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

Author: André Coste, Benjamin Verillaud, Jean François Papon, Valentin Favier, Emilie Bequignon, Clémentine Daveau, Florent Carsuzaa, Maxime Fieux, Clair Vandersteen, Laurent Castillo, Ludovic de Gabory, Nicolas Saroul, Cécile Rumeau, Roger Jankowski, Justin Michel, Guillaume de Bonnecaze, Jean-Baptiste Lecanu, Olivier Malard, and Geoffrey Mortuaire
Subjects: Medicine
Abstract: 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.
Published: 2024
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2. Guided Self-rehabilitation Contract vs conventional therapy in chronic peripheral facial paresis: VISAGE, a multicenter randomized controlled trial

Author: Marjolaine Baude, Marina Guihard, Caroline Gault-Colas, Ludovic Bénichou, André Coste, Jean-Paul Méningaud, David Schmitz, Pierre-André Natella, Etienne Audureau, and Jean-Michel Gracies
Subjects: Facial paralysis, Rehabilitation, Neuronal plasticity, Efferent pathways, Guided self-rehabilitation contract, Motion capture, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background One year after persistent peripheral facial paresis (PFP), prescriptions of conventional rehabilitation are often downgraded into maintenance rehabilitation or discontinued, the patient entering what is seen as a chronic stage. This therapeutic choice is not consistent with current knowledge about behavior-induced plasticity, which is available all life long and may allow intense sensorimotor rehabilitation to remain effective. This prospective, randomized, multicenter single-blind study in subjects with chronic unilateral PFP evaluates changes in facial motor function with a Guided Self-rehabilitation Contract (GSC) vs. conventional therapy alone, carried out for six months. Methods Eighty-two adult subjects with chronic unilateral PFP (> 1 year since facial nerve injury) will be included in four tertiary, maxillofacial surgery (2), otolaryngology (1) and rehabilitation (1) centers to be randomized into two rehabilitation groups. In the experimental group, the PM&R specialist will implement the GSC method, which for PFP involves intensive series of motor strengthening performed daily on three facial key muscle groups, i.e. Frontalis, Orbicularis oculi and Zygomatici. The GSC strategy involves: i) prescription of a daily self-rehabilitation program, ii) teaching of the techniques involved in the program, iii) encouragement and guidance of the patient over time, in particular by requesting a quantified diary of the work achieved to be returned by the patient at each visit. In the control group, participants will benefit from community-based conventional therapy only, according to their physician’s prescription. The primary outcome measure is the composite score of Sunnybrook Facial Grading System. Secondary outcome measures include clinical and biomechanical facial motor function quantifications (Créteil Scale and 3D facial motion analysis through the Cara system), quality of life (Facial Clinimetric Evaluation and Short-Form 12), aesthetic considerations (FACE-Q scale) and mood representations (Hospital Anxiety and Depression scale). Participants will be evaluated every three months by a blinded investigator, in addition to four phone calls (D30/D60/D120/D150) to monitor compliance and tolerance to treatment. Discussion This study will increase the level of knowledge on the effects of intense facial motor streng- Facial paralysisthening prescribed through a GSC in patients with chronic peripheral facial paresis. Trial registration ClinicalTrials.gov, NCT04074018 . Registered 29 August 2019. Protocol version Version N°4.0—04/02/2021.
Published: 2023
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3. Desloratadine, an FDA-approved cationic amphiphilic drug, inhibits SARS-CoV-2 infection in cell culture and primary human nasal epithelial cells by blocking viral entry

Author: Margot Morin-Dewaele, Sophie Bartier, François Berry, Rozenn Brillet, Dennis Salomón López-Molina, Công Trung Nguyễn, Pascale Maille, Kevin Sereno, Quentin Nevers, Laurent Softic, Jean-Marie Vaugeois, Bruno Louis, Emilie Bequignon, Patrice Bruscella, André Coste, Jean-Michel Pawlotsky, Stéphane Jamain, and Abdelhakim Ahmed-Belkacem
Subjects: Medicine, Science
Abstract: Abstract The 2019 global coronavirus (COVID-19) pandemic has brought the world to a grinding halt, highlighting the urgent need for therapeutic and preventive solutions to slow the spread of emerging viruses. The objective of this study was to assess the anti-SARS-CoV-2 effectiveness of 8 FDA-approved cationic amphiphilic drugs (CADs). SARS-CoV-2-infected Vero cells, Calu-3 cells and primary Human Nasal Epithelial Cells (HNEC) were used to investigate the effects of CADs and revealed their antiviral mode of action. Among the CADs tested, desloratadine, a commonly used antiallergic, well-tolerated with no major side effects, potently reduced the production of SARS-CoV-2 RNA in Vero-E6 cells. Interestingly, desloratadine was also effective against HCoV-229E and HCoV-OC43 showing that it possessed broad-spectrum anti-coronavirus activity. Investigation of its mode of action revealed that it targeted an early step of virus lifecycle and blocked SARS-CoV-2 entry through the endosomal pathway. Finally, the ex vivo kinetic of the antiviral effect of desloratadine was evaluated on primary Human Nasal Epithelial Cells (HNEC), showing a significant delay of viral RNA production with a maximal reduction reached after 72 h of treatment. Thus, this treatment could provide a substantial contribution to prophylaxis and systemic therapy of COVID-19 or other coronaviruses infections and requires further studies.
Published: 2022
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4. The Prognostic Value of Olfactory Dysfunction in Patients with COVID-19: The COVIDORA Study

Author: Anne-Laure Hamel, Léo Delbos, Pierre-André Natella, Thomas Radulesco, Mihaela Alexandru, Emmanuel Bartaire, Sophie Bartier, Gonda Benoite, Emilie Bequignon, Laurent Castillo, Florence Canouï-Poitrine, Florent Carsuzaa, Alain Corré, André Coste, Vincent Couloigner, Clémentine Daveau, Paul De Boissieu, Guillaume De Bonnecaze, Ludovic De Gabory, Christian Debry, Simon Deraedt, Xavier Dufour, Wissame El Bakkouri, Laurent Gilain, Stéphane Hans, Charlotte Hautefort, Ruben Hermann, Roger Jankowski, Candice La Croix, Jean-Baptiste Lecanu, Olivier Malard, Justin Michel, Yann Nguyen, Jerome Nevoux, Jean-François Papon, Vincent Patron, Marine Prigent, Virginie Pruliere-Escabasse, Marion Renaud, Cécile Rumeau, Dominique Salmon, Nicolas Saroul, Elie Serrano, Christine Nhung Tran Khai, Stéphane Tringali, Eric Truy, Clair Vandersteen, Benjamin Verillaud, Raphaël Veil, and Maxime Fieux
Subjects: olfactory dysfunction, anosmia, phantosmia, parosmia, COVID-19, taste dysfunction, Science
Abstract: 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.
Published: 2024
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5. Sublabial bioactive glass implantation for the management of primary atrophic rhinitis and empty nose syndrome: Operative technique

Author: Charles‐Henri Hassan, Emeline Malheiro, Emilie Béquignon, André Coste, and Sophie Bartier
Subjects: atrophic rhinitis, bioactive glass, empty nose syndrome, sublabial, vestibular, Otorhinolaryngology, RF1-547, Surgery, RD1-811
Abstract: Abstract Objectives Atrophic rhinitis (AR) and empty nose syndrome (ENS) are chronic diseases characterized by a paradoxical nasal obstruction. These rare syndromes tend to occur after nasal surgery of the inferior turbinates in ENS and can be idiopathic in AR. Medical treatments alone are often insufficient. Surgical options are challenging and numerous resorbable and nonresorbable implants have been described in small series, with as many surgical techniques described. Whereas current surgical procedures are for risk of extrusions, graft rejections or poor lasting results, the use of GlassBONE™ (Sodimed®, Avignon, France), a bioactive glass, for a vestibular approach in AR and ENS has never been reported for this indication. Methods We described an original technique of nasal submucoperiosteal bilateral ceramic glass implantation in two patients with AR and ENS. Results The two cases presented a postoperative satisfying endoscopic and sinus CT‐scan results with filling of the nasal cavities, with less crusts and a complete wound healing. They had no short‐term complications. Conclusion This innovative approach is easily feasible and could be an option considered for the surgical management of AR and ENS. Level of evidence: 4.
Published: 2022
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6. Proviral role of human respiratory epithelial cell‐derived small extracellular vesicles in SARS‐CoV‐2 infection

Author: François Berry, Margot Morin‐Dewaele, Amene Majidipur, Thibaud Jamet, Sophie Bartier, Eva Ignjatovic, Donatella Toniutti, Jeanne Gaspar Lopes, Pascale Soyeux‐Porte, Pascale Maillé, Carolina Saldana, Rozenn Brillet, Nazim Ahnou, Laurent Softic, Benoit Couturaud, Éric Huet, Abdelhakim Ahmed‐Belkacem, Slim Fourati, Bruno Louis, André Coste, Émilie Béquignon, Alexandre de laTaille, Damien Destouches, Francis Vacherot, Jean‐Michel Pawlotsky, Virginie Firlej, and Patrice Bruscella
Subjects: human nasal epithelial cells, SARS‐CoV‐2, small extracellular vesicles, Spike prefusion priming, TMPRSS2, Cytology, QH573-671
Abstract: Abstract Small Extracellular Vesicles (sEVs) are 50–200 nm in diameter vesicles delimited by a lipid bilayer, formed within the endosomal network or derived from the plasma membrane. They are secreted in various biological fluids, including airway nasal mucus. The goal of this work was to understand the role of sEVs present in the mucus (mu‐sEVs) produced by human nasal epithelial cells (HNECs) in SARS‐CoV‐2 infection. We show that uninfected HNECs produce mu‐sEVs containing SARS‐CoV‐2 receptor ACE2 and activated protease TMPRSS2. mu‐sEVs cleave prefusion viral Spike proteins at the S1/S2 boundary, resulting in higher proportions of prefusion S proteins exposing their receptor binding domain in an ‘open’ conformation, thereby facilitating receptor binding at the cell surface. We show that the role of nasal mu‐sEVs is to complete prefusion Spike priming performed by intracellular furin during viral egress from infected cells. This effect is mediated by vesicular TMPRSS2 activity, rendering SARS‐CoV‐2 virions prone to entry into target cells using the ‘early’, TMPRSS2‐dependent pathway instead of the ‘late’, cathepsin‐dependent route. These results indicate that prefusion Spike priming by mu‐sEVs in the nasal cavity plays a role in viral tropism. They also show that nasal mucus does not protect from SARS‐CoV‐2 infection, but instead facilitates it.
Published: 2022
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7. The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Author: Johanna Raidt, Bernard Maitre, Petra Pennekamp, Josje Altenburg, Pinelopi Anagnostopoulou, Miguel Armengot, Lizan D. Bloemsma, Mieke Boon, Melissa Borrelli, Folke Brinkmann, Siobhan B. Carr, Mary P. Carroll, Silvia Castillo-Corullón, André Coste, Renato Cutrera, Eleonora Dehlink, Damien M.S. Destouches, Maria E. Di Cicco, Lucy Dixon, Nagehan Emiralioglu, Ela Erdem Eralp, Eric G. Haarman, Claire Hogg, Bulent Karadag, Helene E. Kobbernagel, Natalie Lorent, Marcus A. Mall, June K. Marthin, Vendula Martinu, Manjith Narayanan, Ugur Ozcelik, Daniel Peckham, Massimo Pifferi, Petr Pohunek, Eva Polverino, Simon Range, Felix C. Ringshausen, Evie Robson, Jobst Roehmel, Sandra Rovira-Amigo, Francesca Santamaria, Anne Schlegtendal, Zsolt Szépfalusi, Petra Tempels, Guillaume Thouvenin, Nicola Ullmann, Woolf T. Walker, Martin Wetzke, Panayiotis Yiallouros, Heymut Omran, and Kim G. Nielsen
Subjects: Medicine
Abstract: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients.
Published: 2022
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8. Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction

Author: Emilie Bequignon, David Mangin, Justine Bécaud, Jennifer Pasquier, Christelle Angely, Mathieu Bottier, Estelle Escudier, Daniel Isabey, Marcel Filoche, Bruno Louis, Jean-François Papon, and André Coste
Subjects: Nasal Polyps, IL-6, Interleukin 6, Inflammation, Repair mechanisms, Mucociliary clearance, Medicine
Abstract: Abstract 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 βIV 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.
Published: 2020
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9. Study protocol: the ear–nose–throat (ENT) prospective international cohort of patients with primary ciliary dyskinesia (EPIC-PCD)

Author: Andreas Anagiotos, Myrofora Goutaki, André Coste, Nagehan Emiralioglu, Amanda Harris, Andrea Burgess, Mieke Boon, Philipp Latzin, Jean François Papon, Eric G Haarman, Natalie Lorent, Yin Ting Lam, Mihaela Alexandru, Miguel Armengot, Emilie Bequignon, Ela Erdem, Sara-Lynn Hool, Bulent Karadag, Sookyung Kim, Ugur Ozcelik, Ana Reula, Jobst Roehmel, Christine van Gogh, Panayiotis Yiallouros, and Soeren Marian Zappe
Subjects: Medicine
Abstract: 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.
Published: 2021
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10. A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part I, experimental analysis.

Author: Mathieu Bottier, Sylvain Blanchon, Gabriel Pelle, Emilie Bequignon, Daniel Isabey, André Coste, Estelle Escudier, James B Grotberg, Jean-François Papon, Marcel Filoche, and Bruno Louis
Subjects: Biology (General), QH301-705.5
Abstract: Mucociliary clearance is one of the major lines of defense of the respiratory system. The mucus layer coating the pulmonary airways is moved along and out of the lung by the activity of motile cilia, thus expelling the particles trapped in it. Here we compare ex vivo measurements of a Newtonian flow induced by cilia beating (using micro-beads as tracers) and a mathematical model of this fluid flow, presented in greater detail in a second companion article. Samples of nasal epithelial cells placed in water are recorded by high-speed video-microscopy and ciliary beat pattern is inferred. Automatic tracking of micro-beads, used as markers of the flow generated by cilia motion, enables us also to assess the velocity profile as a function of the distance above the cilia. This profile is shown to be essentially parabolic. The obtained experimental data are used to feed a 2D mathematical and numerical model of the coupling between cilia, fluid, and micro-bead motion. From the model and the experimental measurements, the shear stress exerted by the cilia is deduced. Finally, this shear stress, which can easily be measured in the clinical setting, is proposed as a new index for characterizing the efficiency of ciliary beating.
Published: 2017
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11. Proteomic analysis of nasal epithelial cells from cystic fibrosis patients.

