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1. Increased mortality in patients with RA-associated interstitial lung disease: data from a French administrative healthcare database

Author: Bruno Crestani, Philippe Dieude, Rene-Marc Flipo, Sebastien Ottaviani, Pierre-Antoine Juge, Lidwine Wemeau-Stervinou, and Joe Zhuo
Subjects: Medicine
Abstract: Objectives Interstitial lung disease (ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). The objectives of this study were to estimate mortality rate in patients with RA-ILD and identify factors affecting mortality.Methods Data from a French national claims database (Système National des Données de Santé) from 2013 to 2018 were analysed. Adults with an RA diagnosis (International Classification of Diseases (ICD)-10 codes M05, M06.0, M06.8 and M06.9) were included. ILD diagnosis was defined with ICD-10 code J84. Mortality rates were compared between patients with RA with and without ILD, using Cox proportional hazards regression, after matching 1:1 for age, sex, age at RA-ILD onset and RA duration.Results Among 173 132 patients with RA, 4330 (3%) also had ILD (RA-ILD). After matching, RA-ILD was associated with an increased mortality rate (HR 3.4, 95% CI 3.1 to 3.9). The HR for mortality was greater for: patients aged
Published: 2023
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2. Pilot experience of multidisciplinary team discussion dedicated to inherited pulmonary fibrosis

Author: Raphael Borie, Caroline Kannengiesser, Laurent Gouya, Clairelyne Dupin, Serge Amselem, Ibrahima Ba, Vincent Bunel, Philippe Bonniaud, Diane Bouvry, Aurélie Cazes, Annick Clement, Marie Pierre Debray, Philippe Dieude, Ralph Epaud, Pascale Fanen, Elodie Lainey, Marie Legendre, Aurélie Plessier, Flore Sicre de Fontbrune, Lidwine Wemeau-Stervinou, Vincent Cottin, Nadia Nathan, and Bruno Crestani
Subjects: Interstitial pulmonary fibrosis, Telomerase, Surfactant, TERT, Familial, multidisciplinary discussion, Medicine
Abstract: Abstract Background Genetic testing is proposed for suspected cases of monogenic pulmonary fibrosis, but clinicians and patients need specific information and recommendation about the related diagnosis and management issues. Because multidisciplinary discussion (MDD) has been shown to improve accuracy of interstitial lung disease (ILD) diagnosis, we evaluated the feasibility of a genetic MDD (geneMDD) dedicated to the indication for and interpretation of genetic testing. The geneMDD group met monthly and included pediatric and adult lung specialists with ILD expertise, molecular and clinical geneticists, and one radiologist. Hematologists, rheumatologists, dermatologists, hepatologists, and pathologists were also invited to attend. Results Since 2016, physicians from 34 different centers in 7 countries have participated in the geneMDD. The medical files of 95 patients (53 males) have been discussed. The median age of patients was 43 years [range 0–77], 10 were ≤ 15 years old, and 6 were deceased at the time of the discussion. Among 85 analyses available, the geneMDD considered the rare gene variants pathogenic for 61: 37 variants in telomere-related genes, 23 variants in surfactant-related genes and 1 variant in MARS. Genetic counseling was offered for relatives of these patients. The geneMDD therapeutic proposals were as follows: antifibrotic drugs (n = 25), steroids or immunomodulatory therapy (n = 18), organ transplantation (n = 21), watch and wait (n = 21), or best supportive care (n = 4). Conclusion Our experience shows that a dedicated geneMDD is feasible regardless of a patient’s age and provides a unique opportunity to adapt patient management and therapy in this very rare condition.
Published: 2019
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3. Long-term evaluation of home-based pulmonary rehabilitation in patients with fibrotic idiopathic interstitial pneumonias

Author: Benoit Wallaert, Louise Duthoit, Elodie Drumez, Hélène Behal, Lidwine Wemeau, Cécile Chenivesse, and Jean-Marie Grosbois
Subjects: Medicine
Abstract: Background Few studies have examined the benefits of pulmonary rehabilitation in patients with fibrotic idiopathic pulmonary pneumonia (f-IIP). Here, we report the results of an observational study in routine clinical practice of home-based pulmonary rehabilitation for f-IIP patients. Methods A total of 112 consecutive patients (61 with idiopathic pulmonary fibrosis and 51 with fibrotic nonspecific interstitial pneumonitis) were enrolled, of whom 65 had mild-to-moderate disease (forced vital capacity (FVC) ≥50% predicted and diffusing capacity of the lung for carbon monoxide (DLCO) ≥30% predicted) and 47 had severe disease (FVC
Published: 2019
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4. Pembrolizumab-induced pneumonitis

Author: Vincent Leroy, Carole Templier, Jean-Baptiste Faivre, Arnaud Scherpereel, Clement Fournier, Laurent Mortier, and Lidwine Wemeau-Stervinou
Subjects: Medicine
Published: 2017
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5. Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial

Author: Abdellatif Tazi, Aurélie Le Borgne-Krams, Marine Cachanado, Tabassome Simon, Sylvain Marchand-Adam, Morgane Didier, Lidwine Wemeau-Stervinou, Sandrine Hirschi, Frédéric Rivière, Arnaud Bourdin, François Lebargy, Stéphane Dominique, Aude Gibelin, Alexandre Chabrol, Tristan Dégot, Jacques Cadranel, Martine Reynaud-Gaubert, Marie-Pierre Debray, Sylvie Leroy, Frédéric Gagnadoux, Emmanuel Bergot, François-Xavier Blanc, Alexandra Rousseau, Raphael Borie, Pierre Yves Brillet, Guillaume Beltramo, Mallorie Kerjouan, Hilario Nunes, Olivia Freynet, Julie Traclet, Bruno Crestani, Anne-Sophie Gamez, Grégoire Prévot, Jean Pastré, Dominique Israel-Biet, Marie-Christine Dombret, Laurent Plantier, Cécile Chenivesse, Laurence Berard, Ana Nieves, Emmanuel Gomez, Dominique Valeyre, Stéphane Jouneau, Anne Gondouin, Elodie Blanchard, C. Launois, Nathalie Bautin, Jean-Marc Naccache, Vincent Cottin, Antoine Parrot, Philippe Bonniaud, 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), Sorbonne Université (SU), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Avicenne [AP-HP], Laboratoire d'Excellence INFLAMEX [Paris], Université Sorbonne Paris Cité (USPC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Saint-Antoine [AP-HP], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, CHU Dijon, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Lille, Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Hospices Civils de Lyon (HCL), Université de Lyon, 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 Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital JeanMinjoz, CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Rouen, Normandie Université (NU), CHU Tenon [AP-HP], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), CHU Montpellier, Université de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Roche, Ministere de la Sante et des Solidarites, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, education.field_of_study, Exacerbation, Cyclophosphamide, business.industry, [SDV]Life Sciences [q-bio], Population, medicine.disease, Placebo, 3. Good health, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, 030228 respiratory system, Methylprednisolone, Internal medicine, Clinical endpoint, Medicine, 030212 general & internal medicine, business, education, Adverse effect, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: Summary Background The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. Methods In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov , NCT02460588 . Findings Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI −3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89–4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12–6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13–0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. Interpretation In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. Funding Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014–502), Roche Pharmaceuticals.
Published: 2022

6. Filamin A Mutations

Author: Victor Valentin, Thomas Smol, J.F. Bervar, Olivier Le Rouzic, Martine Remy, Cécile Chenivesse, Lidwine Wemeau, and Catherine Vincent-Delorme
Subjects: Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Mutation, Lung, business.industry, Connective tissue, respiratory system, Critical Care and Intensive Care Medicine, Filamin, medicine.disease_cause, respiratory tract diseases, medicine.anatomical_structure, medicine, FLNA, Respiratory system, Risk factor, Cardiology and Cardiovascular Medicine, business, Vascular tissue
Abstract: Emphysema is a chronic respiratory disorder characterized by destruction of alveoli, usually due to cigarette smoking or exposure to noxious particles or gases. Dysfunction of proteins that are involved in lung development and maintenance, such as alpha-1 antitrypsin, also contributes to emphysema. Filamin A (FLNA) is an actin-binding protein involved in cytoskeleton reorganization. Mutations in the FLNA gene classically lead to abnormal neuronal migration and connective and vascular tissue anomalies. Pulmonary manifestations consist of a wide range of pulmonary disorders that occur during infancy. We report the first familial case of emphysema in non- and very low-smoking adults who carry a loss-of-function mutation of the FLNA gene. The identification of this new risk factor for emphysema encourages (1) screening, prevention and monitoring of pulmonary disorders in patients with FLNA mutation and (2) screening for FLNA mutation in patients with early-onset emphysema that is associated with low-smoking or vascular or connective tissue anomalies.
Published: 2021

7. Impact of Gender on the Characteristics of Patients with Idiopathic Pulmonary Fibrosis Included in the RaDiCo-ILD Cohort

Author: Sandrine Hirschi, Sonia Gueguen, M. Chevereau, Serge Amselem, Anne-Sophie Gamez, Martine Reynaud-Gaubert, Philippe Bonniaud, Dominique Israel-Biet, Annick Clement, I. Dufaure-Garé, Sylvain Marchand-Adam, Lidwine Wemeau-Stervinou, David Montani, Vincent Cottin, Jacques Cadranel, Hilario Nunes, Sébastien Quétant, Bruno Crestani, Stéphane Jouneau, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, 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 (UPCité), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), 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), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Thorax et Vaisseaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Strasbourg, Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Lapeyronie [Montpellier] (CHU), CHU Trousseau [APHP], French National Research Agency under the 'cohorts' programme of the Investissements d'Avenir (Investments for the Future) French National Research Agency (ANR) [ANR-10-COHO-0003], ANR-10-COHO-0003,RADICO,Cohorte nationale maladies rares(2010), École pratique des hautes études (EPHE), Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Constitutif de Référence des Maladies Pulmonaires Rares [AP-HP Tenon], Centre national de référence des maladies pulmonaires rares [Lyon] (CRMPM)-Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), 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), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Centre national de référence des maladies pulmonaires rares [Lyon] (CRMPM)-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)-CHU Tenon [AP-HP], UF de Génétique moléculaire [CHU Trousseau], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Chard-Hutchinson, Xavier, and Cohortes - Cohorte nationale maladies rares - - RADICO2010 - ANR-10-COHO-0003 - COHO - VALID
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Vital capacity, Registry, [SDV]Life Sciences [q-bio], Idiopathic pulmonary fibrosis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Pulmonary function testing, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, Internal medicine, medicine, Humans, 030212 general & internal medicine, Honeycombing, Idiopathic interstitial pneumonia, 10. No inequality, Emphysema, Patient characteristics, business.industry, Interstitial lung disease, Gender, respiratory system, medicine.disease, Confidence interval, 3. Good health, respiratory tract diseases, [SDV] Life Sciences [q-bio], 030228 respiratory system, Cohort, Quality of Life, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, France, business, Lung Diseases, Interstitial
Abstract: Background: There is growing evidence of gender-specific phenotypic differences among patients with idiopathic pulmonary fibrosis (IPF), which may affect patient outcomes. Objectives: We present the characteristics of patients with IPF at inclusion in the French Rare Disease Cohort – Interstitial Lung Disease (RaDiCo-ILD) with the aim of characterizing gender-specific phenotypic differences. Methods: Patients with IPF who were enrolled in the national, multicentre RaDiCo-ILD cohort were included. Demographic characteristics, comorbidities, health-related quality of life (HRQoL) scores, pulmonary function, chest imaging, and IPF treatment were collected at inclusion and described by gender. Results: The cohort included 724 patients with IPF (54% of RaDiCo-ILD cohort), of whom 82.9% were male. The proportion of male and female patients with a prior history of smoking was 75.0% and 26.8%, respectively. Emphysema was present in 17.0% (95% confidence interval [CI]: 10.0, 24.0) of men and 5.4% (95% CI: 1.2, 9.6) of women. At inclusion, females had poorer HRQoL than males based on St. George’s Respiratory Questionnaire scores (48.5 [95% CI: 43.9, 53.0] and 41.5 [39.4, 43.6], respectively). The mean forced vital capacity per cent predicted was 77.7% (95% CI: 76.2, 79.3) and 87.4% (83.4, 91.4) for males and females, respectively. Honeycombing on high-resolution computed tomography (HRCT) was present in 70.8% (95% CI: 61.0, 80.6) of males and 45.8% (95% CI: 35.1, 56.5) of females. Conclusions: This analysis of patients with IPF at inclusion in the RaDiCo-ILD cohort provides evidence that comorbid emphysema, lung volume reduction, and honeycombing on HRCT are more common characteristics of males than females.
Published: 2022

