Olfactory cleft stenosis and obstruction on paranasal sinus CT scan in pre-septo-rhinoplasty patients: normal variants or pathologic findings?

OBJECTIVE(S): To determine the frequency of olfactory cleft (OC) stenosis and obstruction on paranasal sinus CT scans in pre-septorhinoplasty of patients who had septal deviation, septopyramidal deformation or nasal obstruction without other sinonasal conditions. METHODS: This retrospective study included patients referred to our institution between December 2013 and December 2021 for septorhinoplasty due to nasal obstruction without other sinonasal or neurological conditions. All patients underwent preoperative paranasal sinus CT scan and olfactory testing. OC stenosis was quoted as none, partial, or total (less than 1/3 contact between nasal septum and ethmoid turbinates, 1/3-2/3, more than 2/3, respectively), as well as OC obstruction as none, partial, or complete (obstruction of less than 1/3 of OC, 1/3-2/3, more than 2/3, respectively). Radiologic evaluation was validated by near perfect interobserver agreement. RESULTS: A total of 75 patients (32 women, 43 men) with a mean age of 44.2 ± 15.64 (23-74) years were included, of which 36 were normosmic and 39 hyposmic. OC stenosis was partial in 58.7% (n = 44) of the patients, absent in 28% (n = 21), and total in 13.3% (n = 10), without difference between normosmic and hyposmic patients (p = .66). OC obstruction was absent in 52% (n = 39) and partial in 46.7% (n = 35), without difference between normosmic and hyposmic patients (p = .51). Only one normosmic patient had complete OC obstruction. CONCLUSION: OC partial stenosis and partial obstruction were frequent findings in pre-septorhinoplasty patients without respiratory mucosa disease and did not influence their olfactory status. Total stenosis and complete obstruction were rarer and require further investigation. CLINICAL RELEVANCE STATEMENT: Isolated partial olfactory cleft stenosis and obstruction should be considered normal variants, whereas the impact of complete olfactory cleft stenosis and obstruction on patient's olfactory status remains to be determined. KEY POINTS: • The incidence of olfactory cleft stenosis and obstruction in asymptomatic patients remains unknown, even though it is encountered in clinical practice. • Partial and total olfactory cleft stenosis occurred in 58.7% and 13.3% of the patients; partial obstruction occurred in half of the cases, but complete obstruction was extremely rare. • There are frequent findings of partial olfactory cleft obstruction and stenosis, but complete obstruction and total stenosis should be further investigated.

Anatomy of the nasal latero-lateral cartilage articulation: a micro-MRI study in human specimens.

PURPOSE: To study the anatomy of the latero-lateral joint (LLJ) between the upper lateral (ULC) and lower lateral (LLC) crus of the nasal cartilages, usually described as a scroll articulation. METHODOLOGY: Six nasal pyramids were taken in monobloc from fresh cadavers and imaged on micro-MRI with 0.4 mm slice thickness. Images were jointly interpreted by two head and neck radiologists and one surgeon. The junction between the ULC and LLC, the presence of ligaments and of sesamoid or accessory cartilages were assessed. RESULTS: Eight LLJs could be analyzed, with four types of junctions: hook-shaped cephalic border of the LLC turned towards the nasal fossa and linear caudal border of the ULC (n = 3), hook-shaped caudal border of the ULC and linear cephalic border of the LLC lateral crus (n = 1), hook-shaped border of both cartilaginous edges with clinging (n = 1) (scroll articulation) or without clinging (n = 3). No ligament or sesamoid cartilage was found, but posterior accessory cartilages were seen in 75% of the cases. CONCLUSION: The classical scroll articulation of the LLJ has been observed in only 1/8 cases on micro-MRI images. The anatomy of the LLJ could explain the surgical difficulty in raising the tip of the nose in some patients and not in others.

Efficacy of immunoglobulin replacement therapy and azithromycin in severe asthma with antibody deficiency.

