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1. Epidemiology of interstitial lung disease in systemic lupus erythematosus in France: A nation-wide population-based study over 10 years

Author: Arthur Mageau, Raphaël Borie, Bruno Crestani, Jean‐François Timsit, Thomas Papo, Karim Sacre, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Service de Pneumologie A [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Service de réanimation médicale et infectieuse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), Agence Nationale de la Recherche, Grant/Award Number: ANR-19-CE17- 0029, Fondation pour la Recherche Médicale, Grant/Award Number: FDM202106013488, and ANR-19-CE17-0029,BALUMET,Basophiles dans le Lupus: Mécanismes et Thérapie(2019)
Subjects: interstitial lung disease, Pulmonary and Respiratory Medicine, Scleroderma, Systemic, [SDV]Life Sciences [q-bio], Incidence, respiratory system, behavioral disciplines and activities, respiratory tract diseases, body regions, systemic lupus erythematosus, death, Humans, Lupus Erythematosus, Systemic, epidemiology, skin and connective tissue diseases, Lung Diseases, Interstitial, Proportional Hazards Models
Abstract: International audience; Background and objective: Data regarding interstitial lung disease (ILD) in the setting of systemic lupus erythematosus (SLE) are limited. We used a nationwide database to determine the incidence and the prevalence of ILD in SLE. Methods: Characteristics of all SLE inpatients admitted between 2011 and 2012 in France were analysed through the French medico-administrative database. Features associated with the presence of ILD were studied. Cox hazard model was used to measure the impact of ILD on survival from the first stay to 2020. The incidence of ILD in SLE was estimated by analysing the onset of ILD from 2013 to 2020 in SLE patients who had no evidence of ILD in 2013. Results: Between 2011 and 2012, 10,460 SLE patients had at least one hospital stay and could be traced until 2020. Among them, 134 (1.2%) had an ILD diagnosed at baseline. The frequency of ILD in SLE was higher in patients who had an associated autoimmune disease such as Sjögren's syndrome or systemic sclerosis (29.9% vs. 5.9%, p < 0.0001). ILD was associated with an increased risk of death in SLE in the multivariable analysis (hazard ratio [95% CI] 1.992 [1.420–2.794]; p < 0.0001). Among the 31,029 SLE patients with no evidence of ILD at baseline, ILD occurred in 795 (2.6%) between 2013 and 2020. The incidence rate of ILD in SLE was 10.26 for 1000 patient-years [95% CI: 10.24–10.28]. Conclusion: In SLE, ILD is exceedingly rare, often associated with another systemic autoimmune disorder and appears as a major risk factor for death. © 2022 Asian Pacific Society of Respirology.
Published: 2022
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2. Facteurs environnementaux favorisant le développement d’un asthme

Author: C. Neukirch, Valérie Siroux, Raphaëlle Varraso, Bénédicte Leynaert, Nicole Le Moual, Siroux, Valérie, 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), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fibrose Inflammation Remodelage [Hôpitaux Universitaires Paris Nord Val de Seine] (DHU FIRE ), Hôpitaux Universitaires Paris Nord Val de Seine, Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: MESH: Allergens, MESH: Humans, MESH: Asthma, business.industry, MESH: Environmental Exposure, General Medicine, 010501 environmental sciences, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 01 natural sciences, respiratory tract diseases, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, immune system diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Risk Factors, 13. Climate action, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Medicine, MESH: Animals, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Air Pollution, Indoor, business, Humanities, 0105 earth and related environmental sciences
Abstract: Points essentiels La prevalence de l’asthme a augmente de facon tres marquee depuis le debut des annees 1970, et seules des modifications de l’exposition a certains facteurs d’environnement, indissociables des modifications du mode de vie, peuvent expliquer une augmentation aussi rapide. L’exposition aux allergenes est un facteur de risque de sensibilisation allergique et la sensibilisation allergique un facteur de risque de l’asthme allergique. Toutefois, en dehors de l’exposition aux moisissures vis-a-vis de l’asthme de l’enfant, il est difficile d’etablir des liens de causalite entre l’exposition aux differents allergenes et le developpement de l’asthme. Un nouveau defi pour la recherche est d’analyser la multitude de donnees issues de la caracterisation metagenomique du microbiome environnemental et humain, pour comprendre le role des interactions entre virus, bacteries et allergenes dans le developpement de l’asthme. Il est admis que l’exposition prenatale et postnatale a la pollution de l’air et au tabagisme de la mere augmentent le risque de developper un asthme chez l’enfant. Chez l’adulte, les donnees sont plus rares et les resultats restent controverses quant au role de ces expositions sur l’incidence de l’asthme. Des recherches doivent etre developpees sur le role de l’exposition aux phenols, phtalates et composes perfluores, largement repandus dans notre environnement, et qui pourraient etre associes a l’asthme, notamment chez l’enfant. L’utilisation frequente des produits de nettoyage pour le menage a domicile, notamment sous forme de sprays ; — pratique tres repandue dans la population — est un facteur de risque du developpement de l’asthme de l’adulte, et peut etre aussi pour l’asthme de l’enfant expose a domicile. Les substances chimiques en cause restent mal connues. L’asthme professionnel est un phenotype specifique majeur de l’asthme de l’adulte. L’exposition professionnelle aux produits de nettoyage pourrait etre impliquee. Des relations ont ete montrees entre l’alimentation pendant la grossesse ou dans l’enfance et le risque de developper un asthme chez l’enfant, mais les donnees chez l’adulte sont insuffisantes. Au-dela des facteurs genetiques, la composition corporelle est influencee par les choix alimentaires et par le niveau d’activite physique. Des recherches doivent etre developpees pour clarifier le role des interrelations complexes entre ces facteurs nutritionnels dans le developpement de l’asthme. Le nouveau defi pour la recherche est de decrypter, par une approche holistique, le role de l’ensemble des facteurs d’environnement auxquels l’individu est expose depuis sa conception (« exposome ») dans le developpement de l’asthme.
Published: 2019
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3. Low income and outcome in idiopathic pulmonary fibrosis: An association to uncover

Author: Lucile Sesé, Julien Caliez, Isabella Annesi-Maesano, Vincent Cottin, Giancarlo Pesce, Morgane Didier, Zohra Carton, Dominique Israel-Biet, Bruno Crestani, Stéphanie Guillot Dudoret, Jacques Cadranel, Benoit Wallaert, Abdellatif Tazi, Bernard Maître, Grégoire Prévot, Sylvain Marchand-Adam, Sandrine Hirschi, Sandra Dury, Violaine Giraud, Anne Gondouin, Philippe Bonniaud, Julie Traclet, Karine Juvin, Raphael Borie, Jean François Bernaudin, Dominique Valeyre, Catherine Cavalin, Hilario Nunes, Diane Bouvry, Pierre Yves Brillet, Philippe Camus, Juliette Chabrol, Jean François Cordier, Christophe Cracco, Philippe Delaval, Boris Duchemann, Sevrine Feuillet, Olivia Freynet, Frédéric Gagnadoux, Patrick Germaud, Louise Gindre, André Guetta, Patrick Haussman, Stephane Jouneau, Marianne Kambouchner, Chahera Khouatra, Jacques Lacronique, Anita Molard, Clément Picard, Carole Planes, Paul Andrés Rosental, Olivier Sanchez, Thomas Similowski, Luc Thiberville, Yurdagül Uzuhnan, Service de pneumologie [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Pneumologie, soins intensifs (Pneumo - HEGP), 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 de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie et Immuno-Allergologie [CHU LIlle], Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), 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), 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 pneumologie [Toulouse], CHU Toulouse [Toulouse], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies respiratoires [CHU de Dijon], Service de Pneumologie Soins Intensifs, Appareillage Respiratoire [CHU de Dijon], Institut de Recherche Interdisciplinaire en Sciences Sociales (IRISSO), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Pulmonary and Respiratory Medicine, Low income, medicine.medical_specialty, Prognostic factor, Vital Capacity, Air pollution, Idiopathic pulmonary fibrosis, Disease-Free Survival, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Socioeconomic status, Biosimilar Pharmaceuticals, Poverty, Proportional Hazards Models, business.industry, 1. No poverty, Environmental Exposure, Occupational exposure, medicine.disease, Prognosis, Annual income, 030228 respiratory system, Income, Particulate Matter, France, business
Abstract: International audience; BackgroundLow income, a known prognostic indicator of various chronic respiratory diseases, has not been properly studied in idiopathic pulmonary fibrosis (IPF). We hypothesize that a low income has an adverse prognostic impact on IPF.MethodsPatients were selected from the French national prospective cohort COFI. Patients’ income was assessed through the median city-level income provided by the French National Institute of Statistics and Economic Studies according to their residential address. Patients were classified in two groups as “low income” vs. “higher income” depending on whether their annual income was estimated to be < or ≥18 170 €/year (the first quartile of the income distribution in the study population). The survival and progression-free survival (PFS) of the groups were compared by a log-rank test and a Cox model in multivariate analysis.Results200 patients were included. The average follow-up was 33.8 ± 22.7 months. Patients in the low income group were significantly more likely to be of non-European origin (p < 0.006), and to have at least one occupational exposure (p < 0.0001), and they tended to have a higher cumulative exposure to fine particles PM2.5 (p = 0.057). After adjusting for age, gender, forced vital capacity at inclusion, geographical origin, and occupational exposure having a low-income level was a factor associated with a worse PFS (HR: 1.81; CI95%: 1.24–2.62, p = 0.001) and overall survival (HR: 1.49; CI95%: 1.0006–2.23, p = 0.049).ConclusionsLow income appears to be a prognostic factor in IPF. IPF patients with low incomes may also be exposed more frequently to occupational exposures.
Published: 2021
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4. Mepolizumab in a population with severe eosinophilic asthma and corticosteroid dependence: results from a French early access programme