8. Pilot experience of multidisciplinary team discussion dedicated to inherited pulmonary fibrosis

Author: Ralph Epaud, Serge Amselem, Philippe Bonniaud, Clairelyne Dupin, Aurélie Plessier, Annick Clement, Vincent Cottin, Flore Sicre de Fontbrune, Lidwine Wemeau-Stervinou, Vincent Bunel, Diane Bouvry, Marie Pierre Debray, Caroline Kannengiesser, Aurélie Cazes, Bruno Crestani, Marie Legendre, Raphael Borie, Ibrahima Ba, Nadia Nathan, Philippe Dieudé, Elodie Lainey, Laurent Gouya, Pascale Fanen, Centre de Référence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], Centre de référence 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), Hôpital Avicenne [AP-HP], Centre de Référence des Maladies Pulmonaires Rares [AP-HP Bobigny], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Centre des maladies respiratoires rares Respirare [CHI Créteil], 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), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), AP-HP Hôpital universitaire Robert-Debré [Paris], Hopital Saint-Louis [AP-HP] (AP-HP), Centre de compétences des maladies pulmonaires rares de l'adulte [CHU Lille] (CRMPR), 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)-Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie [Hôpital Louis Pradel – CHU Lyon] (Centre de Référence des Maladies Pulmonaires Rares), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-CHU Lyon, and Couvet, Sandrine
Subjects: Male, MESH: Familial, multidisciplinary discussion, Interstitial pulmonary fibrosis, Surfactant, TERT, Telomerase, Pulmonary Fibrosis, [SDV]Life Sciences [q-bio], lcsh:Medicine, Organ transplantation, 0302 clinical medicine, Pulmonary fibrosis, Pharmacology (medical), 030212 general & internal medicine, Child, Genetics (clinical), medicine.diagnostic_test, Interstitial lung disease, General Medicine, Middle Aged, Pedigree, 3. Good health, [SDV] Life Sciences [q-bio], Child, Preschool, Female, Familial, Adult, medicine.medical_specialty, Adolescent, Genetic counseling, MEDLINE, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Multidisciplinary team, Surface-Active Agents, Young Adult, 03 medical and health sciences, medicine, Humans, Genetic Testing, Intensive care medicine, Aged, Genetic testing, business.industry, Research, lcsh:R, Infant, medicine.disease, Human genetics, 030228 respiratory system, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, RNA, business
Abstract: Background Genetic testing is proposed for suspected cases of monogenic pulmonary fibrosis, but clinicians and patients need specific information and recommendation about the related diagnosis and management issues. Because multidisciplinary discussion (MDD) has been shown to improve accuracy of interstitial lung disease (ILD) diagnosis, we evaluated the feasibility of a genetic MDD (geneMDD) dedicated to the indication for and interpretation of genetic testing. The geneMDD group met monthly and included pediatric and adult lung specialists with ILD expertise, molecular and clinical geneticists, and one radiologist. Hematologists, rheumatologists, dermatologists, hepatologists, and pathologists were also invited to attend. Results Since 2016, physicians from 34 different centers in 7 countries have participated in the geneMDD. The medical files of 95 patients (53 males) have been discussed. The median age of patients was 43 years [range 0–77], 10 were ≤ 15 years old, and 6 were deceased at the time of the discussion. Among 85 analyses available, the geneMDD considered the rare gene variants pathogenic for 61: 37 variants in telomere-related genes, 23 variants in surfactant-related genes and 1 variant in MARS. Genetic counseling was offered for relatives of these patients. The geneMDD therapeutic proposals were as follows: antifibrotic drugs (n = 25), steroids or immunomodulatory therapy (n = 18), organ transplantation (n = 21), watch and wait (n = 21), or best supportive care (n = 4). Conclusion Our experience shows that a dedicated geneMDD is feasible regardless of a patient’s age and provides a unique opportunity to adapt patient management and therapy in this very rare condition.
Published: 2019

9. Idiopathic chronic obliterative bronchiolitis: a multicentric retrospective cohort

Author: Mouhamad Nasser, Yurdagül Uzunhan, Sandrine Hirschi, Stéphane Jouneau, François Lebargy, Aurélien Justet, Camille Taillé, Lidwine Wemeau, Victor Valentin, Raphael Borie, Benoit Godbert, Frédéric Gagnadoux, Laurent Guilleminault, Hilario Nunes, Sylvain Marchand-Adam, and Vincent Cottin
Subjects: Pediatrics, medicine.medical_specialty, business.industry, medicine, Retrospective cohort study, Chronic obliterative bronchiolitis, business
Published: 2021

10. Diffuse Pulmonary Non-Amyloid Light-Chain Deposition Disease: Phenotypes and Outcome

Author: Romain Lazor, Laurent Sohier, Vincent Cottin, Magali Colombat, Antoine Roux, Lidwine Wemeau, Anne Gondouin, François Lestelle, Salim Si-Mohamed, Pierre Rigaud, Yurdagul Uzunhan, Helene Morisse Pradier, David C. Rotzinger, Catherine Beigelman, Vincent Bunel, Grégoire Prévot, Martine Reynaud Gaubert, Mouham Nasser, Emmanuel Gomez, and Sandrine Hirschi
Subjects: Pathology, medicine.medical_specialty, Amyloid, business.industry, medicine, medicine.disease, business, Phenotype, Light chain deposition disease
Published: 2021

11. RCT Abstract - Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomized, double-blind, placebo-controlled, phase 3 trial

Author: Jean-Marc Naccache, Morgane Didier, Hilario Nunes, Julie Traclet, Olivia Freynet, Dominique Israel-Biet, Alexandre Chabrol, Arnaud Bourdin, Nathalie Bautin, Emmanuel Bergot, Grégoire Prévot, Jean Pastré, Sylvie Leroy, Philippe Bonniaud, Tristan Dégot, Frédéric Rivière, Raphael Borie, Cécile Chenivesse, Vincent Cottin, Lidwine Wemeau-Stervinou, Bruno Crestani, Martine Reynaud-Gaubert, Antoine Parrot, Dominique Valeyre, Marie-Christine Dombret, Malorie Kerjouan, Abdellatif Tazi, Anne Gondouin, Stéphane Jouneau, Elodie Blanchard, Sylvain Marchand-Adam, Sandrine Hirschi, C. Launois, Ana Nieves, Stéphane Dominique, François-Xavier Blanc, Jacques Cadranel, Marie-Pierre Debray, Anne-Sophie Gamez, Frédéric Gagnadoux, Marine Cachanado, Laurence Berard, Guillaume Beltramo, Tabassome Simon, Pierre-Yves Brillet, A. Gibelin, Emmanuel Gomez, Aurélie Le Borgne-Krams, François Lebargy, Alexandra Rousseau, and Laurent Plantier
Subjects: medicine.medical_specialty, Cyclophosphamide, Exacerbation, business.industry, medicine.disease, Placebo, Gastroenterology, law.invention, Double blind, Idiopathic pulmonary fibrosis, Randomized controlled trial, law, Internal medicine, Medicine, business, medicine.drug
Published: 2021

12. MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression

Author: David A. Schwartz, Joanne J. van der Vis, Bruno Crestani, Marie-Christophe Boissier, Jan C. Grutters, Athina Trachalaki, Raphaël Porcher, Pierre-Antoine Juge, Thierry Schaeverbeke, Spyros Papiris, Nathalie Saidenberg-Kermanac’h, Catherine Boileau, Christophe Richez, Raphael Borie, Jorge Rojas-Serrano, Yurdagul Uzunhan, Theofanis Karageorgas, Montserrat I González-Pérez, Caroline Kannengiesser, Philippe Dieudé, Anna Jamnitski, Tracy J. Doyle, Leticia Kawano-Dourado, René-Marc Flipo, Dimitrios T. Boumpas, Enrique Ambrocio-Ortiz, Dominique Valeyre, Ramcés Falfán-Valencia, Ivette Buendía-Roldán, Joyce S. Lee, Joshua J. Solomon, Coline H.M. van Moorsel, Marie-Pierre Debray, Romain Garofoli, Paul J. Wolters, Lidwine Wemeau-Stervinou, Fabienne Louis-Sydney, Mayra Mejía, Katarina M. Antoniou, Effrosyni D. Manali, Prodromos Sidiropoulos, and Hilario Nunes
Subjects: Lung Diseases, Vital capacity, medicine.medical_specialty, Clinical Sciences, Rheumatoid Arthritis, Gastroenterology, Interstitial Lung Disease, MUC5B, Autoimmune Disease, Pulmonary function testing, Promoter Regions, Arthritis, Rheumatoid, Idiopathic pulmonary fibrosis, Rare Diseases, Rheumatology, Genetic, Interquartile range, Clinical Research, Internal medicine, Rheumatoid, medicine, Genetics, Humans, Risk factor, Promoter Regions, Genetic, Lung, Aged, Proportional hazards model, business.industry, Mortality rate, Arthritis, Inflammatory and immune system, Interstitial lung disease, respiratory system, medicine.disease, Mucin-5B, Idiopathic Pulmonary Fibrosis, respiratory tract diseases, Arthritis & Rheumatology, Anesthesiology and Pain Medicine, Respiratory, Public Health and Health Services, Female, business, Interstitial, Lung Diseases, Interstitial
Abstract: Background The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. Methods Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. Results Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. Conclusion In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.
Published: 2021

13. Fatal Covid‐19 vasoplegic shock in a recipient few hours before double lung transplantation in high emergency

Author: Hervé Mal, Gaëlle Dauriat, Olaf Mercier, Delphine Deblauwe, Lidwine Wemeau, André Vincentelli, Vincent Bunel, Elie Fadel, Florent Laverdure, and Laura Filaire
Subjects: Transplantation, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Double Lung Transplantation, respiratory system, Virology, Infectious Diseases, Shock (circulatory), medicine, medicine.symptom, Letters to the Editor, business, Letter to the Editor
Abstract: SARS‐Cov2 outbreak has deeply impacted French lung transplant programs by the decreased number of lung donors, the scarcity of intensive care unit (ICU) beds and most importantly, the assumed worse prognosis of Covid‐19 in recipients during perioperative period. Despite no evidence has been published to suggest that lung transplant recipients were at high‐risk of acquiring the virus or developing severe Covid‐19, immunosuppression may worsen the prognosis of such infection in patient transplanted for end‐staged lung diseases.
Published: 2020

14. Efficacy and safety of rituximab in patients with chronic hypersensitivity pneumonitis (cHP): A retrospective, multicentric, observational study

Author: Sylvain Marchand-Adam, Pierre Rigaud, Bruno Crestani, Jean-Charles Dalphin, Sylvie Leroy, Dominique Israel-Biet, Raphael Borie, Lidwine Wemeau, Marion Ferreira, Vincent Cottin, Laurent Plantier, Sébastien Quétant, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 3 'Aérosolthérapie et biothérapies à visée respiratoire' (CEPR. Equipe 3), 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)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Lille, 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), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Grenoble Alpes (UGA), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Le Pennec, Deborah, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Vital capacity, Time Factors, Vital Capacity, Gastroenterology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, DLCO, Internal medicine, Forced vital capacity, Pulmonary fibrosis, medicine, Humans, 030212 general & internal medicine, Respiratory system, Lung, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Retrospective cohort study, Middle Aged, respiratory system, medicine.disease, 3. Good health, Treatment Outcome, 030228 respiratory system, Chronic Disease, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Rituximab, Female, Safety, business, Hypersensitivity pneumonitis, medicine.drug, Alveolitis, Extrinsic Allergic
Abstract: International audience; Background: There are chronic forms of hypersensitivity pneumonitis (cHP) that can progress to pulmonary fibrosis. There is no recommended treatment for patients whose respiratory condition continues to deteriorate in spite of antigen avoidance. Whether rituximab may be beneficial to patients with cHP is unknown. The aim of this study was to describe the course of 20 patients with cHP under rituximab therapy.Methods: This retrospective study was conducted from November 2018 to July 2019 in 7 French university hospitals. Forced Vital Capacity (FVC) was measured 6 months before rituximab therapy onset (M - 6), at rituximab onset (M0), and 6 months later (M+6).Results: FVC decreased significantly in the 6 months preceding the introduction of rituximab (65% [44; 112%] at M - 6 versus 59% [39; 102%] at M0; p = 0.0001), but it did not differ significantly from that at 6 months after the introduction of rituximab (61% [38; 99%]). The decline in FVC between M0 and M+6 (-3% [-15; +19%]) was significantly less than between M - 6 and M0 (-8% [-21; 0%]) (p = 0.0002). Between M0 (37% [16; 73%]) and M + 6 (45% [15; 70%]), the median DLCO remained stable (p = 0.12). DLCO improved at M+6 in 5 of the 8 patients (63%) for whom a DLCO value was available at M+6 improved their DLCO.Conclusion: Rituximab seems well tolerated, and may lead to stabilization or improvement of lung function in some patients.
Published: 2020

15. Interstitial lung diseases associated with mutations of poly(A)-specific ribonuclease: a multicentric retrospective cohort study

Author: Bruno Crestani, Matthieu Rigaud, Dominique Israel Biet, Quentin Philippot, Hervé Mal, Benjamin Bondue, Spyros Papiris, Anne Gondouin, Jean-Marc Naccache, Yurdagul Uzunhan, Martine Reynaud-Gobert, Vincent Cottin, Lidwine Wemeau, Caroline Kannengiesser, Raphael Borie, Frédéric Schlemmer, Sandrine Hirschi, Hilario Nunes, Effrosyne Manali, and Ibrahima Ba
Subjects: medicine.medical_specialty, education.field_of_study, Genetic heterogeneity, business.industry, medicine.medical_treatment, Population, Interstitial lung disease, Retrospective cohort study, respiratory system, medicine.disease, Gastroenterology, respiratory tract diseases, Idiopathic pulmonary fibrosis, FEV1/FVC ratio, Internal medicine, Pulmonary fibrosis, medicine, Lung transplantation, business, education
Abstract: Poly(A)-specific ribonuclease (PARN) mutations have been associated with familial pulmonary fibrosis. However, the phenotype of patients with interstitial lung disease (ILD) and PARN mutations is poorly described. We performed a retrospective, observational, non-interventional study. All the patients with an ILD diagnosis and a pathogenic heterozygous PARN mutation, followed in one of the OrphaLung center, were included. We included 30 patients (24 patients from 11 kindreds and 6 sporadic patients with early onset of ILD or extra-pulmonary phenotype). The median age at diagnosis of ILD was 59 years (range 54 - 64). Twenty-three patients (77 %) had a smoking history and/or a fibrogenic exposure. The pulmonary phenotypes were heterogenous but the most frequent diagnosis was idiopathic pulmonary fibrosis (IPF; n=15, 50%). Hematological abnormalities were identified in 3 patients and liver disease in 2 patients. Twenty-one patients received a specific treatment for ILD: steroids (n=13), antifibrotic (n= 11), immunosuppressants (n=5) and N-acetyl cysteine (n=2). The median decline of FVC for the whole population was 292 ml/year (range 146 - 657). After a median follow-up of 2.8 years 8 patients had died and 6 had undergone lung transplantation. The median transplantation-free survival was 4.5 years. PARN mutation carriers were older, and extra-pulmonary manifestations were less frequent as compared to TERT or TERC mutation carriers. PARN mutations are most frequently associated with IPF, but other ILD may be observed. Such phenotypic heterogeneity requires a thorough evaluation of PARN-associated ILD patients in order to define tailored therapeutic strategies.
Published: 2020

16. Characteristics and management of patients with idiopathic pulmonary fibrosis treated with pirfenidone capsule or tablet formulation

Author: Dominique Israel-Biet, Sonia Gueguen, M. Chevereau, Lidwine Wemeau, Annick Clement, I. Dufaure-Garé, Bruno Crestani, Vincent Cottin, Serge Amselem, Stéphane Jouneau, Hilario Nunes, and Philippe Bonniaud
Subjects: Idiopathic pulmonary fibrosis, medicine.medical_specialty, business.industry, Internal medicine, medicine, Capsule, Pirfenidone, medicine.disease, business, Gastroenterology, medicine.drug
Published: 2020

