Search

Background: Recurrent infections of the nose, sinuses and ears are common problems for people with primary ciliary dyskinesia. While pulmonary exacerbations in primary ciliary dyskinesia are defined, there is no definition for ear-nose-throat exacerbations, a potential outcome for research and clinical trials., Methods: We set up an expert panel of 24 ear-nose-throat specialists, respiratory physicians, other healthcare professionals and patients to develop consensus definitions of sinonasal and otological exacerbations in children and adults with primary ciliary dyskinesia for research settings. We reviewed the literature and used a modified Delphi approach with four electronic surveys., Results: Definitions for both sinonasal and otological exacerbations are based on a combination of major and minor criteria, requiring three major or two major and at least two minor criteria each. Major criteria for a sinonasal exacerbation are 1) reported acute increase in nasal discharge or change in colour, 2) reported acute pain or sensitivity in the sinus regions and 3) mucopurulent discharge on examination. Minor criteria include reported symptoms, examination signs, doctor's decision to treat and improvement after at least 14 days. Major criteria for the otological exacerbation are 1) reported acute ear pain or sensitivity, 2) reported acute ear discharge, 3) ear discharge on examination and 4) signs of otitis media in otoscopy. Minor criteria are reported acute hearing problems, signs of acute complication, and doctor's decision to treat., Conclusion: These definitions might offer a useful outcome measure for primary ciliary dyskinesia research in different settings. They should be validated in future studies and trials together with other potential outcomes, to assess their usability., Competing Interests: Conflict of interest: No potential conflict of interest relevant to this article was reported. Conflict of interest: A-L.M.L. Poirrier received speaker honorarium from GSK outside the submitted work. Conflict of interest: J- F. Papon reports personal fees from Sanofi, GSK, Medtronic and ALK outside the submitted work., (Copyright ©The authors 2024.)

Background: Clinical trials have demonstrated the effectiveness of biologics in treating chronic rhinosinusitis with nasal polyps (CRSwNP). However, real-world evidence regarding patient outcomes and predictors of clinical response remains limited., Methodology: In this multicentric 18-month follow-up study, 326 adult patients who initiated biologic therapy for severe uncontrolled CRSwNP were included. Patient characteristics, including clinical and inflammatory markers, and comorbidities were collected at baseline and at 3, 6, 12, and 18 months of follow-up. We examined success rates based on current guidelines and identified potential factors associated to clinical response at 6 months., Results: We observed a significant decrease of Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score (interquartile range) of 60.5 (47-74) at baseline to 26.0 (11-41) at 3 months. A significant decrease of nasal symptoms and endoscopic nasal polyp score was observed at 3 months. After 6 months of biologic treatment, 59% of patients were classified as excellent responders according to the EUFOREA-EPOS 2023 criteria. Multivariate analysis revealed a suggestive association between baseline eosinophil blood count, type of biologic and an excellent response at 6 months., Conclusions: This real-world study confirms the effectiveness of biologics as an add-on therapy in patients with severe uncontrolled CRSwNP. Biologics lead to rapid and sustained improvement in clinical symptoms. A significant proportion of patients exhibit an excellent response, with no need for systemic corticosteroids.

Ciliary dysfunction may result in chronic airway inflammation and infection causing injury and structural changes to the airway epithelium, leading to a variety of diseases, like bronchiectasis and primary diffuse chronic rhinosinusitis (CRS). Currently, ciliary beating analysis has mainly been studied through the measure of the ciliary beating frequency (CBF) by high-speed digital video microscopy (HSDV). However, a normal CBF has been described in different forms of primary and acquired ciliary dyskinesia.

Background: Despite advances in primary ciliary dyskinesia (PCD) research, many questions remain; diagnosis is complex and no disease-specific therapies exist. Using a mixed-methods approach, we aimed to identify priorities for clinical and epidemiological research and explore barriers to research., Methods: To obtain rich, relevant, diverse data, we performed in-depth semi-structured interviews with PCD specialists selected using purposive sampling. We transcribed, coded and analysed interview data using thematic analysis. Based on interview themes that we identified, we developed an anonymous survey and circulated it widely through the BEAT-PCD network., Results: We interviewed 28 participants from 15 countries across different disciplines and expertise levels. The main themes identified as priorities for PCD research were improving diagnosis; understanding prevalence and disease course; phenotypic variability; disease monitoring; treatment strategies; clinical trial end-points; and poorly researched areas. In total, 136 participants (49% paediatric pulmonologists) from 36 countries completed the survey. Most commonly reported barriers for research were low awareness about PCD and difficulties securing funding - in more than one-third of cases, participants reported undertaking predominantly unfunded research. Research questions ranked highest included priorities related to further improving diagnosis, treating PCD, managing upper and lower airway problems, and studying clinical variability and disease prognosis., Conclusion: We need to overcome barriers of limited funding and low awareness and promote collaborations between centres, disciplines, experts and patients to address identified PCD priorities effectively. Our results contribute to the ongoing efforts of guiding the use of existing limited research resources and setting up a roadmap for future research activities., Competing Interests: Conflict of interest: M. Goutaki reports grants from the Johanna Dürmüller-Bol Foundation outside the submitted work and is Co-Chair of the BEAT-PCD clinical research collaboration. Conflict of interest: Y.T. Lam is Work Package Co-Lead in clinical research collaboration BEAT-PCD funded by the European Respiratory Society. Conflict of interest: J.D. Chalmers reports grants from AstraZeneca, GlaxoSmithKline, Grifols, Gilead Sciences, Boehringer Ingelheim, Trudell, Insmed and Genentech; and consulting fees from AstraZeneca, GlaxoSmithKline, Grifols, Boehringer Ingelheim, Trudell, Insmed, Genentech, Pfizer, Antabio and Zambon, all outside the submitted work; and is an associate editor of this journal. Conflict of interest: J-F. Papon reports grants and consulting fees from Sanofi, GSK, Medtronic, AstraZeneca and ALK; lecture honoraria from Sanofi, GSK and Medtronic; and travel support from Sanofi and GSK, all outside the submitted work. Conflict of interest: J.S. Lucas reports grants from the Medical Research Council, Life Arc, NHS England, NIHR Southampton Biomedical Research Centre, AAIR charity, NIHR Research for Patient Benefit and Wessex Medical Research, outside the submitted work. Conflict of interest: All other authors have nothing to disclose., (Copyright ©The authors 2024.)

