Malm�, Sweden;Lund University, Department of Clinical Sciences, Malm�, Sweden J.N. Lundstr�m Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden;Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden;Monell Chemical Senses Center, Philadelphia, PA, United States 3285 10.4193/Rhin24.369 BACKGROUND: The recommended treatment for hyposmia (a clinically reduced sense of smell) is olfactory training using odor containers that the patients smell twice a day for several weeks. Adherence to the olfactory training regimen is, however, generally low. We aimed to investigate if a new form of odor delivery, using scented nasal inserts, could enhance adherence to olfactory training by allowing participants to be mobile during the training and thereby lower the perceived intrusion on everyday life. METHODS: Using a randomized controlled parallel-group design, individuals (N = 116) with hyposmia underwent 8 weeks of olfactory training. One group was assigned olfactory training using scented nasal inserts (nasal devices that retain nasal patency) while the other group was assigned the standard care regimen currently recommended by the Swedish healthcare system. We assessed objective and subjective olfactory ability before and after olfactory training as well as adherence to training. RESULTS: Both groups significantly improved both their objective and subjective olfactory abilities, and training with nasal inserts produced similar improvement as standard care in overall treatment outcome. However, there was a significantly greater increase in discrimination performance and lower dropout rate (6.7%) in the nasal insert compared to the standard care group (23.2%). Critically, after exclusion of the drop-out participants, the nasal insert group still showed significantly higher adherence to the training regimen. CONCLUSIONS: Olfactory training with nasal inserts could serve as a more effective form of treatment for hyposmia due to patients' improved adherence to protocol and increased tendency to finish their treatment regimen.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40526035 Age-related exacerbation in disease-associated olfactory disorders 486 494 EN H. Shimmura Department of Otorhinolaryngology, The Jikei University School of Medicine Hospital, Tokyo, Japan E. Mori Department of Otorhinolaryngology, The Jikei University School of Medicine Hospital, Tokyo, Japan R. Sekine Department of Otorhinolaryngology, The Jikei University School of Medicine Hospital, Tokyo, Japan;Department of Otorhinolayngology, St. Luke's International Hospital, Tokyo, Japan M. Tei Department of Otorhinolaryngology, The Jikei University School of Medicine Hospital, Tokyo, Japan;Department of Otorhinolaryngology, The Jikei University Katsushika Medical Center, Tokyo, Japan N. Otori Department of Otorhinolaryngology, The Jikei University School of Medicine Hospital, Tokyo, Japan 3301 10.4193/Rhin24.227 Background: Both the physiological degeneration linked to aging and the pathological changes resulting from diseases can impact olfactory function in the patients with olfactory disorder (OD). However, the epidemiological literature addressing the extent of aging's involvement to the diseases which causes OD is limited. Our study aimed to investigate how aging affects olfactory function in major causes of OD by employing psychophysical olfactory sensory testing. Methodology: Non-eosinophilic chronic rhinosinusitis (NECRS), eosinophilic chronic rhinosinusitis (ECRS), post-infectious OD (PIOD), post-traumatic OD, and idiopathic OD were identified as major contributors to OD. Retrospective data from 1986 patients were collected from our smell clinic. We utilized T&T olfactometer thresholds to assess quantitative olfactory function. Patients were categorized into age groups spanning every 10 years from their 20s to 80s, and we analyzed potential differences between age groups and diseases. Additionally, the odds ratio of severe OD was analyzed with respect to gender and age, categorizing patients into two groups: lower than 60 and over or equal to 60. Results: A significant odds ratio was observed for elevated T&T average threshold with respect to age in the detection and recognition thresholds of patients diagnosed with NECRS, PIOD and idiopathic OD. In contrast, no significant odds ratio was observed in patients with ECRS or post-traumatic OD, regardless of age. Conclusion: Analysis of disease-specific OD revealed varying degrees of age-related physiological and disease-pathological across different conditions. These findings underscore the importance for clinicians to consider both age-related physiological changes and the specific disease pathology of the disease when diagnosing and managing OD, particularly in elderly patients.