Author: Ludovic Jeanson, Ida Chiara Guerrera, Jean-François Papon, Cerina Chhuon, Patricia Zadigue, Virginie Prulière-Escabasse, Serge Amselem, Estelle Escudier, André Coste, and Aleksander Edelman
Subjects: Medicine, Science
Abstract: The pathophysiology of cystic fibrosis (CF) lung disease remains incompletely understood. New explanations for the pathogenesis of CF lung disease may be discovered by studying the patterns of protein expression in cultured human nasal epithelial cells (HNEC). To that aim, we compared the level of protein expressions in primary cultures of HNEC from nasal polyps secondary to CF (CFNP, n = 4), primary nasal polyps (NP, n = 8) and control mucosa (CTRL, n = 4) using isobaric tag for relative and absolute quantification (iTRAQ) labeling coupled with liquid chromatography (LC)-MS-MS. The analysis of the data revealed 42 deregulated protein expressions in CFNP compared to NP and CTRL, suggesting that these alterations are related to CF. Overall, AmiGo analysis highlighted six major pathways important for cell functions that seem to be impaired: metabolism, G protein process, inflammation and oxidative stress response, protein folding, proteolysis and structural proteins. Among them, glucose and fatty acid metabolic pathways could be impaired in CF with nine deregulated proteins. Our proteomic study provides a reproducible set of differentially expressed proteins in airway epithelial cells from CF patients and reveals many novel deregulated proteins that could lead to further studies aiming to clarify the involvement of such proteins in CF pathophysiology.
Published: 2014
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12. Automating the measurement of physiological parameters: A case study in the image analysis of cilia motion.

Author: élodie Puybareau, Hugues Talbot, Emilie Bequignon, Bruno Louis, Gabriel Pelle, Jean-François Papon, André Coste, and Laurent Najman
Published: 2016
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13. A regionalized automated measurement of ciliary beating frequency.

Author: élodie Puybareau, Hugues Talbot, Gabriel Pelle, Bruno Louis, Jean-François Papon, André Coste, and Laurent Najman
Published: 2015
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14. Otitis media in severe asthma associated with chronic rhinosinusitis with nasal polyps: a new therapeutic target for biologics

Author: Sophie Bartier, Emilie Béquignon, Charlotte Thibaut de Ménonville, Benjamin Verillaud, Diane Evrard, Maëlys Léger, Jean-François Papon, André Coste, and Camille Taillé
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, Perinatology and Child Health, Immunology and Allergy
Published: 2022
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15. Presentation, Diagnosis, and Management of Subglottic and Tracheal Stenosis During Systemic Inflammatory Diseases

Author: François Gonin, Alexis Régent, Luc Mouthon, Véronique Le Guern, Candice Lacroix, Emmanuel Martinod, André Coste, Paul Legendre, Benjamin Terrier, Xavier Puéchal, Pascal Cohen, J. Catano, Jérémie Dion, Yurdagul Uzunhan, Romain Paule, Christine Lorut, and Sophie Périé
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Sarcoidosis, Subglottic stenosis, Critical Care and Intensive Care Medicine, Crohn Disease, stomatognathic system, Interquartile range, medicine, Humans, Polychondritis, Relapsing, Glucocorticoids, Relapsing polychondritis, Retrospective Studies, Anti-neutrophil cytoplasmic antibody, Laryngoscopy, Skin Diseases, Vesiculobullous, business.industry, Granulomatosis with Polyangiitis, Calcinosis, Laryngostenosis, Amyloidosis, Middle Aged, medicine.disease, Tracheal Stenosis, Stenosis, Methotrexate, Female, Radiology, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, Granulomatosis with polyangiitis, business, Immunosuppressive Agents
Abstract: Background Subglottic stenosis (SGS) and tracheal stenosis (TS) are characterized by a narrowing of the airways. The goal of this study was to describe the characteristics and prognosis of nontraumatic and nontumoral SGS or TS. Research Question What are the inflammatory etiologies of SGS and TS, and what are their characteristics and prognosis? Study Design and Methods This multicenter, observational retrospective study was performed in patients with SGS or TS that was neither traumatic nor tumoral. Results Eighty-one patients were included, 33 (41%) with granulomatosis with polyangiitis (GPA) and 21 (26%) with relapsing polychondritis (RP). GPA-related stenoses exhibited circumferential subglottic narrowing in 85% of cases, without calcifications. In contrast, RP-related stenoses displayed anterior involvement in 76%, in a longer distance from vocal cords (4 cm), with calcifications in 62%, and extension to bronchi in 86%. Other diagnoses included bullous dermatoses (n = 3), amyloidosis (n = 3), sarcoidosis (n = 2), and Crohn’s disease (n = 2); the remaining stenoses (n = 15) were idiopathic. SGS/TS was the initial manifestation of the disease in 66% of cases, with a median interval from stenosis to disease diagnosis of 12 months (interquartile range, 0-48 months). Despite the use of glucocorticoids in 80%, combined with methotrexate in 49%, endoscopic procedures were required in 68% of patients. Relapses of stenoses occurred in 76% without any difference between causes (82% in GPA, 67% in RP, and 75% in idiopathic SGS/TS). Three patients died due to the stenosis, two of RP and one of GPA. Interpretation These data show that GPA and RP are the two main inflammatory diseases presenting with SGS/TS. GPA-related stenoses are mostly subglottic and circumferential, whereas RP-related stenoses are mostly tracheal, anterior, and calcified with a frequent extension to bronchi. Relapses of stenoses are common, and relapse rates do not differ between causes. Diagnosis and management of SGS/TS require a multidisciplinary approach.
Published: 2022
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16. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): in-depth sinus surgery analysis

Author: Wytske J. Fokkens, Joaquim Mullol, David Kennedy, Carl Philpott, Veronica Seccia, Robert C. Kern, André Coste, Ana R. Sousa, Peter H. Howarth, Victoria S. Benson, Bhabita Mayer, Steve W. Yancey, Robert Chan, Simon B. Gane, Ear, Nose and Throat, and AII - Inflammatory diseases
Subjects: refractory, recurrence, Immunology, Immunology and Allergy, mepolizumab, chronic rhinosinusitis with nasal polyps, sinonasal surgery
Abstract: Background: Patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) often require repeat sinus surgery. Mepolizumab reduced the need for sinus surgery in the SYNAPSE trial; this analysis sought to provide a more in-depth assessment of surgery endpoints in SYNAPSE. Methods: SYNAPSE was a double-blind Phase III trial (NCT03085797) in adults with recurrent, refractory, severe, CRSwNP eligible for repeat sinus surgery despite standard of care treatments and previous surgery. Patients were randomized (1:1) to mepolizumab 100 mg subcutaneously or placebo, plus standard of care, every 4 weeks for 52 weeks. Time to first inclusion on a waiting list for sinus surgery and time to first actual sinus surgery (both up to week 52) were assessed; the latter endpoint was also analyzed post hoc according to time since last sinus surgery before study screening and baseline blood eosinophil count. Results: Among 407 patients (mepolizumab: 206; placebo: 201), mepolizumab versus placebo reduced the risk of being included on a waiting list for sinus surgery (week 52 Kaplan–Meier probability estimate [95% confidence interval]: 13.9% [9.8%, 19.5%] vs. 28.5% [22.7%, 35.4%]). Mepolizumab versus placebo reduced the risk of sinus surgery irrespective of time (
Published: 2023

17. Apalutamide Prevents SARS-CoV-2 Infection in Lung Epithelial Cells and in Human Nasal Epithelial Cells

Author: Amene Majidipur, Margot Morin-Dewaele, Jeanne Gaspar Lopes, Francois Berry, Julien Fouchet, Sophie Bartier, Anais Dufros Duval, Pascale Soyeux, Eric Huet, Bruno Louis, André Coste, Émilie Béquignon, Carolina Saldana, Philippe Le Corvoisier, Damien Destouches, Jean-Michel Pawlotsky, Alexandre de la Taille, Francis Vacherot, Patrice Bruscella, and Virginie Firlej
Subjects: Inorganic Chemistry, ARPI, SARS-CoV-2, Organic Chemistry, General Medicine, androgen, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Catalysis, TMPRSS2, Computer Science Applications
Abstract: In early 2020, the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, and rapidly propagated worldwide causing a global health emergency. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) protein for cell entry, followed by proteolytic cleavage of the Spike (S) protein by the transmembrane serine protease 2 (TMPRSS2), allowing fusion of the viral and cellular membranes. Interestingly, TMPRSS2 is a key regulator in prostate cancer (PCa) progression which is regulated by androgen receptor (AR) signaling. Our hypothesis is that the AR signaling may regulate the expression of TMPRSS2 in human respiratory cells and thus influence the membrane fusion entry pathway of SARS-CoV-2. We show here that TMPRSS2 and AR are expressed in Calu-3 lung cells. In this cell line, TMPRSS2 expression is regulated by androgens. Finally, pre-treatment with anti-androgen drugs such as apalutamide significantly reduced SARS-CoV-2 entry and infection in Calu-3 lung cells but also in primary human nasal epithelial cells. Altogether, these data provide strong evidence to support the use of apalutamide as a treatment option for the PCa population vulnerable to severe COVID-19.
Published: 2023
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18. Sublabial bioactive glass implantation for the management of primary atrophic rhinitis and empty nose syndrome: Operative technique

Author: Charles‐Henri Hassan, Emeline Malheiro, Emilie Béquignon, André Coste, and Sophie Bartier
Subjects: vestibular, sublabial, Otorhinolaryngology, RF1-547, RD1-811, bioactive glass, empty nose syndrome, Surgery, atrophic rhinitis, General Medicine
Abstract: Objectives Atrophic rhinitis (AR) and empty nose syndrome (ENS) are chronic diseases characterized by a paradoxical nasal obstruction. These rare syndromes tend to occur after nasal surgery of the inferior turbinates in ENS and can be idiopathic in AR. Medical treatments alone are often insufficient. Surgical options are challenging and numerous resorbable and nonresorbable implants have been described in small series, with as many surgical techniques described. Whereas current surgical procedures are for risk of extrusions, graft rejections or poor lasting results, the use of GlassBONE™ (Sodimed®, Avignon, France), a bioactive glass, for a vestibular approach in AR and ENS has never been reported for this indication. Methods We described an original technique of nasal submucoperiosteal bilateral ceramic glass implantation in two patients with AR and ENS. Results The two cases presented a postoperative satisfying endoscopic and sinus CT‐scan results with filling of the nasal cavities, with less crusts and a complete wound healing. They had no short‐term complications. Conclusion This innovative approach is easily feasible and could be an option considered for the surgical management of AR and ENS. Level of evidence: 4.
Published: 2021
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19. Tracheostomies after SARS-CoV-2 intubation, performed by academic otorhinolaryngologists in the Paris area of France: Preliminary results

Author: C. Gasne, R. Hervochon, Ollivier Laccourreye, L. Tanaka, Diane Evrard, Romain Kania, André Coste, J. Nevoux, B. Barry, F. Tankere, A. Excoffier, S. Bartier, and C. La Croix
Subjects: Paris, medicine.medical_specialty, Percutaneous, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.medical_treatment, 03 medical and health sciences, Tracheostomy, 0302 clinical medicine, Intubation, Intratracheal, medicine, Humans, Intubation, 030223 otorhinolaryngology, Retrospective Studies, Surgeons, Univariate analysis, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, University hospital, Surgery, Otorhinolaryngology, 030220 oncology & carcinogenesis, Original Article, France, business
Abstract: Objective To analyse tracheostomies after intubation for SARS-Cov-2 infection performed by otorhinolaryngologists in 7 university hospitals in the Paris area of France during the month March 24 to April 23, 2020. Material and methods A multicentre retrospective observational study included 59 consecutive patients. The main goals were to evaluate the number, characteristics and practical conditions of tracheostomies, and the COVID-19 status of the otorhinolaryngologists. Secondary goals were to analyse tracheostomy time, decannulation rate, immediate postoperative complications and laryngotracheal axis status. Results Tracheostomy indications were for ventilatory weaning and extubation failure in 86% and 14% of cases, respectively. The technique was surgical, percutaneous or hybrid in 91.5%, 3.4% and 5.1% of cases, respectively. None of the operators developed symptoms consistent with COVID-19. Postoperative complications occurred in 15% of cases, with no significant difference between surgical and percutaneous/hybrid techniques (P = 0.33), although no complications occurred after percutaneous or hybrid tracheostomies. No procedures or complications resulted in death. The decannulation rate was 74.5% with a mean tracheostomy time of 20 ± 12 days. In 55% of the patients evaluated by flexible endoscopy after decannulation, a laryngeal abnormality was found. On univariate analysis, no clinical features had a significant influence on tracheostomy time, decannulation rate or occurrence of laryngeal lesions. Conclusion The main findings of the present retrospective study were: absence of contamination of the surgeons, heterogeneity of practices between centres, a high rate of complications and laryngeal lesions whatever the technique, and the specificities of the patients.
Published: 2021
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20. Biothérapies et traitement de la polypose naso-sinusienne primitive de l’adulte : bases cellulaires et moléculaires

