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1. Comprehensive clinical profiling of the Gauting locoregional lung adenocarcinoma donors

Author

Serge Guyétant, Jürgen Behr, Yves Courty, Kristina A. M. Arendt, Agnès Petit-Courty, Sylvain Marchand-Adam, Valérie Gissot, Anne-Sophie Lamort, Ina Koch, Jan‐Christian Kaiser, Georgios T. Stathopoulos, Ioanna Giopanou, Maria Oplopoiou, Michael Lindner, Ioannis Lilis, Martin E. Eichhorn, Rudolf Hatz, Giannoula Ntaliarda, Mario A.A. Pepe, Laura V. Klotz, Anja Stowasser, Alicia Morresi-Hauf, Sabine J. Behrend, Ludwig Maximilians University of Munich, German Center for Lung Research, Comprehensive pneumology center, Partenaires INRAE, University Hospital, German Centre for Lung Research, Institut National de la Santé et de la Recherche Médicale (INSERM), University-Hospital Munich-Großhadern [München], Heidelberg University, University of Patras, Alexander Fleming Biomedical Sciences Research Center, Asklepios Medical Center, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Asklepios Lung Clinic Gauting, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Ludwig-Maximilians University [Munich] (LMU), and ProdInra, Migration

Subjects
0301 basic medicine, Research design, Male, Cancer Research, Lung Neoplasms, Death risk, Pneumologie et système respiratoire, LADC, lung adenocarcinoma, obstruction, smoking, survival, Pulmonary Surgical Procedures, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, Recurrence, Germany, Medicine, Prospective Studies, Cancer, Original Research, Curative intent, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, résection, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cohort, Adenocarcinoma, Female, Lung resection, medicine.medical_specialty, adénocarcinome, Médecine humaine et pathologie, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma of Lung, lcsh:RC254-282, Time-to-Treatment, 03 medical and health sciences, FEV1/FVC ratio, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, tabagisme, Radiology, Nuclear Medicine and imaging, Mortality, Pulmonology and respiratory tract, Aged, Neoplasm Staging, Lung, business.industry, Clinical Cancer Research, medicine.disease, 030104 developmental biology, poumon, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Human health and pathology, Ladc, Lung Adenocarcinoma, Obstruction, Smoking, Survival, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; A comprehensive characterization of lung adenocarcinoma (LADC) clinical features is currently missing. We prospectively evaluated Caucasian patients with early-stage LADC. Patients with LADC diagnosed between 2011 and 2015 were prospectively assessed for lung resection with curative intent. Fifty clinical, pathologic, radiologic, and molecular variables were recorded. Patients were followed till death/study conclusion. The main findings were compared to a separate cohort from France. Of 1943 patients evaluated, 366 were enrolled (18.8%; 181 female; 75 never-smokers; 28% of registered Bavarian cases over the study period). Smoking and obstruction were significantly more prevalent in GLAD compared with adult Bavarians (P < 0.0001). Ever-smoker tumors were preferentially localized to the upper lobes. We observed 120 relapses and 74 deaths over 704 cumulative follow-up years. Median overall and disease-free survival were >7.5 and 3.6 years, respectively. Patients aged 65 years, resected >60 days postdiagnosis, with abnormal FVC/DLCO VA , N2/N3 stage, or solid histology had significantly decreased survival estimates. These were fit into a weighted locoregional LADC death risk score that outperformed pTNM7 in predicting survival in the GLAD and in our second cohort. We define the clinical gestalt of locoregional LADC and provide a new clinical tool to predict survival, findings that may aid future management and research design

Published
2019
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2. Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling

Author

Morello, Eric, Pérez-Berezo, Teresa, Boisseau, Chloé, Baranek, Thomas, Guillon, Antoine, Bréa, Déborah, Lanotte, Philippe, Carpena, Xavi, Pietrancosta, Nicolas, Hervé, Virginie, Ramphal, Reuben, Cenac, Nicolas, Si-Tahar, Mustapha, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Unite Mixte de Recherche 1100, Institut National de la Santé et de la Recherche Médicale (INSERM), Infectiologie et Santé Publique (ISP), Université de Tours-IFR136, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), Université Pierre et Marie Curie - Paris 6 (UPMC)-ESPCI ParisTech-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-ESPCI ParisTech-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 2 (CEPR. Equipe 2), 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), École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 2 'Mécanismes Protéolytiques dans l'Inflammation' (CEPR. Equipe 2), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), ALBA Synchrotron light source [Barcelone], Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), French Cystic Fibrosis Foundation 'Vaincre la Mucoviscidose' : RF20140501103, FeRI (Federation de Recherche en Infectiologie - Centre Val de Loire Region) : A03-2016, 'INSERM' endowment, 'Universite de Tours' endowment, Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-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)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), pietrancosta, nicolas, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Systèmes glutamatergiques normaux et pathologiques = Normal and Pathologic Glutamatergic Neurons (NPS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Institut National de la Santé et de la Recherche Médicale (France), Université de Tours, Cystic Fibrosis Foundation, and Région des Pays de la Loire

Subjects
[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], infection pulmonaire, Lipoxygenase, Lipid mediators, Pneumologie et système respiratoire, lipid mediators, Pseudomonas aeruginosa, lipoxygenase, lungs, infection, inflammation, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Microbiology, acide gras polyinsaturé, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [CHIM.CHEM] Chemical Sciences/Cheminformatics, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pulmonology and respiratory tract, ComputingMilieux_MISCELLANEOUS, Original Research, Inflammation, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], lipoxygénase, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, médiateur lipidique, Lungs, inflammation pulmonaire, Infection, [CHIM.CHEM]Chemical Sciences/Cheminformatics
Abstract

© 2019 Morello, Pérez-Berezo, Boisseau, Baranek, Guillon, Bréa, Lanotte, Carpena, Pietrancosta, Hervé, Ramphal, Cenac and Si-Tahar., Pseudomonas aeruginosa is an opportunistic bacteria and a major cause of nosocomial pneumonia. P. aeruginosa has many virulence factors contributing to its ability to colonize the host. LoxA is a lipoxygenase enzyme secreted by P. aeruginosa that oxidizes polyunsaturated fatty acids. Based on previous in vitro biochemical studies, several biological roles of LoxA have been hypothesized, including interference of the host lipid signaling, and modulation of bacterial invasion properties. However, the contribution of LoxA to P. aeruginosa lung pathogenesis per se remained unclear. In this study, we used complementary in vitro and in vivo approaches, clinical strains of P. aeruginosa as well as lipidomics technology to investigate the role of LoxA in lung infection. We found that several P. aeruginosa clinical isolates express LoxA. When secreted in the lungs, LoxA processes a wide range of host polyunsaturated fatty acids, which further results in the production of bioactive lipid mediators (including lipoxin A4). LoxA also inhibits the expression of major chemokines (e.g., MIPs and KC) and the recruitment of key leukocytes. Remarkably, LoxA promotes P. aeruginosa persistence in lungs tissues. Hence, our study suggests that LoxA-dependent interference of the host lipid pathways may contribute to P. aeruginosa lung pathogenesis., This work was funded by the “INSERM” and “Université de Tours” endowments as well as with the support of the French Cystic Fibrosis Foundation “Vaincre la Mucoviscidose” (Grant Number RF20140501103) and FeRI (Fédération de Recherche en Infectiologie – Centre Val de Loire Region, Grant Number A03-2016).

Published
2019
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3. Randomized controlled trials of pharmacological treatments to prevent COPD exacerbations: applicability to real-life patients

Author

Laurie Pahus, Pierre-Régis Burgel, Nicolas Roche, Jean-Louis Paillasseur, Pascal Chanez, on behalf of Initiatives BPCO scientific committee, 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), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique Pédiatrique [Marseille], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital d'Enfants de la Timone [Marseille], Assistance Publique - Hôpitaux de Marseille (APHM)-Assistance Publique - Hôpitaux de Marseille (APHM), Université Paris Descartes - Paris 5 (UPD5), AP-HP Hôpitaux Universitaires Paris Centre, and EFFI-STAT