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40407262 The extra cost of biologics as first-line treatment in uncontrolled chronic rhinosinusitis with nasal polyps with no previous sinus surgery is overwhelming: a budget impact analysis 495 504 EN M. Fieux Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d’ORL, d’otoneurochirurgie et de chirurgie cervico-faciale, Pierre Bénite, France; Université de Lyon, Université Lyon 1, Lyon, France; UMR 5305, Laboratoire de Biologie Tissulaire et d'Ingénierie Thérapeutique, Institut de Biologie et Chimie des Protéines, CNRS/Université Claude Bernard Lyon 1, Lyon, France J. Margier Hospices Civils de Lyon, P�le de Santé Publique, Service d’�valuation �conomique en Santé, Research on Healthcare; Performance (RESHAPE), INSERM U1290, Université Claude Bernard Lyon 1, Lyon, France S. Bartier Service d’ORL, de chirurgie cervico faciale, H�pital Henri Mondor, Assistance Publique des H�pitaux de Paris, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France M. Chang Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United States F. Carsuzaa Service ORL, Chirurgie Cervico-Maxillo-Faciale et Audiophonologie, Centre Hospitalier Universitaire de Poitiers, Poitiers, France; Laboratoire Inflammation Tissus Epithéliaux et Cytokines (LITEC), UR15560, Université de Poitiers, Poitiers, France P.H. Hwang Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United States Z.M. Patel Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United States S. Tringali Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d’ORL, d’otoneurochirurgie et de chirurgie cervico-faciale, Pierre Bénite, France;Université de Lyon, Université Lyon 1, Lyon, France; UMR 5305, Laboratoire de Biologie Tissulaire et d'Ingénierie Thérapeutique, Institut de Biologie et Chimie des Protéines, CNRS/Université Claude Bernard Lyon 1, Lyon, France V. Favier Département d’ORL, chirurgie cervico faciale et maxillo-faciale, H�pital Gui de Chauliac, CHU de Montpellier, Montpellier, France; Research-team ICAR, Laboratory of Computer Science, Robotics and Microelectronics of Montpellier (LIRMM), Univ. Montpellier, French National Centre for Scientific Research (CNRS), Montpellier, France T. Savary Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d’ORL, d’otoneurochirurgie et de chirurgie cervico-faciale, Pierre Bénite, France 3294 10.4193/Rhin24.418 BACKGROUND: Both surgery and biologics offer comparable control rates for patients with uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) but differ in terms of cost and complications. The aim was to assess the mean total direct cost per patient of biologics or surgery as first-line treatment in uncontrolled CRSwNP and to perform a budget impact analysis (BIA). METHODS: An economic model was build based on pricing of March 2024, and on the theoretical French population to simulate both the 5-year mean direct cost per patient and the BIA. For the BIA, two scenarios were evaluated: in scenario 1 (the normal one), 18% of patients received biologics as first-line (vs 82% surgery) and in scenario 2 (the less likely one), 90% of patients received biologics as first-line (vs 10% surgery). Within both scenarios, two approaches were considered, the surgical one (when patients received surgery as first-line) and the biological one (when patients received biologics as first-line, no previous sinus surgery). RESULTS: Over 5 years, the estimated mean direct cost per patient per year was significantly lower in the surgical approach compared to the biological one (60,026�). The BIA found that the estimated net overall incremental budget impact was 91,287,924� in scenario 1 and 1,024,768,639� in scenario 2. In both scenarios, the biological approach was the most expensive (+184% and +1048%, respectively). CONCLUSION: At current costs, if biologics were used as a first-line treatment (no previous sinus surgery) in patients with uncontrolled CRSwNP, the extra direct cost would be overwhelming.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40407713 Concomitant cystic fibrosis and NSAID-exacerbated respiratory disease 505 506 EN S.D. Le Bon Department of Otorhinolaryngology, Rhinology-Olfactology Unit, Service of Otorhinolaryngology-Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland J. Plojoux Department of Respiratory Medicine, Geneva University Hospitals, Geneva, Switzerland Y. Coattrenec Department of Immunology and Allergology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland B.N. Landis Department of Otorhinolaryngology, Rhinology-Olfactology Unit, Service of Otorhinolaryngology-Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland 3296 10.4193/Rhin25.132 Chronic rhinosinusitis (CRS) with nasal polyps occurs in 6-57% of individuals with cystic fibrosis (CF). According to the EPOS 2020 guidelines, CF-related CRS is classified as secondary diffuse, non-type-2 CRS. In contrast, most nasal polyposis in the general population is associated with primary, type-2 CRS. This educationally-oriented classification system facilitates the categorization of CRS in distinct groups. However, it may suggest that each type of CRS is caused by a single underlying mechanism, potentially leading clinicians to overlook that, in reality, multiple factors can drive CRS development. The incidence of CRS stemming from multiple etiologies remains currently underexplored. We report an illustrative case of a CF patient with concomitant NSAID-Exacerbated Respiratory Disease (NERD), necessitating two distinct targeted therapies to achieve effective symptomatic relief.