Author: André Coste, S. Bartier, and Emilie Bequignon
Subjects: Otorhinolaryngology, Surgery
Abstract: Resume Ce travail fait le point sur les mecanismes moleculaires et cellulaires impliques dans la physiopathologie de la polypose naso-sinusienne (PNS), qui sous-tendent les modes d’action des biotherapies. On designe par ce terme des substances naturellement produites par l’organisme ou les antagonisant de facon specifique et ciblant un mecanisme pro-inflammatoire. La PNS appartient au groupe des rhinosinusites chroniques (RSC), longtemps divise en deux phenotypes, base sur la presence ou non de polypes. Depuis quelques annees, le concept d’endotypes est apparu avec une definition plus exhaustive des types de RSC selon leurs mecanismes inflammatoires ; ceci ayant pour finalite la mise au point de therapeutiques personnalisees. La physiopathologie de la PNS reste encore mal comprise. La genese des polypes reposerait sur une lesion epitheliale initiale dans un contexte d’inflammation locale chronique, essentiellement de type 2 en Europe, impliquant les eosinophiles, les IgE, des cytokines Th2 (IL-4/IL-13, IL-5) et les lymphocytes T et B. Les biotherapies semblent prometteuses pour le traitement de la PNS. A travers cette mise au point, nous detaillerons les differentes voies physiopathologiques sous-tendant les mecanismes d’actions des biotherapies puis detaillerons les differentes etudes evaluant leur efficacite et modes d’action dans le traitement de la PNS.
Published: 2021
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21. Biotherapy and treatment of adult primary chronic rhinosinusitis with nasal polyps: Cellular and molecular bases

Author: André Coste, Emilie Bequignon, and S. Bartier
Subjects: Adult, Context (language use), Inflammation, Immunoglobulin E, Proinflammatory cytokine, 03 medical and health sciences, Nasal Polyps, 0302 clinical medicine, medicine, Humans, Nasal polyps, Sinusitis, 030223 otorhinolaryngology, Mode of action, Rhinitis, biology, Mechanism (biology), business.industry, medicine.disease, Pathophysiology, Biological Therapy, Otorhinolaryngology, 030220 oncology & carcinogenesis, Chronic Disease, Immunology, biology.protein, Surgery, medicine.symptom, business
Abstract: The present article reviews the molecular and cellular mechanisms involved in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwCRSwNP) and underlying the action mechanisms of biotherapies. Biotherapy uses substances naturally produced by the organism or their specific antagonists targeting a proinflammatory mechanism. CRSwCRSwNP is a form of chronic rhinosinusitis (CRS), which is classically subdivided in to 2 types according to the presence of polyps. In recent years, the concept of endotypes emerged, with a more exhaustive definition of the types of CRS according to inflammatory mechanism, with a view to developing personalized treatments. CRSwNP pathophysiology is poorly understood. Polyps arise from a primary epithelial lesion in a context of chronic local inflammation, mainly type 2 in Europe, implicating eosinophils, IgE, Th2 cytokines (IL-4/IL-13, IL-5) and T and B cells. Biotherapy seems promising in CRSwNP. The present review details the various pathophysiological pathways underlying the action mechanisms of biotherapies, and the various published studies, assessing efficacy and mode of action in the treatment of CRSwNP.
Published: 2021
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22. COVID‐19 pandemic: do surgical masks impact respiratory nasal functions?

Author: Margaux Petitjean, Émilie Béquignon, Maxime Fieux, Bruno Louis, Françoise Zerah, André Coste, Sophie Bartier, Service de physiologie, explorations fonctionnelles [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biomécanique & Appareil Respiratoire (BAR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Service d'ORL [Créteil], Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), and Louis, Bruno
Subjects: nasal mucosa, rhinomanometry, nasal respiratory functions, face mask, Respiration, [SDV]Life Sciences [q-bio], Masks, COVID-19, Nose, [SDV] Life Sciences [q-bio], Otorhinolaryngology, Humans, Immunology and Allergy, Pandemics, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; No abstract available
Published: 2022
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23. CHronic RhINOSinusitis Outcome Registry (CHRINOSOR): establishment of an international outcome registry driven by mHealth technology

Author: Sven F. Seys, Peter W. Hellings, Isam Alobid, Vibeke Backer, Emilie Bequignon, Christian von Buchwald, Carlo Cavaliere, André Coste, Lauren Deneyer, Zuzana Diamant, Julia Eckl-Dorna, Wytske J. Fokkens, Simon Gane, Philippe Gevaert, Christiane Holbaek-Haase, Clemens Holzmeister, Claire Hopkins, Valérie Hox, Caroline Huart, Roger Jankowski, Mark Jorissen, Anette Kjeldsen, Lisa Knipps, Bibi Lange, Rik van der Lans, Anu Laulajainen-Hongisto, Kenneth Larsen, David T. Liu, Valerie Lund, Gert Mariën, Simonetta Masieri, Geoffrey Mortuaire, Joaquim Mullol, Sietze Reitsma, Philippe Rombaux, Sven Schneider, Andreas Steinsvik, Peter-Valentin Tomazic, Sanna K. Toppila-Salmi, Laura Van Gerven, Thibaut Van Zele, Paula Virkkula, Martin Wagenmann, Claus Bachert, UCL - (SLuc) Service d'oto-rhino-laryngologie, and UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie
Subjects: biologic therapy, chronic rhinosinusitis, mobile health technology, nasal polyps, real-world evidence, Immunology and Allergy
Abstract: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on prevalence of uncontrolled CRS and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery or biologics.To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology.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 as well as a set of relevant clinical outcomes. Adult patients with a diagnosis of chronic rhinosinusitis are eligible for inclusion.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.CHRINOSOR is a collaborative effort that aims at improving our understanding of chronic rhinosinusitis, its comorbidities and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by real-world evidence.
Published: 2022

24. Household transmission and incidence of positive SARS-CoV-2 RT-PCR in symptomatic healthcare workers, clinical course and outcome: a French hospital experience

Author: Valérie Garrait, Bernard Maitre, Amine Si Ali, Muriel Cherbit, Camille Jung, Pascal Andujar, Evguenia Krastinova, André Coste, Emmanuelle Varon, Mounira Smati, Isabelle Delacroix, Jean Claude Pairon, and Marie Thérèse Lecam
Subjects: hygiene / occupational hygiene, medicine.medical_specialty, Multivariate analysis, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030501 epidemiology, Hospital experience, health care workers, 03 medical and health sciences, 0302 clinical medicine, Health care, medicine, viruses, 030212 general & internal medicine, Workplace, business.industry, Transmission (medicine), Incidence (epidemiology), Public Health, Environmental and Occupational Health, Clinical course, virus diseases, virology, Emergency medicine, 0305 other medical science, business
Abstract: ObjectivesAlthough healthcare workers (HCWs) have been particularly affected by SARS-CoV-2, detailed data remain scarce. In this study, we investigated infection rates, clinical characteristics, occupational exposure and household transmission among all symptomatic HCWs screened by SARS-CoV-2 RT-PCR between 17 March (French lockdown) and 20 April.MethodsSARS-CoV-2 RT-PCR was proposed to symptomatic (new cough or dyspnoea) HCWs at Creteil Hospital in one of the Parisian suburbs most severely affected by COVID-19. Data on occupational profile, living situation and household, together with self–isolation and mask use at home were collected, as well as the number of cases in the household.ResultsThe incidence rate of symptomatic SARS-CoV-2 was estimated to be 5% (110/2188). A total of 110 (35%) of the 314 HCWs tested positive and 9 (8%) were hospitalised. On multivariate analysis, factors independently associated with positive RT-PCR were occupational profile with direct patient facing (OR 3.1, 95% CI 1.1 to 8.8), pConclusionThis is the first study to report infection rates among HCWs during the peak of the SARS-CoV-2 epidemic in France and the lockdown period, highlighting the risk related to occupational profile and household transmission.
Published: 2020
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25. Rinosinusitis edematosa y purulenta

Author: C Parra, André Coste, Emilie Bequignon, and Virginie Prulière-Escabasse
Subjects: 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, 030223 otorhinolaryngology
Abstract: Resumen Las sinusitis edematosas y purulentas son una forma particular de rinosinusitis cronica (>12 semanas) difusa, con o sin polipos, que afectan de forma bilateral a los senos anteriores (maxilar, celdillas etmoidales anteriores y frontal) y posteriores (celdillas etmoidales posteriores y esfenoidal). El aspecto endoscopico se caracteriza por la presencia de secreciones purulentas y edema en las fosas nasales y los meatos medios y superiores. La constatacion de la presencia de pus de forma repetida por el clinico orienta hacia una sinusitis edematosa y purulenta en lugar de hacia una poliposis nasosinusal. El diagnostico de una sinusitis edematosa y purulenta implica un estudio etiologico exhaustivo y un tratamiento especializado. Se deben buscar principalmente dos etiologias: un origen disinmunitario o un origen genetico. Se deben descartar las enfermedades sistemicas de tipo granulomatosis con polivasculitis y el linfoma NK/T nasal. El tratamiento de las sinusitis edematosas y purulentas es complejo y consiste en cuidados locales y antibioticoterapia por via local o sistemica.
Published: 2020
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26. COVID-19 et chirurgie ORL

Author: Richard Nicollas, E. Bequignon, B. Barry, Marc Makeieff, N. Morel, André Coste, Vincent Couloigner, P. Boudard, Emmanuel Lescanne, and Sébastien Schmerber
Subjects: 03 medical and health sciences, 2019-20 coronavirus outbreak, 0302 clinical medicine, Otorhinolaryngology, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Political science, Surgery, 030223 otorhinolaryngology, Humanities, 030217 neurology & neurosurgery
Abstract: Resume En ORL, l’examen clinique et les gestes invasifs sur les voies respiratoires et leurs annexes exposent a la transmission directe du SARS-CoV-2 par inhalation ou projection oculaire de gouttelettes contaminees, ou indirecte manuportee ou par l’intermediaire d’objets ou de surfaces contaminees. L’estimation d’un R0 de la COVID-19 a environ 3 a justifie de reporter les rendez-vous des consultations presentielles non urgentes et de developper la tele-consultation afin de limiter les risques d’infection par le SARS-CoV-2 des patients ou des agents de sante et de participer au respect du confinement. L’autorite sanitaire a recommande de deprogrammer toute activite ORL chirurgicale ou medicale non urgente et sans prejudice de perte de chance pour les patients. Cette deprogrammation a eu pour objectif d’augmenter tres significativement la capacite de soins critiques, prioriser l’accueil de malades de patients COVID-19, prioriser l’affectation des personnels et la mise a disposition des materiels necessaires a leur fonctionnement, contribuer a la fluidite de l’aval des soins critiques au sein de leur etablissement. Il s’agissait egalement de ne pas exposer les malades concernes a un risque d’exposition infectieuse. Cet article propose des orientations concernant les indications et modalites de realisation de la chirurgie ORL et la gestion des reports d’intervention dans le contexte pandemique actuel. Il ne s’agit que de conseils de bonne pratique qui doivent naturellement etre modules dans chaque region en fonction de l’evolution de l’epidemie et des organisations preexistantes, et ce dans le cadre de concertations entre les equipes ORL, les unites operationnelles d’hygiene et toutes les autres specialites concernees.
Published: 2020
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27. COVID-19 and ENT Surgery

Author: Richard Nicollas, Sébastien Schmerber, N. Morel, Marc Makeieff, André Coste, Emmanuel Lescanne, E. Bequignon, Vincent Couloigner, B. Barry, and P. Boudard
Subjects: medicine.medical_specialty, medicine.diagnostic_test, Otorhinolaryngologic Surgical Procedures, business.industry, Best practice, Physical examination, Surgery, EXPOSE, Otorhinolaryngology, Pandemic, Health care, Medicine, Infection control, business
Abstract: In Otorhinolaryngology - Head and Neck Surgery, clinical examination and invasive procedures on the respiratory tract and on airway-connected cavities, such as paranasal sinuses and the middle ear, expose people to direct transmission of SARS-CoV-2 by inhalation or ocular projection of contaminated droplets, and to indirect transmission by contact with contaminated hands, objects or surfaces. Estimating an R0 of COVID-19 at around 3 justified postponing non-urgent face-to-face consultations and expanding the use of teleconsultation in order to limit the risks of SARS-CoV-2 infection of patients or health workers and comply with the lockdown. The health authority recommends cancellation of all medical or surgical activities, which are not urgent as long as this does not involve a loss of chance for the patient. The purpose of this cancellation is to significantly increase critical care capacity, prioritise the reception of patients with COVID-19, prioritise the allocation of staff and provision of the equipment necessary for their medical or surgical management, and contribute to the smooth running of downstream critical care within their establishment. Another goal is to reduce the risks of patient contamination within healthcare facilities. This document provides guidance on how to proceed with and adapt ENT surgery in the current pandemic context, as well as on the management of postponed operations. This best practice advice must of course be adapted in each region according to the development of the epidemic and pre-existing arrangements. Their local application can only be decided within the framework of collaboration between the ENT teams, the operational hygiene units and all the other specialties concerned.
Published: 2020
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28. Oncostatin M Contributes to Airway Epithelial Cell Dysfunction in Chronic Rhinosinusitis with Nasal Polyps

Author: Florent Carsuzaa, Emilie Bequignon, Sophie Bartier, André Coste, Xavier Dufour, Matthieu Bainaud, Jean Claude Lecron, Bruno Louis, Stéphane Tringali, Laure Favot, and Maxime Fieux
Subjects: Inorganic Chemistry, Organic Chemistry, nasal epithelium, OSM, IL-6, ciliary beating efficiency, epithelial electric resistance, tight junctions, repair rate, CRSwNP, primary culture, General Medicine, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Catalysis, Computer Science Applications
Abstract: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a typical type-2 inflammation involving several cytokines and is associated with epithelial cell dysfunction. Oncostatin M (OSM) (belonging to the interleukin(IL)-6 family) could be a key driver of epithelial barrier dysfunction. Therefore, we investigated the presence of OSM and IL-6 and the expression pattern of tight junctions (TJs) in the nasal tissue of CRSwNP patients and controls using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Then, their potential role in the epithelial barrier was evaluated in vitro in 27 different primary cultures of human nasal epithelial cells (HNECs) by measuring TJ expression and transepithelial electric resistance (TEER) with or without OSM or IL-6 (1, 10, and 100 ng/mL). The effect on ciliary beating efficiency was evaluated by high-speed videomicroscopy and on repair mechanisms with a wound healing model with or without OSM. OSM and IL-6 were both overexpressed, and TJ (ZO-1 and occludin) expression was decreased in the nasal polyps compared to the control mucosa. OSM (100 ng/mL) but not IL-6 induced a significant decrease in TJ expression, TEER, and ciliary beating efficiency in HNECs. After 24 h, the wound repair rate was significantly higher in OSM-stimulated HNECs at 100 ng/mL. These results suggest that OSM could become a new target for monoclonal antibodies.
Published: 2023
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29. Obstruction nasale et vertiges : des symptômes pas si banals