Subjects
Exacerbation, Pneumologie et système respiratoire, Severity of Illness Index, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, Clinical research, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Randomized controlled trial, law, Forced Expiratory Volume, Medicine, 030212 general & internal medicine, Randomized Controlled Trials as Topic, COPD, education.field_of_study, Evidence-Based Medicine, essai randomisé contrôlé, 3. Good health, Bronchodilator Agents, maladie pulmonaire, External validity, COPD exacerbations, Cohort, Disease Progression, patient, Research Article, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Population, 03 medical and health sciences, Humans, tabagisme, education, Intensive care medicine, Pulmonology and respiratory tract, lcsh:RC705-779, traitement pharmacologique, business.industry, Patient Selection, Reproducibility of Results, Evidence-based medicine, lcsh:Diseases of the respiratory system, medicine.disease, Clinical trial, 030228 respiratory system, Quality of Life, Diffusion of Innovation, business
Abstract

International audience; BackgroundIn patients with chronic obstructive pulmonary disease, all efforts should be made to prevent exacerbations because each event modifies the trajectory of the disease. Treatment recommendations are mostly built on results from randomized controlled trials (RCTs) whose methodology ensure internal validity. However, their relevance may be compromised by the lack of generalizability, due to poor representability of study populations compared to real-life patients.In order to delimit to whom the results of studies on current and future treatments apply, we sought to identify and characterize the fraction of COPD population that would be eligible for inclusion into RCTs aiming at decreasing exacerbation risk.MethodsWe used the Initiatives-BPCO database, a French cohort of 1309 real-life COPD patients monitored in academic centers. We identified industry-sponsored phase III and IV trials that enrolled more than 500 patients, lasted at least one year and used exacerbations related endpoints. Eligibility criteria were extracted from each trial and applied to the patients.ResultsThe eligibility criteria of 16 RCTs were applied to the 1309 patients. The most discriminating eligibility criteria were FEV1, minimum exacerbation rate in the previous year and smoking history, responsible for the exclusion of 39.9, 36.7 and 16.8% of patients, respectively. Altogether, 2.3 to 46.7% of our patients would have satisfied all eligibility criteria.ConclusionThese analyses confirm that an important gap exists between real-life patients and clinical trials populations in COPD, which limits the relevance of results and therefore should be considered when grading levels of evidence and designing future studies.

Published
2019
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4. A TUG Value Longer Than 11 s Predicts Fall Risk at 6-Month in Individuals with COPD

Author

Bruno Pereira, Frédéric Costes, Denis Caillaud, Vivien Reynaud, Emmanuel Coudeyre, Ruddy Richard, Annick Greil, Daniela Muti, Service Médecine du Sport et Explorations Fonctionnelles [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service Médecine physique et de réadaptation [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Pneumologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Hôtel Dieu, Clinique Cardio Pneumologique, Biostatistiques, Danone Research, 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, Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Médecine du Sport et des Explorations Fonctionnelles, Service de Médecine Physique et Réadaptation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Reynaud, Vivien, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Hôtel Dieu, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), and Université Clermont Auvergne (UCA)

Subjects
medicine.medical_specialty, Copd patients, Pneumologie et système respiratoire, Pulmonary disease, lcsh:Medicine, Médecine humaine et pathologie, Timed Up and Go test, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Article, 03 medical and health sciences, 0302 clinical medicine, Fall, Medicine, 030212 general & internal medicine, Risk factor, Hypoxia, Pulmonology and respiratory tract, COPD, Chronic obstructive pulmonary disease, Postural balance, business.industry, lcsh:R, General Medicine, Fall risk, medicine.disease, Clinical Practice, 030228 respiratory system, Berg Balance Scale, Physical therapy, Human health and pathology, business, human activities, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

This article belongs to the Section Pulmonology; Risk of a fall is increased in individuals with chronic obstructive pulmonary disease (COPD), and is usually evaluated using the Berg Balance Scale (BBS), but this is difficult to perform in everyday clinical practice. We aimed to prospectively predict short-term fall recurrence in COPD patients using a predetermined cut-off value of the Timed Up and Go test (TUG). In stable COPD patients, we collected self-reported records of the number of falls in the previous year, and measured TUG and BBS scores for each individual. Records of fall recurrence were obtained prospectively at 6-months after the initial evaluation. Among the 50 patients recruited, 23 (46%) had at least one fall during the past year. The optimal diagnosis value for the TUG to detect a fall was 10.9 s with a sensitivity of 100% and a specificity of 97%. A cut-off of 11 s predicted fall recurrence with high sensitivity and specificity (93% and 74%, respectively). The TUG as well as the BBS score detected fallers, and a cut-off value of 11 s predicted fall recurrence. TUG could be easily incorporated into the scheduled functional evaluations of COPD patients, could predict the risk of a fall and when appropriate, could guide specific balance training exercises to prevent fall.