BACKGROUND: Although antibody deficiency (AD) is a well-known cause of recurrent respiratory infections, there are few data on its impact in adults with asthma. The objective of the present study was to assess outcomes in adults with severe asthma and AD after treatment with either azithromycin or subcutaneous immunoglobulins (SCIg). METHODS: We performed a 5-year, prospective, observational, two-centre study of adults with severe asthma and AD in France. Bronchiectasis was ruled out by high-resolution computed tomography. Patients were treated for one year with either azithromycin (250 mg every other day) or SCIg (0.4-0.6 g/kg/months, weekly). All patients were evaluated for exacerbations, asthma control and lung function at baseline and then one year after treatment initiation. RESULTS: Thirty-nine patients with severe asthma were included in the study: 14 had been treated with azithromycin and 25 had been treated with SCIg. Before the initiation of treatment for AD, all patients had an Asthma Control Questionnaire (ACQ-7) score > 1.5 (mean ± SD: 2.71 ± 0.53) despite treatment at GINA step 4 or 5, and had a high exacerbation rate requiring oral corticosteroids and/or rescue antibiotics (∼7.2 ± 2.1/patient/year). One year after treatment initiation, we observed a significantly higher FEV1 (mean: 0.18 ± 0.22 L) and ACQ-7 score (1.26 ± 0.68), and a significantly lower exacerbation rate (1.63 ± 1.24/patient/year). CONCLUSIONS: Treatment of AD dramatically improved asthma outcomes - suggesting that adults with severe asthma and recurrent respiratory infections should be screened and (if appropriate) treated for AD.

EUFOREA consensus on biologics for CRSwNP with or without asthma.

Novel therapies such as type 2 targeting biologics are emerging treatment options for patients with chronic inflammatory respiratory diseases, fulfilling the needs of severely uncontrolled patients. The majority of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and over half of patients with asthma show a type 2 inflammatory signature in sinonasal mucosa and/or lungs. Importantly, both chronic respiratory diseases are frequent comorbidities, ensuring alleviation of both upper and lower airway pathology by systemic biological therapy. Type 2-targeting biologics such as anti-IgE, anti-IL4Rα, anti-IL5, and anti-IL5Rα have entered the market for selected pheno/endotypes of asthma patients and may soon also become available for CRSwNP patients. Given the high prevalence of chronic respiratory diseases and the high cost associated with biologics, patient selection is crucial in order to implement such therapies into chronic respiratory disease care pathways. The European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) organized a multidisciplinary Expert Board Meeting to discuss the positioning of biologics into the care pathways for CRSwNP patients with and without comorbid asthma.

Gamma globulin replacement therapy in uncontrolled, severe asthma associated with humoral immunodeficiency: A series of five case reports.

We report on five adult cases of the rare association of asthma with humoral immunodeficiency (huID). All patients had uncontrolled asthma related to recurrent respiratory infections. Asthma was diagnosed according to the Global Initiative for Asthma (GINA) guidelines, and bronchiectasis was ruled out by a CT chest scan. Two men (aged 28 and 60) presented with pollen allergies, chronic rhinosinusitis, and IgG deficiency (7.8 and 7.6 g/L, respectively). Both patients underwent surgery for nasal polyposis but relapsed with acute sinusitis and severe asthma exacerbations requiring treatment with oral corticosteroids and antibiotics. The immunoglobulin replacement therapy (IRT) partially relieved the asthma by reducing the number of exacerbations. A 55-year-old woman presented with nonallergic, corticosteroid-dependent asthma (20 mg/day prednisone) and IgG deficiency (5.72 g/L). IRT improved asthma control (fall in the Asthma Control Questionnaire (ACQ)-7 score from 3.5 to 1.7) and enabled withdrawal of the corticosteroids. In a 47-year-old woman with an IgG2 subclass deficiency (1.9 g/L) and asthma, IRT increased the degree of asthma control (fall in the ACQ-7 score from 2.8 to 1.1). A 75-year-old woman presented with corticosteroid-dependent asthma (40 mg/day prednisone), IgM and IgG deficiencies (0.28 g/L and 5.36 g/L, respectively), and recurrent respiratory, skin and urinary infections. Again, IRT improved asthma control (fall in the ACQ-7 score from 2.5 to 1.2), reduced the number of hospitalizations for asthma exacerbations, and enabled a 10-mg reduction in the daily dose of prednisone. These observations suggest that IRT may improve disease control in some patients with asthma and associated huID.