Background: Primary ciliary dyskinesia (PCD) is a rare airway disorder caused by defective motile cilia. Only male patients have been reported with pathogenic mutations in X-linked DNAAF6 , which result in the absence of ciliary dynein arms, whereas their heterozygous mothers are supposedly healthy. Our objective was to assess the possible clinical and ciliary consequences of X-chromosome inactivation (XCI) in these mothers., Methods: XCI patterns of six mothers of male patients with DNAAF6 -related PCD were determined by DNA-methylation studies and compared with their clinical phenotype (6/6 mothers), as well as their ciliary phenotype (4/6 mothers), as assessed by immunofluorescence and high-speed videomicroscopy analyses. The mutated X chromosome was tracked to assess the percentage of cells with a normal inactivated DNAAF6 allele., Results: The mothers' phenotypes ranged from absence of symptoms to mild/moderate or severe airway phenotypes, closely reflecting their XCI pattern. Analyses of the symptomatic mothers' airway ciliated cells revealed the coexistence of normal cells and cells with immotile cilia lacking dynein arms, whose ratio closely mirrored their XCI pattern., Conclusion: This study highlights the importance of searching for heterozygous pathogenic DNAAF6 mutations in all female relatives of male PCD patients with a DNAAF6 defect, as well as in females consulting for mild chronic respiratory symptoms. Our results also demonstrate that about one-third-ranging from 20% to 50%-normal ciliated airway cells sufficed to avoid severe PCD, a result paving the way for gene therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: All authors report personal fees as expert consultant for Sanofi and GlaxoSmithKline., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct isotypes form cell type- and context-specific microtubule structures is poorly understood. Based on a cohort of 12 patients with primary ciliary dyskinesia as well as mouse mutants, we identified and characterized variants in the TUBB4B isotype that specifically perturbed centriole and cilium biogenesis. Distinct TUBB4B variants differentially affected microtubule dynamics and cilia formation in a dominant-negative manner. Structure-function studies revealed that different TUBB4B variants disrupted distinct tubulin interfaces, thereby enabling stratification of patients into three classes of ciliopathic diseases. These findings show that specific tubulin isotypes have distinct and nonredundant subcellular functions and establish a link between tubulinopathies and ciliopathies.

Introduction: Nearly all patients with primary ciliary dyskinesia (PCD) report ear-nose-throat (ENT) symptoms. However, scarce evidence exists about how ENT symptoms relate to pulmonary disease in PCD. We explored possible associations between upper and lower respiratory disease among patients with PCD in a multicentre study., Methods: We included patients from the ENT Prospective International Cohort (EPIC-PCD). We studied associations of several reported ENT symptoms and chronic rhinosinusitis (defined using patient-reported information and examination findings) with reported sputum production and shortness of breath, using ordinal logistic regression. In a subgroup with available lung function results, we used linear regression to study associations of chronic rhinosinusitis and forced expiratory volume in 1 s (FEV 1 ) accounting for relevant factors., Results: We included 457 patients (median age 15 years, interquartile range 10-24 years; 54% males). Shortness of breath associated with reported nasal symptoms and ear pain of any frequency, often or daily hearing problems, headache when bending down (OR 2.1, 95% CI 1.29-3.54) and chronic rhinosinusitis (OR 2.3, 95% CI 1.57-3.38) regardless of polyp presence. Sputum production associated with daily reported nasal (OR 2.2, 95% CI 1.20-4.09) and hearing (OR 2.0, 95% CI 1.10-3.64) problems and chronic rhinosinusitis (OR 2.1, 95% CI 1.48-3.07). We did not find any association between chronic rhinosinusitis and FEV 1 ., Conclusion: Reported upper airway symptoms and signs of chronic rhinosinusitis associated with reported pulmonary symptoms, but not with lung function. Our results emphasise the assessment and management of upper and lower respiratory disease as a common, interdependent entity among patients with PCD., Competing Interests: Conflict of interest: J-F. Papon reports personal fees from Sanofi, GSK, Medtronic and ALK, outside the submitted work. Conflict of interest: M. Alexandru received personal fees from Sanofi and ALK outside the submitted work. Conflict of interest: M. Boon reports grants from Forton grant (King Baudouin Foundation) 2020-J1810150-217926 for cystic fibrosis research and personal fees from Vertex outside the submitted work. Conflict of interest: N. Lorent received honoraria to her institution from GSK, INSMED and AN2 Therapeutics outside the submitted work, and a travel grant from Pfizer. Conflict of interest: J. Roehmel received grants, clinical study reimbursement from Vertex, INSMED, Medical Research Council/UK, BMBF and Mukoviszidose Institut, outside the submitted work. Conflict of interest: The other authors report no competing interests., (Copyright ©The authors 2024.)

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.

It has been demonstrated that universal hearing neonatal screening (UHNS) is efficient at providing early diagnosis and rehabilitation for deafness. The risk factors of deafness in children have been identified, but less specifically in those diagnosed after UHNS. In this study, we aim to study these factors in infants who were referred after screening and to compare our experience to recent data. We studied infants referred to our department for diagnosis after screening between January 2018 and December 2021. Their medical history and neonatal hearing risk factors were assessed. Associations between factors were also analyzed. Sixty-six infants were included. A family history of deafness (47%), syndromic deafness (41%), intrauterine growth retardation or prematurity (19.7%), and prolonged NICU admission (18%) were the most observed factors. When analyzing according to these associations, family history of deafness and syndromic cases remained the most prevalent factors (74%), while only five cases (7.8%) presented with other neonatal risk factors only. The majority of congenital hearing loss cases are observed in infants with suspected genetic deafness. Parental counseling, the diagnostic pathway, as well as the healthcare system should be adapted according to these risk factors.

This update aimed to evaluate surgical indications in the management of chronic rhinosinusitis with nasal polyps (CRSwNP). It was conducted and reported according to the criteria stipulated by the Synthesis Without Meta-analysis (SwiM) guidelines. From the PubMed-National Library of Medicine database, 1098 articles were identified for the period 2006-2021 using the key words "nasal polyps" and "surgery". After screening and analysis, 39 publications were selected. The efficacy of surgery on functional improvement in CRSwNP, measured by the specific quality-of-life score SNOT-22, is established, and improvement in olfactory function is expected in 50% of patients. The rate of surgical revision is at least 10-15% at 4 years, but the disease can be controlled for several years, with the interval between primary surgery and symptomatic recurrence exceeding 10 years in some cases. The criteria for surgery are not clearly defined in the literature. However, several authors consider failure of ≥ 8 weeks' well-conducted local medical treatment and use of more than 2 courses of systemic corticosteroids as a reliable indication. No studies or meta-analyses are currently available to determine the superiority of one surgical technique over another., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Neck ultrasound (US) is a widely used and accessible operator-dependent technique that helps characterize thyroid nodules and pathologic parathyroid glands (PPGs). However, thyroid nodules may sometimes be confused with PPGs. PARATH-US study aims at identifying US characteristics to differentiate PPGs from thyroid nodules, as there is no study, at present, which directly compares the US features of these two common neoplasms., Methods: PARATH-US is a single-center study that was conducted at a tertiary referral center, including consecutive lesions from patients undergoing neck US examination from 2016 to 2022., Findings: 176 PPGs (158 patients: serum calcium levels 2.91 [IQR 2.74-3.05] mmol/L, PTH levels 173 [112-296] ng/L) were compared to 232 size- and volume-matched thyroid nodules (204 age- and sex-matched patients). The morphologic patterns, echoic content and vascular status were all different between PPGs and thyroid neoplasms (p < 0.01 for all comparisons). The combined parameters maximally discriminated PPGs from thyroid nodules (OR, 7.6; 95% CI: 3.4, 17.1, p < 0.0001). When applying risk stratification systems developed for thyroid malignancies, 58-63% of PPGs were classified as high-risk lesions. Parathyroid adenomas had larger sizes and volumes than hyperplasias (p = 0.013 and p = 0.029). Serum calcium and PTH levels were significantly correlated with PPG size and volume (p < 0.0001 for all comparisons)., Interpretation: We demonstrate the presence of distinct US characteristics in PPGs, which help differentiate them from thyroid nodules. When mistaken for thyroid nodules, PPGs bear high-risk US features. When dealing with high-risk cervical lesions detected on US, a PPG should be suspected, and an assessment of calcium levels recommended to avoid unnecessary invasive procedures., Funding: CYTO-TRAIN, C2022DOSRH053, funded by the French Regional Health Agency., Competing Interests: None declared., (© 2023 The Author(s).)