Published
2019
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5. Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures

Author

Marin Truchi, Sylvie Leroy, Marie-Jeanne Arguel, Agnès Paquet, Marie Deprez, Ignacio S. Caballero, Brice Marcet, Kevin Lebrigand, Amélie Cavard, Pascal Barbry, Charles-Hugo Marquette, Virginie Magnone, Laure-Emmanuelle Zaragosi, Sandra Ruiz García, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Service de Pneumologie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital de l'Archet, Fondation pour la Recherche Medicale (DEQ20180339158), Labex Signalife (ANR-11-LABX-0028-01), Association Vaincre la Mucoviscidose (RF20180502280), Commissariat aux Grands Investissements (ANR-10-INBS-09-03, ANR-10-INBS-09-02), Chan Zuckerberg Initiative [(Silicon Valley Community Foundation) 2017-175159-5022], Canceropole PACA, 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), Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), 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), Physiological Genomics of the Eukaryotes, Hôpital Pasteur [Nice] (CHU), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), UR Infectiologie animale et Santé publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Barbry, Pascal, and Zaragosi, Laure-Emmanuelle

Subjects
épithélium, Swine, Cell, Pneumologie et système respiratoire, Basal cells, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Transcriptome, Mice, 0302 clinical medicine, Keratin, mucociliary differentiation, RNA-Seq, tractus respiratoire, [SDV.BDD]Life Sciences [q-bio]/Development Biology, immunohistologie, Cells, Cultured, cell trajectory, Goblet cells, chemistry.chemical_classification, 0303 health sciences, Biologie du développement, Wnt signaling pathway, Cell Differentiation, scRNAseq, Development Biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Cell biology, Trachea, medicine.anatomical_structure, Deuterosome, Differentiation, cellule isolée, Keratins, single cell RNA seq, Airway epithelium, Club cells, Multiciliated cells, Pathways, Single-cell RNA-seq, Respiratory Mucosa, Biology, 03 medical and health sciences, Techniques and Resources, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Animals, Humans, Pulmonology and respiratory tract, Molecular Biology, 030304 developmental biology, différenciation cellulaire, Regeneration (biology), Epithelial Cells, voie de signalisation, chemistry, Respiratory epithelium, 030217 neurology & neurosurgery, Function (biology), Developmental Biology
Abstract

The upper airway epithelium, which is mainly composed of multiciliated, goblet, club and basal cells, ensures proper mucociliary function and can regenerate in response to assaults. In chronic airway diseases, defective repair leads to tissue remodeling. Delineating key drivers of differentiation dynamics can help understand how normal or pathological regeneration occurs. Using single-cell transcriptomics and lineage inference, we have unraveled trajectories from basal to luminal cells, providing novel markers for specific populations. We report that: (1) a precursor subgroup of multiciliated cells, which we have entitled deuterosomal cells, is defined by specific markers, such as DEUP1, FOXN4, YPEL1, HES6 and CDC20B; (2) goblet cells can be precursors of multiciliated cells, thus explaining the presence of hybrid cells that co-express markers of goblet and multiciliated cells; and (3) a repertoire of molecules involved in the regeneration process, such as keratins or components of the Notch, Wnt or BMP/TGFβ pathways, can be identified. Confirmation of our results on fresh human and pig airway samples, and on mouse tracheal cells, extend and confirm our conclusions regarding the molecular and cellular choreography at work during mucociliary epithelial differentiation., Highlighted Article: Single-cell RNAseq data in fresh human airway epithelial tissues and air liquid cultures identifies novel cell populations and offers new insights into the molecular mechanisms occurring during mucociliary epithelium regeneration.