Prospective, randomized, controlled, open-label study to compare efficacy of a mineral-rich solution vs normal saline after complete ethmoidectomy.

PURPOSES: The purpose of this study was to compare the efficacy of a mineral-rich solution vs normal saline solution (0.9% NaCl) following endoscopic complete bilateral ethmoidectomy. METHODS: This was a prospective, multicenter, randomized, controlled, open-label trial in subjects suffering from steroid-resistant sinonasal polyposis. Adults performed 4 nasal irrigations of mineral or saline solutions daily for 28 days. Evaluations included subject-reported RHINO quality of life (QoL) and NOSE scores, tolerability, and satisfaction, the Lund-Kennedy endoscopic score and assessments of crusting, secretions and mucociliary clearance (rhinoscintigraphy). RESULTS: A total of 189 subjects were randomized. Clinically relevant improvements (> 20 points) in RhinoQOL and NOSE scores were measured in both groups without any significant inter-group difference. Among the subjects with impaired RhinoQOL at pre-inclusion, the change in Impact-RhinoQOL score was significantly superior in mineral-rich vs saline solution at day 21 (p = 0.028) and day 28 (p = 0.027). The Lund-Kennedy score continuously improved in both groups earlier with the mineral-rich solution. Crusts were significantly fewer in number and less severe/obstructive in patients receiving mineral-rich vs saline solution at day 7 (p = 0.026) and day 14 (p = 0.016). Furthermore, secretions disappeared significantly more quickly and were less thick/purulent with mineral-rich solution at day 14 (p = 0.002) and day 21 (p = 0.043). Less epistaxis was reported in the mineral vs saline solution (p = 0.008 at day 21). CONCLUSIONS: Our findings indicate that the composition of a nasal irrigation solution influences endoscopic scores and QoL after sinus surgery for patients over 60, those with an initially poor QoL and higher symptom score, and smokers.

[Chronic rhinosinusitis of adults: new definition, new diagnosis]. / Rhinosinusites chroniques de l'adulte : nouvelle définition, nouveau diagnostic.

Chronic rhinosinusitis of adults: new definition, new diagnosis. The three-nose theory, which is based on evolution and development of the nose, seems useful for a better understanding of chronic rhinosinusitis (CRS). The nose seems in fact to be composed of three noses (one olfactory, one respiratory and one sinusal nose), each of them being able to be affected by specific diseases. The concept of chronic nasal dysfunction (CND) is based on standardized recording of nose and sinus symptoms, irrespectively of their aetiology. Clinical, endoscopic and CT-scan check up is then aimed to look for a specific disease of one or the other of the three noses (nasal polyposis, chronic respiratory rhinitis, sinusitis…) or for a disease affecting simultaneously the three noses (rhinosinusitis), each disease leading if necessary to specific additional tests (allergic tests, tooth check-up, immune balance tests…). This implies specific therapeutic options, the effectiveness of the choosed one being evaluated by comparing the standardized recordings of nose and sinus symptoms.

Rhinosinusites chroniques de l'adulte : nouvelle définition, nouveau diagnostic. Pour mieux comprendre la rhinosinusite chronique, il peut être utile de s'appuyer sur la théorie des trois nez, issue des connaissances sur l'évolution et le développement de l'organe nasal humain. Celui-ci apparaît comme un assemblage de trois nez différents (nez olfactif, nez respiratoire et nez sinusien) qui peuvent développer chacun des pathologies propres. Le concept de dysfonctionnement nasal chronique repose sur l'enregistrement standardisé des symptômes rhinosinusiens, indépendamment de leur étiologie. Le bilan clinique, endoscopique et tomodensitométrique a alors pour but de rechercher une pathologie spécifique à l'un ou l'autre des trois nez (polypose nasale, rhinite respiratoire chronique, sinusite…) ou une pathologie diffuse touchant les trois nez (rhinosinusite), qui dans chaque cas peut conduire si nécessaire à des investigations complémentaires (bilan allergologique, dentaire, immunitaire…). Il en découle des propositions thérapeutiques spécifiques, l'efficacité de celle retenue étant évaluée par comparaison des recueils de symptômes standardisés.

