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1. Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy—analysis of registry data

Author

Caroline Ovaert, Sylvie Tuffery-Giraud, Sarah Leonard-Louis, Anthony Béhin, Sophie Guillaumont, Maximilien Sochala, Emmanuelle Campana-Salort, Frédérique Audic, Michèle Mayer, Damien Bonnet, Raul Juntas Morales, Mireille Cossée, Isabelle Desguerre, Christophe Meune, Pascal Laforêt, Rabah Ben Yaou, Brigitte Chabrol, Djillali Annane, David Orlikowski, François Godart, Malika Saadi, Helge Amthor, Tanya Stojkovic, Ulrike Walther-Louvier, Frédéric Lofaso, Pascal Amedro, Raphaël Porcher, Céline Tard, Claire Delcourte, Vincent Tiffreau, Karim Wahbi, Christine Barnerias, Guillaume Bassez, Bertrand Fontaine, Arnaud Isapof, Gregoire De La Villeon, Guy Vaksmann, François Rivier, Denis Duboc, Henri Marc Bécane, Philippe Ravaud, Hélène Prigent, Emmanuelle Jaillette, Abdallah Fayssoil, Bruno Eymard, Université de Lille, Univ. Artois, Univ. Littoral Côte d’Opale, Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 [URePSSS], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], 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), Clinique de pneumologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 (URePSSS), Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille, Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pitié-Salpêtrière [AP-HP], Hôpital Cochin [AP-HP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Filière Neuromusculaire (FILNEMUS), Infection et inflammation (2I), Université de Montpellier (UM), Centre Hospitalier de Versailles André Mignot (CHV), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre d’Investigation Clinique 1429 [Garches] (CIC 1429), Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie Pédiatrique [Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Raymond Poincaré [AP-HP], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
Duchenne muscular dystrophy, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Cardiomyopathy, Angiotensin-Converting Enzyme Inhibitors, Heart failure, Angiotensin-converting enzyme inhibitors, 030204 cardiovascular system & hematology, Lower risk, Ventricular Function, Left, Angiotensin Receptor Antagonists, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Registries, cardiovascular diseases, 030212 general & internal medicine, Medical prescription, Child, ComputingMilieux_MISCELLANEOUS, Heart Failure, biology, business.industry, Proportional hazards model, Hazard ratio, Angiotensin-converting enzyme, medicine.disease, Confidence interval, 3. Good health, Muscular Dystrophy, Duchenne, Treatment Outcome, Child, Preschool, biology.protein, Cardiology and Cardiovascular Medicine, business, cardiomyopathy
Abstract

Aims To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD). Methods and results We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115). We estimated the association between the prophylactic prescription of ACEi and event-free survival in 668 patients aged 8 to 13 years, with normal left ventricular function, using (i) a Cox model with intervention as a time-dependent covariate, (ii) a propensity-based analysis comparing ACEi treatment vs. no treatment, and (iii) a set of sensitivity analyses. The study outcomes were overall survival and hospitalizations for heart failure (HF) or acute respiratory failure. Among the 668 patients included in the DMD Heart Registry, 576 (mean age 6.1 ± 2.8 years) were eligible for this study, of whom 390 were treated with ACEi prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with ACEi, respectively. In a Cox model with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACEi treatment was 0.49 [95% confidence interval (CI) 0.34–0.72] and 0.47 (95% CI 0.31–0.17) for overall mortality after adjustment for baseline variables. In the propensity-based analysis, 278 patients were included in the treatment group and 834 in the control group, with 18.5% and 30.4% 12-year estimated probability of death, respectively. ACEi were associated with a lower risk of death (HR 0.39; 95% CI 0.17–0.92) and hospitalization for HF (HR 0.16; 95% CI 0.04–0.62). All other sensitivity analyses yielded similar results. Conclusion Prophylactic ACEi treatment in DMD was associated with a significantly higher overall survival and lower rates of hospitalization for HF.