Author: Céline Pribil, Camille Taillé, Alain Didier, Alina Gruber, S. Bouée, Christophe Pison, Gilles Garcia, Marc Humbert, Pascal Chanez, Gilles Devouassoux, Arnaud Bourdin, Jérémy Charriot, Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de médecine aiguë spécialisée, CHU Grenoble-Hôpital Michallon, Service de pneumologie [Toulouse], CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire d'Epidémiologie [Bourg La Reine], Cemka-eval [Bourg La Reine], Laboratoire GlaxoSmithKline [ Marly-le-Roi], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GlaxoSmithKline 207943 HO-17-18317, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Allergy, Population, Antibodies, Monoclonal, Humanized, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, Internal medicine, medicine, Humans, Anti-Asthmatic Agents, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, education, Retrospective Studies, education.field_of_study, business.industry, Medical record, Retrospective cohort study, Original Articles, Emergency department, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Middle Aged, medicine.disease, Asthma, 3. Good health, Clinical trial, 030228 respiratory system, Female, Observational study, France, business, Mepolizumab, medicine.drug
Abstract: Background Mepolizumab was available in France as part of an early access programme for patients with severe eosinophilic asthma (nominative autorisation temporaire d'utilisation [temporary use authorisation] (nATU)) before its commercialisation. This study aimed to characterise patients who received mepolizumab in the nATU. Methods This retrospective, observational study analysed data from the hospital medical records of patients up to 24 months after treatment initiation. Study objectives were to describe patient baseline characteristics, the evolution of disease severity and treatment modifications during follow-up; safety was also investigated. Findings Overall, 146 patients who received ≥1 dose of mepolizumab were included. At inclusion, patients had a mean age of 58.2 years with a mean severe asthma duration of 13.4 years, and 37.0% had respiratory allergies. Patients experienced, on average, 5.8 exacerbations per patient per year at baseline, 0.6 and 0.5 of which required hospitalisation and emergency department visits, respectively. These values improved to 0.6, 0.1 and 0.1 exacerbations per patient per year, respectively, at 24 months of follow-up. Most patients (92.8%) were using oral corticosteroids at baseline, compared with 34.7% by 24 months of follow-up. Moreover, mean blood eosinophil counts improved from 722 cells·µL−1 at baseline to 92 cells·µL−1 at 24 months of follow-up; lung function and asthma control followed a similar trend. Interpretation Results confirm findings from clinical trials, demonstrating that mepolizumab is associated with important improvements in several clinically meaningful outcomes and has a favourable safety profile in a population with severe eosinophilic asthma, outside of the controlled environment of a clinical trial., Mepolizumab is associated with improvements in several clinically meaningful outcomes and demonstrates a favourable safety profile in a population with severe eosinophilic asthma, outside of the controlled environment of a clinical trial https://bit.ly/3bckeQ3
Published: 2020
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5. How can we minimise the use of regular oral corticosteroids in asthma?

Author: Pierre Val, Y. Martinat, Philippe Chanson, Ian M. Adcock, Pascal Chanez, Cécile Chenivesse, Antoine Deschildre, Arnaud Bourdin, Antoine Magnan, Gilles Devouassoux, Nicolas Roche, Camille Taillé, Alain Didier, Thierry Perez, Philippe Bonniaud, Gilles Garcia, Patrick Berger, Jacques de Blic, Philippe Devillier, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Imperial College London, Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies respiratoires [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Physiologie et physiopathologie endocriniennes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Pneumologie, Immunologie et Allergologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille 2 - Faculté de Médecine, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie, Hôpital Foch [Suresnes], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de pneumologie et allergologie pédiatrique [CHU Toulouse], CHU Toulouse [Toulouse], Hôpital Bicêtre, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Cochin [AP-HP], Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Physiologie et physiopathologie endocriniennes (PHYSENDO), Faculté de Médecine Henri Warembourg - Université de Lille, Service Pneumologie et allergologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Commission of the European Communities, Thoracic Medicine, Imperial College London, London, UK., Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CHU Bordeaux [Bordeaux], Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Lille-II, Laboratory of Pharmacology, Hôpital Foch, Suresnes, Fran, Service de Pneumologie, Hôpital Larrey, Centre Hospitalier Universitaire de Toulouse, Université de Toulouse III, Toulouse, France., Institut du Thorax, Nantes, France, Cabinet de Pneumologie, Lyon, France., Respiratory, Hopital Calmette, CHRU Lille, Lille, France., Lung function, Hôpital Calmette, CHRU Lille, Lille, France., Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), UMR 6293, Clermont Ferrand, France, Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Marseille, Marseille, France, Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), and MORNET, Dominique
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Endotype, Time Factors, Referral, [SDV]Life Sciences [q-bio], Severe asthma, Respiratory System, MEDLINE, Administration, Oral, Risk Assessment, Severity of Illness Index, Tertiary care, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, medicine, Humans, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Intensive care medicine, Lung, Asthma, lcsh:RC705-779, Evidence-Based Medicine, business.industry, lcsh:Diseases of the respiratory system, medicine.disease, 3. Good health, Treatment Outcome, 030228 respiratory system, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 1116 Medical Physiology, Disease Progression, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Research questions, Patient Safety, business, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract: Options to achieve oral corticosteroid (OCS)-sparing have been triggering increasing interest since the 1970s because of the side-effects of OCSs, and this has now become achievable with biologics. The Société de Pneumologie de Langue Française workshop on OCSs aimed to conduct a comprehensive review of the basics for OCS use in asthma and issue key research questions. Pharmacology and definition of regular use were reviewed by the first working group (WG1). WG2 examined whether regular OCS use is associated with T2 endotype. WG3 reported on the specificities of the paediatric area. Key “research statement proposals” were suggested by WG4. It was found that the benefits of regular OCS use in asthma outside episodes of exacerbations are poorly supported by the existing evidence. However, complete OCS elimination couldn’t be achieved in any available studies for all patients and the panel felt that it was too early to conclude that regular OCS use could be declared criminal. Repeated or prolonged need for OCS beyond 1 g·year−1 should indicate the need for referral to secondary/tertiary care. A strategic sequential plan aiming at reducing overall exposure to OCS in severe asthma was then held as a conclusion of the workshop.
Published: 2020
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6. Facteurs environnementaux favorisant le développement d’un asthme

Author: Bénédicte, Leynaert, Nicole, Le Moual, Catherine, Neukirch, Valérie, Siroux, Raphaëlle, Varraso, 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), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fibrose Inflammation Remodelage [Hôpitaux Universitaires Paris Nord Val de Seine] (DHU FIRE ), Hôpitaux Universitaires Paris Nord Val de Seine, Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: MESH: Allergens, MESH: Humans, MESH: Asthma, MESH: Environmental Exposure, Environmental Exposure, Allergens, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Asthma, respiratory tract diseases, Risk Factors, immune system diseases, MESH: Risk Factors, Air Pollution, Indoor, Animals, Humans, MESH: Animals, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Air Pollution, Indoor
Abstract: International audience; The prevalence of asthma has increased rapidly since the early 1970s, and only changes in exposure to environmental factors; which go together with changes in lifestyle, are likely to explain such a rapid increase. Exposure to allergens is a risk factor for allergic sensitization, and allergic sensitization is a risk factor for allergic asthma. However, apart from indoor mold exposure as a risk factor for childhood asthma, there is insufficient evidence to conclude that the associations between allergen exposure and asthma development are causal. A new challenge for research is to analyze the huge amount of data derived from the metagenomic characterization of the environmental and human microbiome, to understand the role of interactions between viruses, bacteria and allergens in the development of asthma. It is recognized that prenatal and postnatal exposure to air pollution and maternal smoking increase the risk of developing asthma in children. In adults, the data are scarce and the results remain controversial as regards these exposures and asthma incidence. Further research is needed to appraise the effect of exposure to phenols, phthalates and perfluorinated compounds, which are widespread in the environment and may be associated with asthma, especially in children. Frequent use of chemicals for home cleaning especially in the form of sprays - which is a common practice at the population level - is a risk factor for the development of adult asthma. The domestic use of cleaning products might also be a risk factor for asthma in children exposed at home. The chemicals involved in these relationships are still to be identified. Occupational asthma is a major phenotype of adult asthma. A significant part of these asthma cases might relate to occupational exposure to cleaning products. While there is evidence of associations between diet during pregnancy or during childhood and the risk of developing asthma in children, the data in adults are insufficient. Beyond genetic factors, body composition is influenced by dietary choices and physical activity. Further research is needed to clarify the complex interplay between these nutritional factors and asthma development. The new challenge for research is to decipher the role of all the environmental factors to which the individual is exposed since conception ("exposome") in the development of asthma, using a holistic approach.
Published: 2019
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7. Impact of a population-based asthma management program in France (Sophia Asthme): A matched controlled before-and-after quasi-experimental study using the French health insurance database (SNDS)

Author: Yann De Rycke, Camille Taillé, Fadia Dib, Florence Tubach, S. Guillo, Alexandre Lafourcade, Chantal Raherison, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Sorbonne Paris Cité (USPC), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), CHU Pitié-Salpêtrière [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), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer environnement (EPICENE ), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie A [Paris], CHU Bordeaux [Bordeaux], 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), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Biostatistique Santé Publique et Information Médicale [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]
Subjects: Adult, Male, medicine.medical_specialty, pharmacoepidemiology, Adolescent, Databases, Factual, National Health Programs, Epidemiology, Population based, disease management program, Asthma management, 030226 pharmacology & pharmacy, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, asthma exacerbation, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Outcome Assessment, Health Care, Quasi experimental study, medicine, Humans, Pharmacology (medical), Anti-Asthmatic Agents, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Reimbursement, Asthma, business.industry, Pharmacoepidemiology, asthma outcomes, medicine.disease, Health insurance database, 3. Good health, asthma control, National health insurance, Controlled Before-After Studies, Family medicine, Insurance, Health, Reimbursement, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business
Abstract: International audience; PURPOSE: Sophia Asthme (SA) is a chronic disease management program of the French national health insurance for adult patients with asthma. We evaluated the early impact of this intervention.METHODS: We conducted a matched controlled, before-and-after quasi-experimental study within the French Health Insurance Database (Système National Des Données de Santé [SNDS]). The SA program was implemented in a set of 18 Départements in France and targeted 18- to 44-year-old subjects, with at least two reimbursement dates for asthma drug therapy during the 12-month period prior to program targeting. Change in outcomes was assessed from the "before program" period (January-December 2014) to the "after program implementation" period (March 2015-February 2016) in the program group (eligible to SA program in the 18 Départements) and in the matched controlled group. The main outcome measure was the before-after change in proportion of subjects with a controllers/(controllers+relievers) ratio greater than 50%.RESULTS: Of the 99 578 subjects of the program group, 9225 (9.3%) actually participated in SA program. The program had no significant impact on the proportion of subjects with a ratio greater than 50%. However, subjects exposed to SA program were significantly more likely to be dispensed controller medications (OR = 1.04; 95% CI, 1.01-1.07) and to sustain their use of these medications (OR = 1.08; 95% CI, 1.05-1.12).CONCLUSION: We did not demonstrate any significant impact of the program on the primary outcome. The modest yet encouraging findings of this early evaluation suggest the need for reformulation of the program and its evaluation.
Published: 2019
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8. Risk of Asthma Onset After Natural and Surgical Menopause: Results From the French E3N Cohort