Fine-tuned evaluation of olfactory function in patients operated for nasal polyposis.

Given the forced-choice procedure of the identification test, patients with profound anosmia are more likely to have higher identification scores by chance than patients with hyposmia or normosmia. This may be a confusing factor when assessing the sense of smell, which alters the appreciation of real olfaction improvement. The aim of this study was to fine-tune the results of the identification Sniffin' Sticks test before and 6 weeks after surgery using the real identification score. A total of 133 patients underwent the Identification (I) and Threshold (T) tests the day before and 6 weeks after nasalization surgery. The scores of the identification test, called I G (global identification), were ranked from 0 to 16. Patients had to specify if their forced-choice answers were given either surely or randomly, called I H (hazard identification). The real score of identification I R was obtained as follow: I R = I G - I H. Patients with an immeasurable threshold according to the T test were more prone to give randomly correct answers. On the basis of I G scores, 43.6% of patients remained hypo-anosmic after surgery compared to 72.9% before surgery. Using I R scores, only 3.8% of patients remained anosmic (I R = 0) at 6 weeks after surgery. Hence, patients with real anosmia (I R = 0) were less prone to improve their olfaction than patients with I R > 0. The analysis of random factor when using identification test allows differentiating a real anosmia from a hyposmia. An I G ≤ 4 could be considered as a profound/real anosmia or a severe hyposmia. This procedure cannot, however, replace the forced-choice method in odor identification testing.

The olfactory fascia: an evo-devo concept of the fibrocartilaginous nose.

PURPOSE: Evo-devo is the science that studies the link between evolution of species and embryological development. This concept helps to understand the complex anatomy of the human nose. The evo-devo theory suggests the persistence in the adult of an anatomical entity, the olfactory fascia, that unites the cartilages of the nose to the olfactory mucosa. METHODS: We dissected two fresh specimens. After resecting the superficial tissues of the nose, dissection was focused on the disarticulation of the fibrocartilaginous noses from the facial and skull base skeleton. RESULTS: Dissection shows two fibrocartilaginous sacs that were invaginated side-by-side in the midface and attached to the anterior skull base. These membranous sacs were separated in the midline by the perpendicular plate of the ethmoid. Their walls contained the alar cartilages and the lateral expansions of the septolateral cartilage, which we had to separate from the septal cartilage. The olfactory mucosa was located inside their cranial ends. CONCLUSION: The olfactory fascia is a continuous membrane uniting the nasal cartilages to the olfactory mucosa. Its origin can be found in the invagination and differentiation processes of the olfactory placodes. The fibrous portions of the olfactory fascia may be described as ligaments that unit the different components of the olfactory fascia one to the other and the fibrocartilaginous nose to the facial and skull base skeleton. The basicranial ligaments, fixing the fibrocartilaginous nose to the skull base, represent key elements in the concept of septorhinoplasty by disarticulation.

Assessment of quality-of-life outcomes after surgery for nasal polyposis with the DyNaChron questionnaire.