Purpose: Hearing rehabilitation through middle ear surgery can be challenging, particularly for patients with chronic otitis media, but new hearing devices offer opportunity to reach this goal. The aim was to compare hearing outcomes and quality of life in patients who were converted from a Baha Attract system to the Osia system., Methods: Prospective observational study, in which each subject acted as their own control. Six patients who were converted from a Baha Attract to an Osia system performed audiometric and quality of life assessments with different sound processor at fitting, 3, 6 and 12 months. The speech performance in noise with the Osia system at 12 months, expressed as dB SNR, was compared to the baseline condition (Baha 5)., Results: The PTA4 hearing thresholds improved from 42.6 ± 11 with Baha 5 Power to 34.8 ± 13.3 with Baha 5 SuperPower and to 25.4 ± 3.5 with the Osia at 12 months, leading to a significant functional gain of 17.2 ± 10.9 dB vs Baha 5 (p < 0.02). Speech understanding in both quiet and noise was clinically improved reaching a mean SNR of less than 1 dB at 12 months with the Osia system. Quality of life outcomes improved by more than 20% at 12-month follow-up., Conclusion: Aided hearing thresholds and speech understanding in noise improved when patients were converted from the Baha Attract system to the Osia system. The aided hearing threshold was maintained up to 8 kHz (26 dB) with the Osia system., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Primary ciliary dyskinesia is a heterogeneous, inherited motile ciliopathy in which respiratory cilia beat abnormally, and some ultrastructural ciliary defects and specific genetic mutations have been associated with particular ciliary beating alterations. Ciliary beating can be evaluated using digital high-speed videomicroscopy (DHSV). However, normal reference values, essential to assess ciliary beating in patients referred for a PCD diagnostic, vary between centres, as minor variations in protocols might influence ciliary beating. Consequently, establishment of normal values is essential for each PCD diagnostic centre. We aimed to evaluate whether delay after sampling, and temperature for conservation of respiratory ciliated samples, might modify assessments of ciliary beating. In total, 37 healthy nasal brushing samples of respiratory ciliated epithelia were collected. Video sequences were recorded at 37 °C immediately using DHSV. Then, the samples were divided and conserved at 4 °C or at room temperature (RT). Ciliated beating edges were then recorded at 37 °C, at 3 h and at 9 h post sampling. In six samples, recordings were continued up to 72 h after sampling. Ciliary beating was assessed manually by ciliary beat frequency (CBF M ) and ciliary beat pattern (CBP). A semi-automatic software was used for quantitative analysis. Both CBF and CBP evaluated manually and by a semi-automated method were stable 9 h after sampling. CBF M was higher when evaluated using samples stored at RT than at 4 °C. CBP and the semi-automated evaluation of ciliary beating were not affected by storage temperature. When establishing normal references values, ciliary beating can be evaluated at 37 °C up to 9 h after nasal brushing, but the storage temperature modifies ciliary beating and needs to be controlled.

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by pulmonary, otological and sino-nasal manifestations. Well-defined clinical outcome measures are needed in such rare diseases research to improve follow-up and treatments. Pulmonary outcome measures have recently been described. The aim of this study was to identify ear and upper airway outcome measures that could be used for longitudinal follow-up of individuals with PCD., Methods: A scoping review was performed by systematically searching MEDLINE, Embase and Cochrane Database of Systematic Reviews online databases for studies published from January 1996 to March 2022 that included at least 10 adult or paediatric PCD patients and reported ear and upper airway outcomes., Results: 33 studies (1794 patients) were included. 10 ear and upper airway outcomes were reported. 17 studies reported audiometry, 16 reported otoscopic findings, and 13 reported rhinoscopic findings and sinus imaging. Health-related quality of life questionnaires were performed in seven studies. There was a high variability in definitions and measurement of outcomes between studies., Conclusions: This scoping review highlights the lack of data regarding ear and upper airway outcomes in PCD. It also reports a high heterogeneity in outcome definitions or measures. We provide well-founded specific suggestions to standardise ear and upper airway outcome definitions and reporting for future PCD research studies., Competing Interests: Conflict of interest: No author has a conflict of interest to declare., (Copyright ©The authors 2023.)

Introduction: The introduction of biotherapies has significantly changed the management of patients with chronic rhinosinusitis with nasal polyps (CRSwNP). These drugs are generally reserved for severe or recurrent CRSwNP. Thus, the concepts of severity of the disease and treatment response must be mastered by otorhinolaryngologists. However, a clear definition of these concepts in CRSwNP is missing., Methods: This article focuses on definitions of severity and treatment response in CRSwNP by providing an expert consensus among French rhinologists, using a Delphi study., Results: The severity assessment should seek the presence of uncontrolled asthma, olfactory disorders, nasal blockage, impaired quality of life (QOL) and cumulative annual dose of systemic corticosteroids.The treatment response should assess the presence of olfactory disorders, nasal blockage, QOL impairment, response to background therapy, resistance and/or dependence to oral corticosteroids, cumulative annual dose of systemic corticosteroids, response to surgery and to biologics.A failure after polypectomy should not be considered as a failure of surgical management of CRSwNP and must discuss the realization of an extended sinus surgery procedure before the prescription of biologics., Conclusion: Definitions of severity, control of CRSwNP, as well as therapeutic strategies to improve patients' QOL achieved high level of consensus.