Author: S. Bartier, André Coste, I. Delacroix, and Emilie Bequignon
Subjects: Otorhinolaryngology, business.industry, Medicine, Surgery, business
Published: 2021
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30. SNOT-22 items and association with objective measures in dupilumab-treated patients with severe chronic rhinosinusitis with nasal polyps from SINUS-24 and SINUS-52 trials

Author: Martin Wagenmann, Shahid S. Siddiqui, Juby A. Jacob-Nara, André Coste, Giorgio Walter Canonica, Asif H. Khan, Peter Hellings, Siddhesh Kamat, Urvi Mujumdar, Yamo Deniz, Scott Nash, Paul Rowe, Joaquim Mullol, and Jerome Msihid
Subjects: medicine.medical_specialty, medicine.anatomical_structure, Chronic rhinosinusitis, business.industry, medicine, Nasal polyps, business, medicine.disease, Dupilumab, Dermatology, Sinus (anatomy)
Published: 2021
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31. Association between hearing loss and hereditary ATTR amyloidosis

Author: Aziz Guellich, Emilie Béquignon, Mounira Kharoubi, Diane Bodez, Sophie Bartier, Thibaud Damy, André Coste, Florence Canoui-Poitrine, and Véronique Chatelin
Subjects: Male, endocrine system, Pathology, medicine.medical_specialty, Heart Diseases, Hearing loss, otorhinolaryngologic diseases, Internal Medicine, medicine, Humans, Prospective Studies, Hearing Loss, Amyloid Neuropathies, Familial, biology, business.industry, Amyloidosis, fungi, food and beverages, nutritional and metabolic diseases, medicine.disease, Transthyretin, Cardiac amyloidosis, biology.protein, Female, medicine.symptom, business, Attr amyloidosis
Abstract: Background: Hereditary transthyretin (TTR) related amyloidosis (ATTRv) is a life-threatening condition, which can potentially affect all organs. The objective was to identify the hearing st...
Published: 2019
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32. Pharyngo-laryngeal involvement in systemic amyloidosis with cardiac involvement: a prospective observational study

Author: André Coste, Carole Henrion, Sophie Bartier, Emilie Bequignon, Mounira Kharoubi, Thibaud Damy, Florence Canoui-Poitrine, Véronique Chatelin, and Diane Bodez
Subjects: Male, Pathology, medicine.medical_specialty, Heart Diseases, Severe disease, macromolecular substances, Prevalence, Internal Medicine, Humans, Medicine, Immunoglobulin Light-chain Amyloidosis, Prospective Studies, Aged, Amyloid Neuropathies, Familial, biology, business.industry, Dysphonia, Dysphagia, Systemic amyloidosis, Transthyretin, Cardiac amyloidosis, biology.protein, Female, Observational study, medicine.symptom, Deglutition Disorders, business
Abstract: Background: Systemic amyloidosis with cardiac involvement (CA) is a severe disease caused by the aggregation of misfolded proteins infiltrating organs and tissues and leading to their dysfunction. ...
Published: 2019
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33. FcRn as a Transporter for Nasal Delivery of Biologics: A Systematic Review

Author: Bruno Louis, Emilie Bequignon, Mikail Nourredine, Maxime Fieux, Caroline Giroudon, André Coste, Sophie Bartier, Sandra Le Quellec, Hospices Civils de Lyon (HCL), IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre Hospitalier Intercommunal de Créteil (CHIC), Biomécanique & Appareil Respiratoire (BAR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Louis, Bruno
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Gene Expression, Review, Receptors, Fc, Bioinformatics, immunoglobulin G, 0302 clinical medicine, Drug Delivery Systems, Immune homeostasis, Biology (General), Spectroscopy, nasal route, neonatal Fc receptor, General Medicine, Computer Science Applications, [SDV] Life Sciences [q-bio], Chemistry, medicine.anatomical_structure, Systematic review, Transcytosis, 030220 oncology & carcinogenesis, Protein Binding, QH301-705.5, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Neonatal Fc receptor, medicine, Animals, Humans, biologics, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Fc-fusion protein, Biological Products, business.industry, Organic Chemistry, Histocompatibility Antigens Class I, Transporter, Biological Transport, Nasal Mucosa, 030104 developmental biology, monoclonal antibody, Respiratory epithelium, Nasal administration, business, Olfactory epithelium, Biomarkers
Abstract: International audience; FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an efficient transporter of biologics across the nasal epithelial barrier is of particular interest, as it would allow a less invasive strategy for the administration of biologics in comparison to subcutaneous, intramuscular or intravenous administrations, which are often used in clinical practice. A focused systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It was registered on the international prospective register of systematic reviews PROSPERO, which helped in identifying articles that met the inclusion criteria. Clinical and preclinical studies involving FcRn and the nasal delivery of biologics were screened, and the risk of bias was assessed across studies using the Oral Health Assessment Tool (OHAT). Among the 12 studies finally included in this systematic review (out of the 758 studies screened), 11 demonstrated efficient transcytosis of biologics through the nasal epithelium. Only three studies evaluated the potential toxicity of biologics’ intranasal delivery, and they all showed that it was safe. This systematic review confirmed that FcRn is expressed in the nasal airway and the olfactory epithelium, and that FcRn may play a role in IgG and/or IgG-derived molecule-transcytosis across the airway epithelium. However, additional research is needed to better characterize the pharmacokinetic and pharmacodynamic properties of biologics after their intranasal delivery.
Published: 2021
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34. Trachéotomies après intubation pour SARS-CoV-2 réalisées par les oto-rhino-laryngologistes universitaires d’Ile de France : résultats préliminaires

Author: Ollivier Laccourreye, L. Tanaka, B. Barry, Romain Kania, J. Nevoux, R. Hervochon, André Coste, F. Tankere, C. Gasne, Diane Evrard, S. Bartier, C. La Croix, and A. Excoffier
Subjects: SARS-CoV-2, otorhinolaryngology, Surgery, tracheostomy, France, Article
Abstract: Resume Objectif: Analyse des tracheotomies post intubation pour SARS-Cov-2 realisees par les otorhinolaryngologistes de 7 centres universitaires d’Ile de France (23/03-23/04/2020). Materiel et Methodes: Etude observationnelle, retrospective, multicentrique, d’une cohorte de 59 patients. Objectifs principaux : evaluer le nombre, les caracteristiques et les modalites pratiques des tracheotomies realisees, ainsi que le statut Covid-19 des operateurs. Objectifs secondaires : preciser la duree de tracheotomie, le taux de decanulation, les complications immediates et l’etat de l’axe laryngo-tracheal. Resultats : Le motif de realisation etait l’aide au sevrage et l’echec d’extubation respectivement dans 86% et 14% de cas. La technique utilisee etait chirurgicale, percutanee et hybride respectivement dans 91,5%, 3,4 % et 5,1% des cas. Aucun des operateurs ne developpait de symptomes compatibles avec une infection par le Covid-19. Une complication post operatoire survenait dans 15 % des cas, sans difference statistiquement significative entre les techniques chirurgicales et percutanee / hybride, meme si aucune complication ne survenait apres tracheotomies percutanees et hybrides. Aucune tracheotomie ni aucune complication n’etait suivie par la mort du patient. Le taux de decanulation etait de 74,5 % avec une duree moyenne de port de la tracheotomie de 20±12 jours. Pour 55% des patients evalues par nasofibroscopie apres decanulation, une anomalie laryngee etait notee. En analyse univariee, aucune des caracteristiques cliniques n'influait, de facon statistiquement significative sur la duree de tracheotomie, le taux de decanulation et la survenue d’une alteration de l’etat larynge. Conclusion: L’absence de contamination des chirurgiens, l’heterogeneite de pratiques selon les centres, le taux eleve de complications et de lesions laryngees quelle que soit la technique utilisee et des particularites des patients sont les quatre points principaux qui ressortent de cette etude retrospective.
Published: 2021

35. Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies

Author: Bousquet, Jean, Cristol, Jean-Paul, Czarlewski, Wienczyslawa, Anto, Josep M, Martineau, Adrian, Haahtela, Tari, Fonseca, Susana C, Iaccarino, Guido, Blain, Hubert, Fiocchi, Alessandro, Canonica, G Walter, Fonseca, Joao A, Vidal, Alain, Choi, Hak-Jong, Kim, Hyun Ju, Le Moing, Vincent, Reynes, Jacques, Sheikh, Aziz, Akdis, Cezmi A, Zuberbier, Torsten, Amir Hamzah Abdul Latiff, Baharudin, Abdullah, Werner, Aberer, Nancy, Abusada, Ian, Adcock, Alejandro, Afani, Ioana, Agache, Xenofon, Aggelidis, Jenifer, Agustin, Cezmi, A Akdis, Mübeccel, Akdis, Mona, Al-Ahmad, Abou Al-Zahab Bassam, Hussam, Alburdan, Oscar, Aldrey-Palacios, Emilio Alvarez Cuesta, Hiba Alwan Salman, Ashraf, Alzaabi, Salma, Amade, Gene, Ambrocio, Rosana, Angles, Isabella, Annesi-Maesano, Ignacio, J Ansotegui, Josep, M Anto, Paula Ara Bardajo, Stefania, Arasi, Margarete, Arrais, Hasan, Arshad, Maria-Cristina, Artesani, Estrella, Asayag, Francesca, Avolio, Khuzama, Azhari, Claus, Bachert, Diego, Bagnasco, Ilaria, Baiardini, Nissera, Bajrović, Petros, Bakakos, Sergio Bakeyala Mongono, Christine, Balotro-Torres, Sergio, Barba, Cristina, Barbara, Elsa, Barbosa, Bruno, Barreto, Joan, Bartra, Xavier, Basagana, Eric, D Bateman, Lkhagvaa, Battur, Anna, Bedbrook, Martín Bedolla Barajas, Bianca, Beghé, Antra, Bekere, Elizabeth, Bel, Ali Ben Kheder, Mikael, Benson, Elena-Camelia, Berghea, Karl-Christian, Bergmann, Roberto, Bernardini, David, Bernstein, Mike, Bewick, Slawomir, Bialek, Artur, Białoszewski, Thomas, Bieber, Nils, E Billo, Maria-Beatrice, Bilo, Carsten, Bindslev-Jensen, Leif, Bjermer, Hubert, Blain, Irina, Bobolea, Malgorzata Bochenska Marciniak, Christine, Bond, Attilio, Boner, Matteo, Bonini, Sergio, Bonini, Sinthia, Bosnic-Anticevich, Isabelle, Bosse, Sofia, Botskariova, Jacques, Bouchard, Louis-Philippe, Boulet, Rodolphe, Bourret, Philippe, Bousquet, Fulvio, Braido, Andrew, Briggs, Christopher, E Brightling, Jan, Brozek, Luisa, Brussino, Roland, Buhl, Roxana, Bumbacea, Rosalva, Buquicchio, María-Teresa Burguete Cabañas, Andrew, Bush, William, W Busse, Jeroen, Buters, Fernan, Caballero-Fonseca, Moïses, A Calderon, Mario, Calvo, Paulo, Camargos, Thierry, Camuzat, R Canevari, F, Antonio, Cano, G Walter Canonica, Arnaldo, Capriles-Hulett, Luis, Caraballo, Vicky, Cardona, Kai-Hakon, Carlsen, Jonas Carmona Pirez, Jorge, Caro, Warner, Carr, Pedro, Carreiro-Martins, Fredelita, Carreon-Asuncion, Ana-Maria, Carriazo, Carme Carrion, Y Ribas, Thomas, Casale, Mary-Ann, Castor, Elizabeth, Castro, G Caviglia, A, Lorenzo, Cecchi, Alfonso Cepeda Sarabia, Maciej, Chalubinski, Ramanathan, Chandrasekharan, Yoon-Seok, Chang, Victoria, Chato-Andeza, Lida, Chatzi, Christina, Chatzidaki, Niels, H Chavannes, Claudia Chaves Loureiro, Aurora-Alejandra Chavez Garcia, Marta, Chelninska, Yuzhi, Chen, Lei, Cheng, Sharon, Chinthrajah, Tomas, Chivato, Ekaterine, Chkhartishvili, George, Christoff, Henry, Chrystyn, Derek, K Chu, Antonio, Chua, Alexander, Chuchalin, Kian Fan Chung, Alberto, Cicerán, Cemal, Cingi, Giorgio, Ciprandi, Ieva, Cirule, Ana-Carla, Coelho, Enrico, Compalati, Jannis, Constantinidis, Jaime Correia de Sousa, Elisio Manuel Costa, David, Costa, María Del Carmen Costa Domínguez, André, Coste, Cottini, M, Linda, Cox, Carlos, Crisci, Maria Angiola Crivellaro, Alvaro, A Cruz, John, Cullen, Adnan, Custovic, Biljana, Cvetkovski, Wienczyslawa, Czarlewski, Gennaro, D'Amato, Jane da Silva, Ronald, Dahl, Sven-Erik, Dahlen, Vasilis, Daniilidis, Louei Darjazini Nahhas, Ulf, Darsow, Janet, Davies, Frédéric de Blay, Giulia De Feo, Eloisa De Guia, José-Ricardo De la Torre Navarrete, Chato De Los Santos, Esteban De Manuel Keenoy, Govert De Vries, Diana, Deleanu, Pascal, Demoly, Judah, Denburg, Philippe, Devillier, Alain, Didier, Sanja Dimic Janjic, Maria, Dimou, Anh Tuan Dinh-Xuan, Ratko, Djukanovic, Maria Do Ceu Texeira, Dejan, Dokic, Margarita Gabriela Domínguez Silva, Habib, Douagui, Nikolaos, Douladiris, Maria, Doulaptsi, Gérard, Dray, Ruta, Dubakiene, Eve, Dupas, Stephen, Durham, Marzia, Duse, Mark, Dykewicz, Didier, Ebo, Natalija, Edelbaher, Thomas, Eiwegger, Patrik, Eklund, Yehia, El-Gamal, Zeinab, A El-Sayed, Shereen, S El-Sayed, Magda, El-Seify, Regina, Emuzyte, Lourdes, Enecilla, Marina, Erhola, Heidilita, Espinoza, Jesús Guillermo Espinoza Contreras, John, Farrell, Lenora, Fernandez, Paola Fimbres Jimenez, Antje Fink Wagner, Alessandro, Fiocchi, Wytske, J Fokkens, Lenia, Folletti, Joao, A Fonseca, Jean-François, Fontaine, Francesco, Forastiere, Jose Miguel Fuentes Pèrez, Emily, Gaerlan-Resureccion, Mina, Gaga, José Luis Gálvez Romero, Amiran, Gamkrelidze, Alexis, Garcia, Cecilia Yvonne García Cobas, María de la Luz Hortensia García Cruz, Valeria Garcia Ortiz, Jacques, Gayraud, Matteo, Gelardi, Bilun, Gemicioglu, Dimitra, Gennimata, Sonya, Genova, José, Gereda, Roy Gerth van Wijk, Antonio, Giuliano, René-Maximiliano, Gomez, Miguel-Ange Gonzalez Ballester, Sandra González Diaz, Maia, Gotua, Christos, Grigoreas, Ineta, Grisle, Marta, Guidacci, Nick, Guldemond, Zdenek, Gutter, Antonieta, Guzmán, Tari, Haahtela, Ramsa, Halloum, David, Halpin, Eckard, Hamelmann, Suleiman, Hammadi, Richard, Harvey, Enrico, Heffler, Joachim, Heinrich, Adnan, Hejjaoui, Birthe, Hellquist-Dahl, Luiana Hernández Velázquez, Mark, Hew, Elham, Hossny, Peter, Howarth, Martin, Hrubiško, Yunuen Rocío Huerta Villalobos, Marc, Humbert, Salina, Husain, Michael, Hyland, Guido, Iaccarino, Moustafa, Ibrahim, Nataliya, Ilina, Maddalena, Illario, Cristoforo, Incorvaia, Antonio, Infantino, Carla, Irani, Zhanat, Ispayeva, Juan Carlos Ivancevich, Edgardo Ej Jares, Deborah, Jarvis, Ewa, Jassem, Klemen, Jenko, Rubén Darío Jiméneracruz Uscanga, Sebastian, L Johnston, Guy, Joos, Maja, Jošt, Kaja, Julge, Ki-Suck, Jung, Jocelyne, Just, Marek, Jutel, Igor, Kaidashev, Omer, Kalayci, Fuat, Kalyoncu, Jeni, Kapsali, Przemyslaw, Kardas, Jussi, Karjalainen, Carmela, A Kasala, Michael, Katotomichelakis, Loreta, Kavaliukaite, Kazi, S Bennoor, Thomas, Keil, Paul, Keith, Musa, Khaitov, Nikolai, Khaltaev, You-Young, Kim, Bruce, Kirenga, Jorg, Kleine-Tebbe, Ludger, Klimek, Fanny, W Ko, Bernard Koffi N'Goran, Evangelia, Kompoti, Peter, Kopač, Gerard, Koppelman, Anja Koren Jeverica, Seppo, Koskinen, Mitja, Košnik, Tomasz, Kostka, Kosta, V Kostov, Marek, L Kowalski, Tanya, Kralimarkova, Karmen Kramer Vrščaj, Helga, Kraxner, Samo, Kreft, Vicky, Kritikos, Dmitry, Kudlay, Mikael, Kuitunen, Inger, Kull, Piotr, Kuna, Maciej, Kupczyk, Violeta, Kvedariene, Marialena, Kyriakakou, Nika, Lalek, Massimo, Landi, Stephen, Lane, Désiree, E Larenas-Linnemann, Susanne, Lau, Daniel, Laune, Jorge, Lavrut, Lan, Le, Martina, Lenzenhuber, Gualtiero, Leo, Marcus, Lessa, Michael, Levin, Jing, Li, Philip, Lieberman, Giuseppe, Liotta, Brian, Lipworth, Xuandao, Liu, Rommel, Lobo, Karin, C Lodrup Carlsen, Carlo, Lombardi, Renaud, Louis, Stelios, Loukidis, Olga, Lourenço, Jorge, A Luna Pech, Bojan, Madjar, Enrico, Maggi, Antoine, Magnan, Bassam, Mahboub, Alpana, Mair, Anke-Hilse Maitland van der Zee, Mika, Makela, Michael, Makris, Hans-Jorgen, Malling, Mariana, Mandajieva, Patrick, Manning, Manolis, Manousakis, Pavlos, Maragoudakis, Gianluigi, Marseglia, Gailen, Marshall, Mohammad Reza Masjedi, Jorge, F Máspero, Juan José Matta Campos, Marcus, Maurer, Sandra, Mavale-Manuel, Cem, Meço, Erik, Melén, Giovanni, Melioli, Elisabete, Melo-Gomes, Eli, O Meltzer, Enrica, Menditto, Andrew, Menzies-Gow, Hans, Merk, Jean-Pierre, Michel, Yann, Micheli, Neven, Miculinic, Luís, Midão, Florin, Mihaltan, Nikolaos, Mikos, Manlio, Milanese, Branislava, Milenkovic, Dimitrios, Mitsias, Bassem, Moalla, Giuliana, Moda, María Dolores Mogica Martínez, Yousser, Mohammad, Frances-Montserrat, Moharra, Mostafa, Moin, Mathieu, Molimard, Isabelle, Momas, Monique, Mommers, Alessandro, Monaco, Stephen, Montefort, Lucia-Elvira, Montenegro, Riccardo, Monti, Dory, Mora, Mario, Morais-Almeida, Ralph, Mösges, Badr Eldin Mostafa, Joaquim, Mullol, Lars, Münter, Antonella, Muraro, Ruth, Murray, Antonio, Musarra, Tihomir, Mustakov, Robert, Naclerio, Kari, C Nadeau, Rachel, Nadif, Alla, Nakonechna, Leyla, Namazova-Baranova, Gretchen, Navarro-Locsin, Hugo, Neffen, Kristof, Nekam, Angelos, Neou, Eustachio, Nettis, Daniel, Neuberger, Laurent, Nicod, Stefania, Nicola, Verena, Niederberger-Leppin, Marek, Niedoszytko, Antonio, Nieto, Ettore, Novellino, Elizabete, Nunes, Dieudonné, Nyembue, Robyn, E O'Hehir, Cvetanka, Odjakova, Ken, Ohta, Yoshitaka, Okamoto, Kimi, Okubo, Brian, Oliver, Gabrielle, L Onorato, Maria Pia Orru, Solange, Ouédraogo, Kampadilemba, Ouoba, Francisco-Javier, Padilla, Pier Luigi Paggiaro, Aris, Pagkalos, Pajno, Giovanni Battista, Gianni, Pala, P Palaniappan, S, Isabella, Pali-Schöll, Susanna, Palkonen, Stephen, Palmer, Carmen Panaitescu Bunu, Petr, Panzner, Nikos, G Papadopoulos, Vasilis, Papanikolaou, Alberto, Papi, Bojidar, Paralchev, Giannis, Paraskevopoulos, Hae-Sim, Park, Giovanni, Passalacqua, Vincenzo, Patella, Ian, Pavord, Ruby, Pawankar, Soren, Pedersen, Susete, Peleve, Simona, Pellegino, Ana, Pereira, Mariana, Pereira, Tamara, Pérez, Andrea, Perna, Diego, Peroni, Oliver, Pfaar, Nhân, Pham-Thi, Bernard, Pigearias, Isabelle, Pin, Konstantina, Piskou, Constantinos, Pitsios, Davor, Plavec, Dagmar, Poethig, Wolfgang, Pohl, Antonija Poplas Susic, Todor, A Popov, Fabienne, Portejoie, Paul, Potter, Lars, Poulsen, Alexandra, Prados-Torres, Fotis, Prarros, David, Price, Emmanuel, Prokopakis, Francesca, Puggioni, Elisa, Puig-Domenech, Robert, Puy, Klaus, Rabe, Silvia, Rabotti, Filip, Raciborski, Josephine, Ramos, Cristina, Recalcati, Marysia, T Recto, Shereen, M Reda, Frederico, S Regateiro, Norbert, Reider, Sietze, Reitsma, Susana, Repka-Ramirez, Erminia, Ridolo, Janet, Rimmer, Daniela Rivero Yeverino, José Angelo Rizzo, Carlos, Robalo-Cordeiro, Graham, Roberts, Karen, Robles, Nicolas, Roche, Mónica Rodríguez González, Eréndira Rodríguez Zagal, Giovanni, Rolla, Christine, Rolland, Regina, Roller-Wirnsberger, Miguel Roman Rodriguez, Antonino, Romano, Jan, Romantowski, Philippe, Rombaux, Joel, Romualdez, Jose, Rosado-Pinto, Nelson, Rosario, Lanny, Rosenwasser, Oliviero, Rossi, Menachem, Rottem, Philip, W Rouadi, Nikoleta, Rovina, Irma Rozman Sinur, Mauricio, Ruiz, Lucy Tania Ruiz Segura, Dermot, Ryan, Hironori, Sagara, Daiki, Sakai, Daiju, Sakurai, Wafaa, Saleh, Johanna, Salimaki, Konstantinos, Samitas, Boleslaw, Samolinski, María Guadalupe Sánchez Coronel, Mario, Sanchez-Borges, Jaime, Sanchez-Lopez, Melissa, Sansonna, Codrut, Sarafoleanu, Faradiba Sarquis Serpa, Joaquin, Sastre, Eleonora, Savi, Agne, Savonyte, Bisher, Sawaf, Glenis, K Scadding, Sophie, Scheire, Peter, Schmid-Grendelmeier, Juan Francisco Schuhl, Holger, Schunemann, Maria, Schvalbová, Jorgen, Schwarze, Nicola, Scichilone, Gianenrico, Senna, Cecilia, Sepúlveda, Elie, Serrano, Sara, Shamai, Aziz, Sheikh, Mike, Shields, Vasil, Shishkov, Nikos, Siafakas, Alexander, Simeonov, Estelle Fer Simons, Juan Carlos Sisul, Brigita, Sitkauskiene, Ingelbjorg, Skrindo, Tanja Soklič Košak, Dirceu, Solé, Martin, Sondermann, Talant, Sooronbaev, Manuel, Soto-Martinez, Manuel, Soto-Quiros, Barnaro Sousa Pinto, Milan, Sova, Michael, Soyka, Krzysztof, Specjalski, Annette, Sperl, Otto, Spranger, Sofia, Stamataki, Lina, Stefanaki, Cristiana, Stellato, Rafael, Stelmach, Timo, Strandberg, Petra, Stute, Abirami, Subramaniam, Charlotte Suppli Ulrik, Michael, Sutherland, Silvia, Sylvestre, Aikaterini, Syrigou, Luis Taborda Barata, Nadejda, Takovska, Rachel, Tan, Frances, Tan, Vincent, Tan, Ing Ping Tang, Masami, Taniguchi, Line, Tannert, Pongsakorn, Tantilipikorn, Jessica, Tattersall, Filippo, Tesi, Uta, Thieme, Carel, Thijs, Mike, Thomas, Teresa, To, Ana Maria Todo-Bom, Alkis, Togias, Peter-Valentin, Tomazic, Vesna, Tomic-Spiric, Sanna, Toppila-Salmi, Maria-José Torres Jaen, Elina, Toskala, Massimo, Triggiani, Nadja, Triller, Katja, Triller, Ioanna, Tsiligianni, Uberti, M, Ruxandra, Ulmeanu, Jure, Urbancic, Marilyn Urrutia Pereira, Martina, Vachova, Felipe, Valdés, Rudolf, Valenta, Marylin Valentin Rostan, Antonio, Valero, Arunas, Valiulis, Mina, Vallianatou, Erkka, Valovirta, Michiel Van Eerd, Eric Van Ganse, Marianne van Hage, Olivier, Vandenplas, Tuula, Vasankari, Dafina, Vassileva, Cesar Velasco Munoz, Maria Teresa Ventura, Cécilia, Vera-Munoz, Frédéric, Viart, Dilyana, Vicheva, Pakit, Vichyanond, Petra, Vidgren, Giovanni, Viegi, Claus, Vogelmeier, Leena Von Hertzen, Theodoros, Vontetsianos, Dimitris, Vourdas, Vu Tran Thien Quan, Martin, Wagenmann, Samantha, Walker, Dana, Wallace, Yun De Wang, Susan, Waserman, Katrin, Wehner, Magnus, Wickman, Sian, Williams, Dennis, Williams, Nicola, Wilson, Gary, Wong, Kent, Woo, Lucyna, Wozniak, John, Wright, Piotr, Wroczynski, Paraskevi, Xepapadaki, Plamen, Yakovliev, Masao, Yamaguchi, Kwok, Yan, Yoke Yeow Yap, Mais, Yassin, Barbara, Yawn, Panayiotis, Yiallouros, Arzu, Yorgancioglu, Shigemi, Yoshihara, Ian, Young, Osman, B Yusuf, Asghar, Zaidi, Fares, Zaitoun, Petra, Zalud, Heather, Zar, T Zedda, M, Mario, E Zernotti, Luo, Zhang, Nanshan, Zhong, Mihaela, Zidarn, Torsten, Zuberbier, Celia, Zubrinich, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Barts & The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Central Hospital [Finland] (HUCH), Departamento de Geociencias, Ambiente e Ordenamento do Territorio (DGAOT), Universidade do Porto = University of Porto, University of Naples Federico II = Università degli studi di Napoli Federico II, Euromov (EuroMov), Université de Montpellier (UM), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Center of Research in Health Technologies and Information Systems (CINTESIS), AgroParisTech, World Institute of Kimchi [Gwangju], Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Edinburgh, Universität Zürich [Zürich] = University of Zurich (UZH), Humboldt-Universität zu Berlin, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Universidade do Porto, University of Naples Federico II, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), MORNET, Dominique, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bousquet J., Cristol J.-P., Czarlewski W., Anto J.M., Martineau A., Haahtela T., Fonseca S.C., Iaccarino G., Blain H., Fiocchi A., Canonica G.W., Fonseca J.A., Vidal A., Choi H.-J., Kim H.J., Le Moing V., Reynes J., Sheikh A., Akdis C.A., Zuberbier T., Abdul Latiff A.H., Abdullah B., Aberer W., Abusada N., Adcock I., Afani A., Agache I., Aggelidis X., Agustin J., Akdis M., Al-Ahmad M., Al-Zahab Bassam A., Alburdan H., Aldrey-Palacios O., Alvarez Cuesta E., Alwan Salman H., Alzaabi A., Amade S., Ambrocio G., Angles R., Annesi-Maesano I., Ansotegui I.J., Ara Bardajo P., Arasi S., Arrais M., Arshad H., Artesani M.-C., Asayag E., Avolio F., Azhari K., Bachert C., Bagnasco D., Baiardini I., Bajrovic N., Bakakos P., Bakeyala Mongono S., Balotro-Torres C., Barba S., Barbara C., Barbosa E., Barreto B., Bartra J., Basagana X., Bateman E.D., Battur L., Bedbrook A., Bedolla Barajas M., Beghe B., Bekere A., Bel E., Ben Kheder A., Benson M., Berghea E.-C., Bergmann K.-C., Bernardini R., Bernstein D., Bewick M., Bialek S., Bialoszewski A., Bieber T., Billo N.E., Bilo M.-B., Bindslev-Jensen C., Bjermer L., Bobolea I., Bochenska Marciniak M., Bond C., Boner A., Bonini M., Bonini S., Bosnic-Anticevich S., Bosse I., Botskariova S., Bouchard J., Boulet L.-P., Bourret R., Bousquet P., Braido F., Briggs A., Brightling C.E., Brozek J., Brussino L., Buhl R., Bumbacea R., Buquicchio R., Burguete Cabanas M.-T., Bush A., Busse W.W., Buters J., Caballero-Fonseca F., Calderon M.A., Calvo M., Camargos P., Camuzat T., Canevari F., Cano A., Canonican G.W., Capriles-Hulett A., Caraballo L., Cardona V., Carlsen K.-H., Carmona Pirez J., Caro J., Carr W., Carreiro-Martins P., Carreon-Asuncion F., Carriazo A.-M., CarrionyRibas C., Casale T., Castor M.-A., Castro E., Caviglia A.G., Cecchi L., Cepeda Sarabia A., Chalubinski M., Chandrasekharan R., Chang Y.-S., Chato-Andeza V., Chatzi L., Chatzidaki C., Chavannes N.H., Chaves Loureiro C., Chavez Garcia A.-A., Chelninska M., Chen Y., Cheng L., Chinthrajah S., Chivato T., Chkhartishvili E., Christoff G., Chrystyn H., Chu D.K., Chua A., Chuchalin A., Chung K.F., Ciceran A., Cingi C., Ciprandi G., Cirule I., Coelho A.-C., Compalati E., Constantinidis J., Correia de Sousa J., Costa E.M., Costa D., del Carmen Costa Dominguez M., Coste A., Cottini M., Cox L., Crisci C., Crivellaro M.A., Cruz A.A., Cullen J., Custovic A., Cvetkovski B., D'Amato G., da Silva J., Dahl R., Dahlen S.-E., Daniilidis V., Darjazini Nahhas L., Darsow U., Davies J., de Blay F., De Feo G., De Guia E., De la Torre Navarrete J.-R., De los Santos C., De Manuel Keenoy E., De Vries G., Deleanu D., Demoly P., Denburg J., Devillier P., Didier A., Dimic Janjic S., Dimou M., Dinh-Xuan A.T., Djukanovic R., Do Ceu Texeira M., Dokic D., Dominguez Silva M.G., Douagui H., Douladiris N., Doulaptsi M., Dray G., Dubakiene R., Dupas E., Durham S., Duse M., Dykewicz M., Ebo D., Edelbaher N., Eiwegger T., Eklund P., El-Gamal Y., El-Sayed Z.A., El-Sayed S.S., El-Seify M., Emuzyte R., Enecilla L., Erhola M., Espinoza H., Espinoza Contreras J.G., Farrell J., Fernandez L., Fimbres Jimenez P., Fink Wagner A., Fokkens W.J., Folletti L., Fontaine J.-F., Forastiere F., Fuentes Perez J.M., Gaerlan-Resureccion E., Gaga M., Galvez Romero J.L., Gamkrelidze A., Garcia A., Garcia Cobas C.Y., de la Luz Hortensia Garcia Cruz M., Ortiz V.G., Gayraud J., Gelardi M., Gemicioglu B., Gennimata D., Genova S., Gereda J., Gerth van Wijk R., Giuliano A., Gomez R.-M., Gonzalez Ballester M.-A., Gonzalez Diaz S., Gotua M., Grigoreas C., Grisle I., Guidacci M., Guldemond N., Gutter Z., Guzman A., Halloum R., Halpin D., Hamelmann E., Hammadi S., Harvey R., Heffler E., Heinrich J., Hejjaoui A., Hellquist-Dahl B., Hernandez Velazquez L., Hew M., Hossny E., Howarth P., Hrubisko M., Huerta Villalobos Y.R., Humbert M., Husain S., Hyland M., Ibrahim M., Ilina N., Illario M., Incorvaia C., Infantino A., Irani C., Ispayeva Z., Ivancevich J.C., Jares E.E., Jarvis D., Jassem E., Jenko K., Jimeneracruz Uscanga R.D., Johnston S.L., Joos G., Jost M., Julge K., Jung K.-S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu F., Kapsali J., Kardas P., Karjalainen J., Kasala C.A., Katotomichelakis M., Kavaliukaite L., Bennoor K.S., Keil T., Keith P., Khaitov M., Khaltaev N., Kim Y.-Y., Kirenga B., Kleine-Tebbe J., Klimek L., Ko F.W., Koffi N'Goran B., Kompoti E., Kopac P., Koppelman G., Koren Jeverica A., Koskinen S., Kosnik M., Kostka T., Kostov K.V., Kowalski M.L., Kralimarkova T., Kramer Vrscaj K., Kraxner H., Kreft S., Kritikos V., Kudlay D., Kuitunen M., Kull I., Kuna P., Kupczyk M., Kvedariene V., Kyriakakou M., Lalek N., Landi M., Lane S., Larenas-Linnemann D.E., Lau S., Laune D., Lavrut J., Le L., Lenzenhuber M., Leo G., Lessa M., Levin M., Li J., Lieberman P., Liotta G., Lipworth B., Liu X., Lobo R., Lodrup Carlsen K.C., Lombardi C., Louis R., Loukidis S., Lourenco O., Luna Pech J.A., Madjar B., Maggi E., Magnan A., Mahboub B., Mair A., Maitland van der Zee A.-H., Makela M., Makris M., Malling H.-J., Mandajieva M., Manning P., Manousakis M., Maragoudakis P., Marseglia G., Marshall G., Masjedi M.R., Maspero J.F., Matta Campos J.J., Maurer M., Mavale-Manuel S., Meco C., Melen E., Melioli G., Melo-Gomes E., Meltzer E.O., Menditto E., Menzies-Gow A., Merk H., Michel J.-P., Micheli Y., Miculinic N., Midao L., Mihaltan F., Mikos N., Milanese M., Milenkovic B., Mitsias D., Moalla B., Moda G., Mogica Martinez M.D., Mohammad Y., Moharra F.-M., Moin M., Molimard M., Momas I., Mommers M., Monaco A., Montefort S., Montenegro L.-E., Monti R., Mora D., Morais-Almeida M., Mosges R., Mostafa B.E., Mullol J., Munter L., Muraro A., Murray R., Musarra A., Mustakov T., Naclerio R., Nadeau K.C., Nadif R., Nakonechna A., Namazova-Baranova L., Navarro-Locsin G., Neffen H., Nekam K., Neou A., Nettis E., Neuberger D., Nicod L., Nicola S., Niederberger-Leppin V., Niedoszytko M., Nieto A., Novellino E., Nunes E., Nyembue D., O'Hehir R.E., Odjakova C., Ohta K., Okamoto Y., Okubo K., Oliver B., Onorato G.L., Orru M.P., Ouedraogo S., Ouoba K., Padilla F.-J., Paggiaro P.L., Pagkalos A., Pajno G., Pala G., Palaniappan S., Pali-Scholl I., Palkonen S., Palmer S., Panaitescu Bunu C., Panzner P., Papadopoulos N.G., Papanikolaou V., Papi A., Paralchev B., Paraskevopoulos G., Park H.-S., Passalacqua G., Patella V., Pavord I., Pawankar R., Pedersen S., Peleve S., Pellegino S., Pereira A., Pereira M., Perez T., Perna A., Peroni D., Pfaar O., Pham-Thi N., Pigearias B., Pin I., Piskou K., Pitsios C., Plavec D., Poethig D., Pohl W., Poplas Susic A., Popov T.A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puggioni F., Puig-Domenech E., Puy R., Rabe K., Rabotti S., Raciborski F., Ramos J., Recalcati C., Recto M.T., Reda S.M., Regateiro F.S., Reider N., Reitsma S., Repka-Ramirez S., Ridolo E., Rimmer J., Rivero Yeverino D., Rizzo J.A., Robalo-Cordeiro C., Roberts G., Robles K., Roche N., Rodriguez Gonzalez M., Rodriguez Zagal E., Rolla G., Rolland C., Roller-Wirnsberger R., Roman Rodriguez M., Romano A., Romantowski J., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rossi O., Rottem M., Rouadi P.W., Rovina N., Rozman Sinur I., Ruiz M., Ruiz Segura L.T., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Samitas K., Samolinski B., Sanchez Coronel M.G., Sanchez-Borges M., Sanchez-Lopez J., Sansonna M., Sarafoleanu C., Sarquis Serpa F., Sastre J., Savi E., Savonyte A., Sawaf B., Scadding G.K., Scheire S., Schmid-Grendelmeier P., Schuhl J.F., Schunemann H., Schvalbova M., Schwarze J., Scichilone N., Senna G., Sepulveda C., Serrano E., Shamai S., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E.F., Sisul J.C., Sitkauskiene B., Skrindo I., Soklic Kosak T., Sole D., Sondermann M., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Pinto B.S., Sova M., Soyka M., Specjalski K., Sperl A., Spranger O., Stamataki S., Stefanaki L., Stellato C., Stelmach R., Strandberg T., Stute P., Subramaniam A., Suppli Ulrik C., Sutherland M., Sylvestre S., Syrigou A., Taborda Barata L., Takovska N., Tan R., Tan F., Tan V., Tang I.P., Taniguchi M., Tannert L., Tantilipikorn P., Tattersall J., Tesi F., Thieme U., Thijs C., Thomas M., To T., Todo-Bom A.M., Togias A., Tomazic P.-V., Tomic-Spiric V., Toppila-Salmi S., Torres Jaen M.-J., Toskala E., Triggiani M., Triller N., Triller K., Tsiligianni I., Uberti M., Ulmeanu R., Urbancic J., Urrutia Pereira M., Vachova M., Valdes F., Valenta R., Valentin Rostan M., Valero A., Valiulis A., Vallianatou M., Valovirta E., Van Eerd M., Van Ganse E., van Hage M., Vandenplas O., Vasankari T., Vassileva D., Velasco Munoz C., Ventura M.T., Vera-Munoz C., Viart F., Vicheva D., Vichyanond P., Vidgren P., Viegi G., Vogelmeier C., Von Hertzen L., Vontetsianos T., Vourdas D., Tran Thien Quan V., Wagenmann M., Walker S., Wallace D., De Wang Y., Waserman S., Wehner K., Wickman M., Williams S., Williams D., Wilson N., Wong G., Woo K., Wozniak L., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y.Y., Yassin M., Yawn B., Yiallouros P., Yorgancioglu A., Yoshihara S., Young I., Yusuf O.B., Zaidi A., Zaitoun F., Zalud P., Zar H., Zedda M.T., Zernotti M.E., Zhang L., Zhong N., and Zidarn M.
Subjects: MAPK/ERK pathway, ARIA group, Allergy, [SDV]Life Sciences [q-bio], NF-KAPPA-B, debelost, Review, Pharmacology, Resveratrol, PROTECTS, chemistry.chemical_compound, 0302 clinical medicine, RESPIRATORY SYNDROME CORONAVIRUS, ENDOPLASMIC-RETICULUM STRESS, Medicine and Health Sciences, Immunology and Allergy, Medicine, OXIDATIVE STRESS, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, 2. Zero hunger, 0303 health sciences, RESPIRATORY, INSULIN-RESISTANCE, Muscle cell proliferation, SULFORAPHANE, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SIGNALING PATHWAY, Signal transduction, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, NRF2 ACTIVATORS, MUSCLE-CELL PROLIFERATION, Immunology, 610 Medicine & health, Lung injury, Settore MED/10 - Malattie Dell'Apparato Respiratorio, ACUTE LUNG INJURY, 03 medical and health sciences, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, udc:616.9, odpornost proti inzulinu, SULFORAPHANE PROTECTS, Transcription factor, PI3K/AKT/mTOR pathway, 030304 developmental biology, Science & Technology, business.industry, SARS-CoV-2, food, medicine.disease, chemistry, hranila, SYNDROME CORONAVIRUS, business, hrana, GREEN TEA
Abstract: There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
Published: 2020
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36. Impact du premier mois de confinement Covid 19 sur l’activité chirurgicale carcinologique des services universitaires d’otorhinolaryngologie en Île-de-France