Author: Dominique Courbon, Sylvie Mesrine, Gianluca Severi, Annabelle Bédard, Camille Taillé, Raphaëlle Varraso, Bobette Matulonga-Diakiese, Agnès Fournier, Margaux Sanchez, Bénédicte Leynaert, Gabriel Thabut, 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), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Gustave Roussy (IGR), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Faraldo, Beatrice
Subjects: Adult, Pediatrics, medicine.medical_specialty, Epidemiology, Ovariectomy, Menopause, Premature, Overweight, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, 03 medical and health sciences, Surgical Menopause, 0302 clinical medicine, Risk Factors, medicine, Reproductive aging, Humans, Sex hormones, Obesity, Body mass index, Aged, Proportional Hazards Models, Asthma, 030219 obstetrics & reproductive medicine, Proportional hazards model, business.industry, Incidence, Hazard ratio, Obstetrics and Gynecology, Middle Aged, medicine.disease, 3. Good health, respiratory tract diseases, Postmenopause, Menopause, Premenopause, 030228 respiratory system, E3N, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, medicine.symptom, business
Abstract: International audience; Background: The gender switch in asthma incidence around puberty has been put forward to suggest a role of sex hormones in asthma. However, there are limited and inconsistent findings on change in asthma incidence with menopause. We aimed to investigate the associations between menopause and asthma incidence, and interactions with overweight/obesity.Methods: Asthma incidence was assessed in 67,872 women free of asthma at baseline (aged 41-68 years) and regularly followed up as a part of the French E3N cohort. Adjusted hazard ratios (aHR) were derived from Cox models considering age as the time-scale, menopausal status as a time-varying covariate and taking into account menopausal treatment.Results: During 843,243 person-years of follow-up, 1205 new-onset asthma cases were identified. Compared with pre-menopause, surgical menopause was associated with an increased risk of asthma onset (aHR = 1.33 [95%CI 1.01-1.75]) but no association was observed for natural menopause (aHR = 1.05 [0.84-1.32]). In women with natural menopause, a further analysis separating the transition through menopause and the later post-menopausal period did not show any change in asthma incidence with menopause in the total sample or in normal-weight women alone. However, in overweight/obese women, peri-menopausal and post-menopausal women had an increased risk of developing asthma compared with pre-menopausal women of the same age (aHR = 1.91 [1.00-3.66] and aHR = 2.08 [1.07-4.06] respectively).Conclusion: Surgical menopause was associated with an increased risk of asthma onset. For natural menopause, no change in asthma incidence was observed in normal-weight women. However, overweight/obese women had an increased risk of developing asthma after natural menopause.
Published: 2018
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9. Rituximab for auto-immune alveolar proteinosis, a real life cohort study

Author: Martine Reynaud-Gaubert, Jean-Marc Naccache, Leonidas Chavez, Lidwine Wemeau-Stervinou, Sylvain Marchand-Adam, Laurent Savale, Abdellatif Tazi, Marie-Pierre Debray, Bruno Crestani, Jacques Cadranel, Hilario Nunes, Sylvie Leroy, Raphael Borie, Berenice Soyez, Vincent Cottin, Cedric Menard, Emmanuel Gomez, Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), LabEx Inflamex, Université Sorbonne Paris Cité (USPC), CHU Pontchaillou [Rennes], Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [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), Centre Hospitalier Universitaire [Grenoble] (CHU), Department of Pneumology [Lyon], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Hôpital Pasteur [Nice] (CHU), Université Pierre et Marie Curie - Paris 6 (UPMC), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), Université Paris 13 (UP13)-UFR SMBH, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Centre de référence des Histiocytoses, Service de pneumologie. Centre de compétence des maladies pulmonaires rares, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Radiologie [Bichat] (DR- Bichat), Fondation du Souffle (FR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), COMBE, Isabelle, Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)
Subjects: Adult, Male, medicine.medical_specialty, Alveolar proteinosis, medicine.medical_treatment, Interstitial lung disease, Pulmonary Alveolar Proteinosis, Bronchoalveolar Lavage, Gastroenterology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Refractory, Internal medicine, Surfactant, medicine, Humans, Immunologic Factors, Lung transplantation, Whole lung lavage, 030212 general & internal medicine, Adverse effect, Autoantibodies, Retrospective Studies, lcsh:RC705-779, business.industry, Research, GM-CSF, lcsh:Diseases of the respiratory system, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Middle Aged, medicine.disease, 3. Good health, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, Rituximab, France, Therapy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, Pulmonary alveolar proteinosis, Follow-Up Studies, medicine.drug, Cohort study
Abstract: International audience; Background: Whole lung lavage is the current standard therapy for pulmonary alveolar proteinosis (PAP) that is characterized by the alveolar accumulation of surfactant. Rituximab showed promising results in auto-immune PAP (aPAP) related to anti-GM-CSF antibody.Methods: We aimed to assess efficacy of rituximab in aPAP in real life and all patients with aPAP in France that received rituximab were retrospectively analyzed.Results: Thirteen patients were included. No patients showed improvement 6 months after treatment, but, 4 patients (30%) presented a significant decrease of alveolar-arterial difference in oxygen after 1 year. One patient received lung transplantation and one patient was lost of follow-up within one year. Although a spontaneous improvement cannot be excluded in these 4 patients, improvement was more frequent in patients naive to prior specific therapy and with higher level of anti-GM-CSF antibodies evaluated by ELISA. No serious adverse event was evidenced. Conclusions: These data do not support rituximab as a second line therapy for patients with refractory aPAP.
Published: 2018
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10. Neutrophil hyperactivation correlates with Alzheimer's disease progression

Author: Dong, Yuan, Lagarde, Julien, Xicota, Laura, Corne, Helene, Chantran, Yannick, Chaigneau, Thomas, Crestani, Bruno, Bottlaender, Michel, Potier, Marie-Claude, Aucouturier, Pierre, Dorothée, Guillaume, Sarazin, Marie, Elbim, Carole, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Système immunitaire et neuroinflammation [CRSA], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat], Unité de recherche en NeuroImagerie Applicative Clinique et Translationnelle (UNIACT), Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Elbim, Carole, Université Pierre et Marie Curie - Paris 6 (UPMC), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: Aged, 80 and over, Male, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.IMM] Life Sciences [q-bio]/Immunology, Neutrophils, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Middle Aged, Neutrophil Activation, Alzheimer Disease, Disease Progression, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cognitive Dysfunction, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Longitudinal Studies, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Aged
Abstract: International audience; OBJECTIVE:Recent studies have underlined the effect of systemic inflammation on the pathophysiology of Alzheimer's disease (AD). Neutrophils are key components of early innate immunity and contribute to uncontrolled systemic inflammation if not tightly regulated. The aim of our study was to fully characterize human circulating neutrophils at different disease stages in AD.METHODS:We analyzed neutrophil phenotypes and functions in 42 patients with AD (16 with mild cognitive impairment and 26 with dementia), and compared them to 22 age-matched healthy subjects. This study was performed directly in whole blood to avoid issues with data interpretation related to cell isolation procedures.RESULTS:Blood samples from AD patients with dementia revealed neutrophil hyperactivation associated with increased reactive oxygen species production and increased levels of intravascular neutrophil extravascular traps. The homeostasis of circulating neutrophils in these patients also changed: The ratio between the harmful hyperreactive CXCR4high /CD62Llow senescent and the CD16bright /CD62Ldim immunosuppressive neutrophil subsets rose in the later stage of the disease. These abnormalities were greater in fast-decliner than in slow-decliner patients.INTERPRETATION:Our results indicate that the inflammatory properties of circulating neutrophils shift as the percentage of aged neutrophils expands in patients with AD-changes that may play an instrumental role in establishing systemic chronic inflammation. Most important, our data strongly suggest that the neutrophil phenotype may be associated with the rate of cognitive decline and may thus constitute an innovative and prognostic blood biomarker in patients with AD. Ann Neurol 2018;83:387-405.
Published: 2018
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11. Computational pan-genomics : Status, promises and challenges