17. Demographics and Baseline Characteristics of Patients with Idiopathic Pulmonary Fibrosis (IPF) in a Real-World Setting: Results of 847 Patients Enrolled in the Radico-ILD Cohort in France

Author: Hilario Nunes, A. Clément, Sylvain Marchand-Adam, J.-M. Naccache, Dominique Israel-Biet, S. Jouneau, I. Dufaure-Garé, Martine Reynaud-Gaubert, RaDiCo-ILD, P. Bonniaud, Sandrine Hirschi, Sébastien Quétant, Lidwine Wemeau, M. Chevereau, Bruno Crestani, David Montani, Vincent Cottin, and J.-C. Dalphin
Subjects: medicine.medical_specialty, Idiopathic pulmonary fibrosis, Demographics, business.industry, Baseline characteristics, Internal medicine, Cohort, medicine, medicine.disease, business
Published: 2020

18. Evaluation of Efficacy and Safety of Rituximab in Hypersensitivity Pneumonitis (HP) Patients: A Retrospective Observational Study

Author: Vincent Cottin, J.-C. Dalphin, Charles-Hugo Marquette, Dominique Israel-Biet, Lidwine Wemeau, M. Ferreira, Sébastien Quétant, B. Crestani, P. Rigaud, R. Borie, and S. Marchand-Adam
Subjects: medicine.medical_specialty, business.industry, Medicine, Rituximab, Retrospective cohort study, business, medicine.disease, Dermatology, Hypersensitivity pneumonitis, medicine.drug
Published: 2020

19. The 1-minute sit-to-stand test to evaluate quadriceps muscle strength in patients with interstitial lung disease

Author: Benoit Wallaert, Lidwine Wemeau, Cécile Chenivesse, Hélène Behal, Justine Briand, and Thierry Perez
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Exercise Tolerance, business.industry, Sit to stand test, Interstitial lung disease, medicine.disease, Quadriceps Muscle, Internal medicine, Pulmonary fibrosis, medicine, Muscle strength, Cardiology, Humans, In patient, Sarcoidosis, Muscle Strength, business, Lung Diseases, Interstitial, Quadriceps muscle strength
Published: 2020

20. Clinical outcomes after lung transplantation for fibrosis in telomerase related genes mutation carriers

Author: Stéphane Jouneau, Sylvain Marchand Adam, Hilario Nunes, Jean-Marc Naccache, Jérôme Le Pavec, Martine Reynaud-Gaubert, Antoine Froidure, Aurélie Le Borgne, Christophe Pison, Bruno Crestani, Lidwine Wemeau-Stervinou, Raphael Borie, François Philit, Antoine Roux, Sandrine Hirschi, Hervé Mal, Vincent Cottin, Romain Lazor, Caroline Kannengiesser, Mathilde Phillips Houlbracq, Service de pneumologie B, 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), Department of Pneumology [Lyon], Hospices Civils de Lyon (HCL), 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), Service de pneumologie (Strasbourg), CHU Strasbourg-Nouvel Hôpital Civil, Service de pneumologie. Centre de compétence des maladies pulmonaires rares, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de chirurgie thoracique et transplantation pulmonaire, Centre chirurgical Marie Lannelongue, 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), Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), 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), Contaminants Chimiques, immunité et Inflammation, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), Université Paris 13 (UP13)-UFR SMBH, Hôpital Nord [CHU - APHM], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Centre Chirurgical Marie Lannelongue (CCML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Diderot - Paris 7 (UPD7)-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), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Idiopathic pulmonary fibrosis, Neutropenia, Gastroenterology, Liver disease, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Median follow-up, Internal medicine, Pulmonary fibrosis, medicine, Transplantation pulmonaire, Lung transplantation, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Lung, business.industry, Fibrose pulmonaire, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, medicine.anatomical_structure, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business
Abstract: International audience; Carriers of telomerase related genes (TRG) mutation seem to present a worst prognosis with more common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT and identify pre-LT prognosis factors in a multicenter cohort of lung transplant recipients with TRG mutation.We retrospectively reviewed all identified patients with pathogenic TRG mutation (n=38; TERT, n=22, TERC, n=10, RTEL1, n=6) who received LT in France, Switzerland and Belgium between 2009 and 2018. The median age at LT was 54 years (46-59), 70% were male, and 60% had idiopathic pulmonary fibrosis (IPF). At diagnosis of pulmonary fibrosis, 84% had a hematological disease, including 8 with myelodysplasia, and 45% had a liver disease. After a median follow up of 2.2 years (1,2-3,7), 16 received a single LT, 22 a double LT and 2 a combined liver-LT.The overall post-LT median survival was 3.75 years (1.8-NA). Patients with myelodysplasia before LT had an increased risk of death after LT (HR= 4.12 (1.47-11.53) p=0.007). After LT, all patients showed anemia, 70% thrombocytopenia, and 60% neutropenia. Four patients showed severe liver disease: portal hypertension, cirrhosis. Sixteen patients (42%) experienced acute renal failure and 18 (47%) developed chronic renal insufficiency during follow up. Four developed chronic lung allograft dysfunction.Overall survival after LT supports LT in TRG mutation carriers. Careful evaluation at diagnosis, might limit LT indication for patients with established myelodysplasia.
Published: 2019

21. Long-term effects of pulmonary rehabilitation on daily life physical activity of patients with stage IV sarcoidosis: A randomized controlled trial

Author: Maeva Kyheng, Sandrine Stelianides, Benoit Wallaert, Lidwine Wemeau, Jean Marie Grosbois, Julien Labreuche, and University of Lille
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Respiratory Therapy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Quality of life, Patient Education as Topic, Sarcoidosis, Pulmonary, law, Behavior Therapy, Internal medicine, Activities of Daily Living, medicine, Humans, Pulmonary rehabilitation, 030212 general & internal medicine, Patient Reported Outcome Measures, Prospective cohort study, Exercise, Depression (differential diagnoses), Fatigue, Aged, Exercise Tolerance, business.industry, Psychosocial Support Systems, Middle Aged, Combined Modality Therapy, Confidence interval, 3. Good health, Exercise Therapy, Mood, Dyspnea, Treatment Outcome, 030228 respiratory system, Quality of Life, Anxiety, Female, medicine.symptom, business, Physical Conditioning, Human
Abstract: Introduction Pulmonary rehabilitation (PR) is known to improve exercise tolerance, mood, and quality of life in patients with chronic respiratory diseases. The aim of this work was to determine whether PR provides long-term benefits in increasing daily life physical activity in patients with chronic sarcoidosis. Methods This randomized prospective study (registered ClinicalTrials.gov NCT02044939 ) of 38 patients with stage IV chronic sarcoidosis was performed between 2012 and 2016. Patients were assigned to participate in a 2-month PR program (n = 20) or receive counseling (n = 18). Assessments were performed at baseline, 2 months (end of the PR program), 6 months, and 12 months, and included daily life physical activity parameters (measured for 5 consecutive days), exercise tolerance, dyspnea, anxiety, depression, fatigue, and quality of life. The primary outcome was the 12-month change in time spent in activities above an estimated energy expenditure of 2.5 metabolic equivalents (METs). Secondary daily life physical activity outcomes included number of steps per day, total daily energy expenditure, and total energy expenditure above 2.5 METs. Results The primary outcome did not differ between the two groups; mean between-group differences were −13.2 min (95% confidence interval [CI]: −76.3 to 49.8) at 6 months and −18.1 min (95% CI: −55.7 to 19.4) at 12 months. Although PR had no effect on secondary daily life physical activity outcomes, it did significantly increase exercise tolerance at 6 and 12 months and decrease the dyspnea score at 6 months and the fatigue score at 12 months. Conclusion This trial failed to demonstrate a beneficial effect of PR on daily life physical activity in sarcoidosis patients, suggesting that long-term behavioral programs may be necessary to complement PR.
Published: 2019

22. Characterisation of a new clinical presentation of chronic lymphocytic leukaemia: symptomatic bronchial involvement, a study from the FILO group

Author: Mathieu Wemeau, Kamel Laribi, Romain Dubois, Brigitte Dreyfus, Stéphanie Poulain, Cécile Tomowiak, Jehan Dupuis, Frédéric Wallyn, Hélène Demarquette, Héloïse Dapvril, Florence Cymbalista, Charles Herbaux, Jacques-Olivier Bay, Jean-Baptiste Bossard, Franck Morschhauser, Morgane Nudel, Lidwine Wemeau, Stéphane Leprêtre, Fanny Baran-Marszak, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor, Centre Hospitalier Le Mans (CH Le Mans), CHU Clermont-Ferrand, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Rouen, Normandie Université (NU), CH de Roubaix, CHADEYRON, DOMINIQUE, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, medicine.medical_specialty, endobronchial nodules, extramedullary involvement, MEDLINE, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Extramedullary Involvement, medicine, Humans, treatment criterion, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, Lymphocytic leukaemia, business.industry, Retrospective cohort study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, symptomatic bronchial involvement, Leukemia, 030220 oncology & carcinogenesis, Female, Presentation (obstetrics), business, chronic lymphocytic leukaemia, 030215 immunology
Abstract: International audience; No abstract available
Published: 2019

23. Regulator of telomere length 1 ( RTEL1 ) mutations are associated with heterogeneous pulmonary and extra-pulmonary phenotypes

Author: Arturo Londoño-Vallejo, Clément Gauvain, Julie Traclet, Tristan Dégot, Vincent Cottin, Marie Wislez, Raphael Borie, Bruno Crestani, Stéphane Dominique, Lidwine Wemeau-Stervinou, Patrick Revy, Aurélie Cazes, Caroline Kannengiesser, Pierre-Antoine Juge, Hilario Nunes, Christelle Ménard, Diane Bouvry, Catherine Boileau, Jacques Cadranel, Marie-Pierre Debray, Sébastien Quétant, Anne Sophie Gamez, Hervé Mal, Grégoire Prévot, Philippe Dieudé, Madeleine Jaillet, Arnaud Mailleux, 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 Sorbonne Paris Cité (USPC), Rétrovirus et Pathologie Comparée (RPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Département de Radiologie [Bichat] (DR- Bichat), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie et réanimation [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Service de Rhumatologie, AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité-AP-HP, CHU Rouen, Normandie Université (NU), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Telomeres and Cancer Laboratory, Institut Curie, 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), Service de cardiologie, Service de Pneumologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), Université Paris 13 (UP13)-UFR SMBH, Service de pneumologie [Toulouse], CHU Toulouse [Toulouse]-Hôpital Larrey, Centre Hospitalier Universitaire [Grenoble] (CHU), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Université de Lyon-Université de Lyon, Service de pneumologie. Centre de compétence des maladies pulmonaires rares, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Theranoscan, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), 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), 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 Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Centre de Recherche Saint-Antoine (UMRS893), Université Paris Diderot - Paris 7 (UPD7)-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), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), UFR SMBH-Université Paris 13 (UP13), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), 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)-PRES Sorbonne Paris Cité, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Gene mutation, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Fibrosis, Pulmonary fibrosis, Medicine, Telomerase reverse transcriptase, Exome, Exome sequencing, business.industry, Interstitial lung disease, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, respiratory system, medicine.disease, 3. Good health, respiratory tract diseases, 030104 developmental biology, 030228 respiratory system, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, business
Abstract: Regulator of telomere length 1 (RTEL1) mutations have been evidenced in 5–9% of familial pulmonary fibrosis; however, the phenotype of patients with interstitial lung disease (ILD) and RTEL1 mutations is poorly understood.Whole exome sequencing was performed in 252 probands with ILD and we included all patients with ILD and RTEL1 mutation. RTEL1 expression was evaluated by immunochemistry in the lungs of controls, as well as in RTEL1 and telomerase reverse transcriptase (TERT) mutation carriers.We identified 35 subjects from 17 families. Median age at diagnosis of ILD was 53.1 years (range 28.0–80.6). The most frequent pulmonary diagnoses were idiopathic pulmonary fibrosis (n=20, 57%), secondary ILD (n=7, 20%) and unclassifiable fibrosis or interstitial pneumonia with autoimmune features (n=7, 20%). The median transplant-free and overall survival periods were 39.2 months and 45.3 months, respectively. Forced vital capacity at diagnosis was the only factor associated with decreased transplant-free survival. Extra-pulmonary manifestations were less frequent as compared to other telomere-related gene mutation carriers. A systematic analysis of the literature identified 110 patients with ILD and RTEL1 mutations (including this series) and confirmed the heterogeneity of the pulmonary phenotype, the prevalence of non-idiopathic diseases and the low prevalence of extra-pulmonary manifestations.Immunohistochemistry showed that RTEL1 was expressed by bronchial and alveolar epithelial cells, as well as by alveolar macrophages and lymphocytes, but not by fibroblasts.
Published: 2019

24. Changes in the physical and affective dimensions of dyspnoea after a home-based pulmonary rehabilitation in fibrotic idiopathic interstitial pneumonias

Author: Cécile Chenivesse, Sarah Gephine, Martin Dornbierer, Victor Valentin, Olivier Le Rouzic, Lidwine Wémeau, and Jean-Marie Grosbois
Subjects: Medicine
Abstract: Background Our objective was to evaluate the short-, medium- and long-term benefits of home-based pulmonary rehabilitation (PR) on the physical and affective components of dyspnoea in people with fibrotic idiopathic interstitial pneumonias (f-IIPs). Anxiety and depressive symptoms, fatigue, health-related quality of life and exercise tolerance were also assessed. Methods Data on 166 individuals with f-IIPs who enrolled in an 8-week home-based PR programme (weekly supervised 90-min session) were retrospectively analysed. Assessments included the Dyspnoea-12 (D-12) questionnaire, Hospital Anxiety and Depression Scale, Fatigue Assessment Scale, Visual Simplified Respiratory Questionnaire and 6-min stepper test, and were performed at home at short, medium (6 months) and long (12 months) term. Results Among the 166 individuals with f-IIPs who enrolled in PR, 75 (45%) and 91 (55%) participants had a diagnosis of idiopathic pulmonary fibrosis and fibrosing non-specific interstitial pneumonia, respectively, and 87 (52%) participants concluded a full year of follow-up. In the total group, both physical and affective components of dyspnoea were improved, at short, medium and long term, after PR. Overall, half of the participants reached the minimally important difference of 3 points of the D-12 questionnaire at the end of PR, and at the 6- and 12-month follow-ups. Anxiety and depressive symptoms, fatigue and health-related quality of life were also improved, while the short-term benefits in exercise tolerance were not maintained 1 year after PR. Conclusion An individualised home-based PR programme resulted in short-, medium- and long-term improvements in both physical and affective components of dyspnoea assessed by the D-12 questionnaire.
Published: 2024
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25. Methotrexate and rheumatoid arthritis associated interstitial lung disease