This prospective study assesses outcomes at 6 weeks and 7 months after radical ethmoid surgery in 65 patients with nasal polyposis using a new and detailed instrument, the DyNaChron questionnaire, which was filled in the day prior to surgery and at 6 weeks and 7 months after surgery at follow-up visits. Before surgery, the leading bothersome symptoms were olfactory disturbances (7.74 ± 2.81) and nasal obstruction (6.66 ± 2.28). After surgery (6th week and 7th month), there was a clear improvement of all symptoms including nasal obstruction, olfactory disturbances, anterior rhinorrhea, postnasal discharge, facial pain/headache and cough in comparison to baseline (p < 0.0001). Nasal obstruction was the most improved symptom (effect size of 2.24). At 7th post-operative month, the sense of smell continued to improve slightly. By contrast, the postnasal discharge score that was significantly improved at 6th post-operative week tended to worsen at 7 months (p = 0.0045). Before surgery, strong psychosocial impacts were observed in association with nasal obstruction and anterior rhinorrhea. The physical impacts of each symptom were proportionally correlated to the symptom score before and after surgery. The quality of life (QOL) related to each symptom was clearly better at 6 weeks and remained steady at 7 months after surgery. In conclusion, olfactory disorders and postnasal rhinorrhea were the main remaining symptoms after sinus surgery despite a global improvement of symptoms and quality of life. The earlier time point to stabilize QOL outcomes of endoscopic sinus surgery could be suggested at 6 weeks after surgery.

The forgotten foramina: a study of the anterior cribriform plate.

PURPOSE: The olfactory cleft has garnered interest since the advent of endoscopic skull base surgery. Its precise anatomy, however, is still partially unknown. According to Rouvière, an "ethmoidal foramen" is located in its antero-medial part and contains a process of the dura mater. In a more lateral and anterior location, a second foramen, the "cribroethmoidal foramen", contains the anterior ethmoidal nerve. The aim of this study was to verify the existence of these elements and to establish landmarks for surgery. METHODS: We performed an anatomical and histological study of eight olfactory clefts in four cadavers using both endonasal endoscopic and endocranial dissection. RESULTS: An ethmoidal and a cribroethmoidal foramen were found in, respectively, 100 and 75% of cases. Their mean length was, respectively, 4.1 and 1.8 mm. They were located, respectively, in mean at 5.3 and 5.8 mm from the anterior ethmoidal artery. CONCLUSION: Our anatomical study demonstrates the existence of both foramina. The ethmoidal foramen clearly represents an area of least resistance in the anterior part of the olfactory cleft, which could predispose to anterior skull base cerebrospinal fluid leaks and meningoceles.

Olfactory neuroblastoma behavior inside and outside the olfactory cleft.

PURPOSE: Olfactory neuroblastoma (ONB) is a rare malignant tumor of the nose. The currently available evidence links this disease with cells of the olfactory epithelium. The detailed description of tumor site and its extension is the key of treatment. The aim of the present study was to describe the way ONB develops inside and outside the olfactory cleft. METHODS: Thirteen consecutive patients treated between 2004 and 2014 for ONB with unequivocal pathologic diagnosis, complete diagnostic imaging and endonasal endoscopy surgery were enrolled in this retrospective study. The site of origin and local extension of each tumor were studied in detail based on computed tomography/magnetic resonance imaging, surgical report, registered videotape of the surgery, and pathological reports. RESULTS: This series shows the behavior of a tumor arising either in the olfactory clefts (11 cases) or in the ethmoidal labyrinth (2 cases). When the setting begins with a tumor located in the olfactory cleft (below or in contact with the cribriform plate), the further step can be the extension to the ethmoidal labyrinth before intracranial or intraorbital extension. When tumors originate inside the ethmoidal labyrinths, the extension can first be into frontal sinus or orbital cavity. CONCLUSIONS: This fine anatomic and radiologic description shows the natural behavior of ONB inside and outside the olfactory cleft. As a consequence, the staging system developed by Kadish seems inadequate and Dulguerov's staging system could be improved. However, the preliminary proposed modification has to be evaluated in a prospective and large, multicenter cohort of patients.

Multicenter study to assess endoscopic resection of 159 sinonasal adenocarcinomas.