Published
2019
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6. Quadriceps Endurance Increases Following Cycling Exercise With Non-Invasive Ventilation In Moderate-To-Severe COPD Patients. A Non-Randomized Controlled Study

Author

Frédéric Costes, Léonard Féasson, Mathieu Berger, Isabelle Court Fortune, Samuel Verges, Pierre Labeix, Physiologie Clinique et Exercice, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), EA 7424, Laboratoire Interuniversitaire Biologie Motricité, Université de Lyon, Université Jean Monnet - Saint-Étienne (UJM), Système Nerveux Autonome, Epidémiologie, Physiologie, Ingénierie, Santé (SNA- EPIS), Pneumologie & Oncologie Thoracique, HP2 Laboratoire d'Hypoxie et Physiopathologie Cardiovasculaire et Respiratoire, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Grenoble, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Médecine du Sport et Explorations Fonctionnelles, CHU Clermont-Ferrand, Association Lyonnaise de Logistique Posthospitaliere, Lyon, France, Costes, Frédéric, ProdInra, Archive Ouverte, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université Jean Monnet (Saint-Etienne), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), and Centre Hospitalier Universitaire de Clermont-Ferrand

Subjects
Male, Time Factors, Copd patients, medicine.medical_treatment, Pneumologie et système respiratoire, Severity of Illness Index, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Quadriceps Muscle, law.invention, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Randomized controlled trial, law, 030212 general & internal medicine, Respiratory system, Lung, Original Research, endurance, COPD, Exercise Tolerance, exercise, non-invasive ventilation, General Medicine, Middle Aged, Exercise Therapy, 3. Good health, Treatment Outcome, Breathing, Cardiology, Female, Cycling, Moderate to severe, medicine.medical_specialty, limb muscle, macromolecular substances, International Journal of Chronic Obstructive Pulmonary Disease, 03 medical and health sciences, Internal medicine, medicine, Humans, Pulmonary rehabilitation, Pulmonology and respiratory tract, Aged, lcsh:RC705-779, Noninvasive Ventilation, business.industry, copd, Recovery of Function, lcsh:Diseases of the respiratory system, medicine.disease, Bicycling, respiratory tract diseases, 030228 respiratory system, non invasive ventilation, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract

Pierre Labeix,1,2 Mathieu Berger,3 Isabelle Court Fortune,4 Léonard Feasson,2,5 Samuel Verges,6 Frédéric Costes7,8 1Centre VISAS, Service de Physiologie Clinique et de l’Exercice, CHU St Etienne, France; 2Univ Lyon, UJM Saint-Etienne, Laboratoire Interuniversitaire de Biologie de la Motricité, EA 7424, Saint-Etienne F-42023, France; 3Univ Lyon, UJM Saint-Etienne, laboratoire SNA-EPIS, EA4607, Saint-Etienne, France; 4Service de Pneumologie et d’Oncologie Thoracique, CHU St Etienne, France; 5Unité de Myologie, CHU St Etienne, France; 6Université Grenoble Alpes, Inserm, Laboratoire HP2, Grenoble, France; 7Université Clermont Auvergne, INRA, UNH Clermont Ferrand, France; 8Service de Médecine du Sport et des Explorations Fonctionnelles, CHU Clermont Ferrand, FranceCorrespondence: Frédéric CostesService de Médecine du Sport et des Explorations Fonctionnelles CHU Gabriel Montpied, 58 rue Montalembert, F63002 Clermont Ferrand cedex 1, FranceTel +33473751665Email fcostes@chu-clermontferrand.frPurpose: Application of non-invasive ventilation (NIV) during exercise improves exercise tolerance in severe COPD patients; however, the underlying mechanism is only partially unraveled. As part of its known effect to unload the respiratory muscles, we looked for the influence of NIV on post-exercise quadriceps muscle endurance.Patients and methods: We included 25 severe COPD patients entering an outpatient pulmonary rehabilitation program. They performed, on successive days, three quadriceps endurance tests at 70% of the maximal strength (1RM) to task failure (TlimQ); 1) control condition; 2) following constant load cycling exercise to exhaustion without Inspiratory Pressure Support (TlimQ IPS-); 3) following the same cycling exercise with IPS (TlmQ IPS+).Results: Dyspnea Borg score was significantly reduced at the end of the constant load cycling exercise with IPS+ compared to IPS- (3.5±2.6 to 4.3±2.3, p

Published
2019
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7. Curcumin inhibits the TGF-β1-dependent differentiation of lung fibroblasts via PPARγ-driven upregulation of cathepsins B and L

Author

Saidi, Ahlame, Kasabova, Mariana, Vanderlynden, Lise, Wartenberg, Mylene, Kara-Ali, Ghania Hounana, Marc, Daniel, Lecaille, Fabien, and Lalmanach, Gilles