Author: Lodewyk F. A. Wessels, Jan O. Korbel, Jasmijn A. Baaijens, Francesca Chiaromonte, Gunnar W. Klau, Kai Ye, Alexander Schönhuth, Francesca D. Ciccarelli, Tobias Marschall, Robin Cijvat, Matthias Schlesner, Adam M. Novak, Eleazar Eskin, Ashley D. Sanders, Sven Rahmann, Carl Shneider, Wigard P. Kloosterman, Knut Reinert, Eric-Wubbo Lameijer, Sandra Smit, Benedict Paten, Mohammed El-Kebir, Valentina Boeva, Evan E. Eichler, Cornelia M. van Duijn, Can Alkan, Jeroen de Ridder, Benjamin Langmead, Dick de Ridder, Jiayin Wang, David Porubsky, Fabio Vandin, Erwin Datema, Ben Raphael, Paul Kersey, Nadia Pisanti, Corinna Ernst, Klaasjan G. Ouwens, Y. Zhang, Thomas Abeel, Erik Garrison, Veli Mäkinen, Paul I.W. de Bakker, Victor Guryev, Siavash Sheikhizadeh, Manja Marz, Marcel Martin, Ole Schulz-Trieglaff, Pieter B. Neerincx, Rayan Chikhi, Eric Rivals, John C. Mu, Raoul J. P. Bonnal, Bas E. Dutilh, Paul Medvedev, Louis Dijkstra, Pierre Peterlongo, Ali Ghaffaari, Daniel Valenzuela, Epidemiology, Gastroenterology & Hepatology, Erasmus MC other, Alkan, Can, Saarland University [Saarbrücken], Max Planck Institute for Informatics [Saarbrücken], Karlsruhe Institute of Technology (KIT), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Delft Bioinformatics Lab [Delft], Delft University of Technology (TU Delft), Computational Science Lab [Amsterdam], University of Amsterdam [Amsterdam] (UvA), Theoretical Biology & Bioinformatics [Utrecht], University Medical Center [Utrecht], Universidade Federal do Rio de Janeiro (UFRJ), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Section genetics [Utrecht], Center for Molecular medicine [Utrecht], University Medical Center [Utrecht]-University Medical Center [Utrecht], Helsinki Institute for Information Technology, Department of Computer Science [Helsinki], Falculty of Science [Helsinki], University of Helsinki-University of Helsinki, Howard Hughes Medical Institute [Santa Cruz] (HHMI), Center for Biomolecular Science & Engineering, European Research Institute for the Biology of Ageing [Groningen] (ERIBA), University Medical Center Groningen [Groningen] (UMCG), Institut de Biologie Computationnelle (IBC), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Department of Computer Engineering (Bilkent-CS), Bilkent, Life Sciences [Amsterdam] (MAC4), Centrum Wiskunde & Informatica (CWI), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), PSL Research University (PSL), Centre de Bioinformatique (CBIO), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University (PSL), Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Integrative Biology Program [Milano], Istituto Nazionale Genetica Molecolare [Milano] (INGM), Department of Statistics [Pennsylvania], Pennsylvania State University (Penn State), Penn State System-Penn State System, Bioinformatics and Sequence Analysis (BONSAI), Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189 (CRIStAL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Centrale de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Centrale de Lille-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Monet DB Solutions [Amsterdam], KeyGene [Wageningen], Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Howard Hughes Medical Institute [Berkeley], University of California [Berkeley], University of California-University of California, Genome Informatics [Duisburg], Universität Duisburg-Essen [Essen], Departement of human genetics [Los Angeles], Computer Science Department [Los Angeles] (UCLA), University of California [Los Angeles] (UCLA), University of California-University of California-University of California [Los Angeles] (UCLA), The Wellcome Trust Sanger Institute [Cambridge], Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Universiteit Leiden [Leiden], Department of Computer Science [Baltimore], Johns Hopkins University (JHU), Centre de Physique des Particules de Marseille (CPPM), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Aix Marseille Université (AMU), University of Pennsylvania [Philadelphia], China Agricultural University (CAU), University of Groningen [Groningen], Department of Biological Psychology [Amsterdam], Vrije Universiteit Amsterdam [Amsterdam] (VU), Scalable, Optimized and Parallel Algorithms for Genomics (GenScale), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Dipartimento di Informatica [Pisa] (DI), University of Pisa - Università di Pisa, Faculty of Computer Science [Dortmund], Technische Universität Dortmund [Dortmund] (TU), Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Department of Mathematics and Computer Science (Freie Universität Berlin), Freie Universität Berlin, Wageningen University and Research Centre [Wageningen] (WUR), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Division of Theoretical Bioinformatics [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Illumina Cambridge, Illumina, Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, Bioinformatics Group [Wageningen], Leiden Observatory [Leiden], Regeneron Pharmaceuticals [Tarrytown], Shaanxi University of Science and Technology, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Universita degli Studi di Padova, The Netherlands Organization for Scientific Research (NWO) Vidi (639.072.309 to A.S., 864.14.004 to B.E.D.), CAPES/BRASIL (to B.E.D.), the Academy of Finland (284598 [CoECGR] to V.M. and D.V.), the Russian Scientific Foundation (14–11–00826 to L.D.), Institut de Biologie Computationnelle (ANR-11-BINF- 0002 to E.R.), and the French Colib’read project (ANR–12– BS02–0008 to E.R.). NSFC 31671372 (to K. Y.), the Dutch Graduate School for Experimental Plant Sciences (054EPS15 to S.S.), the EMGO Institute for Health and Care Research (EMGO+) to K.O., the National Human Genome Research Institute (1U54HG007990 [BD2K] to B.P. and A.M.N., 5U41HG007234 [GENCODE] to B.P.), the W. M. Keck Foundation (DT06172015 to B.P. and A.M.N.), the Simons Foundation (SFLIFE# 351901 to B.P. and A.M.N.), the ARCS Foundation (2014–15 ARCS fellowship to A.M.N.), Edward Schulak (Edward Schulak Fellowship in Genomics to A.M.N.), ANR-11-BINF-0002,IBC,Institut de Biologie Computationnelle de Montpellier(2011), ANR-12-BS02-0008,Colib'read,Méthodes d'extraction d'information biologique dans les données HTS non assemblées(2012), Karlsruhe Institute of Technology ( KIT ), Broad Institute of MIT and Harvard ( BROAD INSTITUTE ), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston] ( MGH ) -Massachusetts Institute of Technology ( MIT ), Delft University of Technology ( TU Delft ), University of Amsterdam [Amsterdam] ( UvA ), Universidade Federal do Rio de Janeiro ( UFRJ ), European Bioinformatics Institute [Hinxton] ( EMBL-EBI ), European Molecular Biology Laboratory [Hinxton], Department of Computer Science, Howard Hughes Medical Institute [Santa Cruz] ( HHMI ), European Research Institute for the Biology of Ageing [Groningen] ( ERIBA ), University Medical Center Groningen [Groningen] ( UMCG ), Institut de Biologie Computationnelle ( IBC ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Méthodes et Algorithmes pour la Bioinformatique ( MAB ), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier ( LIRMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Engineering ( Bilkent-CS ), Life Sciences [Amsterdam] ( MAC4 ), Centrum Wiskunde & Informatica ( CWI ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), PSL Research University ( PSL ), Centre de Bioinformatique ( CBIO ), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University ( PSL ), MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Istituto Nazionale Genetica Molecolare [Milano] ( INGM ), PennState University [Pennsylvania] ( PSU ), Bioinformatics and Sequence Analysis ( BONSAI ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189 ( CRIStAL ), Ecole Centrale de Lille-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut Mines-Télécom [Paris]-Université de Lille-Centre National de la Recherche Scientifique ( CNRS ) -Ecole Centrale de Lille-Institut Mines-Télécom [Paris]-Université de Lille-Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique ( CNRS ), Erasmus University Medical Center [Rotterdam], Computer Science Department [Los Angeles] ( UCLA ), University of California at Los Angeles [Los Angeles] ( UCLA ) -University of California at Los Angeles [Los Angeles] ( UCLA ), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale ( ERABLE ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ), Johns Hopkins University ( JHU ), Centre de Physique des Particules de Marseille ( CPPM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Aix Marseille Université ( AMU ), China Agricultural University ( CAU ), Vrije Universiteit Amsterdam [Amsterdam] ( VU ), Scalable, Optimized and Parallel Algorithms for Genomics ( GenScale ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -GESTION DES DONNÉES ET DE LA CONNAISSANCE ( IRISA_D7 ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -IMT Atlantique Bretagne-Pays de la Loire ( IMT Atlantique ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -IMT Atlantique Bretagne-Pays de la Loire ( IMT Atlantique ) -Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -IMT Atlantique Bretagne-Pays de la Loire ( IMT Atlantique ), Dipartimento di Informatica [Pisa] ( DI ), University of Pisa [Pisa], Technische Universität Dortmund [Dortmund] ( TU ), Department of Mathematics and Computer Science ( Freie Universität Berlin ), Freie Universität Berlin [Berlin], Wageningen University and Research Centre [Wageningen] ( WUR ), K.U.Leuven, German Cancer Research Center [Heidelberg] ( DKFZ ), Helmholtz-Gemeinschaft-Helmholtz-Gemeinschaft, BC Cancer Agency ( BCCRC ) -British Columbia Cancer Agency Research Centre, Netherlands Cancer Institute ( NKI ), ANR-11-BINF-0002,IBC,Institut de Biologie Computationnelle de Montpellier ( 2011 ), ANR-12-BS02-0008,Colib'read,Méthodes d'extraction d'information biologique dans les données HTS non assemblées ( 2012 ), Helsinki Institute for Information Technology (HIIT), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Aalto University, Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of California [Santa Cruz] (UC Santa Cruz), University of California (UC), Bilkent University [Ankara], Université Paris sciences et lettres (PSL), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Statistics [PennState], Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Washington [Seattle], Howard Hughes Medical Institute (HHMI), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Universiteit Leiden, Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Mathematics and Computer Science, Wageningen University and Research [Wageningen] (WUR), Università degli Studi di Padova = University of Padua (Unipd), ANR-11-BINF-0002,IBC,Institut de biologie Computationnelle(2011), Aalto University-University of Helsinki, University of California [Santa Cruz] (UCSC), University of California, Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), MINES ParisTech - École nationale supérieure des mines de Paris, Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), and Groningen Research Institute for Asthma and COPD (GRIAC)
Subjects: 0301 basic medicine, Data structures, Computer science, Medizin, 02 engineering and technology, computer.software_genre, Genome, Computational and Statistical Genetics, data structures, haplotypes, pan-genome, read mapping, sequence graph, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], 0303 health sciences, education.field_of_study, Point (typography), Genomics, Papers, Data mining, Sequence graph, Computational problem, Construct (philosophy), Algorithms, Human, Information Systems, Bioinformatics, 0206 medical engineering, Population, Pan-genome, 03 medical and health sciences, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], Bioinformatica, Humans, Haplotypes, Read mapping, Computational Biology, Genome, Human, Software, Molecular Biology, education, Representation (mathematics), 030304 developmental biology, Computational genomics, Data structure, Data science, Human genetics, 030104 developmental biology, Paradigm shift, ddc:004, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], EPS, computer, 020602 bioinformatics
Abstract: Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case ofHomo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic datasets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension ofcomputational pan-genomics, a new sub-area of research in computational biology. In this paper, we generalize existing definitions and understand apan-genomeas any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies, and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains.
Published: 2018
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12. Is chronic exposure to air pollutants a risk factor for the development of idiopathic pulmonary fibrosis?

Author: Bruno Crestani, Valérie Siroux, Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), 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), Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fibrose Inflammation Remodelage [Hôpitaux Universitaires Paris Nord Val de Seine] (DHU FIRE ), Hôpitaux Universitaires Paris Nord Val de Seine, Siroux, Valérie, and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Pulmonary and Respiratory Medicine, Chronic exposure, medicine.medical_specialty, MESH: Air Pollution, MESH: Air Pollutants, MESH: Idiopathic Pulmonary Fibrosis, Pulmonary Fibrosis, Gastroenterology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Air pollutants, MESH: Risk Factors, Risk Factors, Internal medicine, Air Pollution, Pulmonary fibrosis, medicine, Humans, 030212 general & internal medicine, MESH: Incidence, Risk factor, ComputingMilieux_MISCELLANEOUS, Air Pollutants, MESH: Humans, MESH: Pulmonary Fibrosis, business.industry, Incidence (epidemiology), Incidence, MESH: Italy, medicine.disease, Idiopathic Pulmonary Fibrosis, 3. Good health, 030228 respiratory system, Italy, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 13. Climate action, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: For the first time, a role of air pollution in the development of idiopathic pulmonary fibrosis is suggested http://ow.ly/EH2V30hBapf
Published: 2017
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13. Smoking, telomere length and lung function decline: a longitudinal population-based study