Importance: Otologic disease is common among people with primary ciliary dyskinesia (PCD), yet little is known about its spectrum and severity., Objective: To characterize otologic disease among participants with PCD using data from the Ear-Nose-Throat Prospective International Cohort., Design, Setting, and Participants: This cross-sectional analysis of baseline cohort data from February 2020 through July 2022 included participants from 12 specialized centers in 10 countries. Children and adults with PCD diagnoses; routine ear, nose, and throat examinations; and completed symptom questionnaires at the same visit or within 2 weeks were prospectively included., Exposures: Potential risk factors associated with increased risk of ear disease., Main Outcomes and Measures: The prevalence and characteristics of patient-reported otologic symptoms and findings from otologic examinations, including potential factors associated with increased risk of ear inflammation and hearing impairment., Results: A total of 397 individuals were eligible to participate in this study (median [range] age, 15.2 [0.2-72.4] years; 186 (47%) female). Of the included participants, 204 (51%) reported ear pain, 110 (28%) reported ear discharge, and 183 (46%) reported hearing problems. Adults reported ear pain and hearing problems more frequently when compared with children. Otitis media with effusion-usually bilateral-was the most common otoscopic finding among 121 of 384 (32%) participants. Retracted tympanic membrane and tympanic sclerosis were more commonly seen among adults. Tympanometry was performed for 216 participants and showed pathologic type B results for 114 (53%). Audiometry was performed for 273 participants and showed hearing impairment in at least 1 ear, most commonly mild. Season of visit was the strongest risk factor for problems associated with ear inflammation (autumn vs spring: odds ratio, 2.40; 95% CI, 1.51-3.81) and age 30 years and older for hearing impairment (41-50 years vs ≤10 years: odds ratio, 3.33; 95% CI, 1.12-9.91)., Conclusion and Relevance: In this cross-sectional study, many people with PCD experienced ear problems, yet frequency varied, highlighting disease expression differences and possible clinical phenotypes. Understanding differences in otologic disease expression and progression during lifetime may inform clinical decisions about follow-up and medical care. Multidisciplinary PCD management should be recommended, including regular otologic assessments for all ages, even without specific complaints.

In the aftermath of acute infection with the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), a large number of symptoms persist or appear, constituting a real syndrome called "long COVID-19" or "post-COVID- 19" or "post-acute COVID-19 syndrome". Its incidence is very high, half of patients showing at least one symptom at 4-6 months after Coronarovirus infectious disease 2019 (COVID-19). They can affect many organs. The most common symptom is persistent fatigue, similar to that seen after other viral infections. Radiological pulmonary sequelae are relatively rare and not extensive. On the other hand, functional respiratory symptoms, primarily dyspnoea, are much more frequent. Dysfunctional breathing is a significant cause of dyspnoea. Cognitive disorders and psychological symptoms are also very common, with anxiety, depression and post-traumatic stress symptoms being widely described. On the other hand, cardiac, endocrine, cutaneous, digestive or renal sequelae are rarer. The symptoms generally improve after several months, even if their prevalence at two years remains significant. Most of the symptoms are favored by the severity of the initial illness, and the psychic symptoms by the female sex. The pathophysiology of most symptoms is poorly understood. The influence of the treatments used in the acute phase is also important. Vaccination, on the other hand, seems to reduce their incidence. The sheer number of affected patients makes long-term COVID-19 syndrome a public health challenge., (© 2023 Published by Elsevier Masson SAS on behalf of l'Académie nationale de médecine.)

Background: Sinonasal symptoms are a common feature of primary ciliary dyskinesia (PCD); however, literature about their severity and frequency, particularly during the life course, is scarce. Using baseline data from the Ear, nose and throat (ENT) Prospective International Cohort of PCD patients, we describe sinonasal disease in PCD., Methods: We included participants who had a routine sinonasal examination during which they completed a symptoms questionnaire. We compared frequency of reported symptoms and examination findings among children and adults, and identified characteristics potentially associated with higher risk of sinonasal disease using ordinal regression., Results: 12 centres contributed 384 participants; median age was 16 years (IQR 9-22), and 54% were male. Chronic nasal problems were the most common feature, reported by 341 (89%). More adults (33; 24%) than children (10; 4%) described hyposmia. Quality of life was moderately affected by rhinosinusitis among 136 participants with completed SNOT-22 questionnaires (median score 31; IQR 23-45). Examinations revealed nasal polyps among 51 of 345 participants (15%) and hypertrophic inferior nasal turbinates among 127 of 341 participants (37%). Facial pain was detected in 50 of 342 participants (15%). Nasal polyps, hypertrophic turbinates, deviated septum and facial pain were found more commonly in adults than children. The only characteristic associated with higher risk of sinonasal disease was age 10 years and older., Conclusions: Based on our findings, regular sinonasal examinations are relevant for patients with PCD of all ages. There is a need for improved management of sinonasal disease supported by evidence-based guidelines., Competing Interests: Conflict of interest: P. Latzin received grants or honoraria for participation in data safety monitoring boards or advisory boards from Vertex, Vifor, OM Pharma, Polyphor, Santhera (DMC) and Sanofi Aventis within the last 36 months. J. Roehmel received grants and clinical study remuneration from Vertex, INSMED, Medical Research Council/UK, BMBF and Mukoviszidose Institut. All other authors have nothing to declare., (Copyright ©The authors 2023.)

Aims: The main aim of the present study was to report the annual volume of surgeries performed for chronic rhinosinusitis with nasal polyps (CRSwNP) in France, based on health insurance data. The secondary objectives were to describe the different characteristics of the surgeries and their complications, and to estimate the number of patients eligible for biotherapy., Material and Methods: This was a descriptive observational retrospective study using data from French national health insurance databases for the period 2011-2018. Inclusion criteria comprised all hospital stays with procedures related to CRSwNP according to the French Common Classification of Medical Acts and consistent with French practices., Results: Ninety-two thousand one hundred and fourty one patients (92,141) for 92,884 admissions for CRSwNP surgery were analyzed, providing an accurate representation of CRSwNP surgery in France between 2011 and 2018. The revision surgery rate for patients operated on in 2011 was 13.0% (1,457/11,212), corresponding to an average annual rate of 1.86% over 7 years. In the 11,750 sinus surgery admissions in 2018, the complications rate was only 0.65% (77/11,750)., Conclusion: Sinus surgery is safe (0.65% complications) and reliable (estimated revision rate, 5.5%: 5,078/92,884). This study provides the first evaluation of the target population for biotherapy in France., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNPs) is associated with otitis media with effusion (OME) in about 25% of cases. The objective of this study was to assess the clinical efficacy of the 4 biologic agents currently available in France for severe asthma (omalizumab, mepolizumab, benralizumab and dupilumab) in 17 patients followed for both asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and presenting otitis media with effusion (OME) on otoscopy. Methods: It was a multicenter retrospective study performed in 4 academic ENT and respiratory departments in Paris, France, with assessment of the clinical evolution of 17 patients with severe eosinophilic asthma and with chronic refractory OME and CRSwNPs treated by biologic agents. Global evaluation of treatment effectiveness (GETE) on asthma, CRSwNP and OME was classified on a 5-point scale as 1, excellent; 2, good; 3, moderate; 4, poor; or 5, symptoms worsening. Response was defined as an excellent/good score (1 or 2). Results: 17 patients were prescribed a total of 30 biologics. The evolution of OME did not follow that of asthma and CRSwNPs in 15 (88%) and 12 (70%) cases, respectively. Concerning OME, 19/30 (63%) patients were non-responders. Among the 10 patients who successively received ≥ 2 biologic agents, the OME response differed, depending on the considered agent Dupilumab had the highest response rate. Conclusions: Resistant OME, associated with asthma and chronic rhinosinusitis with nasal polyps, can present a disconnected evolution under biologics. CRSwNP-associated OME requires a specific evaluation to define the best treatment.