Author: Kevin D. Deane, Eric L. Matteson, Leticia Kawano-Dourado, Yannick Allanore, René-Marc Flipo, Christophe Richez, Sébastien Ottaviani, David A. Schwartz, Karina Bonfiglioli, Montserrat I González-Pérez, Yurdagul Uzunhan, Gabriel Thabut, Jorge Rojas Serrano, Raphael Borie, Thierry Schaeverbeke, Benoit Wallaert, Ivan O. Rosas, Ramcés Falfán-Valencia, Lorenzo Cavagna, Marie-Elise Truchetet, Pascal Richette, Marco Sebastiani, Tracy J. Doyle, Emanuele Bozzalla Cassione, Gouri Koduri, Esther Ebstein, Jay H. Ryu, Lidwine Wemeau-Stervinou, Huguette Lioté, Dominique Valeyre, Pedro Rodríguez-Henriquez, Raphaël Porcher, Bruno Crestani, Jessica Lau, Steven Gazal, Marie-Christophe Boissier, Marie-Pierre Debray, Hilario Nunes, Mayra Mejía, Ivette Buendía-Roldán, Sylvain Marchand-Adam, Robert Vassallo, Andreina Teresa Manfredi, Nathalie Saidenberg-Kermanac’h, Joshua J. Solomon, Claire Dromer, Joyce S. Lee, Gloria Pérez-Rubio, Catherine Boileau, V. Michael Holers, Pierre-Antoine Juge, Marcio Valente Yamada Sawamura, Ronaldo Adib Kairalla, Caroline Kannengiesser, and Philippe Dieudé
Subjects: 030203 arthritis & rheumatology, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Extramural, business.industry, Diffuse lung disease, respiratory system, behavioral disciplines and activities, Article, respiratory tract diseases, Arthritis, Rheumatoid, body regions, 03 medical and health sciences, Methotrexate, 0302 clinical medicine, Antirheumatic Agents, Case-Control Studies, Family medicine, medicine, Humans, In patient, 030212 general & internal medicine, Lung Diseases, Interstitial, business, Lung
Abstract: Background: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Its use has been associated with hypersensitivity pneumonitis and diffuse lung disease. Whether MTX exposure increases the risk of interstitial lung disease (ILD) in patients with RA is disputed. Objectives: We aimed to evaluate the association of antecedent MTX use with development of RA-ILD. Methods: Through a case-control study design with derivation and international validation samples, we examined the association of MTX exposure with ILD in 482 patients with RA-ILD and 741 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. Results: Analysis of the derivation sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.25 to 0.92; P=0.028), which was confirmed in the validation samples (pooled adjusted OR, 0.39; 95% CI, 0.23 to 0.68; P Conclusion: Our results suggest that MTX is not a risk factor for RA-ILD and support a possible disease modifying effect of MTX on development of RA-ILD. Disclosure of Interests: Pierre-Antoine Juge: None declared, Joyce S. Lee Consultant of: Celgene, Genentech, Boehringer Ingelheim, Jessica Lau: None declared, Leticia Kawano: None declared, Jorge Rojas-Serrano: None declared, Marco Sebastiani: None declared, Gouri Koduri: None declared, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking, Karina Bonfiglioli Consultant of: Roche, Abbvie, Pfizer, Janssen and BMS, Marcio Sawamura: None declared, Ronaldo Kairalla: None declared, Lorenzo Cavagna: None declared, Emanuele Bozzalla Cassione: None declared, Andreina Manfredi: None declared, Mayra Mejia: None declared, Pedro Rodriguez Henriquez: None declared, Montserrat I. Gonzalez-Perez: None declared, Ramces Falfan-Valencia: None declared, Ivette Buendia-Roldan: None declared, Glora Perez-Rubio: None declared, Esther Ebstein Consultant of: BMS, Employee of: BMS, Steven Gazal: None declared, Raphael Borie Consultant of: Roche, Boehringer Ingelheim, Sebastien Ottaviani: None declared, Caroline Kannengiesser: None declared, Benoit Wallaert Consultant of: Roche, Boehringer Ingelheim, Yurdagul Uzunhan Consultant of: Roche, Boehringer Ingelheim,, Hilario Nunes: None declared, Dominique Valeyre Consultant of: Astra Zeneca, Roche, Boehringer Ingelheim, Nathalie Saidenberg Kermanac’h: None declared, marie-Christophe Boissier: None declared, Lidwine Wemeau Stervinou Consultant of: Roche, Janssen, BMS, Boehringer Ingelheim, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Sylvain Marchand-Adam Consultant of: Roche, Novartis, Boehringer Ingelheim, Pascal Richette: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi, Claire Dromer: None declared, Marie-Elise Truchetet: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Thierry Schaeverbeke: None declared, Huguette Liote: None declared, Gabriel Thabut Employee of: Astra Zeneca, Kevin Deane Grant/research support from: Janssen, Consultant of: Inova, ThermoFisher, Janseen, BMS and Microdrop, Joshua Solomon: None declared, Tracy Doyle: None declared, Jay H. Ryu: None declared, Ivan O. Rosas Consultant of: Boehringer Ingelheim, Gerentech, Three Lakes Partners, V. Michael Holers Grant/research support from: Janssen, Celgene, and BMS, Catherine Boileau: None declared, Marie-Pierre Debray: None declared, Raphael Porcher: None declared, David A. Schwartz Consultant of: NuMedii, Robert Vassallo Shareholder of: Pfizer, BMS, SunPharma, Bruno Crestani Shareholder of: Apellis, Boehringer Inghelheim, Medillune, Roche, Consultant of: Boehringer Ingelhiem, Astra Zeneca, Roche, Sanofi, Philippe Dieude: None declared
Published: 2020

26. Multidisciplinary team dedicated to suspected heritable pulmonary fibrosis

Author: Nadia Nathan, Serge Amselem, Ralph Epaud, Philippe Dieudé, Laurent Gouya, Bruno Crestani, Vincent Cottin, Olivier Brugière, Pascale Fanen, Lidwine Wemeau-Stervinou, Annick Clement, Caroline Kannengiesser, Flore Sicre de Fontbrune, Clairelyne Dupin, Diane Bouvry, and Raphael Borie
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Mean age, Lung biopsy, medicine.disease, Multidisciplinary team, Patient management, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Pulmonary fibrosis, medicine, Lung transplantation, 030212 general & internal medicine, Intensive care medicine, business, Genetic testing
Abstract: Genetic testing is proposed for suspected cases of pulmonary fibrosis of genetics origin but clinicians and patients need advice about the related diagnostic and management issues. Because multidisciplinary team (MDT) has been shown to improve accuracy of ILD diagnosis, we evaluated the feasibility of an MDT dedicated to the indication and interpretation of genetic testing. The MDT met monthly, included pneumologists experts in ILD in adults, children, geneticists, radiologist. Hematologists, rheumatologists, dermatologists, hepatologists, and pathologists were also invited to attend. Since 2016, 70 patients (37 males, 33 females) were discussed, from 31 different centers (7 countries). Mean age was 46.4 years [0-71] including 3 patients The MDT therapeutic proposals were: antifibrotic drugs (n=23), best supportive care (n=4), surgical lung biopsy (n=2), steroids (n=7), lung transplantation (n=16), or watch and wait (n=9). Our experience shows that a dedicated MDT with genetic analysis is feasible including patients of all ages and provides a unique opportunity to improve knowledge and to adapt patient management and therapy.
Published: 2018

27. Pulmonary hypertension in patients with idiopathic pulmonary fibrosis and combined pulmonary fibrosis and emphysema: hemodynamic severity

Author: Emmanuel Bergot, Fabrice Piegay, Martine Reynaud-Gaubert, Xavier Jaïs, Lize Kiakouama-Maleka, Mouhamad Nasser, Laurent Bertoletti, David Montani, Julie Traclet, Vincent Cottin, Sylvain Marchand-Adam, Stéphanie Polazzi, Kais Ahmad, Hilario Nunes, Emmanuel Gomez, Maria Laura Graziani, Lidwine Wemeau-Stervinou, Boubou Camara, Anna Nieves, Sabrina Zeghmar, Anne-Marie Schott-Pethelaz, Dominique Israel-Biet, Virginie Zarza, Microbes évolution phylogénie et infections (MEPHI), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Assistance Publique-Hôpitaux de Marseille (AP-HM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie (Hôpital Louis Pradel), Hospices Civils de Lyon (HCL), Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), Clinique de pneumologie, CHU Grenoble, Service de Pneumologie A, Centre de Compétences des Maladies Pulmonaires Rares, Université Paris Descartes - Paris 5 (UPD5), Université Paris-Sud - Paris 11 (UP11), Département de Pneumologie [HCL, Lyon], Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie et Réanimation Respiratoire (DHU TORINO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre-Centre de Référence de l'Hypertension Pulmonaire Sévère, Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), Université Paris 13 (UP13)-UFR SMBH, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de pneumologie. Centre de compétence des maladies pulmonaires rares, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pôle Information Médicale Evaluation Recherche (IMER), Hôpital Louis Pradel – Service de Pneumologie – Centre de Référence des Maladies Pulmonaires Rares, Department of Pneumology [Lyon], Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), Groupe de recherche sur la thrombose, pharmacologie des antithrombotiques et situations à risque (GRT), Université Jean Monnet - Saint-Étienne (UJM), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre-Centre de Référence de l'Hypertension Pulmonaire Sévère, and Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: medicine.medical_specialty, business.industry, respiratory system, medicine.disease, Combined pulmonary fibrosis and emphysema, Pulmonary hypertension, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, respiratory tract diseases, 3. Good health, Idiopathic pulmonary fibrosis, FEV1/FVC ratio, medicine.anatomical_structure, DLCO, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine.artery, Internal medicine, Pulmonary artery, Pulmonary fibrosis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine, Cardiology, Vascular resistance, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, business, ComputingMilieux_MISCELLANEOUS
Abstract: Background: Idiopathic pulmonary fibrosis (IPF) and combined pulmonary fibrosis with emphysema (CPFE) are associated with an increased risk of pulmonary hypertension (PH). Few data are available regarding PH severity and correlation with respiratory physiology. Aim: To evaluate baseline respiratory and hemodynamic characteristics of patients with IPF-PH and CPFE-PH. Methods: Patients with a diagnosis of IPF or CPFE were analysed from a prospective multicenter observational study (HYPID) conducted in French expert centers for rare pulmonary diseases and/or PH (NCT01443598). Severe PH was defined as mean pulmonary artery pressure (mPAP) > 35 mmHg or cardiac index (CI) Results: Out of 220 patients included in the cohort, 61 had IPF-PH and 75 CPFE-PH. Patients were 74% males, with a mean age of 69 ± 9 years. The mean FVC at baseline was 75 ± 25%, and mean DLco was 25 ± 10%. NYHA class was I-II in 18% of patients, III in 56%, IV in 24%, N/A in 2%. Six-min walk distance was 276 ± 145 m. Hemodynamic characteristics were mPAP 38 ± 9 mmHg, CI 2.5 ± 0.6 L/min/m², and pulmonary vascular resistance (PVR) 8.7 ± 3 WU. Kco was lower in CPFE-PH than in IPF-PH (table); other parameters were comparable between groups. DLco at baseline significantly correlated with mPAP (p=0.01 in IPF and 0.04 in CPFE group). DLco also correlated with PVR and CI in IPF-PH (p=0.001 and 0.01 respectively), but not in CPFE-PH. Conclusion: Hemodynamic severity is comparable in patients with IPF-PH and CPFE-PH, and correlates with DLco. Further study is needed to evaluate the prognostic significance of hemodynamic severity.
Published: 2018

28. OP0284 Muc5b promoter variant rs35705950 is a risk factor for rheumatoid arthritis – interstitial lung disease

Author: A. Gross, Naoyuki Tsuchiya, Ramcés Falfán-Valencia, N. Saidenberg, Shomi Oka, Joyce S. Lee, Bruno Crestani, E. Ebstein, Ivette Buendía-Roldán, M. Schwarz, David A. Schwartz, J. van der Vis, Kevin D. Deane, Sébastien Ottaviani, D. Assayag, Theofanis Karageorgas, C. Kannengiesser, Avram D Walts, Timothy B. Niewold, M.-P. Debray, René-Marc Flipo, Paul J. Wolters, Lidwine Wemeau-Stervinou, P. Dieudé, Catherine Boileau, C. Van Moorsel, K. Antoniou, Mayra Mejía, Pierre-Antoine Juge, Spyros Papiris, Effrosyni D. Manali, Dimitrios T. Boumpas, Hilario Nunes, J. Rojas-Serrano, Benoit Wallaert, Tasha E. Fingerlin, Shigeto Tohma, R. Borie, Y. de Man, Eric L. Matteson, Dominique Valeyre, Jan C. Grutters, Montserrat I González-Pérez, M. Holers, S. Gazal, Y. Wang, Tracy J. Doyle, Hiroshi Furukawa, Sylvain Marchand-Adam, Joshua J. Solomon, and E. Dobrinskikh
Subjects: medicine.medical_specialty, education.field_of_study, business.industry, Population, Interstitial lung disease, respiratory system, medicine.disease, Gastroenterology, respiratory tract diseases, Idiopathic pulmonary fibrosis, Usual interstitial pneumonia, Rheumatoid arthritis, Internal medicine, Cohort, medicine, Immunohistochemistry, Risk factor, business, education
Abstract: Background Rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and idiopathic pulmonary fibrosis (IPF) share phenotypic similarities. The gain-of-function MUC5B promoter variant rs35705950 is the strongest risk factor for development of IPF Objectives We hypothesised that rs35705950 would also contribute to the risk of ILD in RA patients. Methods Using a French discovery population and multi-ethnic validation populations from 6 different countries, we tested the association of the MUC5B promoter variant in RA-ILD (n=620), RA without ILD (n=614), and unaffected controls (n=5448). Results The discovery population revealed an association of the MUC5B promoter variant with RA-ILD when compared to unaffected controls (ORadj=3.8 95% CI: 2.8 to 5.2; p=9.7x10–17) (figure 1A). Similar to the discovery cohort, the MUC5B promoter variant was significantly over-represented among the cases of RA-ILD in the multi-ethnic study cohorts when compared to unaffected controls (ORadj=5.5 95% CI: 4.2 to 7.2; p=4.7x10–35) (figure 1A), and when the discovery population and the multi-ethnic cohorts were combined (ORcombined=4.7 95% CI: 3.9 to 5.8; p=1.3x10–49) (figure 1A). Additionally, the MUC5B promoter variant was found to increase the risk of ILD among patients with RA (ORcombined=3.1 95% CI: 1.8 to 5.4; p=7.4x10–5), however, no statistical association with the MUC5B promoter variant was observed for RA without ILD (figure 1B). The association of the MUC5B promoter variant with RA-ILD increased significantly when restricted to the usual interstitial pneumonia (UIP) by high-resolution computed tomography (ORcombined=6.1 95% CI: 2.9 to 13.1; p=2.5x10–6) (figure 1C). Immunohistochemical and in-situ hybridization analysis of RA-ILD lung tissue demonstrated expression of MUC5B by type 2 alveolar epithelial cells undergoing endoplasmic reticulum stress. Conclusions Our findings demonstrate that MUC5B promoter variant rs35705950 is a risk factor for RA-ILD specifically associated with radiologic evidence of UIP. Disclosure of Interest None declared
Published: 2018