Author: Laurent Boyer, Bénédicte Leynaert, Pascal Demoly, Jorge Boczkowski, Serge Adnot, Isabelle Pin, Deborah Jarvis, Pascal Andujar, Catherine Neukirch, Emilie Bizard, Gabriel Thabut, Dominique Courbon, Elisabeth Marcos, 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), Service de Pneumologie [CHI Créteil], CHI Créteil, 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), Université Paris Diderot - Paris 7 (UPD7), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'allergologie et de pneumologie [Hôpital Arnaud de Villeneuve], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Grenoble Alpes (UGA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Service de pneumologie B, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, Gerontology, Longitudinal study, Tobacco and the lung, European community, Respiratory System, Physiology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Pulmonary Disease, Chronic Obstructive, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Forced Expiratory Volume, Leukocytes, medicine, Humans, Longitudinal Studies, 030212 general & internal medicine, Respiratory system, Lung, Telomere Shortening, Lung function, COPD, Heavy smoking, business.industry, Smoking, Telomere Homeostasis, 1103 Clinical Sciences, Telomere, medicine.disease, Health Surveys, 3. Good health, Population based study, Cross-Sectional Studies, 030228 respiratory system, Spirometry, Female, France, business, COPD epidemiology, Biomarkers, Follow-Up Studies
Abstract: Telomere shortening is associated with COPD and impaired lung function in cross-sectional studies, but there is no longitudinal study. We used data from 448 participants recruited as part of the French follow-up of the European Community Respiratory Health Survey. We found no relationship between telomere length at baseline and FEV1 decline after 11 years of follow-up. However, heavy smoking was associated with an accelerated FEV1 decline in individuals with short telomeres, but not in subjects with longer telomeres (p for interaction p=0.08). Our findings suggest that short telomere length in peripheral leucocytes might be a marker for increased susceptibility to the effect of smoking.
Published: 2017
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14. Heterozygous RTEL1 mutations areassociated with familial pulmonary fibrosis

Author: Kannengiesser, Caroline, Raphael, Borie, Ménard, Christelle, Réocreux, Marion, Nitschké, Patrick, Gazal, Steven, Mal, Hervé, Taillé, Camille, Cadranel, Jacques, Nunes, Hilario, Valeyre, Dominique, Cordier, Jean François, Callebaut, Isabelle, Boileau, Catherine, Cottin, Vincent, Grandchamp, Bernard, Revy, Patrick, Crestani, Bruno, APHP Service de Génétique, Hôpital Bichat, Université Paris Diderot - Paris 7 (UPD7), Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), PfGC-Nord, Plateforme de Génétique constitutionnelle-Nord, APHP Service de Pneumologie B, Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Tenon [APHP], APHP, Service de Pneumologie, Hôpital Avicenne, Université Paris 13 (UP13), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de Pneumologie, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 ( UPD7 ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Infection, Antimicrobiens, Modélisation, Evolution ( IAME ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service de pneumologie, Université Paris 13 ( UP13 ), Université Claude Bernard Lyon 1 ( UCBL ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Institut de minéralogie, de physique des matériaux et de cosmochimie ( IMPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Muséum National d'Histoire Naturelle ( MNHN ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de recherche pour le développement [IRD] : UR206, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS)
Subjects: [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; Pulmonary fibrosis is a fatal disease with progressive loss of respiratory function. Defectivetelomere maintenance leading to telomere shortening is a cause of pulmonary fibrosis, as mutations in thetelomerase component genes TERT (reverse transcriptase) and TERC (RNA component) are found in 15% offamilial pulmonary fibrosis (FPF) cases. However, so far, about 85% of FPF remain genetically uncharacterised.Here, in order to identify new genetic causes of FPF, we performed whole-exome sequencing, with acandidate-gene approach, of 47 affected subjects from 35 families with FPF without TERT and TERC mutations.We identified heterozygous mutations in regulator of telomere elongation helicase 1 (RTEL1) in fourfamilies. RTEL1 is a DNA helicase with roles in DNA replication, genome stability, DNA repair and telomeremaintenance. The heterozygous RTEL1 mutations segregated as an autosomal dominant trait in FPF, andwere predicted by structural analyses to severely affect the function and/or stability of RTEL1. In agreementwith this, RTEL1-mutated patients exhibited short telomeres in comparison with age-matched controls.Our results provide evidence that heterozygous RTEL1 mutations are responsible for FPF and, thereby,extend the clinical spectrum of RTEL1 deficiency. Thus, RTEL1 enlarges the number of telomereassociatedgenes implicated in FPF.
Published: 2015
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15. Efficacy of plasma exchange in patients with anti-MDA5 rapidly progressive interstitial lung disease.

Author: Bay P, de Chambrun MP, Rothstein V, Mahevas M, De Prost N, Roux A, Zuber B, Biet DI, Hervier B, Tazi A, Mouthon L, Mekinian A, Deligny C, Borie R, Meurice JC, Meyer A, Priou P, Savale L, De Saint Martin L, Gallay L, Cottin V, Blanchard E, Brillet PY, Khafagy P, Benveniste O, Nunes H, Allenbach Y, and Uzunhan Y
Subjects: Humans, Female, Adult, Middle Aged, Retrospective Studies, Plasma Exchange, Lung Diseases, Interstitial therapy
Abstract: Background: Rapidly progressive interstitial lung disease (RP-ILD) is a frequent and severe manifestation of anti-MDA5 dermatomyositis (MDA5-DM) associated with poor outcome. The optimal treatment regimen for MDA5-DM RP-ILD is yet to be determined. Specifically, the value of adding plasma exchange (PLEX) to corticosteroids and immunosuppressants remains unclear. We aimed to evaluate the effect of PLEX on the outcome of patients with MDA5-DM RP-ILD., Methods: This French nationwide multicentre retrospective study included all MDA5-DM RP-ILD patients from 2012 to 2021 admitted to 18 centres. The primary endpoint was one-year transplant-free survival., Results: 51 patients with MDA5-DM RP-ILD (female 67%; mean age at disease onset: 51 ± 11.6 years) were included. Thirty-two (63%) patients required mechanical ventilation and twenty-five (49%) received PLEX. One-year mortality or lung transplant occurred in 63% cases after a median follow-up of 77 [38-264] days. The Cox proportional hazards multivariable model only retained mechanical ventilation but not PLEX (p = 0.7) as independent predictor of the primary endpoint. One-year transplant-free survival rates in PLEX + vs. PLEX-were 20% vs. 54% (p = 0.01), respectively. The Kaplan-Meier estimated probabilities of one-year transplant-free survival was statistically higher in PLEX-compared to PLEX + patients (p = 0.05). PLEX + compared to PLEX-patients more frequently received mechanical ventilation and immunosuppressants suggesting PLEX + patients had a more severe disease., Conclusion: MDA5-DM RP-ILD is associated with poor rate of one-year transplant-free survival. The use of PLEX was not associated with a better outcome albeit they were mainly given to more severe patients. While our study reports the largest series of MDA5-DM RP-ILD given PLEX, these results needs to be interpreted with caution owing the numerous selection, indication and interpretation bias. Further studies are needed to evaluate their efficacy in this setting., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
Published: 2022
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16. Influenza A Virus Pre-Infection Exacerbates Pseudomonas aeruginosa -Mediated Lung Damage Through Increased MMP-9 Expression, Decreased Elafin Production and Tissue Resilience.

Author: Villeret B, Solhonne B, Straube M, Lemaire F, Cazes A, Garcia-Verdugo I, and Sallenave JM
Subjects: Animals, Cell Line, Coinfection chemically induced, Coinfection metabolism, Cystic Fibrosis immunology, Cytokines metabolism, Disease Susceptibility metabolism, Epithelial Cells metabolism, Humans, Inflammation chemically induced, Inflammation immunology, Lung immunology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Animal, Pneumonia metabolism, Staphylococcal Infections immunology, Coinfection immunology, Elafin metabolism, Influenza A virus immunology, Matrix Metalloproteinase 9 metabolism, Pseudomonas aeruginosa immunology
Abstract: Individuals with impaired immune responses, such as ventilated and cystic fibrosis patients are often infected with Pseudomonas aeruginosa ( P.a ) bacteria, and a co-infection with the Influenza virus (IAV) is often present. It has been known for many years that infection with IAV predisposes the host to secondary bacterial infections (such as Streptococcus pneumoniae or Staphylococcus aureus ), and there is an abundance of mechanistic studies, including those studying the role of desensitization of TLR signaling, type I IFN- mediated impairment of neutrophil chemokines and antimicrobial production, attenuation of IL1β production etc., showing this. However, little is known about the mechanistic events underlying the potential deleterious synergy between Influenza and P.a co-infections. We demonstrate here in vitro in epithelial cells and in vivo in three independent models (two involving mice given IAV +/- P.a , and one involving mice given IAV +/- IL-1β) that IAV promotes secondary P.a -mediated lung disease or augmented IL-1β-mediated inflammation. We show that IAV- P.a -mediated deleterious responses includes increased matrix metalloprotease (MMP) activity, and MMP-9 in particular, and that the use of the MMP inhibitor improves lung resilience. Furthermore, we show that IAV post-transcriptionally inhibits the antimicrobial/anti-protease molecule elafin/trappin-2, which we have shown previously to be anti-inflammatory and to protect the host against maladaptive neutrophilic inflammation in P.a infections. Our work highlights the capacity of IAV to promote further P.a -mediated lung damage, not necessarily through its interference with host resistance to the bacterium, but by down-regulating tissue resilience to lung inflammation instead. Our study therefore suggests that restoring tissue resilience in clinical settings where IAV/ P.a co-exists could prove a fruitful strategy., (Copyright © 2020 Villeret, Solhonne, Straube, Lemaire, Cazes, Garcia-Verdugo and Sallenave.)
Published: 2020
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17. The impaired proteases and anti-proteases balance in Idiopathic Pulmonary Fibrosis.

Author: Menou A, Duitman J, and Crestani B
Subjects: Gene Expression Regulation, Humans, Matrix Metalloproteinases metabolism, Signal Transduction, Tissue Inhibitor of Metalloproteinases metabolism, Idiopathic Pulmonary Fibrosis metabolism, Peptide Hydrolases metabolism, Proteinase Inhibitory Proteins, Secretory metabolism
Abstract: Idiopathic Pulmonary Fibrosis (IPF) is a devastating chronic, progressive and irreversible disease that remains refractory to current therapies. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of MMPs (TIMPs), have been implicated in the development of pulmonary fibrosis since decades. Coagulation signalling deregulation, which influences several key inflammatory and fibro-proliferative responses, is also essential in IPF pathogenesis, and a growing body of evidence indicates that Protease-Activated Receptors (PARs) inhibition in IPF may be promising for future evaluation. Therefore, proteases and anti-proteases aroused great biomedical interest over the past years, owing to the identification of their potential roles in lung fibrosis. During these last decades, numerous other proteases and anti-proteases have been studied in lung fibrosis, such as matriptase, Human airway trypsin-like protease (HAT), Hepatocyte growth factor activator (HGFA)/HGFA activator inhibitor (HAI) system, Plasminogen activator inhibitor (PAI)-1, Protease nexine (PN)-1, cathepsins, calpains, and cystatin C. Herein, we provide a general overview of the proteases and anti-proteases unbalance during lung fibrogenesis and explore potential therapeutics for IPF., (Copyright © 2018. Published by Elsevier B.V.)
Published: 2018
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18. Optimising experimental research in respiratory diseases: an ERS statement.