Published
2021

2. Is CCL18 a potential biomarker of type-2 asthma endotypes?

Author

Pascal Chanez, Jonathan Giovannelli, Camille Taillé, Anne Tsicopoulos, Cécile Chenivesse, Patrick Berger, Joanne Balsamelli, Arnaud Bourdin, Helen Fouquet, Marina Pretolani, Antoine Magnan, Thierry Perez, S. Fry, Patricia de Nadai, Clinique de pneumologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie et Immuno-Allergologie [CHU LIlle], Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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), Institut d'Immunologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'explorations fonctionnelles respiratoires [Lille], 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)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de pneumologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Unité de recherche de l'institut du thorax (ITX-lab), and MORNET, Dominique

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Endotype, Multivariate analysis, phenotype, [SDV]Life Sciences [q-bio], allergic, Ligands, Gastroenterology, 03 medical and health sciences, Nasal Polyps, 0302 clinical medicine, Interquartile range, Internal medicine, CCL18, medicine, Humans, Immunology and Allergy, Eosinophilia, 030212 general & internal medicine, endotype, biomarker chemokine, Asthma, business.industry, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, 030228 respiratory system, Chemokines, CC, Pediatrics, Perinatology and Child Health, Cohort, Biomarker (medicine), Female, Chemokines, medicine.symptom, business, Biomarkers
Abstract

International audience; Objective: This exploratory cross-sectional study aimed to evaluate the associations between the chemokine ligand 18 (CCL18) blood level and phenotypic characteristics of asthma.Methods: We evaluated in a sample of 173 asthmatic adult patients from the Cohort of Bronchial obstruction and Asthma (63.4% women; median age 50 +/- interquartile range 27.5 years; median level of CCL18 was 44.1 +/- interquartile range 27.5 ng/mL) the association between CCL18 blood level and allergic features of asthma using a multivariate analysis. Results: We found an association between the log-transformed value of blood CCL18 and age (+0.7% [0.1; 1.3] per 1-year increase, p = 0.033), gender (-25.1% [-42; -3.2] in women, p = 0.029), and nasal polyposis (+38.1% [11.6; 70.9], p = 0.004). No association was observed between CCL18 level and the other main phenotypic characteristics of asthma. Conclusions: Our exploratory study suggests that CCL18 is not an effective biomarker of allergic asthma endotype but may rather be a biomarker of tissue eosinophilia as supported by its association with nasal polyposis.

Published
2020

3. TTC12 loss-of-function mutations cause primary ciliary dyskinesia and unveil distinct dynein assemblymechanisms in motile cilia versus flagella

Author

THOMAS, Lucie, Bouhouche, Khaled, Whitfield, Marjorie, Thouvenin, Guillaume, Coste, André, Louis, Bruno, Szymanski, Claire, Bequignon, Emilie, Papon, Jean-François, Castelli, Manon, Lemullois, Michel, Dhalluin, Xavier, Drouin-Garraud, Valérie, Montantin, Guy, Tissier, Sylvie, Duquesnoy, Philippe, Copin, Bruno, Dastot - Le Moal, Florence, Couvet, Sandrine, Barbotin, Anne Laure, Faucon, Catherine, Honoré, Isabelle, Maitre, Bernard, Beydon, Nicole, Tamalet, Aline, Rives, Nathalie, Koll, France, Escudier, Estelle, Tassin, Anne-Marie, Touré, Aminata, Mitchell, Valerie, Amselem, Serge, Legendre, Marie, Couvet, Sandrine, 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), Gif-sur-Yvette, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Centre Hospitalier Intercommunal de Créteil (CHIC), IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'ORL et de Chirurgie Cervico-Faciale (LILLE - ORL et CCF), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d’ORL et de chirurgie cervico-faciale [CHU Le Kremlin-Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Clinique de pneumologie [CHRU Lille], Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Reproductive Biology and Spermiology-CECOS Lille, University Medical Center, Lille, 59037, France., Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), and UF de Génétique moléculaire [CHU Trousseau]

Subjects
dynein arm assembly, [SDV] Life Sciences [q-bio], [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV]Life Sciences [q-bio], cilia, primary ciliary dyskinesia, CRISPR-Cas9, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, TTC12, sperm flagella
Abstract