Primary ciliary dyskinesia (PCD) is a rare genetical disease characterized by an abnormal structure or function of the cilia, causing sinusitis, otitis, and bronchiectasis. Hearing loss affects 60% of PCD patients, but data are lacking concerning hearing and temporal bone imaging in adults. Our aim was to describe clinical and radiological ear disease in adults with genetically confirmed PCD. Data were recorded from January 2018 to December 2019. PCD patients were compared with controls with bronchiectasis without PCD. Clinical examination included otomicroscopy and auditory tests. A temporal bone CT scan (TBCT) was systematically performed. Seventeen patients (34 ears) were included in each group. The eardrums were abnormal in 25 (74%) PCD ears versus 8 (24%) ears in the controls (p < 0.05). Conductive hearing loss was more frequent in the PCD group (24% vs. 12% in controls). TBCT were abnormal in 94% PCD patients vs. 32% in the controls (p < 0.05). The Main CT-scan images in PCD were middle ear inflammation (65%), mastoid condensation (62%), or ossicular anomalies (35%). With its excellent sensitivity, TBCT gives typical arguments for PCD diagnosis, adding otological signs to the usual sinus CT signs (hypoplasia, aplasia). Systematic TBCT could be useful in the initial evaluation of patients with suspicion of PCD.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has resulted in millions of deaths and a major strain on health systems worldwide. Medical treatments for COVID-19 (anticoagulants, corticosteroids, anti-inflammatory drugs, oxygenation therapy and ventilation) and vaccination have improved patient outcomes. The majority of patients will recover spontaneously or after acute-phase management, but clinicians are now faced with long-term complications of COVID-19 including a large variety of symptoms, defined as "post-acute COVID-19 syndrome". Most studies have focused on patients hospitalised for severe COVID-19, but acute COVID-19 syndrome is not restricted to these patients and exists in outpatients. Given the diversity of symptoms and the high prevalence of persistent symptoms, the management of these patients requires a multidisciplinary team approach, which will result in the consumption of large amounts of health resources in the coming months. In this review, we discuss the presentation, prevalence, pathophysiology and evolution of respiratory complications and other organ-related injuries associated with post-acute COVID-19 syndrome., Competing Interests: Conflict of interest: D. Montani has no conflicts to disclose. Conflict of interest: L. Savale has no conflicts to disclose. Conflict of interest: N. Noel has no conflicts to disclose. Conflict of interest: O. Meyrignac has no conflicts to disclose. Conflict of interest: R. Colle has no conflicts to disclose. Conflict of interest: M. Gasnier has no conflicts to disclose. Conflict of interest: E. Corruble has no conflicts to disclose. Conflict of interest: A. Beurnier has no conflicts to disclose. Conflict of interest: E-M. Jutant has no conflicts to disclose. Conflict of interest: T. Pham has no conflicts to disclose. Conflict of interest: A-L. Lecoq has no conflicts to disclose. Conflict of interest: J-F. Papon has no conflicts to disclose. Conflict of interest: S. Figuereido has no conflicts to disclose. Conflict of interest: A. Harrois has no conflicts to disclose. Conflict of interest: M. Humbert has no conflicts to disclose. Conflict of interest: X. Monnet has no conflicts to disclose., (Copyright ©The authors 2022.)

Context: The measurement of parathyroid hormone(PTH) in situ (PTHis) by fine-needle aspiration (FNA) has been proposed as a tool to preoperatively help localize parathyroid glands detected on ultrasound. However, the accuracy of PTHis is highly variable according to the few available studies., Aim: We aimed to develop and validate the PTHis procedure and assessed the performance of PTHis in a large series of patients with hyperparathyroidism and/or undetermined cervical lesions., Patients and Methods: The technique set-up consisted of PTHis measurement in thyroid samples from patients with thyroid nodules and patients with high circulating PTH levels (tertiary hyperparathyroidism). Consecutive patients were recruited at one tertiary referral centre from 2017 to 2020 and submitted to ultrasound-guided FNA-PTHis determination., Results: During the method set-up, we obtained undetectable PTHis levels in all non-parathyroid tissues after sample dilutions. PTHis was higher in patients with hyperparathyroidism (n = 145; 1817 ± 3739 ng/L; range: <4.6-31 140) than in those with thyroid or undetermined cervical lesions (n= 34; <4.6 ng/mL; P < 0.0001). When evaluating PTHis performance in histologically proven samples (158 lesions from 121 patients), PTHis was detectable in 85/97 parathyroid lesions (87%; range: 22-31;140 ng/L) and undetectable in all non-parathyroid lesions (n = 61; P < 0.0001). The specificity and positive predictive value were 100%, and the sensitivity was 87.6%. False-negative lesions (n= 12) were smaller (9.4 ± 5.9 mm) and more often consisted of hyperplasias (75%) than true-positive lesions (16.1 ± 8.4 mm and 33%, P = 0.009 and P = 0.0089, respectively). The method was safe and well tolerated. Four educational cases are also provided., Conclusions: PTHis determination is a safe and well-tolerated procedure that enhances the specificity of ultrasound-detected lesions. If accurately set-up, it confirms the parathyroid origin of uncharacterized cervical lesions.