Author: Bonniaud P, Fabre A, Frossard N, Guignabert C, Inman M, Kuebler WM, Maes T, Shi W, Stampfli M, Uhlig S, White E, Witzenrath M, Bellaye PS, Crestani B, Eickelberg O, Fehrenbach H, Guenther A, Jenkins G, Joos G, Magnan A, Maitre B, Maus UA, Reinhold P, Vernooy JHJ, Richeldi L, and Kolb M
Subjects: Advisory Committees, Animals, Europe, Humans, Societies, Medical, Animal Experimentation ethics, Biomedical Research standards, Disease Models, Animal, Respiration Disorders
Abstract: Experimental models are critical for the understanding of lung health and disease and are indispensable for drug development. However, the pathogenetic and clinical relevance of the models is often unclear. Further, the use of animals in biomedical research is controversial from an ethical perspective.The objective of this task force was to issue a statement with research recommendations about lung disease models by facilitating in-depth discussions between respiratory scientists, and to provide an overview of the literature on the available models. Focus was put on their specific benefits and limitations. This will result in more efficient use of resources and greater reduction in the numbers of animals employed, thereby enhancing the ethical standards and translational capacity of experimental research.The task force statement addresses general issues of experimental research (ethics, species, sex, age, ex vivo and in vitro models, gene editing). The statement also includes research recommendations on modelling asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung infections, acute lung injury and pulmonary hypertension.The task force stressed the importance of using multiple models to strengthen validity of results, the need to increase the availability of human tissues and the importance of standard operating procedures and data quality., Competing Interests: Conflict of interest: P. Bonniaud reports personal fees (board/advice) from Roche, Boehringer, Novartis, TEVA and AstraZeneca, and travel reimbursement (ERS meetings) from Chiesi, outside the submitted work. Conflict of interest: A. Fabre reports grants from Pfizer, reagents from Roche, and personal fees from MSD (Merck Sharp & Dohme Corp.), outside the submitted work. Conflict of interest: T. Maes reports grants from Belgian Science Policy (Federal Government Belgium-Interuniversity attraction Poles), Ghent University (Concerted Research Action and Spearhead Immunology) and Novartis, and personal fees (GSK Clinical Science award: prize for best abstract presentation at Belgian Pulmonology Society Meeting 2015) and non-financial support (travel/accommodation/meeting expenses) from GlaxoSmithKline, outside the submitted work; and is shareholder of Oryzon Genomics. Conflict of interest: W. Shi reports grants from National Institute of Health and Department of Defense, outside the submitted work. Conflict of interest: M. Stampfli reports grants from RespiVert and MedImmune, and personal fees from AstraZeneca and Boehringer Ingelheim, outside the submitted work. Conflict of interest: S. Uhlig reports grants from Germany Research Foundation (DFG), during the conduct of the study. Conflict of interest: E. White reports grants and other support from NIH, personal fees for consulting from Akcea Therapeutics and Kadmon Pharmaceuticals, and research grants and personal fees for consulting from Boehringer-Ingelheim, outside the submitted work. Conflict of interest: M. Witzenrath reports grants and personal fees from Bayer Health Care, Boehringer Ingelheim, Biotest and Vaxxilon, and personal fees from Actelion, Berlin Chemie, AstraZeneca, GlaxoSmithKline and Novartis, outside the submitted work. Conflict of interest: B. Crestani has receieved an honorarium for speaking from Aventis, honoraria for speaking, grants for research and congress travel support grants from Boehringer Ingelheim and Roche, grants for research from CARDIF and LVL, an honorarium for speaking and congress travel support from AstraZeneca, and a grant for research and congress travel support from MedImmune, outside the submitted work. Conflict of interest: O. Eickelberg reports grants from the Helmholtz Association, the German Center of Lung Research, Roche, and Bayer and consultancy/lecture fees from BMS, Novartis, Bayer, Intermune, McKinsey, and MorphoSys. Conflict of interest: A. Guenther reports research funding, and compensation for lectures and consulting from Roche, compensation for lectures and consulting from Boehringer Ingelheim and Teva, and research funding from Sanofi, outside the submitted work. Conflict of interest: G. Jenkins reports grants from GlaxoSmithKline (institutional funding for the PROFILE study) and the Medical Research Council (co-funder of the PROFILE study with GSK through MICA award), during the conduct of the study; grants from Biogen (SRA for work on integrins in IPF), personal fees (consulting and data monitoring committees on lung fibrosis) from Boehringer Ingelheim, grants (PhD studentship) from Galecto, personal fees (advisory board on IPF) from GlaxoSmithKline and Intermune, grants and personal fees (consulting on IPF, PhD studentship) from MedImmune, personal fees (consulting on IPF) from PharmAkea, personal fees (advisory board on IPF and lecture fees) from Roche, consulting on IPF (with no payment received to date) for Pliant Therapeutics, participating in scientific advisory boards (with no payment received to date) for NuMedii, and personal fees from Pulmatrix, outside the submitted work; and is a trustee for the charities Action for Pulmonary Fibrosis and the British Thoracic Society. Conflict of interest: G. Joos reports grants, personal fees and non-financial support from AstraZeneca, grants and personal fees from Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Novartis, and personal fees from Mundipharma, Sandoz and Teva, outside the submitted work. Conflict of interest: U.A. Maus reports grants from Federal Ministry of Education and Research, German Research Foundation and Lower Saxony Society for the Control of Tuberculosis and Bronchial Diseases, outside the submitted work. Conflict of interest: L. Richeldi reports grants and personal fees (for advisory board membership) from InterMune, personal fees (for advisory board membership) from Medimmune, Roche and FibroGen, personal fees (for consulting activity) from Biogen, Sanofi-Aventis, ImmuneWorks, Celgene and Nitto, personal fees (for speaking) from Shionogi, and personal fees (for membership of steering committee) from Boehringer Ingelheim, outside the submitted work. Conflict of interest: M. Kolb reports grants and personal fees from Roche, Boehringer Ingelheim, GSK, Gilead, Prometic and Alkermes, grants from Actelion, Respivert and Synairgen, and personal fees from AstraZeneca and Genoa, outside the submitted work., (Copyright ©ERS 2018.)
Published: 2018
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19. Smoking, telomere length and lung function decline: a longitudinal population-based study.

Author: Andujar P, Courbon D, Bizard E, Marcos E, Adnot S, Boyer L, Demoly P, Jarvis D, Neukirch C, Pin I, Thabut G, Boczkowski J, and Leynaert B
Subjects: Adult, Biomarkers metabolism, Cross-Sectional Studies, Female, Follow-Up Studies, Forced Expiratory Volume genetics, France, Health Surveys, Humans, Leukocytes, Longitudinal Studies, Male, Risk Factors, Spirometry methods, Telomere Homeostasis, Telomere Shortening, Young Adult, Forced Expiratory Volume physiology, Lung physiopathology, Pulmonary Disease, Chronic Obstructive genetics, Smoking adverse effects, Telomere metabolism
Abstract: Telomere shortening is associated with COPD and impaired lung function in cross-sectional studies, but there is no longitudinal study. We used data from 448 participants recruited as part of the French follow-up of the European Community Respiratory Health Survey. We found no relationship between telomere length at baseline and FEV 1 decline after 11 years of follow-up. However, heavy smoking was associated with an accelerated FEV 1 decline in individuals with short telomeres, but not in subjects with longer telomeres (p for interaction p=0.08). Our findings suggest that short telomere length in peripheral leucocytes might be a marker for increased susceptibility to the effect of smoking., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
Published: 2018
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20. CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis.

Author: JanWillem D, Lin C, Moog S, Jaillet M, Castier Y, Cazes A, Borensztajn KS, Crestani B, and Spek CA
Abstract: Background: Idiopathic pulmonary fibrosis is a devastating fibrotic diffuse parenchymal lung disorder that remains refractory to pharmacological therapies. Therefore, novel treatments are urgently required. CCAAT/enhancer binding protein delta (C/EBPδ) is a transcription factor that mediates critical cellular functions in pathophysiology and which was recently suggested to be a key regulatory component in IPF. The purpose of this study was to prove or refute the importance of C/EBPδ in pulmonary fibrosis., Methods: Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type and C/EBPδ deficient mice. At different time intervals after bleomycin instillation, fibrosis was assessed by hydroxyproline analysis, histochemistry and q-PCR for fibrotic marker expression., Results: C/EBPδ deficient mice developed pulmonary fibrosis to a similar degree as wildtype mice as evident from similar Ashcroft scores, hydroxyproline levels and expression levels of collagen, fibronectin and α-smooth muscle actin at both 14 and 21 days after bleomycin instillation. The resolution of fibrosis, assessed at 48 days after bleomycin instillation, was also similar in wildtype and C/EBPδ deficient mice. In line with the lack of effect of C/EBPδ on fibrosis progression/resolution, macrophage recruitment and/or differentiation were also not different in wildtype or C/EBPδ deficient mice., Conclusions: Overall, C/EBPδ does not seem to affect bleomycin-induced experimental pulmonary fibrosis and we challenge the importance of C/EBPδ in pulmonary fibrosis., Relevance for Patients: This study shows that the transcription factor C/EBPδ does not play a major role in the development of pulmonary fibrosis. Pharmacological targeting of C/EBPδ is therefore not likely to have a beneficial effect for patients suffering from pulmonary fibrosis.
Published: 2018