International audience; Cilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs/IDAs). Defects in ODAs/IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. To date PCD mutations in assembly factors cause a combined ODA/IDA defect, affecting both cilia and flagella. We identified four loss-of-function mutations in TTC12, which encodes a cytoplasmic protein, in four independent families in which affected individuals displayed a peculiar PCD phenotype characterized by the absence of ODAs and IDAs in sperm flagella, contrasting with the sole absence of IDAs in respiratory cilia. We analysed both primary cells from individuals carrying TTC12 mutations and human differentiated airway cells invalidated for TTC12 by a CRISPR-Cas9 approach, as well as TTC12 depletion in the ciliated model, Paramecium tetraureli. Our results revealed an IDA defect restricted to a subset of single-headed IDAs different in flagella and cilia, while TTC12 depletion in Paramecium tetraurelia recapitulated the sperm phenotype. Overall, our study, which identifies TTC12 as a new gene involved in PCD, unveils distinct dynein assembly mechanisms in human motile cilia versus flagella.

Published
2022

4. An expert statment on clinical considerations before treating NTM lung infection

Author

Nicolas Veziris, Margot Drevait, Fatma Tritar, Emilie Catherinot, Maria Cristina Patrizi, Zeina Aoun, Jean Francois Bervar, Vincent Bouix, Bruno Crestani, François-Xavier Blanc, Arnaud Bourdin, Stéphane Jouneau, Cristina Audoly, Anne Bergeron, Massongo Massongo, Léa Colombain, Thomas Maitre, Jean Louis Couderc, Cécile Toper, Magali Dupuy Grasset, Gaëtan Deslée, Jean Francois Boitiaux, Raphaël Chiron, A. Prevotat, Benoit Douvry, Diane Bouvry, Annabelle Payet, Claire Andrejak, Jean Pierre Mallet, Marlène Murris Espin, Gérard Chatté, Wouter Hoefsloot, Frédéric Schlemmer, Mallorie Kerjouan, Jacques Cadranel, Pauline Pradere, Christophe Rogé, Sylvie Leroy, L. Slim, Damien Basille, Amira Benattia, Julien Crouzet, Hôpital Lapeyronie [Montpellier] (CHU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Radboud university [Nijmegen], Saint Joseph Medical Center [Beirut], Hôpital Saint-Joseph [Marseille], CHU Amiens-Picardie, CHU Cochin [AP-HP], CHU Saint Louis [APHP], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier René Dubos [Pontoise], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre Hospitalier Saint Jean de Perpignan, Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Reims (CHU Reims), CHI Créteil, CHU Limoges, 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 ), CHU Pontchaillou [Rennes], Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 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), Hôpital Central de Yaoundé, CHU Toulouse [Toulouse], CHU Sud Saint Pierre [Ile de la Réunion], Groupe hospitalier Paris Saint-Joseph - Hôpital, CH Morlaix, CHU Henri Mondor, Centre Hospitalier Alès-Cévennes (CHAC), 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)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Unité de Virologie clinique et fondamentale (UVCF), Hopital Saint-Louis [AP-HP] (AP-HP), Clinique de pneumologie [CHRU Lille], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Chimie Moléculaire (CRCM), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), École des Hautes Études en Santé Publique [EHESP] (EHESP), 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), Hôpital Abderrahmen Mami, 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), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Radboud University [Nijmegen], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), 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 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Henri Mondor [Créteil], and Unité de recherche de l'institut du thorax (ITX-lab)

Subjects
medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Lung infection, education, Treatments, Delphi method, Subject (documents), Computer-assisted web interviewing, 3. Good health, Pulmonology, Family medicine, Internal medicine, medicine, Treatment decision making, business, ComputingMilieux_MISCELLANEOUS
Abstract

Objective: There are a number of factors that go into a recommendation to treat non-tuberculous mycobacterial lung infection (NTM-LI). The purpose of the study is to validate consensus recommendations on clinical considerations before treating a NTM-LI. Methods: We engaged respiratory physicians of the "Mycobacterioses" working group, part of the research and teaching group in pulmonology and infectious diseases (GREPI), on behalf of the SPLF (Societe de Pneumologie de Langue Francaise) in a Delphi survey concerning three areas of interest for physicians before they had to decide to treat (Diagnosis, Definition of the level of severity and Clinical assessment before deciding to treat) in order to create a decision algorithm. Each assertion was subjected to rating and free comments by these experts via an online questionnaire. The scores were weighted by the number of patients seen each year by the experts. The assertions having obtained a weighted average greater than 9/10 were validated. Otherwise they were subject to re-evaluation during round 2 until reaching 9/10. Results: A total of 37 experts responded. At first round, 9/38 assertions obtained a strong agreement (median ≥7 and 80% of responses >7). Other assertions from all domains, in particular the definition of the level of severity, were revised and new assertions added for submission to scoring in round 2. Fifty-one assertions were finally assessed. Agreement was strong in 78% of the assertions (40/51); moderate in 22% (11/51). There was no disagreement. Conclusion: We obtained a consensus from physicians about clinical considerations before deciding to treat NTM-LI and we propose a decision algorithm to guide a treatment decision.