29. Effects of pulmonary rehabilitation on daily life physical activity of fibrotic idiopathic interstitial pneumonia patients

Author: Olivier Le Rouzic, Nicolas Masson, Benoit Wallaert, Lidwine Wemeau-Stervinou, Baptiste Chéhère, and Jean-Marie Grosbois
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, medicine.medical_treatment, lcsh:R, MEDLINE, Physical activity, Original Reserach Letters, lcsh:Medicine, medicine.disease, respiratory tract diseases, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Quality of life, Internal medicine, Medicine, Anxiety, Pulmonary rehabilitation, 030212 general & internal medicine, medicine.symptom, business, Idiopathic interstitial pneumonia, Depression (differential diagnoses)
Abstract: According to the international consensus statement of 2011, idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (NSIP) are classified as fibrotic idiopathic interstitial pneumonia (f-IIP) of unknown aetiology [1]. f-IIP patients display persistent and significant dyspnoea, exercise intolerance and poor health-related quality of life [2]. f-IIP is also associated with a marked reduction in daily life physical activity (DLPA) [3], which is related to morbidity and mortality in many chronic diseases, including f-IIP [4–6]., Fibrotic idiopathic interstitial pneumonia patients derived benefit from a pulmonary rehabilitation programme in terms of exercise tolerance, anxiety, depression and quality of life without increasing their daily life physical activity http://ow.ly/WV7U30kgNkU
Published: 2018

30. 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

31. Reply to Gilchrist et al. and to Musher

Author: Hugues Melliez, David Launay, Benjamin Lopez, Benoit Wallaert, Mathilde Bahuaud, Anne Boucher, Lidwine Wemeau-Stervinou, Pierre-Yves Hatron, Eric Hachulla, Sylvain Dubucquoi, Geoffrey Mortuaire, Myriam Labalette, Frédéric Batteux, Guillaume Lefèvre, Karine Faure, Frédéric Wallet, and Louis Terriou
Subjects: 0301 basic medicine, Microbiology (medical), Adult, medicine.medical_specialty, business.industry, 030106 microbiology, MEDLINE, Immunologic Deficiency Syndromes, Bacterial Infections, Dermatology, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Polysaccharides, medicine, Humans, 030212 general & internal medicine, business
Published: 2018

32. Safety and efficacy of pirfenidone in patients carrying telomerase complex mutation

Author: Anne Gondouin, Martine Reynaud-Gaubert, Eline Magois, Anne Sophie Gamez, Hilario Nunes, Maria Molina Molina, Sylvain Marchand-Adam, Aurélien Justet, Lidwine Wemeau, Raphael Borie, Gabriel Thabut, Vincent Cottin, Caroline Kannengiesser, Bruno Crestani, Grégoire Prévot, Cécile Tromeur, Jacques Cadranel, Spyros Papiris, Effrosyni D. Manali, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), 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 B, 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), 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), Department of Pneumology [Lyon], Hospices Civils de Lyon (HCL), Service de Pneumologie, oncologie thoracique et allergologie respiratoire [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), Université Paris 13 (UP13)-UFR SMBH, Pneumology and Intensive Care, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de pneumologie [Toulouse], CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département des Maladies Respiratoires [Montpellier], Hôpital Arnaud de Villeneuve-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Microbes évolution phylogénie et infections (MEPHI), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Département Hospitalo-Universitaire Fibrosis, Inflammation, Remodeling in cardiovascular, respiratory and renal diseases (Paris), LabEx Inflamex, Université Sorbonne Paris Cité (USPC), Service de Pneumologie [Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Centre de Compétence pour les Maladies Pulmonaires Rares, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Service de pneumologie et réanimation [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Service de Pneumologie [Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz-Université de Franche-Comté (UFC), UFR SMBH-Université Paris 13 (UP13), Université de Brest (UBO), CHU Toulouse [Toulouse]-Hôpital Larrey, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre de Compétence pour les Maladies Pulmonaires Rares, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, Pulmonary and Respiratory Medicine, Oncology, Heterozygote, medicine.medical_specialty, Telomerase, Pyridones, Pulmonary Fibrosis, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Humans, Medicine, In patient, 030212 general & internal medicine, Lung function, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Greece, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Retrospective cohort study, Pirfenidone, Middle Aged, respiratory system, humanities, 3. Good health, body regions, 030228 respiratory system, Multicenter study, Spain, Mutation, Mutation (genetic algorithm), RNA, Female, France, Patient Safety, business, medicine.drug
Abstract: In this retrospective study, a beneficial effect of pirfenidone on lung function decline could not be demonstrated in patients carrying TERT/TERC mutation
Published: 2018

33. The 1-minute sit-to-stand test to detect exercise-induced oxygen desaturation in patients with interstitial lung disease

Author: Benoit Wallaert, Hélène Behal, Justine Briand, Cécile Chenivesse, Lidwine Wemeau-Stervinou, CHU Lille, Université de Lille, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Centre de compétences des maladies pulmonaires rares de l'adulte [CHU Lille] (CRMPR), 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)-Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), The authors wish to thank Anne M. O’Rourke for editing the manuscript., and Université de Lille, LillOA
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Time Factors, Health Status, Walk Test, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, interstitial lung disease, 6-min walk test, 1-min sit-to-stand test, exercise, functional tests, Internal medicine, Humans, Medicine, Pharmacology (medical), In patient, 030212 general & internal medicine, Lung, Aged, Retrospective Studies, Original Research, lcsh:RC705-779, Exercise Tolerance, Oxygen desaturation, Pulmonary Gas Exchange, business.industry, Sit to stand test, Interstitial lung disease, Reproducibility of Results, lcsh:Diseases of the respiratory system, Gold standard (test), Middle Aged, medicine.disease, 030228 respiratory system, Spirometry, Walk test, Exercise Test, Cardiology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, Lung Diseases, Interstitial, business
Abstract: Background: Although the 6-min walk test (6MWT) is the gold standard for assessing exercise-induced impairment of gas exchange, it cannot easily be performed in a clinical office environment. The aim of this study was to compare the 1-min sit-to-stand test (1STST) with the 6MWT for the ability to assess exercise-induced oxygen desaturation in patients with interstitial lung diseases (ILDs). Methods: A total of 107 patients were enrolled and classified into three groups: sarcoidosis, fibrotic idiopathic interstitial pneumonia (f-IIP), and other forms of ILD. The 6MWT and 1STST were performed on the same day, and pulmonary function tests, pulse oxygen saturation (SpO2), and dyspnea and fatigue (modified Borg scale) were assessed. SpO2 desaturation was evaluated by intraclass correlation coefficient (ICC), Bland–Altman analysis, and kappa (κ) coefficient in the whole population and the patient subgroups. Results: The SpO2 nadir during the 1STST and 6MWT showed good consistency [mean ± standard deviation: 92.5% ± 5% and 90% ± 7%, respectively; ICC 0.77, 95% confidence interval (CI) 0.71–0.83] and correlated strongly ( r = 0.9, p < 0.0001). The frequency of patients with oxygen desaturation ⩾4% was also consistent for the two exercise tests ( κ = 0.68, 95% CI 0.54–0.82). The number of repetitions in the 1STST correlated with the 6MWT distance ( r = 0.5, p < 0.0001), but the dyspnea scores were higher during the 1STST than the 6MWT ( p < 0.0001). These findings did not differ for the three patient subgroups. Conclusion: The 1STST can measure exercise-induced desaturation in ILD patients and could be used as an alternative test to the 6MWT in office practice.
Published: 2018

34. MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease

Author: Yaping Wang, Annick Clement, Nadia Nathan, Joanne J. van der Vis, Huguette Lioté, Aryeh Fischer, Dominique Valeyre, David A. Schwartz, Jan C. Grutters, Timothy B Niewold, Michael A. Nalls, Ivette Buendía-Roldán, Dimitrios Boumpas, Vincent Cottin, Marie-Christophe Boissier, Theofanis Karageorgas, Mayra Mejía, Yaël A de Man, Kevin D. Deane, Effrosyni D. Manali, Katarina M. Antoniou, Joshua J. Solomon, Jay H. Ryu, Pierre-Antoine Juge, Martin Soubrier, Jean Sibilia, Hilario Nunes, Marie-Pierre Debray, Christophe Richez, Spyros Papiris, Steven Gazal, Catherine Boileau, Deborah Assayag, Nathalie Saidenberg-Kermanac’h, Tasha E. Fingerlin, Claire Dromer, Marvin I. Schwarz, Esther Ebstein, Michael Holers, Tracy J. Doyle, Ivan O. Rosas, Bruno Crestani, Hiroshi Furukawa, Evgenia Dobrinskikh, Cornelis Blauwendraat, Paul J. Wolters, Naoyuki Tsuchiya, Thierry Schaeverbeke, Ramcés Falfán-Valencia, Lidwine Wemeau-Stervinou, Gabriel Thabut, Shigeto Tohma, Coline H.M. van Moorsel, Montserrat I González-Pérez, Andrew J. Gross, Benoit Wallaert, Shomi Oka, Caroline Kannengiesser, Joyce S. Lee, Enrique Ambrocio-Ortiz, Aline Frazier, Sylvain Marchand-Adam, René-Marc Flipo, Eric L. Matteson, Pascal Richette, S. Amselem, Raphael Borie, Jorge Rojas-Serrano, Yannick Allanore, Sébastien Ottaviani, Philippe Dieudé, Avram D Walts, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Colorado School of Medicine, Université de Tsukuba = University of Tsukuba, Sagamihara National Hospital [Kanagawa, Japan], Harvard T.H. Chan School of Public Health, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Athens, 'Attikon' Hospital, National and Kapodistrian University of Athens (NKUA), University of Crete [Heraklion] (UOC), St. Antonius Hospital [Nieuwegein], Nanjing Medical University, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Avicenne [AP-HP], Physiopathologie, Cibles et Thérapies de la Polyarthrite Rhumatoïde, Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Lariboisière-Fernand-Widal [APHP], Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], 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), Hôpital de Hautepierre [Strasbourg], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA), CHU Bordeaux [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), National Jewish Health (NJH), Mayo Clinic and Mayo College of Medicine, Rochester, New York University School of Medicine, NYU System (NYU), McGill University = Université McGill [Montréal, Canada], University of California [San Francisco] (UC San Francisco), University of California (UC), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Societe Francaise de Rhumatologie, Club Rhumatismes Inflammation, la Chancellerie des Universites de Paris (legs Poix), Sorbonne Paris Cite (FPI-SPC Program), Agence Nationale de la Recherche ANR-10-LABX-46 ANR-10-EQPX-07-01 ANR-14-CE10-0006 ANR-10-INBS-09, France Genomique National Infrastructure, Pfizer, Chugai, Centre de Resources Biologiques Hopital Bichat Paris FranceFondation Arthritis, Département Hospitalo-Universitaire Fibrose Inflammation Remodelage, National Heart, Lung, and Blood Institute (UH2/3-HL123442, R01-HL097163, R21/R33-HL120770, P01-HL092870, and K23-HL138131), National Institute of Arthritis and Musculoskeletal and Skin Diseases (K23-AR051461), National Institute of Allergy and Infectious Diseases (U01-AI101981), U.S. Department of Defense (W81XWH-17-1-0597), National Center for Advancing Translational Science (UCSF-CTI KL2TR000143), the Nina Ireland Program for Lung Health, the Intramural Research Program of the National Institute of Aging, part of the National Institutes of Health, Department of Health and Human Services (Z01-AG000949–02), and the Japanese Society for the Promotion of Science., Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), and Societe Francaise de Rhumatologie, Club Rhumatismes Inflammation, la Chancellerie des Universites de Paris (legs Poix), Sorbonne Paris Cite (FPI-SPC Program), Agence Nationale de la Recherche ANR-10-LABX-46 ANR-10-EQPX-07-01 ANR-14-CE10-0006 ANR-10-INBS-09, France Genomique National Infrastructure, Pfizer, Chugai, Centre de Resources Biologiques Hopital Bichat Paris France
Subjects: Male, Lung Diseases, medicine.medical_specialty, Genotype, [SDV]Life Sciences [q-bio], Population, Arthritis, behavioral disciplines and activities, Gastroenterology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Promoter Regions, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Genetic, Internal medicine, Gain of Function Mutation, Odds Ratio, Medicine, Humans, Genetic Predisposition to Disease, Rheumatoid/complications/*genetics, Risk factor, education, Aged, 030203 arthritis & rheumatology, Lung/chemistry/pathology, education.field_of_study, business.industry, Interstitial lung disease, General Medicine, Odds ratio, respiratory system, Middle Aged, medicine.disease, respiratory tract diseases, 3. Good health, body regions, Minor allele frequency, 030228 respiratory system, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Rheumatoid arthritis, Female, Interstitial/complications/*genetics, Mucin-5B/analysis/*genetics, business, Idiopathic Pulmonary Fibrosis/genetics
Abstract: International audience; BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7x10(-17)). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7x10(-35)) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3x10(-49)). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4x10(-5)), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5x10(-6)). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Societe Francaise de Rhumatologie and others.).
Published: 2018