Author: F. Tankéré, André Coste, H. Mirghani, Romain Kania, Ollivier Laccourreye, L. Brugel, B. Barry, Pierre Bonnefont, Bertrand Baujat, Sarah Atallah, Diane Evrard, Service d'ORL et de Chirurgie Cervicofaciale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Oto-Rhino-Laryngologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Gynecology, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), otorhinolaryngology, Covid 19, Article, 3. Good health, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, 030220 oncology & carcinogenesis, Medicine, cancer, Surgery, 030223 otorhinolaryngology, business
Abstract: Resume Objectif Evaluation de l’impact du premier mois de confinement lors de l’epidemie Covid 19 sur l’activite de chirurgie carcinologique des services universitaires d’otorhinolaryngologie en Ile-de-France. Materiel et methodes Etude observationnelle, prospective, multicentrique menee au sein de 6 services universitaires (Paris Centre, Nord, Est et Sorbonne) d’otorhinolaryngologie sur le mois precedant (Groupe A) et suivant (Groupe B) le confinement instaure le 17/03/2020. Objectif principal : evaluer l’impact sur l’activite carcinologique chirurgicale. Objectifs secondaires : evaluer les caracteristiques de la population, les modalites pratiques des interventions, les suites operatoires, l’evolution Covid des patients et des otorhinolaryngologistes et les effets nefastes. Resultats Deux cent vingt-quatre interventions etaient realisees. Une diminution de 10,9 % de l’activite etait notee, sans difference significative entre les services. Les carcinomes epidermoides et la localisation au niveau du larynx, de l’hypopharynx, de l’oropharynx, de la cavite buccale, des fosses nasales et sinus de la face predominaient, avec respectivement 79 % et 75,8 % des interventions, sans difference significative entre les groupes. Les tumeurs classees T3/4 et N2/3 etaient plus frequentes au sein du Groupe B (p = 0,002 et 0,0004). Il n’existait pas de difference significative entre les groupes en termes d’abord chirurgical, de modalites de reconstruction, de suites operatoires et de duree de sejour en soins intensifs ou en reanimation, de tracheotomie, de sonde nasogastrique et d’hospitalisation. Aucun patient n’etait teste positif pour la Covid 19 au sein du Groupe A pour trois au sein du Groupe B, sans effets nefastes. Les otorhinolaryngologistes qui participaient aux interventions ne developpaient pas de symptomes evocateurs d’une infestation par la Covid 19. Conclusion Cette etude souligne que l’epidemie Covid 19 et le confinement n’ont que legerement altere la chaine diagnostique et therapeutique chirurgicale des cancers pris en charge dans les services universitaires ORL d’Ile-de-France, conservant toutes les chances de survie, sans favoriser la diffusion du virus.
Published: 2020
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37. COVID-19 and rhinology, from the consultation room to the operating theatre