Published
2020

5. Effect of Early Initiation of Varenicline on Smoking Cessation in COPD Patients Admitted for Exacerbation: The Save Randomized Clinical Trial

Author

Anne Le Brestec, Cécile Tromeur, Stéphane Jouneau, Raphael Le Mao, A. Proust, Jean-Dominique Dewitte, Antoine Magnan, Nicolas Paleiron, Francis Couturaud, Angelina Dion, Corinne Hayem-Vannimenus, Christophe Leroyer, Olivier Sanchez, Gaelle Larhantec, Nicolas Roche, Frédéric Gagnadoux, Anne Dansou, CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Innovations thérapeutiques en hémostase (IThEM - U1140), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Pontchaillou [Rennes], 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 ), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Clinique de pneumologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Programme Hospitalier de Recherche Clinique (French Department of Health) [PHRCN-12008-0437], Ministere de la sante a pharmaceutical grant from Pfizer France, University Hospital of Brest, Ministere de la Sante, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Université de Brest (UBO), 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 ), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), 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
Pulmonary and Respiratory Medicine, Counseling, Male, medicine.medical_specialty, Exacerbation, Copd patients, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Pulmonary disease, Early initiation, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Early Medical Intervention, Medicine, COPD, Humans, 030212 general & internal medicine, tobacco smoking, Varenicline, Aged, Smoking Cessation Agents, business.industry, Tobacco Use Disorder, Middle Aged, medicine.disease, respiratory tract diseases, 3. Good health, Hospitalization, Treatment Outcome, 030228 respiratory system, chemistry, Disease Progression, Smoking cessation, Female, Smoking Cessation, business
Abstract

Our main objective was to demonstrate that, in smoker patients hospitalised for Chronic Obstructive Pulmonary Disease (COPD) exacerbation, early initiation of varenicline during 12 weeks, combined with an intensive counselling, is associated with a higher continuous abstainers rate (CAR) at one year as compared to intensive counselling alone. In this multicenter, prospective, double-blind, randomised study, 81 smoking COPD patients hospitalised for an acute exacerbation for at least 24 h were allocated to receive either varenicline (n = 42) or placebo (n = 39) for 12 weeks, in association with an intensive counselling in the 2 groups, and followed up for 40 weeks. The primary outcome was CAR at week 52. Secondary outcomes included CAR at week 12 and 26, partial abstinence rate (PAR) at week 12, 26 and 52, nicotinic substitute consumption and adverse events. At week 52, CAR was not different in placebo and varenicline groups (25.6%). At week 12, CAR was significantly higher in the varenicline group (50%) as compared to placebo group (27%) (p = 0.041). Nicotine consumption was significantly higher at week 52 in the placebo group (55.3%) as compared to the varenicline group (24.4%) (p = 0.005). There was no significant difference in PAR at week 12, 26 and 52; the frequency of adverse events was similar between the two groups. Among active smoker COPD patients with exacerbation, 12-week varenicline associated with intensive counselling for smoking cessation increased the rate of continuous abstainers as compared to placebo. However, benefit was not maintained after varenicline discontinuation. Clinical Trials Registration: URL: http://www.controlled-trials.com. Unique identifier: NCT01694732