35. Prevalence of Venoatrial Compression by Lymphadenopathy in Sarcoidosis

Author: Sofiane Bendaoud, Jacques Remy, Martine Remy-Jardin, Benoit Wallaert, Alain Duhamel, Jean-Baptiste Faivre, Lidwine Wemeau-Stervinou, and Matthieu Gomes
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Sarcoidosis, Left atrium, Computed tomography, Young Adult, Prevalence, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, Heart Atria, Lymphatic Diseases, Aged, medicine.diagnostic_test, business.industry, Middle Aged, Compression (physics), medicine.disease, medicine.anatomical_structure, Pulmonary Veins, cardiovascular system, Female, Radiology, Tomography, X-Ray Computed, business
Abstract: The purpose of the study was to evaluate the prevalence of compressive lymphadenopathy on pulmonary veins (PV) and left atrium (LA) in patients with sarcoidosis.A total of 101 consecutive patients underwent a chest computed tomography angiographic examination with specific analysis of: (a) 3 nodal stations (ie, 7, 8, and 9 stations) for detection of LA compression; (b) 2 nodal stations (ie, 10 and 11 right and left stations) for detection of PV compression.Lymphadenopathy was present in 64 patients (64/101; 63.4%) with computed tomography features of venoatrial compression in 17 patients (17/101; 16.8%). This subgroup included 10 patients with LA compression alone (10/64; 15.6%), 6 patients with PV compression alone (6/64; 9.4%), and 1 patient with both (1/64; 1.5%). The mean diameter of enlarged lymph nodes compressing the LA and PVs was 3.18 ± 0.73 cm (range: 2.1 to 4.4 cm) and 1.9 ± 0.45 cm (range: 1 to 2.9 cm), respectively. PV compression was depicted in a total of 7 patients (7/101; 6.9%), observed as a unilateral (n = 5) or bilateral (n = 2) finding, with a mean number of 3.0 PVs compressed per patient (range: 1 to 7). A total of 10 venous sections showed features of compression, at the level of a lobar confluence (n = 6) or individual segmental veins (V6; n = 4), with a mean reduction in the venous cross-sectional area of 51.09% ± 12.85% (median: 50.06%). Nonfibrotic lung infiltration associated with sarcoidosis was observed in 88.2% of patients with compressive lymphadenopathy (15/17).The prevalence of venoatrial compression in sarcoidosis is 16.8% in the studied population.
Published: 2015

36. AB0007 Shared genetic predisposition in rheumatoid arthritis–interstitial lung disease and familial pulmonary fibrosis

Author: Serge Amselem, Marie-Christophe Boissier, Catherine Boileau, Benoit Wallaert, Aurélien Justet, Gabriel Thabut, Baptiste Coustet, A Clément, Bruno Crestani, Martin Soubrier, Yannick Allanore, Vincent Cottin, S. Ottaviani, Nadia Nathan, Christelle Ménard, Olivier Sand, Steven Gazal, Hilario Nunes, Lidwine Wemeau-Stervinou, H. Lioté, Isabelle Callebaut, Philippe Dieudé, Pierre-Antoine Juge, Marie-Pierre Debray, P. Richette, R.M. Flipo, Patrick Revy, Dominique Valeyre, Dlm Florence, S. Marchand-Adam, J. Sibilia, T. Schaeverbeke, Aline Frazier, Christophe Richez, Caroline Kannengiesser, Raphael Borie, Claire Dromer, and N. Saidenberg
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Pathology, Mutation, business.industry, Interstitial lung disease, Odds ratio, respiratory system, medicine.disease, medicine.disease_cause, respiratory tract diseases, Pathogenesis, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Usual interstitial pneumonia, 030220 oncology & carcinogenesis, Rheumatoid arthritis, Internal medicine, Pulmonary fibrosis, medicine, Genetic predisposition, business
Abstract: Background Despite its high prevalence and mortality, little is known about the pathogenesis of RA–associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA–ILD frequently share the usual interstitial pneumonia pattern and common environmental risk factors, we hypothesized that the two diseases may share additional risk factors including FPF-linked genes. Objectives Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD. Methods We used whole-exome sequencing (WES) followed by restricted analysis of a discrete number of FPF-linked genes and performed a Burden test to assess the excess number of mutations in RA–ILD patients compared to controls. Results Among the 101 RA–ILD patients included, 12 (11.9%) had 13 WESidentified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA–ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations for RA–ILD patients (p=9.45’10-4, odds ratio [OR] 3.17 95% CI 1.53 – 6.12). Telomeres were shorter for RA-ILD patients with a TERT, RTEL1 or PARN mutation than controls (p=2.87x10-2). Conclusions Our results support the contribution of FPF-linked genes to RA–ILD susceptibility. Disclosure of Interest None declared
Published: 2017

37. Pembrolizumab-induced pneumonitis

Author: C. Templier, Jean-Baptiste Faivre, Lidwine Wemeau-Stervinou, Laurent Mortier, Arnaud Scherpereel, Vincent Leroy, and Clement Fournier
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, Original Research Letters, lcsh:R, MEDLINE, lcsh:Medicine, Pembrolizumab, medicine.disease, Dermatology, Organising pneumonia, Surgery, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, 030212 general & internal medicine, business, Pneumonitis
Abstract: Immune checkpoint inhibitors are promising new therapies for advanced cancers. In particular, antibodies against programmed cell death 1 (PD-1), such as nivolumab and pembrolizumab, increase anti-tumour T cell responses by blocking the interaction between PD-1 on T cells and its ligand PD-L1 on cancer cells [1]. Enhanced T-cell responses resulting from checkpoint inhibition can lead to an unusual spectrum of side effects called immune-related adverse events, which involve numerous organs, particularly the skin, liver, and gastrointestinal and endocrine systems [2–11]. Pneumonitis is a potentially lethal side effect of immune checkpoint inhibition, occurring in 1–5% of patients enrolled in trials [2–11]. However, little is known about the clinical and radiological features of checkpoint inhibitor-induced lung disease. Here, we report three cases of pembrolizumab-induced acute interstitial lung disease (ILD). The medical data of the patients presented below were collected in accordance with French regulations, none of which was opposed to their uses., Three cases of pembrolizumab-induced pneumonitis are described, two being consistent with organising pneumonia http://ow.ly/Dvhc308QI39
Published: 2017

38. Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis

Author: Steven Gazal, Hilario Nunes, Jean Sibilia, Christelle Ménard, Aurélien Justet, Philippe Dieudé, Isabelle Callebaut, Amélie Bonnefond, Martin Soubrier, Patrick Revy, Catherine Boileau, Pierre-Antoine Juge, Thierry Schaeverbeke, Aline Frazier, Nathalie Saidenberg, Sébastien Ottaviani, Nadia Nathan, Bruno Crestani, Christophe Béroud, Baptiste Coustet, Vincent Cottin, Lidwine Wemeau-Stervinou, Jean-Pierre Desvignes, Marie-Christophe Boissier, Florence Dastot-Le Moal, Serge Amselem, Philippe Froguel, Yannick Allanore, Annick Clement, Olivier Sand, Gabriel Thabut, Marie-Pierre Debray, Pascal Richette, Caroline Kannengiesser, Benoit Wallaert, Christophe Richez, Dominique Valeyre, Sylvain Marchand-Adam, Huguette Lioté, Nicolas Leulliot, René-Marc Flipo, Raphael Borie, Claire Dromer, David Salgado, Service de Rhumathologie, Hôpital Bichat - Claude Bernard, Assistance Publique - Hôpitaux de Paris (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Service de Pneumologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), UMR 1152, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), UMR 1149, Centre de Recherches sur l'Inflammation, Ecologie et Ecophysiologie Forestières [devient SILVA en 2018] (EEF), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Plateforme de génomique constitutionnelle, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Université de Lille, Service de Radiologie, Hospices Civils de Lyon (HCL), UMR 1100, Université Francois Rabelais [Tours], Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Rhumatologie, CH Belfort-Montbéliard, UMR 5164, Immuno ConcEpT Lab, Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Sorbonne Université (SU), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), 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), Institut de Recherche pour le Développement (IRD [France-Ouest]), Muséum national d'Histoire naturelle (MNHN), Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université de Lille, Droit et Santé, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UMR 1132, Service de Rhumatologie, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Department of Genomics of Common Diseases, Imperial College London, Service Rhumatologie A, Hôpital Cochin [AP-HP], 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), Service Imagerie, service de Rhumatologie, Centre Hospitalier Universitaire de Lille (CHU de Lille), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service Rhumatologie, Hôpital La Rabta [Tunis], FMTS, CRHI, Laboratoire Immunologie Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA), Fédération Hospitalo-Universitaire OMICARE, Rétrovirus et Pathologie Comparée (RPC), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL), Maladie Pulmonaires Rares, Hôpital Louis Pradel [CHU - HCL], UMR U1125 Service rhumatologie, service de rhumatologie, CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Hôpital Avicenne [AP-HP], service de génétique, Societe Francaise de Rhumatologie, Club Rhumatismes Inflammation, la Chancellerie des Universites de Paris (legs Poix), Sorbonne Paris Cite (FPI-SPC Program), Agence Nationale de la Recherche ANR-10-LABX-46 ANR-10-EQPX-07-01 ANR-14-CE10-0006 ANR-10-INBS-09, France Genomique National Infrastructure, Pfizer, Chugai, Centre de Resources Biologiques Hopital Bichat Paris France, ANR-14-CE10-0006,GENEXGERTEL,Rôles génomiques et extragénomiques de RTEL1(2014), Hôpital Bichat - Claude Bernard, Assistance Publique - Hôpitaux de Paris ( AP-HP ), Université Paris Diderot (Paris 7), Université Sorbonne Paris Cité ( USPC ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Saint-Etienne, UMR 1137, Fac Sci, 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 ), Service de Pneumologie et Immuno-Allergologie, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hospices Civils de Lyon ( HCL ), Service de Pneumologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie (Paris 6), Centre National de la Recherche Scientifique ( CNRS ), Université de Bordeaux ( UB ), Sorbonne Universités, Institut de minéralogie, de physique des matériaux et de cosmochimie ( IMPMC ), 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 ), Institut de Recherche pour le Développement ( IRD [France-Ouest] ), Muséum National d’Histoire Naturelle ( MNHN ), Laboratoire de cristallographie et RMN biologiques ( LCRB - UMR 8015 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Droit et Santé (Lille 2) ( UDSL ), European Genomic Institute for Diabetes ( EGID ), Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Lariboisière, Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Université de Lille-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), CHU Cochin [AP-HP], Institut Cochin ( UM3 (UMR 8104 / U1016) ), Centre Hospitalier Universitaire de Lille ( CHU de Lille ), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques, Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Hôpital La Rabta [Tunis), Université de Strasbourg ( UNISTRA ), Rétrovirus et Pathologie Comparée ( RPC ), Institut National de la Recherche Agronomique ( INRA ) -École pratique des hautes études ( EPHE ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon ( ENVL ), Département Génétique, Institut de l'Elevage, Centre Reference Maladies Respiratoires Rares, Hôpital Armand Trousseau, Assistance Publique - Hôpitaux de Paris ( AP-HP ), Centre Hospitalier Universitaire de Clermont-Ferrand, Unité de Nutrition Humaine - Clermont Auvergne ( UNH ), Université Clermont Auvergne ( UCA ) -Institut national de la recherche agronomique [Auvergne/Rhône-Alpes] ( INRA Auvergne/Rhône-Alpes ), Centre de Recherche en Nutrition Humaine d'Auvergne ( CRNH d'Auvergne ), Hôpital Avicenne, Assistance Publique - Hôpitaux de Paris ( AP-HP ), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Institut de l'élevage (IDELE), ProdInra, Archive Ouverte, Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de génétique et embryologie médicales [CHU Trousseau], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], 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), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), European Genomic Institute for Diabetes [Lille] (EGID), Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Hôpital Armand Trousseau, Assistance Publique - Hôpitaux de Paris (AP-HP), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Hôpital Avicenne, Assistance Publique - Hôpitaux de Paris (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), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pathology, medicine.disease_cause, Arthritis, Rheumatoid, 0302 clinical medicine, Risk Factors, Pulmonary fibrosis, Exome, Telomerase, Exome sequencing, Mutation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Interstitial lung disease, Middle Aged, 3. Good health, Europe, Polyarthrite rhumatoïde, maladie pulmonaire, Phenotype, Rheumatoid arthritis, Female, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Heterozygote, fibrose pulmonaire, 03 medical and health sciences, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, respiratory system diseases, Genetic Association Studies, Aged, 030203 arthritis & rheumatology, pulmonary fibrosis, business.industry, Case-control study, DNA Helicases, Sequence Analysis, DNA, medicine.disease, 030228 respiratory system, Case-Control Studies, Immunology, business, Lung Diseases, Interstitial, Software, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53–6.12; p=9.45×10−4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p=2.87×10−2).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.
Published: 2017