Subjects
fibrose pulmonaire, curcumine, cathepsine l, collagène, Pneumologie et système respiratoire, Médecine humaine et pathologie, Human health and pathology, Pulmonology and respiratory tract, cathepsine b
Abstract

Pulmonary fibrosis is a progressive disease characterized by a widespread accumulation of myofibroblasts and extracellular matrix components. Growing evidences support that cysteine cathepsins, embracing cathepsin B (CatB) that affects TGF-β1-driven Smad pathway, along with their extracellular inhibitor cystatin C, participate in myofibrogenesis. Here we established that curcumin, a potent antifibrotic drug used in traditional Asian medicine, impaired the expression of both α-smooth muscle actin and mature TGF-β1 and inhibited the differentiation of human lung fibroblasts (CCD-19Lu cells). Curcumin induced a compelling upregulation of CatB and CatL. Conversely cystatin C was downregulated, which allowed the recovery of the peptidase activity of secreted cathepsins and the restoration of the proteolytic balance. Consistently, the amount of both insoluble and soluble type I collagen decreased, reaching levels similar to those observed for undifferentiated fibroblasts. The signaling pathways activated by curcumin were further examined. Curcumin triggered the expression of nuclear peroxisome proliferator-activated receptor γ (PPARγ). Contrariwise PPARγ inhibition, either by an antagonist (2-chloro-5-nitro-N-4-pyridinyl-benzamide) or by RNA silencing, restored TGF-β1-driven differentiation of curcumin-treated CCD-19Lu cells. PPARγ response element (PPRE)-like sequences were identified in the promoter regions of both CatB and CatL. Finally, we established that the transcriptional induction of CatB and CatL depends on the binding of PPARγ to PPRE sequences as a PPARγ/Retinoid X Receptor-α heterodimer.

Published
2019

8. Blood gene expression predicts bronchiolitis obliterans syndrome

Author

Danger, Richard, Royer, Pierre-Joseph, Reboulleau, Damien, Durand, Eugenie, Loy, Jennifer, Tissot, Adrien, Lacoste, Philippe, Roux, Antoine, Reynaud-Gaubert, Martine, Gomez, Carine, Kessler, Romain, Mussot, Sacha, Dromer, Claire, Brugière, Olivier, Mornex, Jean-Francois, Guillemain, Romain, Dahan, Marcel, Knoop, Christiane, Botturi, Karine, Foureau, Aurore, Pison, Christophe, Koutsokera, Angela, Nicod, Laurent P., Brouard, Sophie, Magnan, Antoine, Cohort of Lung Transplantation, and Systems prediction of Chronic Lung Allograft Dysfunction

Subjects
maladie pulmonaire, lung transplantation, bronchiolitis obliterans syndrome, gene expression, biomarkers, blood, Pneumologie et système respiratoire, sang, Pulmonology and respiratory tract, biomarqueur, humanities, expression des gènes
Abstract

Bronchiolitis obliterans syndrome (BOS), the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group), and 26 samples at or after BOS diagnosis (diagnosis group). An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group). We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A), and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p < 0.01) and are not associated with time posttransplantation. This is the first published large-scale gene expression analysis of blood after lung transplantation. The three-gene blood signature could provide clinicians with new tools to improve follow-up and adapt treatment of patients likely to develop BOS.

Published
2018

9. The European Respiratory Review: farewell from the editor with confidence for the future

Author

Vincent Cottin, Rétrovirus et Pathologie Comparée, 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, and Hospices Civils de Lyon (HCL)

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Biomedical Research, MEDLINE, Pneumologie et système respiratoire, Review Literature as Topic, 030204 cardiovascular system & hematology, Bibliometrics, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Access to Information, 03 medical and health sciences, 0302 clinical medicine, Pulmonary medicine, Pulmonary Medicine, medicine, Humans, Respiratory system, Intensive care medicine, Pulmonology and respiratory tract, ComputingMilieux_MISCELLANEOUS, lcsh:RC705-779, business.industry, lcsh:Diseases of the respiratory system, 3. Good health, Access to information, maladie respiratoire, 030228 respiratory system, Periodicals as Topic, business, Editorial Policies, Forecasting
Abstract

The European Respiratory Review will continue to develop and to accompany respiratory physicians in their practice http://ow.ly/TcDKh

Published
2015
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10. Rare pulmonary diseases and orphan drugs: where do we stand and where are we going to?