Aim: Altered sense of smell and/or taste is a leading symptom of SARS-CoV-2 infection, but its prevalence at a population-level is unknown., Methods: From a questionnaire addressed to a representative subset of the French general adult (≥18-year) population over a 6-week period during the first French lockdown (April 7 to May 19 2020), self-reported new cases of altered sense of smell and/or taste were collected., Results: From 29,660 participants, new altered sense of smell and/or taste was 2.18% and 2.11% after direct standardization on the French population representing more than 1,110,000 subjects in France. Moreover, 0.5% of participants reported a positive SARS-CoV-2 test, among which 47.4% reported a newly altered sense of smell and/or taste. Male participants, younger ones together with those presenting with chronic condition had higher odds of reporting a newly altered sense of smell and/or taste., Conclusion: This study provides an accurate estimate of new cases of altered sense of smell and/or taste in the general population at a nationwide level during the Covid-19 first wave., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: Primary ciliary dyskinesia (PCD) is a rare, genetic, multiorgan disease with an estimated prevalence of 1 in 10 000. It affects mainly the upper and lower airways due to impaired mucociliary clearance. Almost all patients have sinonasal or otologic (ear-nose-throat, ENT) problems, although the ENT clinical phenotype may present great variability. Despite that, data on PCD ENT manifestations are scarce and based on small single-centre studies. To date, we know little about the spectrum and severity of PCD ENT disease, its association with lung disease, its course over life and its determinants of prognosis.This study protocol describes the aims and methods of the first prospective, observational, multinational cohort study focusing on ENT disease in patients with PCD., Methods and Analysis: The ENT prospective international cohort of patients with PCD (EPIC-PCD) is a prospective standardised observational clinical cohort set up as a multinational multicentre study, embedded into routine patient care. It aims to longitudinally characterise ENT disease in patients with PCD and its association with lung disease, and to identify determinants of its prognosis. Patients of all ages, diagnosed with PCD who undergo an ENT clinical assessment at least once a year at one of the participating centres will be invited to participate. Collected data include diagnostic test results, results of ENT examinations, lung function measurements, information on management of ENT disease and patient-reported data on clinical symptoms and health-related quality of life (QoL). Data are collected using the standardised PCD-specific FOLLOW-PCD form and the validated QoL-PCD questionnaire., Ethics and Dissemination: The study has been reviewed and approved by the Human Research Ethics Committees at all participating centres, based on local legislation. The results of the study will be published in scientific journals, presented at scientific conferences and disseminated to participants and national patient organisations., Trial Registration: NCT04611516., Competing Interests: Competing interests: PL reports personal fees from Gilead, Novartis, OM pharma, Polyphor, Roche, Santhera, Schwabe, Vertex, Vifor and Zambon, and grants from Vertex, all outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The rapid spread of the coronavirus disease 2019 and the implementation of quarantine in many European countries led to a swift change in health care delivery. Telemedicine was implemented in many otolaryngological departments to ensure the continuous care. The purpose of this study is to report our experience about telemedicine in 86 patients consulting virtually in our departments., Methods: A total of 86 patients benefited from telemedicine consultation from April to Mai May 2020. Patients and physicians were invited to fulfill a satisfaction survey over the 3 days after the consultation., Results: Patients consulted in the following fields: laryngology, voice and swallowing (N=15; 17.4%), head and neck or plastic surgery (N=34; 39.5%), rhinology (N=31; 36.1%) and otology (N=6; 7.0%). Practitioners estimated that the clinical examination would not have changed the consultation issue in 73.2% of cases. The realization of delayed clinical examination was rapidly necessary in 9.3% of cases and useless in 33.7% of cases. Five percent of patients estimated that the consultation did not bring reliable conclusion. Although the majority of patient (87.7%) would recommend telemedicine consultation to friend/family in the context of pandemic, only 44.6% would accept to replace office- consultation by telemedicine consultation outside the pandemic., Conclusion: Telemedicine appears to be an interesting alternative approach in situation of pandemic and lock-down. Because the patient motivation to further participate to telemedicine appears to be conditioned by the context, efforts are still required to understand the patient perception, satisfaction and fears in view of future implementation outside pandemic., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Primary ciliary dyskinesia (PCD) is a rare inherited ciliopathy in which respiratory cilia are stationary or dyskinetic. The clinical presentation of PCD is highly non-specific since it includes infections and disorders of the upper (otitis and rhinosinusitis) and lower (neonatal respiratory distress, bronchitis, pneumonia and bronchiectasis) airways, starting in early life. Clinical examination alone does not allow a PCD diagnosis, which relies on several concordant tests, since none are sensitive or specific enough alone. Despite being the most sensitive and specific test to diagnose PCD, digital high-speed videomicroscopy (DHSV) is not sufficiently standardized, preventing its use with complete confidence as a confirmatory diagnostic test for PCD, or its inclusion in a diagnostic algorithm. Since the 2017 ERS recommendations for PCD diagnosis, three main issues remain to be solved in order to optimize DHSV ciliary beating evaluation: the problem in defining an accurate sensitivity and specificity as there is no gold standard method to diagnose all PCD cases, a lack of standardization in the operating procedure for processing respiratory samples, and in the choice of measured parameters (self-operating or not). The development of new automated analysis approaches is promising and will require full clinical validation.

Background: Primary ciliary dyskinesia (PCD) is a heterogeneous inherited disorder caused by mutations in approximately 50 cilia-related genes. PCD genotype-phenotype relationships have mostly arisen from small case series because existing statistical approaches to investigating relationships have been unsuitable for rare diseases., Methods: We applied a topological data analysis (TDA) approach to investigate genotype-phenotype relationships in PCD. Data from separate training and validation cohorts included 396 genetically defined individuals carrying pathogenic variants in PCD genes. To develop the TDA models, 12 clinical and diagnostic variables were included. TDA-driven hypotheses were subsequently tested using traditional statistics., Results: Disease severity at diagnosis, measured by forced expiratory volume in 1 s (FEV 1 ) z-score, was significantly worse in individuals with CCDC39 mutations (compared to other gene mutations) and better in those with DNAH11 mutations; the latter also reported less neonatal respiratory distress. Patients without neonatal respiratory distress had better preserved FEV 1 at diagnosis. Individuals with DNAH5 mutations were phenotypically diverse. Cilia ultrastructure and beat pattern defects correlated closely to specific causative gene groups, confirming these tests can be used to support a genetic diagnosis., Conclusions: This large scale, multi-national study presents PCD as a syndrome with overlapping symptoms and variations in phenotype according to genotype. TDA modelling confirmed genotype-phenotype relationships reported by smaller studies ( e.g. FEV 1 worse with CCDC39 mutation) and identified new relationships, including FEV 1 preservation with DNAH11 mutations and diversity of severity with DNAH5 mutations., Competing Interests: Conflict of interest: B. Rubbo has nothing to disclose. Conflict of interest: M. Legendre has nothing to disclose. Conflict of interest: M.R. Fassad has nothing to disclose. Conflict of interest: E.G. Haarman has nothing to disclose. Conflict of interest: S. Best has nothing to disclose. Conflict of interest: I.C.M. Bon has nothing to disclose. Conflict of interest: J. Brandsma has nothing to disclose. Conflict of interest: P-R. Burgel reports personal fees for lectures and advisory board work from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, Teva and Vertex, as well as personal fees for lectures from GSK, Pfizer and Zambon, outside the submitted work. Conflict of interest: G. Carlsson has nothing to disclose. Conflict of interest: S.B. Carr reports non-financial support and other (advisory board, lecture fee, travel, steering committee) from Vertex Pharmaceuticals, other (advisory board) from Profile Pharmaceuticals and other (lectures) from Teva Pharmaceuticals, as well as non-financial support and other (advisory board, travel, accommodation) from Chiesi Pharmaceuticals, outside the submitted work. Conflict of interest: M. Carroll has nothing to disclose. Conflict of interest: M. Edwards has nothing to disclose. Conflict of interest: E. Escudier has nothing to disclose. Conflict of interest: I. Honoré has nothing to disclose. Conflict of interest: D. Hunt has nothing to disclose. Conflict of interest: G. Jouvion has nothing to disclose. Conflict of interest: M.R. Loebinger reports personal fees for advisory board work and consultancy from AstraZeneca, Insmed, Polyphor, Bayer and Griffols, outside the submitted work. Conflict of interest: B. Maitre has nothing to disclose. Conflict of interest: D. Morris-Rosendahl has nothing to disclose. Conflict of interest: J-F. Papon has nothing to disclose. Conflict of interest: C.M. Parsons has nothing to disclose. Conflict of interest: M.P. Patel has nothing to disclose. Conflict of interest: N.S. Thomas has nothing to disclose. Conflict of interest: G. Thouvenin has nothing to disclose. Conflict of interest: W.T. Walker has nothing to disclose. Conflict of interest: R. Wilson has nothing to disclose. Conflict of interest: C. Hogg has nothing to disclose. Conflict of interest: H.M. Mitchison has nothing to disclose. Conflict of interest: J.S. Lucas has nothing to disclose. Conflict of interest: A. Shoemark has nothing to disclose., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Gitelman syndrome (GS) is a rare salt-losing tubulopathy caused by an inactivating mutation in the SLC12A3 gene, encoding the thiazide-sensitive sodium chloride cotransporter (NCC). Patients with GS frequently complain of vertigo, usually attributed to hypovolemia. Because NCC is also located in the endolymphatic sac, we hypothesized that patients with GS might have vestibular dysfunction. Between April 2013 and September 2016, 20 (22%) out of 90 patients followed at the reference center complained of vertigo in the absence of orthostatic hypotension. Sixteen of them were referred to an otology department for investigation of vestibular function. The vertigo was of short duration and triggered in half of them by head rotation. Seven patients (44%) had a vestibular syndrome. Vestibular syndrome was defined: (1) clinically, as nystagmus triggered by the head shaking test ( n = 5); and/or (2) paraclinically, as an abnormal video head impulse test ( n = 0), abnormal kinetic test ( n = 4) and/or abnormal bithermal caloric test ( n = 3). Five patients had associated auditory signs (tinnitus, aural fullness or hearing loss). In conclusion, we found a high frequency of vestibular disorder in GS patients suffering from vertigo, suggesting a role of NCC in the inner ear. Referent physicians of these patients should be aware of this extrarenal manifestation that requires specific investigations and treatment.