Author: L. Le Taillandier De Gabory, André Coste, Cécile Rumeau, Justin Michel, Vincent Couloigner, Benjamin Verillaud, Elie Serrano, François Simon, Neck Surgery, Thomas Radulesco, Jean-François Papon, Patrick Dessi, E. Bequignon, Roger Jankowski, and Sébastien Vergez
Subjects: Rhinology, Operating Rooms, medicine.medical_specialty, 2019-20 coronavirus outbreak, Nasal spray, Infectious Disease Transmission, Patient-to-Professional, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, MEDLINE, Article, Allergic rhinitis, Otolaryngology, 03 medical and health sciences, Endonasal treatment, 0302 clinical medicine, Nasopharynx, Health care, medicine, Corticosteroids, Humans, Medical prescription, Sinus, 030223 otorhinolaryngology, Pandemics, SARS-CoV-2, business.industry, Decision Trees, COVID-19, Endoscopy, medicine.disease, Otorhinolaryngologic Surgical Procedures, Coronavirus, Otorhinolaryngologic Diseases, Otorhinolaryngology, Nasal lavages, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Surgery, Medical emergency, Coronavirus Infections, business, Nasal cavity, Sinonasal polyposis
Abstract: 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.
Published: 2020
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38. Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia

Author: Mathieu Bottier, Aline Tamalet, Jean-François Papon, Annick Clement, Guy Montantin, Marie Legendre, Serge Amselem, Catherine Faucon, André Coste, Nathalie Collot, Florence Dastot, Bruno Copin, Sylvain Blanchon, Marcel Filoche, Estelle Escudier, Bruno Louis, Laboratoire de physique de la matière condensée (LPMC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'ORL [Créteil], Service d’ORL et de chirurgie cervico-faciale [CHU Le Kremlin-Bicêtre], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
Subjects: Adult, Male, 0301 basic medicine, Candidate gene, Axoneme, Adolescent, Genotype, Video microscopy, Biology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Humans, Abnormal ciliary motility, Cilia, [PHYS.COND.CM-DS-NN]Physics [physics]/Condensed Matter [cond-mat]/Disordered Systems and Neural Networks [cond-mat.dis-nn], Child, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Primary ciliary dyskinesia, Microscopy, Video, Cilium, Infant, Newborn, Genetic disorder, High-Throughput Nucleotide Sequencing, Infant, Axonemal Dyneins, Middle Aged, medicine.disease, Molecular biology, Phenotype, DNA-Binding Proteins, Cytoskeletal Proteins, 030104 developmental biology, 030228 respiratory system, Child, Preschool, Mutation, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Female, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], Ciliary Motility Disorders
Abstract: BackgroundPrimary 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.MethodsWe 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).ResultsSixty-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.ConclusionQuantitative 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.
Published: 2020
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39. Impact of the first month of Covid-19 lockdown on oncologic surgical activity in the Ile de France region university hospital otorhinolaryngology departments

Author: H. Mirghani, Bertrand Baujat, L. Brugel, Diane Evrard, F. Tankéré, Ollivier Laccourreye, Romain Kania, B. Barry, S. Atallah, Pierre Bonnefont, André Coste, CCSD, Accord Elsevier, Service ORL et Chirurgie Cervico-Faciale [Hôpital Européen], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oto-Rhino-Laryngologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Intercommunal de Créteil (CHIC), Oto-Rhino-Laryngologie Chirurgie cervico-faciale [CHU Tenon], CHU Tenon [AP-HP], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’ORL et de chirurgie cervico-faciale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, Larynx, medicine.medical_specialty, Time Factors, Adolescent, Otorhinolaryngologic Surgical Procedures, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Pneumonia, Viral, Population, Article, Hospitals, University, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Tracheotomy, Intensive care, Humans, Medicine, Prospective Studies, 030223 otorhinolaryngology, education, Prospective cohort study, Adverse effect, Pandemics, Aged, Cancer, Aged, 80 and over, education.field_of_study, business.industry, General surgery, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Otorhinolaryngologic Neoplasms, medicine.anatomical_structure, Otorhinolaryngology, 030220 oncology & carcinogenesis, Quarantine, Female, Surgery, France, Coronavirus Infections, business, Covid-19
Abstract: eAbstract Objective To evaluate the impact of the first month of lockdown related to the Covid-19 epidemic on the oncologic surgical activity in the Ile de France region university hospital otorhinolaryngology departments. Material and methods A multicenter prospective observational assessment was conducted in 6 university hospital otorhinolaryngology departments (Paris Centre, Nord, Est and Sorbonne) during the 1-month periods before (Month A) and after (Month B) lockdown on March 17, 2020. The main goal was to evaluate lockdown impact on oncologic surgical activity in the departments. Secondary goals were to report population characteristics, surgery conditions, postoperative course, progression of Covid status in patients and surgeons, and adverse events. Results 224 procedures were performed. There was 10.9% reduction in overall activity, without significant difference between departments. Squamous cell carcinoma and larynx, hypopharynx, oropharynx, oral cavity and nasal cavity and sinus locations were predominant, at 79% and 75.8% of cases respectively, with no significant differences between months. T3/4 and N2/3 tumors were more frequent in Month B (P = .002 and .0004). There was no significant difference between months regarding surgical approach, type of reconstruction, postoperative course, tracheotomy and nasogastric feeding-tube time, intensive care stay or hospital stay. None of the Month A patients were Covid-19-positive, versus 3 in Month B, without adverse events. None of the otorhinolaryngologists involved in the procedures developed symptoms suggesting Covid-19 infestation. Conclusion The present study underscored the limited impact of the Covid-19 epidemic and lockdown on surgical diagnosis and cancer surgery in the Ile de France university otorhinolaryngology departments, maintaining chances for optimal survival without spreading the virus.
Published: 2020
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40. Multicenter assessment of exclusive endoscopic endonasal approach for the treatment of 53 olfactory neuroblastomas

Author: Héloïse de Kermadec, P.-L. Bastier, Cécile Rumeau, Philippe Herman, Olivier Choussy, Louis Crampette, André Coste, Sébastien Vergez, Justin Michel, Elie Serrano, Christian Righini, Anjarasoa Tsaranazy, Emile Reyt, Benjamin Verillaud, Ludovic de Gabory, V. Trevillot, Geoffrey Mortuaire, Roger Jankowski, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Lariboisière, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'ORL et de chirurgie cervicale, CHU Grenoble, Service d'ORL, chirurgie cervico-faciale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'ORL, Hôpital Gui de Chauliac (CHRU de Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital de Rangueil, CHU Toulouse [Toulouse], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Adult, Male, Natural Orifice Endoscopic Surgery, medicine.medical_specialty, medicine.medical_treatment, Nose Neoplasms, Esthesioneuroblastoma, Olfactory, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, olfactory cleft, Disease-Free Survival, endoscopic surgery, neuroblastoma, 03 medical and health sciences, 0302 clinical medicine, Neuroblastoma, Positive Margins, sinus cancer, Humans, Medicine, Pathological, Craniotomy, Aged, Retrospective Studies, Periorbita, Olfactory Neuroblastoma, business.industry, Head and neck cancer, Middle Aged, medicine.disease, 3. Good health, Surgery, Survival Rate, Treatment Outcome, Otorhinolaryngology, 030220 oncology & carcinogenesis, Female, Nasal Cavity, business, Meningitis, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND:Given the particularities of olfactory neuroblastoma (ONB) and the lack of studies on the subject, a multicenter collaborative study was conducted to assess treatment strategy.METHODS:Fifty-three patients with ONB were included from the French Rare Head and Neck Cancer Expert Network (REFCOR) database: 16T1, 8T2, 19T3, and 10T4. All cases were treated endoscopically with skull base removal and repair in 26 cases (49%) and without external craniotomy.RESULTS:The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 87% and 71%, respectively, with mean follow-up of 45.4 ± 26.5 months. The complication rate was 18.8% with 4 cases of meningitis. Pathological analysis showed positive margins in 26.8%, notably on the dura-mater and periorbita, without impairment of OS or DFS. Forty-eight patients received adjuvant radiotherapy on T ± N. Ten patients had a recurrence (18.9%). Six patients died of their disease. Prophylactic neck irradiation seemed to reduce the recurrence rate.CONCLUSION:Exclusively endoscopic treatment proved efficient and reliable in a large controlled series.
Published: 2018
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41. Exophytic sinonasal papillomas and nasal florid papillomatosis: A retrospective study

Author: Romain Glâtre, L. Brugel, Virginie Prulière-Escabasse, André Coste, Heloïse De Kermadec, Anne Gauthier, Emilie Bequignon, Cécile Badoual, Claire Parra, and Issam Abd Alsamad
Subjects: Adult, Male, medicine.medical_specialty, Nasal tumor, Nose Neoplasms, Papillomatosis, Risk Assessment, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Human papillomavirus, 030223 otorhinolaryngology, Nasal Septum, Retrospective Studies, Papilloma, Inverted, business.industry, virus diseases, Endoscopy, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Dermatology, Survival Rate, body regions, Treatment Outcome, Otorhinolaryngology, Dysplasia, 030220 oncology & carcinogenesis, Papilloma, Female, Neoplasm Recurrence, Local, medicine.symptom, Tomography, X-Ray Computed, business, Paranasal Sinus Neoplasms
Abstract: Background Sinonasal exophytic papillomas are rare. The multifocal form, florid papillomatosis, has not been yet described in literature. We report on the clinical features and the management of the different forms of exophytic papilloma. Methods A retrospective study was conducted that included all patients with exophytic papilloma treated in our center over the past 12 years. We recorded clinical presentation, treatments, recurrences, pathology (p16 expression and human papillomavirus [HPV] status). Results We included 13 patients with a mean follow-up of 5 years. The main location of exophytic papilloma was the anterior part of the septum. Lesions were multifocal in 3 patients corresponding to florid papillomatosis. The main treatment was surgery. Cases of HPV-11 or HPV-6 were present in all forms of exophytic papilloma (dysplasia in 4 cases). Late recurrences occurred in 3 patients (2 patients with florid papillomatosis) over a period of 3 years. Conclusion Exophytic papilloma has 2 clinical presentations: localized and diffuse. Patients with florid papillomatosis should be monitored closely as recurrence seems to be frequent.
Published: 2018
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42. Nasal obstruction and dizziness are not always purely benign symptoms

Author: S. Bartier, Emilie Bequignon, I. Delacroix, and André Coste
Subjects: medicine.medical_specialty, Text mining, Otorhinolaryngology, business.industry, Vertigo, Humans, Medicine, Surgery, Nasal Obstruction, business, Dizziness, Dermatology
Published: 2021
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43. L’immunotherapie antiallergenique dans la rhinite allergique