Published
2019

6. MRI of the cervical spinal cord predicts respiratory dysfunction in ALS

Author

Alain Duhamel, Gregory Kuchcinski, David Devos, Caroline Moreau, Renaud Lopes, Jean-Christophe Devedjian, Patrice Jissendi-Tchofo, Maeva Kyheng, Thierry Perez, Pierre-François Pradat, Régis Bordet, Guillaume Grolez, Charlotte Laloux, Maud Pétrault, Véronique Danel-Brunaud, Florent Auger, Kelly Timmerman, Pierre Besson, Luc Defebvre, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinique de pneumologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, CNRS, Inserm, Institut Pasteur de Lille, Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV], Troubles cognitifs dégénératifs et vasculaires - U1171, 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], Université de Lille, LillOA, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
0301 basic medicine, Internal capsule, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Respiratory Tract Diseases, lcsh:Medicine, Mice, Superoxide Dismutase-1, 0302 clinical medicine, Amyotrophic lateral sclerosis, Respiratory system, lcsh:Science, Motor Neurons, Medulla Oblongata, Multidisciplinary, medicine.diagnostic_test, Motor Cortex, Magnetic Resonance Imaging, White Matter, 3. Good health, medicine.anatomical_structure, Spinal Cord, Disease Progression, Cardiology, Neurodegeneration, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.medical_specialty, Neuroprotection, Article, White matter, 03 medical and health sciences, Atrophy, Phénomènes atmosphériques, Internal medicine, medicine, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business.industry, lcsh:R, Cervical Cord, Magnetic resonance imaging, medicine.disease, Spinal cord, Disease Models, Animal, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, 030104 developmental biology, lcsh:Q, business, 030217 neurology & neurosurgery
Abstract

For patients with amyotrophic lateral sclerosis (ALS), the primary therapeutic goal is to minimize morbidity. Non-invasive ventilation improves survival. We aim to assess whether Magnetic Resonance Imaging (MRI) of the cervical spinal cord predicts the progression of respiratory disorders in ALS. Brain and spinal MRI was repeatedly performed in the SOD1G86R mouse model, in 40 patients and in healthy controls. Atrophy, iron overload, white matter diffusivity and neuronal loss were assessed. In Superoxide Dismutase-1 (SOD1) mice, iron accumulation appeared in the cervical spinal cord at symptom onset but disappeared with disease progression (after the onset of atrophy). In ALS patients, the volumes of the motor cortex and the medulla oblongata were already abnormally low at the time of diagnosis. Baseline diffusivity in the internal capsule was predictive of functional handicap. The decrease in cervical spinal cord volume from diagnosis to 3 months was predictive of the change in slow vital capacity at 12 months. MRI revealed marked abnormalities at the time of ALS diagnosis. Early atrophy of the cervical spinal cord may predict the progression of respiratory disorders, and so may be of value in patient care and as a primary endpoint in pilot neuroprotection studies., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

7. Emergence of Aspergillus fumigatus azole resistance in azole-naïve patients with chronic obstructive pulmonary disease and their homes

Author

Eric Viscogliosi, Maiken Cavling Arendrup, O. Le Rouzic, Boualem Sendid, Saad Nseir, P. Le Pape, Philippe Gosset, N. Bautin, Gabriel Reboux, C. Dauchy, S. Fry, René Wintjens, Emilie Fréalle, Service de Parasitologie-Mycologie [CHRU LIlle], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinique de pneumologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université libre de Bruxelles (ULB), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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), Lille Inflammation Research International Center - U 995 (LIRIC), 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 Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Statens Serum Institut [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital, University of Copenhagen = Københavns Universitet (KU), Acting for a healthier population, the Région Hauts- de- France funded this work (Environment Health program, grant no. 2010- 12266 & 2010- 12268), which was also supported by GILEAD Sciences, MSD, and Pfizer grants., This work is dedicated to the memory of Eduardo Dei‐Cas, who actively contributed to the initial design and practical achievement of the FungiCOPD project. We also would like to thank Stéphanie Delvart, Sandrine Bonaventure, Dorothée Monvillers, Michèle Wauquier, Filoména Naji, and Nausicaa Gantois for technical assistance, Dr Isabelle Durand‐Joly, Pr El Moukhtar Aliouat, and Dr Annie Standaert‐Vitse for their steady interest in the work and for fruitful discussions, and all the physicians who participated to the recruitment of patients. This work was partially presented as an oral communication at the 'European Congress of Clinical Microbiology and Infectious Diseases' in 2014, at the congress of the 'French Medical Mycology Society' in 2016, and as a poster at the TIMM‐7 in 2015. RW is a Research Associate at the National Fund for Scientific Research FNRS‐FRS (Belgium)., Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), and University of Copenhagen = Københavns Universitet (UCPH)