Author

Harold R. Collard, Marc Humbert, Carlo Vancheri, Marco Matucci-Cerinic, Gérald Simonneau, Athol U. Wells, Sergio Harari, Vincent Cottin, Francesco Blasi, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, UO Pneumol, Faculté de Médecine, Université Paris Sud (Paris 11), Centre de Référence de l’Hypertension Pulmonaire Sévère, Département Hospitalo-Universitaire (DHU) Thorax Innovation (TORINO), Service de Pneumologie, Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris (AP-HP), INSERM, UMR_S 999, Laboratoire d’Excellence (LabEx) en Recherche sur le Médicament et l’Innovation Thérapeutique (LERMIT), Department of Pathophysiology and Transplantation, University of Milan, University of California [San Francisco] (UCSF), University of California, Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, School of Medicine, University of Florence (UNIFI), Department of Clinical and Experimental Biomedicine, Section of Respiratory Diseases, Regional Center for Interstitial and Rare Lung Diseases, Università degli Studi di Catania (UniCT), Royal Brompton and Harefield NHS Foundation Trust, 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), Service de Pneumologie, Centre de Référence National des Maladies Pulmonaires Rares, Hospices Civils de Lyon (HCL), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), 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), ProdInra, Archive Ouverte, Università degli Studi di Milano = University of Milan (UNIMI), University of California [San Francisco] (UC San Francisco), University of California (UC), Università degli Studi di Firenze = University of Florence (UniFI), and Università degli studi di Catania = University of Catania (Unict)

Subjects
Lung Diseases, Biomedical Research, Orphan Drug Production, rare disease/diagnosis/drug therapy/physiopathology, Medical Physiology, Respiratory System, lung/drug effects, Respiratory System Agents, Pneumologie et système respiratoire, chemotherapy, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, pathologie, Lung, appareil urinaire, Pediatric, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 3. Good health, maladie pulmonaire, medicine.anatomical_structure, Respiratory, lung disease/diagnosis, biomedical research/trends, Pulmonary and Respiratory Medicine, medicine.medical_specialty, endocrine system, Chronic Obstructive Pulmonary Disease, education, physiopathologie, Médecine humaine et pathologie, forecasting, respiratory system agents/therapeutic use, Orphan drug, Rare Diseases, medicine, Humans, respiratory system diseases, human, Intensive care medicine, thérapeutique médicamenteuse, Pulmonology and respiratory tract, lcsh:RC705-779, business.industry, appareil respiratoire, lcsh:Diseases of the respiratory system, respiratory tract, Orphan Drug, orphan drug production, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Human health and pathology, urinary system, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Forecasting
Abstract

Updates on rare pulmonary diseases from the 6th International Meeting on Pulmonary Rare Diseases and Orphan Drugs http://ow.ly/PYUCC

Published
2015
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11. Pollutants in pet dogs: a model for environmental links to breast cancer

Author

Ingrid Guiffard, Jérôme Abadie, Sabine Sévère, Philippe Marchand, Floriane Morio, Jean-Philippe Antignac, Anaïs Vénisseau, Bruno Le Bizec, Bruno Veyrand, Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), LUNAM Université [Nantes Angers Le Mans], and Sévère, Sabine

Subjects
medicine.medical_specialty, Etiology, polluant organique persistant, Pneumologie et système respiratoire, Dog model, Context (language use), Disease, Bioinformatics, Ecotoxicologie, Ecotoxicology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Pathogenesis, Breast cancer, Epidemiology, animal modèle, Medicine, cancer du poumon, pathogénèse, Pulmonology and respiratory tract, Aryl hydrocarbon receptor, Multidisciplinary, Comparative oncology, business.industry, facteur environnemental, Research, Persistent organic pollutants, Cancer, medicine.disease, substance toxique, 3. Good health, 13. Climate action, oncologie, chien, [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology, business
Abstract