Objectives: To determine the frequency of SARS-CoV-2 positive samples in a subset of patients consulting for primarily isolated acute (<7 days) loss of smell and to assess the diagnostic accuracy of olfactory/gustatory dysfunction for COVID-19 diagnosis in the overall population tested for COVID-19 in the same period., Methods: Prospective multicentric cohort study in four olfactory ENT units and a screening center for COVID-19., Results: i) Among a subset of 55 patients consulting for primarily recent loss of smell, we found that 51 (92.7%) had a COVID-19 positive test (median viral load of 28.8 cycle threshold). Loss of smell was mostly total (anosmia), rarely associated with nasal obstruction but associated with a taste disorder in 80%. Olfactory dysfunction occurred suddenly, either as first complaint or preceded by mild symptoms occurring a median of 3 days. The majority of patients (72.9%) partially recovered the sense of smell within 15 days. ii) In a population of 1824 patients tested for COVID-19, the positive predictive value and the specificity of loss of smell and/or taste were 78.5% and 90.3% respectively (sensitivity (40.8%), negative predictive value (63.6%))., Conclusions: Self-reported loss of smell had a high predictive positive value to identify COVID-19. Making this sign well known publicly could help to adopt isolation measures and inform potential contacts., Competing Interests: Declaration of Competing Interest All the authors have read and agreed with the paper's content. No authors have financial or personal conflicts. Neither the work nor any part of its essential substance, tables or figures have been or will be published or submitted to another scientific journal or are being considered for publication elsewhere., (Copyright © 2020. Published by Elsevier Ltd.)

This consensus statement about the indications and modalities of corticosteroid treatment in the context of the COVID-19 pandemic was jointly written by experts from the French Association of Otology and Oto-Neurology (AFON) and from the French Society of Otorhinolaryngology, Head and Neck Surgery (SFORL). There is currently not enough data in favour of danger or benefit from corticosteroids in COVID-19, so until this matter is resolved it is advisable to limit their indications to the most serious clinical pictures for which it is well established that this type of treatment has a positive impact on the progression of symptoms. In Grade V and VI Bell's palsy according to the House-Brackmann grading system, a week's course of oral corticosteroids is recommended. Corticosteroid therapy is also recommended in cases of sudden hearing loss of more than 60dB, either in the form of intratympanic injections or a week's course of oral medication. In rhinology, there is no indication for systemic corticosteroid therapy in the current situation. However, patients are advised to continue with their local corticosteroid therapy in the form of a nasal spray or by inhalation. Treatments with corticosteroid nasal sprays can still be prescribed if there is no alternative. Finally, systemic or local corticosteroid therapy is not indicated for bacterial ENT infections., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The purpose of this article is to give rhinologists advice on how to adapt their standard practice during the COVID-19 pandemic. The main goal of these recommendations is to protect healthcare workers against COVID-19 while continuing to provide emergency care so as to prevent loss of chance for patients. We reviewed our recommendations concerning consultations, medical prescriptions and surgical activity in rhinology., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Limited data is available concerning the safety of active middle ear implants (AMEI) during Magnetic Resonance Imaging (MRI). Measurements in temporal bones are the gold standard for preclinical assessment of device safety. In this study the coupling stability of an actuator as used in a fully implantable AMEI was determined in temporal bones. Eleven temporal bones were implanted with the actuator according to the manufacturer's surgical guidelines. The actuator was coupled on the incus short process as recommended for sensorineural hearing loss. Temporal bones were exposed 10 times to the MRI magnetic field by entering the MRI suite in a clinically relevant way. Computed Tomography (CT) images were acquired before and after the experiment to investigate the risk of actuator dislocation. Based on the electrical impedance of the actuator, the loading of the actuator to the incus was confirmed. Relative actuator displacement was determined on the CT images by comparing the initial with the final actuator position in 3D space. Impedance curves were analyzed after each exposure to check the loading of the actuator to the ossicles. Analysis of CT images with a 0.30.6 mm in-plane resolution indicate no actuator displacement. The maximum detected change in impedance for all actuators was 8.43 Ω at the actuator's resonance frequency. Impedance curves measured when the actuator was retracted from the short process after the experiment still indicate the presence of a clear resonance peak. No actuator displacement or dislocation could be detected in the analysis of CT images and the measured impedance curves. Impedance curves obtained when the actuator was retracted from the incus short process still show a clear resonance peak, indicating the device is still functional after the MRI exposures., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: GF is an employee of Cochlear Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype., Methods: We prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV)., Results: Sixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of DNAI1 mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of CCDC39 mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of RSPH1 mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF., Conclusion: Quantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by an alteration in airway epithelial cell functions including barrier function, wound repair mechanisms, mucociliary clearance. The mechanisms leading to epithelial cell dysfunction in nasal polyps (NPs) remain poorly understood. Our hypothesis was that among the inflammatory cytokines involved in NPs, IL-6 could alter epithelial repair mechanisms and mucociliary clearance. The aim of this study was to evaluate the in vitro effects of IL-6 on epithelial repair mechanisms in a wound repair model and on ciliary beating in primary cultures of Human Nasal Epithelial Cells (HNEC)., Methods: Primary cultures of HNEC taken from 38 patients during surgical procedures for CRSwNP were used in an in vitro model of wound healing. Effects of increasing concentrations of IL-6 (1 ng/mL, 10 ng/mL, and 100 ng/mL) and other ILs (IL-5, IL-9, IL-10) on wound closure kinetics were compared to cultures without IL-modulation. After wound closure, the differentiation process was characterized under basal conditions and after IL supplementation using cytokeratin-14, MUC5AC, and β IV tubulin as immunomarkers of basal, mucus, and ciliated cells, respectively. The ciliated edges of primary cultures were analyzed on IL-6 modulation by digital high-speed video-microscopy to measure: ciliary beating frequency (CBF), ciliary length, relative ciliary density, metachronal wavelength and the ciliary beating efficiency index., Results: Our results showed that: (i) IL-6 accelerated airway wound repair in vitro, with a dose-response effect whereas no effect was observed after other ILs-stimulation. After 24 h, 79% of wounded wells with IL6-100 were fully repaired, vs 46% in the IL6-10 group, 28% in the IL6-1 group and 15% in the control group; (ii) specific migration analyses of closed wound at late repair stage (Day 12) showed IL-6 had the highest migration compared with other ILs (iii) The study of the IL-6 effect on ciliary function showed that CBF and metachronal wave increased but without significant modifications of ciliary density, length of cilia and efficiency index., Conclusion: The up-regulated epithelial cell proliferation observed in polyps could be induced by IL-6 in the case of prior epithelial damage. IL-6 could be a major cytokine in NP physiopathology.