PURPOSE: This study was designed to assess the efficacy and morbidity of the endoscopic endonasal approach for the treatment of sinonasal adenocarcinomas. METHODS: This was a retrospective, multicenter study of nine French tertiary referral centers, including untreated patients. All patients were operated by an endoscopic approach. Tumors were classified according to the UICC 2002. Demographic, therapeutic, histological, morbidity data, and the course of the disease were recorded. Survival rates were obtained using the Kaplan-Meier method. RESULTS: A total of 159 patients were included with a mean age of 69 years. There were 19T1, 62T2 (1M1), 36T3 (1N1), 26T4a, and 16T4b (1N2a-1N2c). The mean duration of hospitalization was 4.4 days. The histologic outcomes showed that the olfactory cleft, the posterior and anterior ethmoid sinus, and the sphenoid, maxillary, and frontal sinuses were invaded in 95, 64, 55, 19, 7, and 3 % of cases, respectively. Histologic margins were positive in 17 % (1T1, 4T2, 3T3, 2T4a, and 8T4b). In total, 130 patients received adjuvant radiotherapy on the primary tumor site (58 Gy), 24 cases were not irradiated, and 5 refused treatment. The mean follow-up was 32.5 ± 24 months. The complication rate was 19 %: 6 epistaxis, 3 meningitis, 6 CSF leaks, 2 dacryocystitis, and 8 septoplasties. The recurrence rate was 17.6 % (28 cases) within 23 ± 21 months. Eleven patients underwent a second surgical procedure. Nine patients died of their disease (3T2, 2T3, 4T4b). The global and disease-specific, recurrence-free survival rate at 3 years was 74 and 84 % respectively. CONCLUSIONS: The endoscopic approach seems to be efficient to remove sinonasal adenocarcinoma with low morbidity.

Is pneumosinus dilatans an osteogenic disease that mimics the formation of a paranasal sinus?

PURPOSE: Pneumosinus dilatans is a disease that produces an abnormal expansion of a paranasal sinus cavity, which contains only air and is lined by normal mucosa, and whose bony walls are displaced outwardly to cause facial embossing or intracranial, orbital or ethmoidal encroachment. Objective was to evaluate the hypothesis that pneumosinus dilatans is primarily an osteogenic disease. METHODS: A detailed clinical history of three consecutive patients with pneumosinus dilatans was taken. Each patient also underwent computed tomography (CT), fluorine-deoxyglucose positron emission tomography-CT (FDG PET-CT), fluorine 18-labeled sodium fluoride PET-CT (NaF PET-CT), and bone pathology. RESULTS: The FDG PET-CT and pathology confirmed that the mucosa inside the pneumosinus dilatans was normal and devoid of inflammatory cell infiltrate. Significant uptake of (18)F-NaF on PET-CT images correlated well with bone pathology, showing intense and diffuse bone remodeling. At a 1-year follow-up, following a frontotomy for case #1 and a middle antrostomy for case #2, there was a marked resolution of the patients' clinical symptoms and deformities, new bone formation on the walls, stabilization of the new sinus shape and volume, and persistence of significant uptake of (18)F-NaF. CONCLUSIONS: Pneumosinus dilatans is a rare disease. Its diagnosis is based on CT scan images. This study has shown that (18)F-NaF PET-CT and bone pathology are useful modalities for the positive diagnosis of difficult cases. Pneumosinus dilatans appears to be an osteogenic disease. Further research is needed to investigate a possible link between mechanisms involved in paranasal sinus formation and those involved in pneumosinus dilatans.