21. FGF9 prevents pleural fibrosis induced by intrapleural adenovirus injection in mice.

Author: Justet A, Joannes A, Besnard V, Marchal-Sommé J, Jaillet M, Bonniaud P, Sallenave JM, Solhonne B, Castier Y, Mordant P, Mal H, Cazes A, Borie R, Mailleux AA, and Crestani B
Subjects: Animals, Cell Differentiation, Epithelial Cells drug effects, Epithelial Cells pathology, Epithelium pathology, Epithelium virology, Humans, Idiopathic Pulmonary Fibrosis metabolism, Idiopathic Pulmonary Fibrosis prevention & control, Lung virology, Mice, Inbred C57BL, Pleura drug effects, Rats, Adenoviridae drug effects, Cell Movement drug effects, Fibroblast Growth Factor 9 pharmacology, Idiopathic Pulmonary Fibrosis virology, Lung pathology
Abstract: Fibroblast growth factor 9 (FGF9) is necessary for fetal lung development and is expressed by epithelium and mesothelium. We evaluated the role of FGF9 overexpression on adenoviral-induced pleural injury in vivo and determined the biological effects of FGF9 on mesothelial cells in vitro. We assessed the expression of FGF9 and FGF receptors by mesothelial cells in both human and mouse lungs. Intrapleural injection of an adenovirus expressing human FGF9 (AdFGF9) or a control adenovirus (AdCont) was performed. Mice were euthanized at days 3 , 5 , and 14 Expression of FGF9 and markers of inflammation and myofibroblastic differentiation was studied by qPCR and immunohistochemistry. In vitro, rat mesothelial cells were stimulated with FGF9 (20 ng/ml), and we assessed its effect on proliferation, survival, migration, and differentiation. FGF9 was expressed by mesothelial cells in human idiopathic pulmonary fibrosis. FGF receptors, mainly FGFR3, were expressed by mesothelial cells in vivo in humans and mice. AdCont instillation induced diffuse pleural thickening appearing at day 5 , maximal at day 14 The altered pleura cells strongly expressed α-smooth muscle actin and collagen. AdFGF9 injection induced maximal FGF9 expression at day 5 that lasted until day 14 FGF9 overexpression prevented pleural thickening, collagen and fibronectin accumulation, and myofibroblastic differentiation of mesothelial cells. In vitro, FGF9 decreased mesothelial cell migration and inhibited the differentiating effect of transforming growth factor-β1. We conclude that FGF9 has a potential antifibrotic effect on mesothelial cells., (Copyright © 2017 the American Physiological Society.)
Published: 2017
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22. Human airway trypsin-like protease, a serine protease involved in respiratory diseases.

Author: Menou A, Duitman J, Flajolet P, Sallenave JM, Mailleux AA, and Crestani B
Subjects: Animals, Biocatalysis, Fetal Development, Humans, Models, Biological, Respiration Disorders embryology, Respiration Disorders pathology, Serine Endopeptidases chemistry, Respiration Disorders enzymology, Serine Endopeptidases metabolism
Abstract: More than 2% of all human genes are coding for a complex system of more than 700 proteases and protease inhibitors. Among them, serine proteases play extraordinary, diverse functions in different physiological and pathological processes. The human airway trypsin-like protease (HAT), also referred to as TMPRSS11D and serine 11D, belongs to the emerging family of cell surface proteolytic enzymes, the type II transmembrane serine proteases (TTSPs). Through the cleavage of its four major identified substrates, HAT triggers specific responses, notably in epithelial cells, within the pericellular and extracellular environment, including notably inflammatory cytokine production, inflammatory cell recruitment, or anticoagulant processes. This review summarizes the potential role of this recently described protease in mediating cell surface proteolytic events, to highlight the structural features, proteolytic activity, and regulation, including the expression profile of HAT, and discuss its possible roles in respiratory physiology and disease., (Copyright © 2017 the American Physiological Society.)
Published: 2017
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23. The pro-apoptotic BAX protein influences cell growth and differentiation from the nucleus in healthy interphasic cells.

Author: Brayer S, Joannes A, Jaillet M, Gregianin E, Mahmoudi S, Marchal Sommé J, Fabre A, Mordant P, Cazes A, Crestani B, and Mailleux AA
Subjects: Apoptosis physiology, Cell Nucleus metabolism, Fibroblasts metabolism, Humans, Mitochondria metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Cell Differentiation physiology, Cell Proliferation physiology, Interphase, bcl-2-Associated X Protein metabolism
Abstract: It has become more and more evident that the BCL-2 family proteins mediate a wide range of non-apoptotic functions. The pro-apoptotic BAX protein has been reported in interphasic nuclei. Whether the nuclear form of BAX could be involved in non-apoptotic function is still unknown. Our study showed for the first time that BAX was associated with chromatin in vitro. Next, we used gain and loss of function approaches to decipher the potential role of nuclear BAX in non-apoptotic cells. In vitro, nuclear BAX promoted cell proliferation in lung epithelial cells and primary human lung fibroblasts by modulating CDKN1A expression. Interestingly, BAX occupancy of CDKN1A promoter was specifically enriched close to the transcription-starting site. Nuclear BAX also modulated the basal myofibroblastic differentiation and migration of primary human lung fibroblasts. Finally, BAX nuclear localization was associated in vivo with the remodelling of lung parenchyma during development, tumorigenesis as well as fibrosis compared to control adult human lungs. Hence, our study established for the first time, a strong link between the nuclear localization of the pro-apoptotic BAX protein and key basic cellular functions in the non-apoptotic setting.
Published: 2017
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24. Human lung fibroblasts may modulate dendritic cell phenotype and function: results from a pilot in vitro study.

Author: Freynet O, Marchal-Sommé J, Jean-Louis F, Mailleux A, Crestani B, Soler P, and Michel L
Subjects: Cell Proliferation physiology, Cells, Cultured, Cytokines immunology, Humans, In Vitro Techniques, Phenotype, Pilot Projects, Cell Communication immunology, Dendritic Cells cytology, Fibroblasts cytology, Fibroblasts immunology, Lung cytology, Lung immunology
Abstract: In human lung fibrotic lesions, fibroblasts were shown to be closely associated with immature dendritic cell (DC) accumulation. The aim of the present pilot study was to characterize the role of pulmonary fibroblasts on DC phenotype and function, using co-culture of lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and from control patients, with a DC cell line MUTZ-3. We observed that co-culture of lung control and IPF fibroblasts with DCs reduced the expression of specific DC markers and down-regulated their T-cell stimulatory activity. This suggests that pulmonary fibroblasts might sustain chronic inflammation in the fibrotic lung by maintaining in situ a pool of immature DCs.
Published: 2016
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25. Methacholine-Induced Variations in Airway Volume and the Slope of the Alveolar Capnogram Are Distinctly Associated with Airflow Limitation and Airway Closure.

Author: Plantier L, Marchand-Adam S, Boyer L, Taillé C, and Delclaux C
Subjects: Adult, Bronchial Provocation Tests, Female, Forced Expiratory Volume drug effects, Forced Expiratory Volume physiology, Humans, Lung drug effects, Lung physiology, Male, Middle Aged, Tidal Volume drug effects, Bronchoconstrictor Agents pharmacology, Methacholine Chloride pharmacology
Abstract: Mechanisms driving alteration of lung function in response to inhalation of a methacholine aerosol are incompletely understood. To explore to what extent large and small airways contribute to airflow limitation and airway closure in this context, volumetric capnography was performed before (n = 93) and after (n = 78) methacholine provocation in subjects with an intermediate clinical probability of asthma. Anatomical dead space (VDaw), reflecting large airway volume, and the slope of the alveolar capnogram (slope3), an index of ventilation heterogeneity linked to small airway dysfunction, were determined. At baseline, VDaw was positively correlated with lung volumes, FEV1 and peak expiratory flow, while slope3 was not correlated with any lung function index. Variations in VDaw and slope3 following methacholine stimulation were correlated to a small degree (R2 = -0.20). Multivariate regression analysis identified independent associations between variation in FEV1 and variations in both VDaw (Standardized Coefficient-SC = 0.66) and Slope3 (SC = 0.35). By contrast, variation in FVC was strongly associated with variations in VDaw (SC = 0.8) but not Slope3. Thus, alterations in the geometry and/or function of large and small airways were weakly correlated and contributed distinctly to airflow limitation. While both large and small airways contributed to airflow limitation as assessed by FEV1, airway closure as assessed by FVC reduction mostly involved the large airways.
Published: 2015
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26. Forkhead Box F1 represses cell growth and inhibits COL1 and ARPC2 expression in lung fibroblasts in vitro.

Author: Melboucy-Belkhir S, Pradère P, Tadbiri S, Habib S, Bacrot A, Brayer S, Mari B, Besnard V, Mailleux A, Guenther A, Castier Y, Mal H, Crestani B, and Plantier L
Subjects: Actin-Related Protein 2-3 Complex genetics, Animals, Apoptosis, Cell Nucleus metabolism, Cell Proliferation, Cells, Cultured, Dinoprostone pharmacology, Female, Fibroblasts cytology, Fibroblasts metabolism, Fibroblasts transplantation, Forkhead Transcription Factors biosynthesis, Forkhead Transcription Factors genetics, Gene Expression Profiling, Humans, Lung cytology, Lung metabolism, Male, Mice, Mice, Inbred C57BL, Middle Aged, RNA Interference, RNA, Messenger biosynthesis, RNA, Small Interfering, Transforming Growth Factor beta1 metabolism, Transforming Growth Factor beta1 pharmacology, Actin-Related Protein 2-3 Complex biosynthesis, Collagen Type I biosynthesis, Forkhead Transcription Factors metabolism, Idiopathic Pulmonary Fibrosis pathology
Abstract: Aberrant expression of master phenotype regulators or alterations in their downstream pathways in lung fibroblasts may play a central role in idiopathic pulmonary fibrosis (IPF). Interrogating IPF fibroblast transcriptome datasets, we identified Forkhead Box F1 (FOXF1), a DNA-binding protein required for lung development, as a candidate actor in IPF. Thus we determined FOXF1 expression levels in fibroblasts cultured from normal or IPF lungs in vitro, and explored FOXF1 functions in these cells using transient and stable loss-of-function and gain-of-function models. FOXF1 mRNA and protein were expressed at higher levels in IPF fibroblasts compared with normal fibroblasts (mRNA: +44%, protein: +77%). Immunohistochemistry showed FOXF1 expression in nuclei of bronchial smooth muscle cells, endothelial cells, and lung fibroblasts including fibroblastic foci of IPF lungs. In normal lung fibroblasts, FOXF1 repressed cell growth and expression of collagen-1 (COL1) and actin-related protein 2/3 complex, subunit 2 (ARPC2). ARPC2 knockdown inhibited cell growth and COL1 expression, consistent with FOXF1 acting in part through ARPC2 repression. In IPF fibroblasts, COL1 and ARPC2 repression by FOXF1 was blunted, and FOXF1 did not repress growth. FOXF1 expression was induced by the antifibrotic mediator prostaglandin E2 and repressed by the profibrotic cytokine transforming growth factor-β1 in both normal and IPF lung fibroblasts. Ex vivo, FOXF1 knockdown conferred CCL-210 lung fibroblasts the ability to implant in uninjured mouse lungs. In conclusion, FOXF1 functions and regulation were consistent with participation in antifibrotic pathways. Alterations of pathways downstream of FOXF1 may participate to fibrogenesis in IPF fibroblasts., (Copyright © 2014 the American Physiological Society.)
Published: 2014
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27. Increased expression of protease nexin-1 in fibroblasts during idiopathic pulmonary fibrosis regulates thrombin activity and fibronectin expression.