Clinical data on primary ciliary dyskinesia (PCD) are limited, heterogeneous and mostly derived from retrospective chart reviews, leading to missing data and unreliable symptoms and results of physical examinations. We need standardised prospective data collection to study phenotypes, severity and prognosis and improve standards of care. A large, international and multidisciplinary group of PCD experts developed FOLLOW-PCD, a standardised clinical PCD form and patient questionnaire. We identified existing forms for clinical data collection via the Better Experimental Approaches to Treat PCD (BEAT-PCD) COST Action network and a literature review. We selected and revised the content items with the working group and patient representatives. We then revised several drafts in an adapted Delphi process, refining the content and structure. FOLLOW-PCD has a modular structure, to allow flexible use based on local practice and research focus. It includes patient-completed versions for the modules on symptoms and lifestyle. The form allows a comprehensive standardised clinical assessment at baseline and for annual reviews and a short documentation for routine follow-up. It can either be completed using printable paper forms or using an online REDCap database. Data collected in FOLLOW-PCD version 1.0 is available in real-time for national and international monitoring and research. The form will be adapted in the future after extensive piloting in different settings and we encourage the translation of the patient questionnaires to multiple languages. FOLLOW-PCD will facilitate quality research based on prospective standardised data from routine care, which can be pooled between centres, to provide first-line and real-time evidence for clinical decision-making., Competing Interests: Conflict of interest: M. Goutaki has nothing to disclose. Conflict of interest: J-F. Papon has nothing to disclose. Conflict of interest: M. Boon reports COST BEAT-PCD Action (BM 1407) during the conduct of the study, and Postdoc KOOR funding from the University Hospital Leuven and MyCyFAPP Horizon 2020 EU funding outside the submitted work. Conflict of interest: C. Casaulta has nothing to disclose. Conflict of interest: E. Eber has nothing to disclose. Conflict of interest: E. Escudier has nothing to disclose. Conflict of interest: F.S. Halbeisen has nothing to disclose. Conflict of interest: A. Harris has nothing to disclose. Conflict of interest: C. Hogg has nothing to disclose. Conflict of interest: I. Honore has nothing to disclose. Conflict of interest: A. Jung has nothing to disclose. Conflict of interest: B. Karadag has nothing to disclose. Conflict of interest: C. Koerner-Rettberg has nothing to disclose. Conflict of interest: M. Legendre has nothing to disclose. Conflict of interest: B. Maitre has nothing to disclose. Conflict of interest: K.G. Nielsen has nothing to disclose. Conflict of interest: B. Rubbo has nothing to disclose. Conflict of interest: N. Rumman has nothing to disclose. Conflict of interest: L. Schofield has nothing to disclose. Conflict of interest: A. Shoemark has nothing to disclose. Conflict of interest: G. Thouvenin has nothing to disclose. Conflict of interest: H. Wilkins has nothing to disclose. Conflict of interest: J.S. Lucas reports COST Action BM1407 BEAT-PCD during the conduct of the study. Conflict of interest: C.E. Kuehni has nothing to disclose., (Copyright ©ERS 2020.)

Cilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs and IDAs). Defects in ODAs and IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. PCD mutations in assembly factors have been shown to cause a combined ODA-IDA defect, affecting both cilia and flagella. We identified four loss-of-function mutations in TTC12, which encodes a cytoplasmic protein, in four independent families in which affected individuals displayed a peculiar PCD phenotype characterized by the absence of ODAs and IDAs in sperm flagella, contrasting with the absence of only IDAs in respiratory cilia. Analyses of both primary cells from individuals carrying TTC12 mutations and human differentiated airway cells invalidated for TTC12 by a CRISPR-Cas9 approach revealed an IDA defect restricted to a subset of single-headed IDAs that are different in flagella and cilia, whereas TTC12 depletion in the ciliate Paramecium tetraurelia recapitulated the sperm phenotype. Overall, our study, which identifies TTC12 as a gene involved in PCD, unveils distinct dynein assembly mechanisms in human motile cilia versus flagella., (Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objectives: To draw up guidelines for ENT management associated with dental implant surgery with or without sinus lift., Materials and Methods: The methodology followed the rules of laid down by the French Health Authority (HAS): "Methodological bases for drawing up professional recommendations by formalized consensus". The chosen method was the RAND/UCLA "RAND appropriateness method" (short version)., Results: In the pre-implantation check-up, it is recommended to systematically screen for sinonasal pathology on medical interview and to favor 3D CT or cone-beam imaging. It is recommended that imaging include the entire maxillary sinus when the patient does not have sinonasal history or functional signs on interview. Otherwise, examination of all sinonasal cavities is recommended. This attitude enables simultaneous analysis of maxillary infrastructure for pre-implantation work-up and assessment of sinonasal cavity status. Sinus mucosal incidentalomas are very common in the healthy population and must be assessed with reference to the clinical, endoscopic and radiological context., Conclusion: This formalized expert consensus establishes a common base of knowledge, to clarify the issues and clinical situations and to standardize practices., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)