Study protocol: the biologics in severe chronic rhinosinusitis with nasal polyps survey.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of intranasal corticosteroids and short-term use of oral corticosteroids, in adjunct with saline solution rinses. Surgical management is proposed in patients who failed after medical treatment. In France, two biologics are reimbursed in case of severe uncontrolled CRSwNP despite medical treatment and endoscopic sinus surgery. Waiting for head-to-head biologics comparison, studies should report the efficacy and safety of biologics in large real-life cohorts. This study protocol describes the aims and methods of a prospective, observational, national, multicentric cohort of patients with CRSwNP treated with biologics. METHODS AND ANALYSIS: The BIOlogics in severe nasal POlyposis SurvEy is a French multicentre prospective observational cohort study. The main aim is to assess the efficacy and tolerance of biologics in patients with CRSwNP, with or without association with other type 2 diseases, and to determine the strategies in case of uncontrolled disease under biologics. Patients over 18 years old requiring biologics for CRSwNP in accordance with its marketing approval in France (ie, severe nasal polyposis, with lack of control under nasal corticosteroid, systemic corticosteroids and surgery) are invited to participate. Collected data include topical history of surgical procedures and biologics, medication and use of systemic corticosteroids, visual analogical scales for specific symptoms, Sino-Nasal Outcome Test-22 questionnaire, nasal polyp score, asthma control test, Lund-Mackay score on CT scan and IgE concentration and eosinophilic count on blood sample. TRIAL REGISTRATION: NCT05228041/DRI_2021/0030.

The Prognostic Value of Olfactory Dysfunction in Patients with COVID-19: The COVIDORA Study.

BACKGROUND: Among all studies describing COVID-19 clinical features during the first wave of the pandemic, only a few retrospective studies have assessed the correlation between olfac-tory dysfunction (OD) and the evolution of disease severity. The main aim was to assess whether OD is a predictive factor of COVID-19 severity based on the patient's medical management (outpa-tient care, standard hospital admission, and ICU admission). METHODS: A national, prospective, mul-ticenter cohort study was conducted in 20 public hospitals and a public center for COVID-19 screen-ing. During the first wave of the pandemic, from 6 April to 11 May 2020, all patients tested positive for COVID-19 confirmed by RT-PCR underwent two follow-up ENT consultations within 10 days of symptom onset. The main outcome measures were the evolution of medical management (out-patient care, standard hospital admission, and ICU admission) at diagnosis and along the clinical course of COVID-19 disease. RESULTS: Among 481 patients included, the prevalence of OD was 60.7%, and it affected mostly female patients (74.3%) under 65 years old (92.5%), with fewer comor-bidities than patients with normal olfactory function. Here, 99.3% (290/292) of patients with OD presented with non-severe COVID-19 disease. Patients reporting OD were significantly less hospi-talized than the ones managed as outpatients, in either a standard medical unit or an ICU. Conclu-sions: As regards the clinical course of COVID-19 disease, OD could predict a decreased risk of hospitalization during the first wave of the pandemic.

Multiple Biologics for Multiple T2 Diseases: A Pharmacoepidemiological Algorithm for Sorting Out Patients by Indication.

Background: Several biologics (Bx) and targeted synthetic drugs (TSD) exist to treat T2 diseases, including chronic spontaneous urticaria (CSU), severe asthma (SA), chronic rhinosinusitis with nasal polyposis (CRSwNP) or atopic dermatitis (AD). Objective: To identify patients treated with Bx/TSD from a dynamic dispensing database using an algorithm-based methodology. Methods: We used the LRx database (Lifelink Treatment dynamics, IQVIA) which covers nearly 45% of the French retail pharmacies. Patients who had at least one Bx/TSD dispensing from April 2021 to March 2022 were included. An algorithm was designed to determine the indication of the Bx/TSD prescription analyzing all previous drug dispensation since March 2012 following a 3-steps procedure. Results: A total of 21,677 patients received at least one Bx/TSD between March 2021 and April 2022. The algorithm identified 91.7% (n = 19,884) patients with a T2 disease (AD = 18.4%, CRSwNP = 1.5%, SA = 59.5%, and CSU = 12.4%), the rest having either an association of diseases (1%) or an undetermined one (7.3%). SA was the main reason for Bx/TSD initiation (52%), followed by AD (29%), CSU (14%) and CRSwNP (5%). For SA patients already under biologic at entry, omalizumab was the most frequently prescribed (48%) followed by benralizumab, mepolizumab (22% each) and dupilumab (8%). Dupilumab was mostly prescribed for AD patients (89% for patient-initiated vs 96% for patient-renewed) followed by baricitinib. Conclusion: The algorithm was able to identify patients with T2 diseases under Bx/TSD treatments. This tool may help to follow the evolution of prescription patterns in the future.