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40586793 The CFTR gene variants in paediatric nasal polyposis: a study in the Italian population 507 509 EN S. Santarsiero Department of Otorhinolaryngology, Bambino GesÃ� Children's Hospital IRCCS, Rome, Italy E. Sitzia Department of Otorhinolaryngology, Bambino GesÃ� Children's Hospital IRCCS, Rome, Italy F. Majo Paediatric Pulmonology and Cystic Fibrosis Unit, Bambino GesÃ� Children's Hospital IRCCS, Rome, Italy G. Marini Department of Otorhinolaryngology, Bambino GesÃ� Children's Hospital IRCCS, Rome, Italy L. Sinibaldi Department of Genetics, Bambino GesÃ� Children's Hospital IRCCS, Rome, Italy G. Cristalli Department of Otorhinolaryngology, Bambino GesÃ� Children's Hospital IRCCS, Rome, Italy R. Cutrera Paediatric Pulmonology and Cystic Fibrosis Unit, Bambino GesÃ� Children's Hospital IRCCS, Rome, Italy A.G. Fiocchi Paediatric Allergy and Cystic Fibrosis Research Unit, Bambino GesÃ� Children's Hospital IRCCS, Rome, Italy F. Ciciriello Paediatric Allergy and Cystic Fibrosis Research Unit, Bambino GesÃ� Children's Hospital IRCCS, Rome, Italy M.C. Artesani Paediatric Allergy and Cystic Fibrosis Research Unit, Bambino GesÃ� Children's Hospital IRCCS, Rome, Italy 3307 10.4193/Rhin24.568 Chronic rhinosinusitis with nasal polyps (CRSwNP) is a relatively uncommon condition in the paediatric population, with a prevalence estimated at 0.1â€"0.8%, compared to approximately 4% in adults (1, 2). The early onset of CRSwNP emphasises the significant role of genetic factors in its pathophysiology (3). Approximately 20% of paediatric patients with CRSwNP are associated with systemic genetic disorders, with cystic fibrosis (CF) being the most prevalent (2). CF is characterised by a dysfunction of the CF transmembrane conductance regulator (CFTR) protein. Over 2,000 distinct CFTR variants have been identified, resulting in varying organ involvement and disease severity. In 2000, the World Health Organization introduced the term â€�CFTR-related disordersâ€� (CFTR-RDs) to include clinical entities associated with CFTR dysfunction that do not meet the diagnostic criteria for CF (4). CFTR-RDs include congenital bilateral absence of the vas deferens (CBAVD), recurrent pancreatitis (RP), and disseminated bronchiectasis (DB). However, recent studies emphasised a significant prevalence of heterozygous CFTR pathogenic variants in paediatric and adult CRSwNP populations without CF (4â€"8). We assessed the prevalence of CFTR variants in a paediatric population with CRSwNP.

International Rhinologic Society Rhinology 0300-0729 63 4 2025 8 1 40586754 Topical corticosteroids adherence in chronic rhinosinusitis with nasal polyps patients on dupilumab 510 512 EN S.M. Miotti University Hospital of Zurich, Department of Otorhinolaryngology, Head and Neck Surgery, Zurich, Switzerland;University of Zurich, Zurich, Switzerland C. Brühlmann University Hospital of Zurich, Department of Otorhinolaryngology, Head and Neck Surgery, Zurich, Switzerland;University of Zurich, Zurich, Switzerland A. Yalamanoglu University Hospital of Zurich, Department of Immunology, Zurich, Switzerland U.C. Steiner Department of Rheumatology and Immunology, University Hospital Bern, University of Bern, Bern, Switzerland;Institute of Clinical Chemistry, Inselspital Bern University Hospital, University of Bern, Bern, Switzerland C.M. Meerwein University Hospital of Zurich, Department of Otorhinolaryngology, Head and Neck Surgery, Zurich, Switzerland;University of Zurich, Zurich, Switzerland M.B. Soyka University Hospital of Zurich, Department of Otorhinolaryngology, Head and Neck Surgery, Zurich, Switzerland;University of Zurich, Zurich, Switzerland 3305 10.4193/Rhin25.102 Biologics like dupilumab have revolutionized the management of patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma. However, topical corticosteroids, such as intranasal (INCS) and inhaled (ICS) corticosteroids still play a fundamental role in the management of these conditions. To this day, limited data is available on topical corticosteroids medication adherence combined with dupilumab in achieving CRSwNP and asthma symptom control. Considering the generally poor medication-adherence among chronic patients and the remarkable efficacy of dupilumab, we suspected low adherence to INCS and ICS.