39. Targeting the Hedgehog–Glioma-Associated Oncogene Homolog Pathway Inhibits Bleomycin-Induced Lung Fibrosis in Mice

Author: Stéphanie Brayer, Lidwine Wemeau-Stervinou, Elika Farrokhi Moshai, Arnaud Mailleux, Bruno Crestani, Joëlle Marchal Sommé, and Natacha Cigna
Subjects: Male, Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, animal structures, Pyridines, Pulmonary Fibrosis, Blotting, Western, Clinical Biochemistry, Kruppel-Like Transcription Factors, Fluorescent Antibody Technique, Apoptosis, Lung injury, Real-Time Polymerase Chain Reaction, Zinc Finger Protein GLI1, Receptors, G-Protein-Coupled, Immunoenzyme Techniques, Bleomycin, Mice, Idiopathic pulmonary fibrosis, Transforming Growth Factor beta, GLI1, Fibrosis, medicine, Animals, Anilides, Hedgehog Proteins, RNA, Messenger, Sonic hedgehog, Molecular Biology, Hedgehog, Cell Proliferation, Antibiotics, Antineoplastic, biology, Reverse Transcriptase Polymerase Chain Reaction, Glioma, Cell Biology, respiratory system, medicine.disease, Smoothened Receptor, Hedgehog signaling pathway, respiratory tract diseases, Mice, Inbred C57BL, Pyrimidines, biology.protein, Cancer research, Collagen, Smoothened
Abstract: Idiopathic pulmonary fibrosis has been associated with the reactivation of developmental pathways, notably the Hedgehog-Glioma-associated oncogene homolog (GLI) pathway. In this study, we determined whether the Hedgehog pathway was activated in bleomycin-induced lung injury in mice, and whether targeting the Hedgehog-Gli pathway could decrease bleomycin-induced lung fibrosis. After intratracheal injection of bleomycin on Day 0, C57Bl6 mice received GDC-0449 (an inhibitor of Smoothened, the transducer of the pathway), or 2,2'-[[Dihydro-2-(4-pyridinyl)-1,3(2H,4H)-pyrimidinediyl]bis(methylene)]bis[N,N dimethylbenzenamine (GANT61; an inhibitor of GLI transcription factors in the nucleus), from Day 7 to Day 13. At Day 14, whole-lung homogenates were obtained for morphological analysis, assessment of cell apoptosis and proliferation, collagen quantification, and evaluation of profibrotic (transforming growth factor-β, connective tissue growth factor, plasminogen activator inhibitor 1, vascular endothelial growth factor-A) and proinflammatory mediators (IL-1β) expression. We showed that the Hedgehog pathway was activated in bleomycin-induced lung fibrosis on Day 14 after injury, with an increased lung expression of the ligand, Sonic Hedgehog, and with increased messenger RNA expression and nuclear localization of GLI1 and GLI2. Inhibition of Smoothened with GDC-0449 did not influence the development of bleomycin-induced lung fibrosis. By contrast, the inhibition of GLI activity with GANT61 decreased lung fibrosis and lung collagen accumulation, and promoted an antifibrotic and anti-inflammatory environment. Our results identify the hedgehog-Gli pathway as a profibrotic pathway in experimental fibrosis. Inhibition of the Hedgehog-Gli pathway at the level of GLI transcriptional activity could be a therapeutic option in fibrotic lung diseases.
Published: 2014

40. Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis

Author: Lidwine Wemeau-Stervinou, Julie Mankikian, Patrick Revy, Martine Reynaud Gaubert, Christelle Ménard, Jacques Cadranel, Dominique Israel-Biet, Hervé Mal, Grégoire Prévot, Bruno Crestani, Caroline Kannengiesser, Hilario Nunes, Abdellatif Tazi, Dominique Valeyre, Gabriel Thabut, Vincent Cottin, Marion Reocreux, Raphael Borie, Clément Picard, Stéphane Jouneau, Bernard Grandchamp, Anne Bergeron Lafaurie, Laure Tabèze, Sylvain Marchand-Adam, Jean-François Cordier, Jean-Marc Naccache, 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, 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 compétence des maladies pulmonaires rares, Service de pneumologie B, 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), Service de médecine nucléaire [Bobigny], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Department of Pneumology [Lyon], Hospices Civils de Lyon (HCL), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Service de pneumologie [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Theranoscan, Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Pneumologie, Paris, Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), CHU Marseille, Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironnement et cancer (MiCa), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service des maladies respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Avicenne-Jean Verdier-René Muret, Hôpital Bichat - Claude Bernard, OMMIC S.A.S., OMMIC SAS, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Département Hospitalo-universtaire FIRE (Fibrosis, Inflammation and Remodeling), LabEx Inflamex, Service de pneumologie A, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Bichat, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), OMMIC, Chard-Hutchinson, Xavier, 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), Physiopathologie et Epidémiologie des Maladies Respiratoires, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Centre de compétence des maladies pulmonaires rares, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne-Université Paris 13 ( UP13 ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Hospices Civils de Lyon ( HCL ), Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU, Hôpital Larrey, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Service de pneumologie et réanimation [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Microenvironnement et cancer ( MiCa ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Claude Bernard Lyon 1 ( UCBL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Avicenne-Jean Verdier-René Muret, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Bichat, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Macrocytosis, 030204 cardiovascular system & hematology, Gene mutation, medicine.disease_cause, Gastroenterology, [ SDV.EE ] Life Sciences [q-bio]/Ecology, environment, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Cause of Death, Pulmonary fibrosis, Telomerase rna, medicine, Humans, Interstitial pneumonia, Telomerase reverse transcriptase, Telomerase, Aged, Retrospective Studies, Aged, 80 and over, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, Mutation, [ SDV ] Life Sciences [q-bio], business.industry, Middle Aged, Telomere, medicine.disease, Survival Analysis, Idiopathic Pulmonary Fibrosis, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.EE] Life Sciences [q-bio]/Ecology, environment, Logistic Models, 030228 respiratory system, Multivariate Analysis, RNA, Female, France, business
Abstract: Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis.We retrospectively analysed all the genetic diagnoses made between 2007–2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival.237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested for TERT/TERC DAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence of TERT/TERC DAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2% versus 16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40–60 years. Transplant-free survival was lower with than without TERT/TERC DAV (4.2 versus 7.2 years; p=0.046).TERT/TERC DAV were associated with specific clinical and biological features and reduced transplant-free survival.
Published: 2016

41. Daily life physical activity in patients with chronic stage IV sarcoidosis: A multicenter cohort study

Author: François J. Lhuissier, Sandrine Stelianides, Sarah Froidure, Lidwine Wemeau, Maeva Kyheng, Benoit Wallaert, and Jean Marie Grosbois
Subjects: Vital capacity, medicine.medical_specialty, business.industry, VO2 max, General Medicine, daily life physical activity, anxiety, Confidence interval, Pulmonary function testing, aerobic capacity, pulmonary function test, Interquartile range, Internal medicine, depression, medicine, fatigue, Lung volumes, sarcoidosis, Prospective cohort study, business, Respiratory Medicine, Body mass index, Research Articles, Research Article
Abstract: Background and objectives Little is known about the consequences of chronic sarcoidosis on daily life physical activity (DLPA). The aim of this prospective study was to measure DLPA in patients with chronic sarcoidosis and to determine its relationship to clinical and functional parameters. Methods Fifty‐three patients with chronic sarcoidosis and 28 healthy control subjects were enrolled in this multicenter prospective study. Two markers of DLPA (number of steps walked per day [SPD]) and total daily energy expenditure (TEE) were assessed for five consecutive days with a physical activity monitor. Pulmonary function, aerobic capacity (maximal oxygen uptake [VO2max]), exercise capacity (6‐min walk test [6MWT]), and quality of life (self‐reported questionnaires) were also evaluated. Comparisons of DLPA parameters between the two groups were performed using an analysis of covariance adjusted for age, sex, and body mass index (BMI). Relationships between DLPA parameters and patient characteristics were assessed in multivariable linear regression models. Results Patients with sarcoidosis walked significantly fewer SPD than did the control subjects (6395 ± 4119 and 11 817 ± 3600, respectively; P
Published: 2019

42. The Hedgehog System Machinery Controls Transforming Growth Factor-β–Dependent Myofibroblastic Differentiation in Humans

Author: Elika Farrokhi Moshai, Joëlle Marchal-Somme, Aurelie Fabre, Stéphanie Brayer, Bruno Crestani, Lidwine Wemeau-Stervinou, Paul Soler, Monique Dehoux, Natacha Cigna, Guy Lesèche, Hervé Mal, and Arnaud Mailleux
Subjects: Pathology, medicine.medical_specialty, animal structures, Pathology and Forensic Medicine, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, medicine, Sonic hedgehog, Fibroblast, Transcription factor, Hedgehog, 030304 developmental biology, 0303 health sciences, biology, respiratory system, medicine.disease, Hedgehog signaling pathway, respiratory tract diseases, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, embryonic structures, biology.protein, Cancer research, Smoothened, Transforming growth factor
Abstract: Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown cause. Key signaling developmental pathways are aberrantly expressed in IPF. The hedgehog pathway plays a key role during fetal lung development and may be involved in lung fibrogenesis. We determined the expression pattern of several Sonic hedgehog (SHH) pathway members in normal and IPF human lung biopsies and primary fibroblasts. The effect of hedgehog pathway inhibition was assayed by lung fibroblast proliferation and differentiation with and without transforming growth factor (TGF)-β1. We showed that the hedgehog pathway was reactivated in the IPF lung. Importantly, we deciphered the cross talk between the hedgehog and TGF-β pathway in human lung fibroblasts. TGF-β1 modulated the expression of key components of the hedgehog pathway independent of Smoothened, the obligatory signal transducer of the pathway. Smoothened was required for TGF-β1–induced myofibroblastic differentiation of control fibroblasts, but differentiation of IPF fibroblasts was partially resistant to Smoothened inhibition. Furthermore, functional hedgehog pathway machinery from the primary cilium, as well as GLI-dependent transcription in the nucleus, was required for the TGF-β1 effects on normal and IPF fibroblasts during myofibroblastic differentiation. These data identify the GLI transcription factors as potential therapeutic targets in lung fibrosis.
Published: 2012

43. Specific Polysaccharide Antibody Deficiency Revealed by Severe Bacterial Infections in Adulthood: A Report on 11 Cases

Author: Benoit Wallaert, Mathilde Bahuaud, Eric Hachulla, Louis Terriou, David Launay, Hugues Melliez, Frédéric Wallet, Sylvain Dubucquoi, Myriam Labalette, Guillaume Lefèvre, Benjamin Lopez, Lidwine Wemeau-Stervinou, Anne Boucher, Karine Faure, Pierre-Yves Hatron, Geoffrey Mortuaire, and Frédéric Batteux
Subjects: 0301 basic medicine, Microbiology (medical), Adult, Male, Adolescent, Context (language use), Polysaccharide, Pneumococcal Infections, Microbiology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Medicine, Humans, 030212 general & internal medicine, Encapsulated bacteria, chemistry.chemical_classification, Antibody deficiency, biology, business.industry, Polysaccharides, Bacterial, Age Factors, Immunization, Passive, Immunologic Deficiency Syndromes, Bacterial Infections, Middle Aged, biology.organism_classification, medicine.disease, Antibodies, Bacterial, 030104 developmental biology, Infectious Diseases, Streptococcus pneumoniae, chemistry, Immunology, biology.protein, Primary immunodeficiency, Female, Antibody, business, Bacteria
Abstract: We report on 11 cases of specific polysaccharide antibody deficiency (SPAD) revealed in adulthood by severe infections with encapsulated bacteria. Given that immunoglobulin replacement therapy can effectively prevent the recurrence of bacterial infections in this context, SPAD should be considered once other antibody deficiencies have been ruled out.
Published: 2016

44. Safety and efficacy of pirfenidone in patients with lung fibrosis and TERT mutation

Author: Vincent Cottin, Bruno Crestani, Sylvain Marchand Adam, Emmanuel Bergot, Jean Marc Naccache, Anas Medhaoui, Jacques Cadranel, I. Frachon, Eline Magois, Anne Gondouin, Dominique Valeyre, Caroline Kanengiesser, Aurélien Justet, Hilario Nunes, Bernard Grandchamp, Jean-François Cordier, Lidwine Wemeau-Stervineau, and Raphael Borie
Subjects: medicine.medical_specialty, education.field_of_study, Exacerbation, business.industry, Mortality rate, Population, Pirfenidone, 030204 cardiovascular system & hematology, medicine.disease, Gastroenterology, Surgery, 03 medical and health sciences, FEV1/FVC ratio, Idiopathic pulmonary fibrosis, 0302 clinical medicine, 030228 respiratory system, DLCO, Internal medicine, Pulmonary fibrosis, Medicine, business, education, medicine.drug
Abstract: Background Mutations within TERT and TERC are found in 15% of familial pulmonary fibrosis and are associated with hematologic, liver and dermatological disorders. Pirfenidone has been shown to limit FVC decline and to decrease 12 months mortality rate in idiopathic pulmonary fibrosis (IPF). To our knowledge, pirfenidone has not been specifically evaluated in carriers of TERT / TERC mutations. Objectives The aim of this multicenter retrospective French study was to evaluate the safety and efficacy of pirfenidone in carriers of TERT mutations. Results We identified 18 patients (11 men) with a TERT mutation who received pirfenidone: 16 IPF, 1 pneumoconiosis and 1 rheumatoid arthritis-associated ILD. At diagnosis, mean age was 59 ± 6 years, mean FVC was 78.0% ± 16.4 % and mean DLCO was 52.4± 10.2%. The median duration of treatment was 304 days [14 -791]. Gastro intestinal intolerance was observed in 6 patients (33%). One patient showed a transient thrombocytopenia. Pirfenidone was discontinued in 10 patients (55%) due to disease progression (n=5, 28%), exacerbation (n=2, 11%), increased liver enzymes (n=2, 11%) or gastro intestinal intolerance (n=1, 5%). The median FVC decline was 32.6 mL [0-165] per month before pirfenidone initiation versus 35.7 mL [5-166] per month after treatment initiation; 7 patients showed an FVC decline >10% during treatment. Conclusion These preliminary data suggest that pirfenidone is safe in patients with TERT mutation. Disease progression is frequent in this population and does not seem to be influenced by pirfenidone.
Published: 2016

45. Oxygen desaturation during a 6-minute walk test as a predictor of maximal exercise-induced gas exchange abnormalities in sarcoidosis