Author: François D, Venisse L, Marchal-Somme J, Jandrot-Perrus M, Crestani B, Arocas V, and Bouton MC
Subjects: Case-Control Studies, Fibronectins metabolism, Humans, Thrombin metabolism, Transforming Growth Factor beta metabolism, Fibroblasts enzymology, Idiopathic Pulmonary Fibrosis enzymology, Lung enzymology, Serpin E2 metabolism
Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic diffuse lung disease characterized by an accumulation of excess fibrous material in the lung. Protease nexin-1 (PN-1) is a tissue serpin produced by many cell types, including lung fibroblasts. PN-1 is capable of regulating proteases of both coagulation and fibrinolysis systems, by inhibiting, respectively, thrombin and plasminergic enzymes. PN-1 is thus a good candidate for regulating tissue remodeling occurring during IPF. We demonstrated a significant increase of PN-1 expression in lung tissue extracts, lung fibroblasts and bronchoalveolar lavage fluids of patients with IPF. The increase of PN-1 expression was reproduced after stimulation of control lung fibroblasts by transforming growth factor-β, a major pro-fibrotic cytokine involved in IPF. Another serpin, plasminogen activator inhibitor-1 (PAI-1) is also overexpressed in fibrotic fibroblasts. Unlike PAI-1, cell-bound PN-1 as well as secreted PN-1 from IPF and stimulated fibroblasts were shown to inhibit efficiently thrombin activity, indicating that both serpins should exhibit complementary roles in IPF pathogenesis, via their different preferential antiprotease activities. Moreover, we observed that overexpression of PN-1 induced by transfection of control fibroblasts led to increased fibronectin expression, whereas PN-1 silencing induced in fibrotic fibroblasts led to decreased fibronectin expression. Overexpression of PN-1 lacking either its antiprotease activity or its binding capacity to glycosaminoglycans had no effect on fibronectin expression. These novel findings suggest that modulation of PN-1 expression in lung fibroblasts may also have a role in the development of IPF by directly influencing the expression of extracellular matrix proteins. Our data provide new insights into the role of PN-1 in the poorly understood pathological processes involved in IPF and could therefore give rise to new therapeutic approaches.
Published: 2014
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28. Is the patient's baseline inhaled steroid dose a factor for choosing the budesonide/formoterol maintenance and reliever therapy regimen?

Author: Aubier M, Haughney J, Selroos O, van Schayck OC, Ekström T, Ostinelli J, and Buhl R
Subjects: Administration, Inhalation, Adolescent, Adrenal Cortex Hormones administration & dosage, Adult, Aged, Aged, 80 and over, Anti-Asthmatic Agents administration & dosage, Asthma physiopathology, Budesonide administration & dosage, Budesonide, Formoterol Fumarate Drug Combination, Dose-Response Relationship, Drug, Drug Combinations, Ethanolamines administration & dosage, Female, Humans, Male, Middle Aged, Severity of Illness Index, Surveys and Questionnaires, Time Factors, Treatment Outcome, Young Adult, Adrenal Cortex Hormones therapeutic use, Anti-Asthmatic Agents therapeutic use, Asthma drug therapy, Budesonide therapeutic use, Ethanolamines therapeutic use
Abstract: Objective: Baseline inhaled corticosteroid (ICS) dose may be a factor for prescribers to consider when they select a budesonide/formoterol maintenance and reliever therapy regimen for symptomatic asthmatics., Methods: A 6-month randomized study compared two maintenance doses of budesonide/formoterol 160/4.5 µg, 1 × 2 and 2 × 2, plus as needed, in 8424 asthma patients with symptoms when treated with ICS ± an inhaled long-acting β(2)-agonist (LABA). In the total study population, 1339 (17%) were high-dose ICS (HD) users (≥ 1600 µg/day budesonide). This HD stratum was compared with the rest of the study population, divided into low-dose (LD; 400 µg/day) and medium-dose strata (MD; 401-1599 µg/day) with regard to severe asthma exacerbations and mean changes in five-item Asthma Control Questionnaire (ACQ(5)) scores from baseline., Results: In all three strata there were fewer exacerbations in the 2 × 2 treatment groups (yearly rates 0.268, 0.172 and 0.094) than in the 1 × 2 treatment groups (yearly rates 0.232, 0.138 and 0.764). In no stratum was the difference between the treatment groups statistically significant. There was no statistically significant difference in time to the first severe exacerbation between the treatments 2 × 2 and 1 × 2 in the HD group (hazard ratio 0.944, p = 0.75). The adjusted mean changes in ACQ(5) scores in the HD, MD and LD strata were -0.89, -0.61 and -0.65, respectively, with 1 × 2 treatment and -0.90, -0.74 and -0.76, respectively, with 2 × 2 treatment. In the MD and LD strata, the difference between doses was significant in favour of 2 × 2 (MD p < 0.0001; LD p = 0.004), but not in the HD stratum (p = 0.870). No difference in serious adverse events was seen., Conclusion: Compared with the LD and MD strata, the HD stratum patients had more exacerbations and a shorter time to first exacerbation. However, there were no differences in response between the 1 × 2 and 2 × 2 groups in any of the strata. This indicates that patients using budesonide/formoterol maintenance and reliever therapy, irrespective of baseline ICS dose, can be switched to 1 × 2 with its lower steroid load. ACQ(5) scores improved more in the HD stratum than in the MD and LD strata indicating, among other things, that HD patients were not overtreated at baseline.
Published: 2011
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29. ANCA-associated lung fibrosis: analysis of 17 patients.

Author: Foulon G, Delaval P, Valeyre D, Wallaert B, Debray MP, Brauner M, Nicaise P, Cadranel J, Cottin V, Tazi A, Aubier M, and Crestani B
Subjects: Aged, Bronchoalveolar Lavage Fluid immunology, Case-Control Studies, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neutrophils immunology, Peroxidase immunology, Pulmonary Fibrosis complications, Pulmonary Fibrosis mortality, Retrospective Studies, Smoking, Statistics, Nonparametric, Survival Rate, Vasculitis complications, Vasculitis mortality, Antibodies, Antineutrophil Cytoplasmic blood, Pulmonary Fibrosis immunology, Vasculitis immunology
Abstract: In this retrospective study, we analyzed 17 patients presenting with pulmonary fibrosis and a positive ANCA testing. This group was compared with a control group of 12 patients with IPF and negative ANCA testing. Patients were 15 males and 2 females, with a mean age of 66 years. Eight patients were past smokers, 3 current smokers and 6 non-smokers. Lung function tests at diagnosis were as follows (% predicted): total lung capacity 73%+/-18, vital capacity 82%+/-23, forced expiratory volume in 1 s (FEV(1)) 88%+/-24, carbon monoxide diffusion capacity of the lung 49%+/-2 (% predicted). Bronchoalveolar lavage results showed an increased cellularity with increased neutrophils counts. High resolution computed tomography of the chest showed prominent fibrosis with some degree of ground-glass attenuation in all patients. These characteristics were similar to the control group. Microscopic polyangiitis (MPA) was a major complicating event in ANCA-positive patients, occurring in 7 patients (anti-myeloperoxidase specificity in 5 patients). Pulmonary fibrosis predated occurrence of MPA in 6 patients and was diagnosed concomitantly with MPA in 1 patient. During the follow-up, 10/17 patients died. The death was directly related to vasculitis in 3 patients. We conclude that patients with pulmonary fibrosis should be evaluated for the presence of ANCA. Patients with positive ANCA testing, particularly if anti-myeloperoxidase, should be carefully monitored to detect the occurrence of microscopic polyangiitis.
Published: 2008
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29 results on '"Service de Pneumologie A [Paris]"'

1. Epidemiology of interstitial lung disease in systemic lupus erythematosus in France: A nation-wide population-based study over 10 years

2. Facteurs environnementaux favorisant le développement d’un asthme

3. Low income and outcome in idiopathic pulmonary fibrosis: An association to uncover

4. Mepolizumab in a population with severe eosinophilic asthma and corticosteroid dependence: results from a French early access programme

5. How can we minimise the use of regular oral corticosteroids in asthma?

6. Facteurs environnementaux favorisant le développement d’un asthme

7. Impact of a population-based asthma management program in France (Sophia Asthme): A matched controlled before-and-after quasi-experimental study using the French health insurance database (SNDS)

8. Risk of Asthma Onset After Natural and Surgical Menopause: Results From the French E3N Cohort

9. Rituximab for auto-immune alveolar proteinosis, a real life cohort study

10. Neutrophil hyperactivation correlates with Alzheimer's disease progression

11. Computational pan-genomics : Status, promises and challenges

12. Is chronic exposure to air pollutants a risk factor for the development of idiopathic pulmonary fibrosis?

13. Smoking, telomere length and lung function decline: a longitudinal population-based study

14. Heterozygous RTEL1 mutations areassociated with familial pulmonary fibrosis

15. Efficacy of plasma exchange in patients with anti-MDA5 rapidly progressive interstitial lung disease.

16. Influenza A Virus Pre-Infection Exacerbates Pseudomonas aeruginosa -Mediated Lung Damage Through Increased MMP-9 Expression, Decreased Elafin Production and Tissue Resilience.

17. The impaired proteases and anti-proteases balance in Idiopathic Pulmonary Fibrosis.

18. Optimising experimental research in respiratory diseases: an ERS statement.

19. Smoking, telomere length and lung function decline: a longitudinal population-based study.

20. CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis.

21. FGF9 prevents pleural fibrosis induced by intrapleural adenovirus injection in mice.

22. Human airway trypsin-like protease, a serine protease involved in respiratory diseases.

23. The pro-apoptotic BAX protein influences cell growth and differentiation from the nucleus in healthy interphasic cells.

24. Human lung fibroblasts may modulate dendritic cell phenotype and function: results from a pilot in vitro study.

25. Methacholine-Induced Variations in Airway Volume and the Slope of the Alveolar Capnogram Are Distinctly Associated with Airflow Limitation and Airway Closure.

26. Forkhead Box F1 represses cell growth and inhibits COL1 and ARPC2 expression in lung fibroblasts in vitro.

27. Increased expression of protease nexin-1 in fibroblasts during idiopathic pulmonary fibrosis regulates thrombin activity and fibronectin expression.

28. Is the patient's baseline inhaled steroid dose a factor for choosing the budesonide/formoterol maintenance and reliever therapy regimen?

29. ANCA-associated lung fibrosis: analysis of 17 patients.

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29 results on '"Service de Pneumologie A [Paris]"'

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