Subjects
Drug Resistance, Fungal -- genetics, 0301 basic medicine, Azoles, Male, Antifungal Agents, Exacerbation, MESH: Fungal Proteins/isolation & purification, [SDV]Life Sciences [q-bio], Colony Count, Microbial, Aspergillus fumigatus, MESH: Aspergillus fumigatus/drug effects, MESH: Cytochrome P-450 Enzyme System/drug effects, MESH: Genotype, Pulmonary Disease, Chronic Obstructive, dwelling, Cytochrome P-450 Enzyme System, Genotype, Pulmonary Disease, Chronic Obstructive -- microbiology, Prevalence, Prospective Studies, chemistry.chemical_classification, MESH: Aged, COPD, Azole-resistance, MESH: Middle Aged, biology, MESH: Drug Resistance, Fungal/genetics, Mold environmental exposure, Sciences bio-médicales et agricoles, Middle Aged, 3. Good health, MESH: Pulmonary Disease, Chronic Obstructive/microbiology, MESH: Housing, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Air Pollution, Indoor, Acute Disease, Disease Progression, MESH: Acute Disease, MESH: Cytochrome P-450 Enzyme System/isolation & purification, MESH: Disease Progression, Female, medicine.drug, medicine.medical_specialty, Environmental Engineering, Itraconazole, MESH: Fungal Proteins/drug effects, 030106 microbiology, Aspergillus fumigatus -- drug effects -- genetics -- isolation & purification, MESH: Azoles/pharmacology, Fungal Proteins -- drug effects -- isolation & purification, chronic obstructive pulmonary disease, Microbiology, Fungal Proteins, 03 medical and health sciences, azole resistance, MESH: Air Pollution, Indoor/analysis, Drug Resistance, Fungal, Internal medicine, medicine, Humans, MESH: Aspergillus fumigatus/genetics, Dwelling, MESH: Colony Count, Microbial, MESH: Prevalence, Aged, Aspergillus, MESH: Humans, Azoles -- pharmacology, electrostatic dust collector, Public Health, Environmental and Occupational Health, mold environmental exposure, Electrostatic dust collector, Building and Construction, medicine.disease, biology.organism_classification, MESH: Male, MESH: Prospective Studies, chemistry, Cytochrome P-450 Enzyme System -- drug effects -- isolation & purification, Housing, Azole, ARAF, MESH: Aspergillus fumigatus/isolation & purification, Antifungal Agents -- pharmacology, MESH: Antifungal Agents/pharmacology, MESH: Female, Air Pollution, Indoor -- analysis
Abstract

Azole-resistant Aspergillus fumigatus (ARAF) has been reported in patients with chronic obstructive pulmonary disease (COPD) but has not been specifically assessed so far. Here, we evaluated ARAF prevalence in azole-naïve COPD patients and their homes, and assessed whether CYP51A mutations were similar in clinical and environmental reservoirs. Sixty respiratory samples from 41 COPD patients with acute exacerbation and environmental samples from 36 of these patient's homes were prospectively collected. A. fumigatus was detected in respiratory samples from 11 of 41 patients (27%) and in 15 of 36 domiciles (42%). Cyp51A sequencing and selection on itraconazole medium of clinical (n = 68) and environmental (n = 48) isolates yielded ARAF detection in 1 of 11 A. fumigatus colonized patients with COPD (9%) and 2 of 15 A. fumigatus-positive patient's homes (13%). The clinical isolate had no CYP51A mutation. Two environmental isolates from two patients harbored TR34/L98H mutation, and one had an H285Y mutation. Coexistence of different cyp51A genotypes and/or azole resistance profiles was detected in 3 of 8 respiratory and 2 of 10 environmental samples with more than one isolate, confirming the need for a systematic screening of all clinically relevant isolates. The high prevalence of ARAF in patients with COPD and their homes supports the need for further studies to assess the prevalence of azole resistance in patients with Aspergillus diseases in Northern France., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017

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