Author: Sarah Boulanger, Carole Langlois, Thierry Perez, Cécile Chenivesse, Benoit Wallaert, and Lidwine Wemeau-Stervinou
Subjects: Pulmonary and Respiratory Medicine, 030213 general clinical medicine, medicine.medical_specialty, Oxygen desaturation, business.industry, fungi, respiratory system, medicine.disease, Surgery, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, DLCO, Cardiopulmonary exercise test, Internal medicine, Diffusing capacity, medicine, Cardiology, 6-minute walk test, Original Article, Sarcoidosis, Maximal exercise, business, Peak exercise
Abstract: Common tests for evaluating gas exchange impairment have different strengths and weaknesses. Alveolar-to-arterial oxygen pressure difference (AaDO2) at peak exercise is a sensitive indicator but it cannot be measured repeatedly. Diffusing capacity of the lung for carbon monoxide (DLco) is measured at rest and may be too insensitive to predict the effects of exercise on gas exchange impairment. Oxygen desaturation during a 6-minute walk test (∆SpO2-6MWT) can be measured repeatedly, but its value in sarcoidosis is unknown. Here, we evaluated the ability of ∆SpO2-6MWT and DLco to predict gas exchange impairment during exercise in sarcoidosis.This retrospective study of 130 subjects with sarcoidosis investigated the relationship between DLco, ∆SpO2-6MWT, and peak AaDO2 using correlation tests, inter-test reliability analyses, and predictive values. For the analyses of inter-test reliability and predictive values, DLco, peak AaDO2, and ∆SpO2-6MWT were considered as binary variables (normal/abnormal) according to previously defined thresholds.Correlation coefficients between DLco, ∆SpO2-6MWT, and peak AaDO2 were intermediate (0.53-0.67, P0.0003) and Kappa coefficients were low (0.21-0.42, P=0.0003-0.02). DLco predicted (I) increased peak AaDO2 with a positive predictive value (PPV) of 66% and a negative predictive value (NPV) of 78% and (II) increased ∆SpO2-6MWT with a PPV at 36% and an NPV at 88%. Normal DLco was a good predictor of the absence of severe desaturation during the 6MWT (94% NPV) and at peak exercise during cardiopulmonary exercise test (CPET) (100% NPV). ∆SpO2-6MWT predicted peak AaDO2 increase with a PPV of 74% and an NPV of 60%.In a large population of sarcoidosis patients, neither ∆SpO2-6MWT nor DLco was a good predictor of increased peak AaDO2. In contrast, normal DLco was a good predictor of the absence of severe desaturation during the 6MWT and at peak exercise during CPET.
Published: 2016

46. Krypton Ventilation Imaging Using Dual-Energy CT in Chronic Obstructive Pulmonary Disease Patients: Initial Experience

Author: Jean-François Cazaubon, Jean-Baptiste Faivre, Jacques Remy, François Pontana, Lidwine Wemeau-Stervinou, A.L. Hachulla, Thierry Perez, Alain Duhamel, Martine Remy-Jardin, Benoit Wallaert, Patrick Devos, and Suonita Khung
Subjects: Male, medicine.medical_specialty, MEDLINE, Pulmonary disease, chemistry.chemical_element, Statistics, Nonparametric, Radiographic image interpretation, law.invention, Pulmonary Disease, Chronic Obstructive, law, medicine, Humans, Radiology, Nuclear Medicine and imaging, business.industry, Krypton, Middle Aged, Respiratory Function Tests, chemistry, Ventilation (architecture), Radiographic Image Interpretation, Computer-Assisted, Female, Radiology, Tomography, Dual energy ct, Tomography, X-Ray Computed, business
Abstract: To evaluate the tolerance and level of enhancement achievable after inhalation of stable krypton.This study was approved by the institutional review board and the local ethics committee. Written informed consent was obtained from all subjects. The study was planned as a Fleming two-stage design, enabling one to assess the effectiveness of a newer treatment or technique on a small number of patients. At the end of each stage, the results are computed, and the trial can be stopped if the effectiveness is less than a minimum success rate or greater than an expected success rate. After informed consent was obtained, a total of 32 patients (ie, two successive series of 16 patients each) with severe emphysema underwent a dual-source, dual-energy chest computed tomographic (CT) examination after inhalation of a mixture of stable krypton (80%) and oxygen (20%), with reconstruction of diagnostic and ventilation images. For each patient, two regions of interest were selected on a diagnostic image, one in a region of severe emphysema (presumed to be poorly ventilated or not ventilated) and a second one in a region devoid of structural abnormalities (presumed to be normally ventilated), with measurements of attenuation values on the corresponding ventilation image.All examinations were successfully performed, without adverse effects. Differences in attenuation between normal lung and emphysematous areas were found in 28 patients (88%; 95% confidence interval: 71%, 96.5%). The maximal level of attenuation within normal lung was 18.5 HU. Krypton attenuation difference between normal and emphysematous lung was significant, with a median value of 51.8% (P.001).The level of enhancement after inhalation of krypton and its excellent clinical tolerance makes this gas eligible for ventilation CT examinations.
Published: 2012

47. Contents Vol. 82, 2011

Author: D.F. Heigener, K.F. Rabe, Michael W. Moore, Guy Brusselle, Sophie Robin, Osamu Nishiyama, Lucas M. Donovan, Yuji Higashimoto, Guy Joos, Hiroaki Kume, Lisette Stolk, Rhyuji Satoh, Masahide Oki, C.T. Bolliger, Demet Karnak, M. Bernasconi, Kazushige Maeda, Benoit Wallaert, Alain Duhamel, Dror Rosengarten, Albert Hofman, J. Richard Skelly, Yuji Tohda, Lies Lahousse, Masato Muraki, Hideo Saka, Noritsugu Honda, Gözde Köycü, Kanji Fukuda, Satz Mengensatzproduktion, Dmitry Zemtzov, Toshiki Matsuoka, Katia M.C. Verhamme, Masafumi Yamaguchi, Uri Carmi, Carl B. Gillombardo, Katsuyuki Tomita, Mordechai R. Kramer, André G. Uitterlinden, A.H. Diacon, Lidwine Wemeau-Stervinou, Yoichiro Kobashi, Christelle Talleu, Bernard Aguilaniu, Takashi Iwanaga, Toshiyuki Yamagata, James F. X. Jones, Kingman P. Strohl, RA O'Connell, Mark Eijgelsheim, Serpil Dizbay Sak, Tetsuhiro Shiota, Druck Reinhardt Druck Basel, Sam Chai, Yannick M.T.A. van Durme, Ichiro Miyai, Daan W. Loth, Esra Erdemli, Takayuki Miyara, Bruno H. Stricker, Hiroyuki Sano, Monique M.B. Breteler, Oren Fruchter, Ken D. O'Halloran, E. Irusen, and Yusuf Kağan Kadıoğlu
Subjects: Pulmonary and Respiratory Medicine, Traditional medicine, business.industry, Medicine, business
Published: 2011

48. Reduction of Maximal Oxygen Uptake in Sarcoidosis: Relationship with Disease Severity

Author: Alain Duhamel, Bernard Aguilaniu, Christelle Talleu, Benoit Wallaert, Lidwine Wemeau-Stervinou, and Sophie Robin
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Anaerobic Threshold, Sarcoidosis, Rest, Severity of Illness Index, Pulmonary function testing, Young Adult, Disease severity, Predictive Value of Tests, Forced Expiratory Volume, Internal medicine, Severity of illness, Humans, Medicine, Young adult, Aged, Retrospective Studies, Exercise Tolerance, Pulmonary Gas Exchange, business.industry, VO2 max, Middle Aged, medicine.disease, Surgery, Oxygen, Dyspnea, Predictive value of tests, Exercise Test, Cardiology, Female, business, Anaerobic exercise
Abstract: Background: Patients with sarcoidosis frequently exhibit exertional dyspnea. Although the functional limitation might be related to ventilatory problems, some patients exhibited exertional dyspnea without significant abnormalities of pulmonary function tests (PFT). Therefore, the mechanisms responsible for exercise intolerance remain unclear. Objectives: The aim of this retrospective study was to determine the mechanisms responsible for exercise intolerance. Methods: Cardiopulmonary exercise testing (CPET) was performed in 157 dyspneic sarcoid patients (stage I: 29; stage II–III: 95; stage IV: 33) and VO2 peak was correlated with radiological stage and resting PFT. Results: VO2 peak was decreased in 73% patients, did not differ according to radiological stage and was correlated with VC, FVC, FEV1, TLC and DLCO. FVC was the major significant predictor of VO2 peak explaining 17% of VO2 variation. Among CPET variables, peak heart rate and VE/VO2 at ventilatory threshold explained 22% of VO2 alteration in stage I and stage II–III, and 9% in stage IV. In stage IV, VD/VT peak explained 41% of VO2 alteration. Conclusion: In conclusion, in the lower stages circulatory impairment and impaired heart rate response to exercise are involved in the exercise capacity limitation, whereas in stage IV the ventilatory and gas exchange impairment may be more important. CPET must be performed to accurately characterize the mechanisms responsible for exercise limitation and help the clinician in the management of the disease.
Published: 2011

49. Severe hematologic complications after lung transplantation in patients with telomerase complex mutations

Author: Lidwine Wemeau-Stervinou, Jean-François Cordier, Emmanuel Bergot, Hervé Mal, Bruno Crestani, Gabriel Thabut, Régis Peffault de la Tour, François Philit, Vincent Cottin, David Boutboul, Jean-Marc Naccache, Jérôme Le Pavec, Caroline Kannengiesser, Patrick Revy, Raphael Borie, Stéphane Jouneau, Sandrine Hirschi, Service de Pneumologie A, AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Centre de compétence des maladies pulmonaires rares, Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de pneumologie (Strasbourg), CHU Strasbourg-Nouvel Hôpital Civil, Service de chirurgie thoracique et transplantation pulmonaire, Centre chirurgical Marie Lannelongue, Service de pneumologie B, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Service de Pneumologie, CHU Caen, Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA ), Service de pneumologie. Centre de compétence des maladies pulmonaires rares, CHU Tenon [APHP], Laboratory of Genome Dynamics in the Immune System, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 ( UPD7 ) -CHU Saint Louis [APHP], Service d'Hématologie Greffe, Hospital Saint Louis, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), 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 ), Hospices Civils de Lyon ( HCL ), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Service de pneumologie A, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Bichat, Département Hospitalo-universtaire FIRE (Fibrosis, Inflammation and Remodeling), LabEx Inflamex, Department of Pneumology [Lyon], Cadieu, Muriel, 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 compétence des maladies pulmonaires rares, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Chirurgical Marie Lannelongue (CCML), 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), Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], thrombocytopenia, Neutropenia, Severity of Illness Index, Gastroenterology, Idiopathic pulmonary fibrosis, Internal medicine, Pulmonary fibrosis, medicine, Humans, Lung transplantation, genetics, Telomerase, Retrospective Studies, Transplantation, Lung, [ SDV ] Life Sciences [q-bio], business.industry, Myelodysplastic syndromes, Bone marrow failure, familial, Middle Aged, Prognosis, medicine.disease, idiopathic pulmonary fibrosis, Hematologic Diseases, myelodysplastic syndromes, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Mutation, Female, Surgery, Cardiology and Cardiovascular Medicine, business, Lung Transplantation
Abstract: International audience; BACKGROUND: Mutations in the telomerase complex (TERT and TR) are associated with pulmonary fibrosis and frequent hematologic manifestations. The aim of this study was to characterize the prognosis of lung transplantation in patients with TERT or TR mutations. METHODS: Patients with documented TERT or TR mutations who received a lung transplant between 2007 and 2013 in France were identified via an exhaustive search of the lung transplantation network, one expert genetic laboratory, and the clinical research network on rare pulmonary diseases. RESULTS: There were 9 patients (7 men) with TERT (n = 6) or TR (n = 3) mutations who received a single (n = 8) or a double (n = 1) lung transplant for pulmonary fibrosis. Median age was 50 years (range, 35-61 years) at diagnosis and 52 years (range, 37-62 years) at the time of lung transplantation. Thrombocytopenia was present in 7 patients before lung transplantation. After lung transplantation, 6 patients developed myelodysplasia and/or bone marrow failure, directly contributing to death in 4 cases. Anemia was observed in 9 patients, and neutropenia was observed in 3 patients. The median survival after lung transplantation was 214 days (range, 59-1,709 days). CONCLUSIONS: Patients with mutations of the telomerase complex are at high risk of severe hematologic complications after lung transplantation, in particular, bone marrow failure. Specific recommendations should be developed for appropriate guidance regarding hematologic risk assessment before transplantation and management of the post-transplantation immunosuppressive regimen.
Published: 2015

50. Physical activity in daily life of patients with fibrotic idiopathic interstitial pneumonia

Author: Julia Salleron, Olivier Le Rouzic, Benoit Wallaert, Jean-Marie Grosbois, Lidwine Wemeau-Stervinou, and Emmanuel Monge
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Activities of daily living, Pulmonary Fibrosis, Vital Capacity, Motor Activity, Critical Care and Intensive Care Medicine, Hospital Anxiety and Depression Scale, Pulmonary function testing, Idiopathic pulmonary fibrosis, Internal medicine, Pulmonary fibrosis, Activities of Daily Living, medicine, Humans, Idiopathic Interstitial Pneumonias, Oximetry, Idiopathic interstitial pneumonia, Lung, Depression (differential diagnoses), business.industry, Middle Aged, medicine.disease, Respiratory Function Tests, Physical therapy, Exercise Test, Anxiety, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: The 6-min walk test (6MWT) is commonly used to assess exercise capacity in patients with fibrotic idiopathic interstitial pneumonia (f-IIP). However, it is not known whether patients with f-IIP have reduced levels of physical activity in daily life (DLPA) or whether pulmonary function tests and the 6MWT correlate with their DLPA.The aim of this study was to measure DLPA in patients with f-IIP and to determine the relationships between DLPA and the 6MWT, pulmonary functional parameters, and anxiety and depression scores. Fifty patients with f-IIP and 25 sex- and age-matched healthy control subjects were enrolled. Markers of DLPA were assessed with a physical activity monitor for 4 consecutive days. Hospital Anxiety and Depression Scale (HADS) scores were evaluated.DLPA parameters were significantly reduced in patients with f-IIP compared with control subjects (all P.001). The mean number of steps per day correlated strongly with diffusing capacity of the lung for carbon monoxide (Dlco), FVC, the 6MWT distance, and the 6MWT lowest oxygen saturation as measured by pulse oximetry (Spo₂). DLPA was unrelated to HADS scores. Multivariate analysis showed that Dlco and 6MWT distance explained only 31% of the variance in the number of steps per day. Dlco, 6MWT distance, 6MWT lowest Spo₂, and DLPA were significant predictors of mortality, but only Dlco and 6MWT distance were independent predictors.Quantitation of DLPA is a novel patient-centered approach to assess function in f-IIP and may be a useful tool for clinical care and assessing response to therapy.
Published: 2013

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