Author: Justin Michel, Louis Crampette, J.-F. Papon, André Coste, D. Ebbo, Roger Jankowski, Olivier Malard, Elie Serrano, and Geoffrey Mortuaire
Subjects: 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030228 respiratory system, Otorhinolaryngology, Surgery
Abstract: Resume La rhinite allergique (RA) est une pathologie frequente dont la severite ou le mauvais controle peut aboutir a une alteration significative de la qualite de vie des patients. L’immunotherapie antiallergenique (ITA) constitue a l’heure actuelle le seul traitement etiologique susceptible de modifier l’histoire naturelle de la maladie allergique. Bien connue des allergologues, cette option therapeutique est encore insuffisamment maitrisee par les ORL. Cette mise au point basee sur les meta-analyses et les essais les plus recents souligne l’efficacite de l’ITA sur l’amelioration des symptomes de la RA et sur la reduction de la consommation des traitements medicaux (corticoides, antihistaminiques). L’ITA serait aussi susceptible de reduire le risque d’apparition d’un asthme et de nouvelles sensibilisations lorsqu’elle est introduite suffisamment precocement. Les analyses immunobiologiques montrent bien une modification du profil inflammatoire apres ITA en faveur d’une immunotolerance impliquant les lymphocytes T regulateurs et la production d’IgG. La voie sublinguale en gouttes apporte des resultats comparables a ceux de la voie sous-cutanee tout en proposant une utilisation plus simple reduisant le risque anaphylactique. Une standardisation des protocoles d’etude en termes de mesure de l’effet therapeutique et de gradation des effets indesirables est neanmoins necessaire pour ameliorer les etudes comparatives. Les formes sublinguales en comprimes plus recemment introduites constituent une reelle opportunite pour ouvrir le champ de l’ITA aux ORL dans la RA pollinique et prochainement la RA aux acariens.
Published: 2017
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44. Nasal compliance measurement for diagnosis of idiopathic non-allergic rhinitis: A prospective case-controlled study of 63 patients

Author: Christian Larger, J.-F. Papon, André Coste, Daniel Isabey, Bruno Louis, M. Devars du Mayne, Françoise Zerah-Lancner, and E. Bequignon
Subjects: Adult, Male, Allergy, medicine.medical_specialty, Non-allergic rhinitis, Mucous membrane of nose, Sensitivity and Specificity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Acoustic rhinometry, Nonallergic rhinitis, otorhinolaryngologic diseases, medicine, Humans, Prospective Studies, 030223 otorhinolaryngology, Prospective cohort study, Rhinitis, medicine.diagnostic_test, business.industry, Airway Resistance, Case-control study, Middle Aged, medicine.disease, Dermatology, Nasal Mucosa, 030228 respiratory system, Otorhinolaryngology, Case-Control Studies, Anesthesia, Female, Rhinomanometry, business, Compliance
Abstract: • Idiopathic non allergic rhinitis (i-NAR) is a frequent cause of non-allergic rhinitis and associates nonspecific symptoms. There is no simple direct procedure to establish i-NAR diagnosis. • Diagnosis of i-NAR is currently based on an absence of a definite causal factor and a lack of evidence for IgE-mediated allergy by skin prick tests and allergen-specific serum IgE • Measurement of nasal compliance with acoustic rhinometry evaluates the vasomotricity-related deformability of the nasal mucosa. It has been already suggested that nasal compliance could be abnormal in i-NAR. • In this prospective case-controlled study of 42 patients with chronic rhinitis and 21 control patients, after topical decongestion, compliances in i-NAR group were significantly increased compared to allergic rhinitis (AR) and Control group (n=21) (p
Published: 2017
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45. Unilateral recurrent laryngeal nerve palsy post-thyroidectomy: Looking for hyperventilation syndrome

Author: Laurent Boyer, Françoise Zerah-Lancner, Jean-François Papon, André Coste, E. Bequignon, H. Dang, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cytosquelette et développement (CD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital A. Chenevier [Créteil], Hôpital Henri Mondor, Centre Hospitalier Intercommunal de Créteil (CHIC), Biomécanique & Appareil Respiratoire (BAR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and CCSD, Accord Elsevier
Subjects: Adult, Male, Hyperventilation syndrome, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Unilateral vocal fold paralysis, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Swallowing, Hyperventilation, medicine, Recurrent laryngeal nerve, Humans, Prospective Studies, 030223 otorhinolaryngology, Aged, Palsy, Lung, Hypocapnia, Recurrent Laryngeal Nerve palsy, business.industry, Thyroidectomy, Syndrome, Middle Aged, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Dyspnea, medicine.anatomical_structure, Otorhinolaryngology, 030220 oncology & carcinogenesis, Anesthesia, Arterial blood, Female, Surgery, Blood Gas Analysis, medicine.symptom, business, Vocal Cord Paralysis, Alkalosis, Respiratory
Abstract: International audience; Aims: Unilateral Recurrent Laryngeal Nerve (RLN) palsy is responsible for dysphonia and difficulties in swallowing. The role of unilateral RLN palsy on dyspnea is not fully elucidated. Our hypothesis is that air leak could be responsible for development of hyperventilation syndrome (HVS).Objective: The objective of this study was to determine in patients with unilateral RLN palsy if dyspnea could be associated with HVS.Material and methods: Over a 12-month period, all patients with permanent unilateral RLN palsy after thyroidectomy complaining from the onset of unexplained dyspnea were tested. Measurement of Nijmegen score, an hyperventilation test, an arterial blood gas, lung function and cardiac tests were performed. The diagnosis of HVS was defined if at least two criteria were present among: Nijmegen score>23; reproduction of at least 2 usual symptoms during hyperventilation test; an expirated pressure of CO2 (EpCO2)
Published: 2019
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46. « Paralysie récurrentielle unilatérale après thyroïdectomie : savoir rechercher un syndrome d’hyperventilation »

Author: Laurent Boyer, F. Zerah-Lancner, André Coste, J.-F. Papon, H. Dang, E. Bequignon, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cytosquelette et développement (CD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital A. Chenevier [Créteil], CHI Créteil, Hôpital Henri Mondor, Biomécanique & Appareil Respiratoire (BAR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and CCSD, Accord Elsevier
Subjects: 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, 030228 respiratory system, Otorhinolaryngology, [SPI] Engineering Sciences [physics], Surgery, 030223 otorhinolaryngology, 3. Good health
Abstract: International audience; La paralysie unilatérale du nerf récurrent peut être responsable d’une dysphonie et de troubles de la déglutition. La physiopathologie de l’apparition d’une dyspnée induite par une paralysie récurrentielle unilatérale n’est pas complètement élucidée. Notre hypothèse est que la fuite d’air au niveau glottique pourrait être responsable du développement d’un syndrome d’hyperventilation (SHV).ObjectifL’objectif de cette étude était de déterminer, chez les patients atteints de paralysie récurrentielle unilatérale, si la dyspnée pouvait être associée au SHV.Matériel et méthodesSur une période de 12 mois, tous les patients atteints de paralysie récurrentielle unilatérale permanente (> 6 mois) après thyroïdectomie se plaignant de l’apparition d’une dyspnée inexpliquée ont été explorés. Les tests suivants ont été réalisés : score de Nijmegen, test d’hyperventilation provoquée, gazométrie artérielle, épreuves fonctionnelles respiratoires et tests cardiaques. Le diagnostic de SHV a été posé si au moins deux critères étaient présents parmi les suivants : score de Nijmegen > 23 ; reproduction d’au moins 2 symptômes habituels lors du test d’hyperventilation ; pression télé-expiratoire en CO2 (PetCO2) < 30 mmHg ou < 90 % de la PetCO2 initiale après une période de récupération de 5 min à la suite d’une hyperventilation volontaire de 3 min.RésultatsDix patients sur 366 opérés d’une thyroïdectomie pour une maladie bénigne présentaient une paralysie récurrentielle unilatérale permanente et une dyspnée. Parmi les 10 patients inclus, chez 8 le diagnostic de SHV a été retenu lors du test d’hyperventilation provoquée sans dysfonctionnement cardiaque/pulmonaire.ConclusionEn résumé, cette étude est en faveur de l’implication du SHV dans la dyspnée associée à la paralysie récurrentielle unilatérale.
Published: 2019
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47. Follow-Up and Management of Chronic Rhinosinusitis in Adults with Primary Ciliary Dyskinesia: Review and Experience of Our Reference Centers

Author: Virginie Escabasse, Laurence Bassinet, Françoise Zerah-Lancner, Isabelle Honoré, Jean-François Papon, Marie Devars du Mayne, Bruno Crestani, Estelle Escudier, Emilie Bequignon, Laurence Dupuy, Marie Legendre, André Coste, Bernard Maitre, Centre Hospitalier Intercommunal de Créteil (CHIC), CHU Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de physiologie, explorations fonctionnelles [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Pneumologie [CHI Créteil], CHI Créteil, Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Hospitalo-Universitaire Fibrosis, Inflammation, Remodeling in cardiovascular, respiratory and renal diseases (Paris), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Service de Génétique et d'Embryologie Médicales [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], and Physiopathologie des maladies génétiques d'expression pédiatrique
Subjects: medicine.medical_specialty, Meatus, Chronic rhinosinusitis, lcsh:Medicine, primary ciliary dyskinesia, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, otorhinolaryngologic diseases, Medicine, Sampling (medicine), 030223 otorhinolaryngology, Sinus (anatomy), Primary ciliary dyskinesia, business.industry, chronic rhinosinusitis, lcsh:R, Retrospective cohort study, General Medicine, medicine.disease, Work-up, 3. Good health, Surgery, Pseudomonas aeruginosa, medicine.anatomical_structure, 030228 respiratory system, Sputum, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business
Abstract: Chronic rhinosinusitis is the foremost manifestation in adult patients with primary ciliary dyskinesia (PCD). We present a retrospective series of 41 adult patients with a confirmed diagnosis of PCD followed in our reference centers. As part of the diagnostic work up in our centers, sinus computed tomography scans (CTs) are systematically performed. All patients also undergo a sampling of purulent secretions sampled from the middle meatus under endoscopic view for bacteriological analysis. In our series, CT opacities were consistent in all the patients, as well as mainly partial and located in ethmoid cells (100% of patients) and in maxillary sinuses (85.4% of patients), and stayed stable over time. In the 31 patients who had purulent secretions, bacteriological culture showed at least one bacterium in 83.9% (n = 26). There was no significant difference in positive cultures for Pseudomonas aeruginosa in patients &gt, 40 years old versus those &lt, 40 (p = 0.17, Fisher). Surgical management was performed in only 19% of patients in order to improve sinonasal mechanical drainage. Our data support the hypothesis that the sinuses can be considered as a bacterial reservoir. From this retrospective study, we have introduced several changes into our routine clinical practice in our reference centers. Based on our analyses, medical and surgical treatments benefit from incorporating bacteriological information and sinonasal symptoms much more than CT scan evaluation alone. All patients now undergo systematically an annual simultaneous bacteriological sampling of the middle meatus and sputum to follow the relationship between ENT and lung disease and to help to antibiotic therapy strategy.
Published: 2019
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48. Diagnostic différentiel et pathologies mixtes

Author: P.-L. Bastier, V. Prulière-Escabasse, Cécile Rumeau, P. Herman, D. Ebbo, Emilie Bequignon, V. Patron, Geoffrey Mortuaire, Laurent Gilain, B. Verillaud, N. Benoît-Oker, and André Coste
Published: 2019
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49. FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy?

Author: Estelle Escudier, Bruno Louis, André Coste, Daniel Isabey, Lucie Thomas, Christelle Angely, Mathieu Bottier, Jean-François Papon, Christine Dhommée, Emilie Bequignon, Valérie Gouilleux-Gruart, Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Sorbonne Université (SU), Service d’ORL et de chirurgie cervico-faciale [CHU Le Kremlin-Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Tours, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: 0301 basic medicine, Receptors, Fc, lcsh:Chemistry, 0302 clinical medicine, Drug Delivery Systems, Nasal polyps, lcsh:QH301-705.5, Spectroscopy, neonatal Fc receptor, Chemistry, Antibodies, Monoclonal, Cell Differentiation, General Medicine, respiratory system, 3. Good health, Computer Science Applications, Cell biology, medicine.anatomical_structure, Transcytosis, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], monoclonal antibodies, medicine.drug_class, transcytosis, Nose, Monoclonal antibody, chronic rhinosinusitis with nasal polyps, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Neonatal Fc receptor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, otorhinolaryngologic diseases, Humans, RNA, Messenger, Physical and Theoretical Chemistry, Molecular Biology, Organic Chemistry, Histocompatibility Antigens Class I, Epithelial Cells, human nasal epithelial cells, medicine.disease, Mucus, Epithelium, 030104 developmental biology, HEK293 Cells, lcsh:Biology (General), lcsh:QD1-999, Respiratory epithelium, Nasal administration
Abstract: Monoclonal antibodies (mAbs) are promising therapies to treat airway chronic inflammatory disease (asthma or nasal polyps). To date, no study has specifically assessed, in vitro, the potential function of neonatal Fc receptor (FcRn) in IgG transcytosis through the human nasal airway epithelium. The objective of this study was to report the in vitro expression and function of FcRn in nasal human epithelium. FcRn expression was studied in an air&ndash, liquid interface (ALI) primary culture model of human nasal epithelial cells (HNEC) from polyps. FcRn expression was characterized by quantitative RT-PCR, western blot, and immunolabeling. The ability of HNECs to support mAb transcytosis via FcRn was assessed by transcytosis assay. This study demonstrates the expression of FcRn mRNA and protein in HNEC. We report a high expression of FcRn in the cytosol of ciliated, mucus, and basal cells by immunohistochemistry with a higher level of FcRn proteins in differentiated HNEC. We also proved in vitro transepithelial delivery of an IgG1 therapeutic mAb with a dose&ndash, response curve. This is the first time that FcRn expression and mAb transcytosis has been shown in a model of human nasal respiratory epithelium in vitro. This study is a prerequisite for FcRn-dependent nasal administration of mAbs.
Published: 2019
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50. Liste des auteurs

Author: Louis Crampette, André Coste, Alain Didier, Roger Jankowski, Olivier Malard, Elie Serrano, Dominique Allard, Flore Amat, Pierre-Louis Bastier, Natalie Benoît-Oker, Émilie Béquignon, Frédéric de Blay, Guillaume de Bonnecaze, Pascal Demoly, Patrick Dessi, David Ebbo, Valentin Favier, Ludovic de Gabory, Laurent Gilain, Stéphane Guez, Laurent Guilleminault, Philippe Herman, Cyrille Hoarau, Sayon Kourouma, Nicolas Leboulanger, Antoine Magnan, Christophe Marcot, Valérie Mercier, Justin Michel, Geoffrey Mortuaire, Jean-François Papon, null Vincent Patron, null Virginie Prulière-Escabasse, Thomas Radulesco, Cécile Rumeau, Alain Thillay, Émilie Uhlrich, and Benjamin Verillaud
Published: 2019
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