Multicenter study to assess surgical treatments of 452 sinonasal intestinal-type adenocarcinomas: A REFCOR study.

PURPOSE: The objective was to assess the local oncological outcomes of endoscopic versus external surgical treatment of sinonasal intestinal-type adenocarcinomas (ITAC) and the factors of recurrence. METHODS: a retrospective non-randomized case-control multicenter study was carried out, including 452 untreated sinonasal ITACs recruited from 10 tertiary referral centers. The tumors were re-classified according to the UICC 2017 (pT). Survival curves were obtained using the Kaplan-Meier method. Univariate analysis was done with the log-rank test. Multivariate analysis was performed with a Cox model adjusted for age, T stage, and radiotherapy. A binary logistic regression compared surgical complications and performed two supplementary analyses on positive margins. RESULTS: We compared 195 and 257 patients operated by the external and endoscopic approach, respectively. The mean follow-up was 59.2 ± 48.7 months. Post-operative margins were invaded in 30.6 versus 18.9% of patients, respectively (p = 0.007). The overall recurrence rate was 33.8 versus 24.6%, respectively (p = 0.034). There was a significant difference in favor of the endoscopic approach regarding local recurrence-free survival thanks to better surgical margins in univariate and multivariate analysis (Odd Ratio = 2.01 (1.2-3.36) p = 0.0087). The complication rate (Odds Ratio = 3.4 (1.79-6.32) p < 0.001) was significantly lower in the endoscopic group. The histological positivity of signet-ring cells shows a statistically significant difference in recurrence-free survival (p = 0.0028). CONCLUSION: the oncological control of ITAC is better through the endoscopic approach, with negative margins and the absence of signet-ring-cells, two independent factors of recurrence.

Chronic Rhinosinusitis Outcome Registry (CHRINOSOR): Establishment of an International Outcome Registry Driven by mHealth Technology.

BACKGROUND: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on the prevalence of uncontrolled chronic rhinosinusitis (CRS) and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of the effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery, or biologics. OBJECTIVE: To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology. METHODOLOGY: A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes, and a set of relevant clinical outcomes. Adult patients with a diagnosis of CRS are eligible for inclusion. RESULTS: A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy, and data security aspects. Up to 300 patients have already been included. CONCLUSIONS: CHRINOSOR is a collaborative effort that aims at improving our understanding of CRS, its comorbidities, and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by RWE.

Respiratory epithelial adenomatoid hamartomas of the olfactory clefts.

The objective of this study is to report a 5-year experience with Respiratory Epithelial Adenomatoid Hamartoma (REAH) of the olfactory clefts. The study design is retrospective observational study and the setting is in a Tertiary medical center. The charts of all adult patients operated on bilateral nasal polyps between 2003 and 2008 were retrospectively checked up on the diagnosis of REAH. Three periods have been distinguished according to our experience with REAH. REAH can be observed either as bilateral pseudotumours confined to the olfactory clefts (n = 12 between 2003 and 2008) or associated to nasal polyposis of the ethmoid labyrinths. As the diagnosis of associated REAH became more evident, the number of recognized cases increased from 0% in 2003 and 2004 to 1.6% in 2005 (1/64 patients) and 12.5% in 2006 (10/80 patients) (period 1). Systematic endoscopy of the olfactory clefts during ethmoid labyrinth surgery increased the proportion to 27% (27/100 patients) (period 2). Systematic biopsies of abnormal mucosa in the olfactory clefts during ethmoid surgery increased the proportion to 48% (31/65 patients). The histopathological diagnosis of REAH has been described in 1995 and added to the World Health Organization classification of tumours in 2005. Pseudotumoural REAH confined to the olfactory clefts represent a differential diagnosis for bilateral naso-ethmoidal polyposis. The significance of REAH associated to naso-ethmoidal polyposis is unclear.