2193-1801 Severe, Sabine Marchand, Philippe Guiffard, Ingrid Morio, Floriane Venisseau, Anais Veyrand, Bruno Le Bizec, Bruno Antignac, Jean-Philippe Abadie, Jerome Journal Article Switzerland Springerplus. 2015 Jan 22;4:27. doi: 10.1186/s40064-015-0790-4. eCollection 2015.; International audience; PURPOSE: Invasive breast carcinoma is the most common cancer in women as in non-ovariectomised pet dogs, which are already identified as a valuable spontaneous preclinical model for that disease. Geographical and time trends suggest that environmental factors may play an important role in the etiology and pathogenesis of breast cancer. Persistent organic pollutants (POPs) fit perfectly with these trends and are known to interact with hormonal receptors implicated in breast cancer subtyping. The aim of this innovating study was to evaluate the interest of the companion dog model in assessing chemical exposure and breast cancer associations, in order to identify common etiological features with the human disease in a context of comparative oncology. METHODS: We monitored a hundred of molecules belonging to a large panel of POPs (dioxins, dioxin-like and non dioxin-like polychlorobisphenyls, organochlorine pesticides, brominated flame retardants, perfluorinated alkylated substances) in companion dogs diagnosed for mammary adenocarcinoma (n = 54) and non cancer controls (n = 47). RESULTS: All targeted chemical families were able to be detected in canine samples. We identified pollutants associated with mammary cancer belonging to the dioxin like-PCB family (notably PCB-118, -156, -105, -114) that were already pointed out in human epidemiological studies on breast cancer, and that fit with the fundamental role of the Aryl Hydrocarbon Receptor in the promotion of breast cancer. CONCLUSIONS: Similarities observed in the spontaneous dog model are very helpful to progress in interpretation of human breast cancer-environment relationships. This study provides a new insight focusing on this discrete but recurrent signature.

Published
2015
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12. Idiopathic inflammatory myopathies and the lung

Author

Alexandre Belot, Isabelle Durieu, Nicole Fabien, Jean-Christophe Lega, Quitterie Reynaud, Vincent Cottin, Service de Médecine Interne Vasculaire, Hospices Civils de Lyon (HCL), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology, Hôpital Femme-Mère-Enfant, Département Immunologie (DéPARTEMENT IMMUNOLOGIE), 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), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), and Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Pathology, Time Factors, Pneumologie et système respiratoire, morbidity, Comorbidity, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, Risk Factors, morbidité, Lung, maladie inflammatoire, Myositis, Interstitial lung disease, respiratory system, Prognosis, 3. Good health, inflammatory disease, maladie pulmonaire, medicine.anatomical_structure, Disease Progression, Drug Therapy, Combination, Immunosuppressive Agents, myopathy, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Malignancy, 03 medical and health sciences, Pleural disease, Predictive Value of Tests, medicine, Animals, Humans, respiratory system diseases, Pulmonology and respiratory tract, Autoantibodies, myopathie, 030203 arthritis & rheumatology, lcsh:RC705-779, business.industry, lcsh:Diseases of the respiratory system, Dermatomyositis, medicine.disease, mortality, 030228 respiratory system, Inclusion body myositis, business, Lung Diseases, Interstitial, mortalité, Biomarkers
Abstract

Idiopathic inflammatory myositis (IIM) is a group of rare connective tissue diseases (CTDs) characterised by muscular and extramuscular signs, in which lung involvement is a challenging issue. Interstitial lung disease (ILD) is the hallmark of pulmonary involvement in IIM, and causes morbidity and mortality, resulting in an estimated excess mortality of 50% in some series. Except for inclusion body myositis, these extrapulmonary disorders are associated with the general and visceral involvement frequently found in other CTDs including fever, Raynaud's phenomenon, arthralgia, nonspecific cutaneous modifications and ILD, for which the prevalence is estimated to be up to 65%. Substantial heterogeneity exists within the spectrum of IIMs, and each condition is associated with various frequencies and subtypes of pulmonary involvement. This heterogeneity is partly related to the presence of various autoantibodies encompassing anti-synthetase, anti-MDA5 and anti-PM/Scl. ILD is present in all subsets of IIM including juvenile myositis, but is more frequent in dermatomyositis and overlap myositis. IIM can also be associated with other presentations of respiratory involvement, namely pulmonary arterial hypertension, pleural disease, infections, drug-induced toxicity, malignancy and respiratory muscle weakness. Here, we critically review the current knowledge about adult and juvenile myositis-associated lung disease with a detailed description of therapeutics for chronic and rapidly progressive ILD.

Published
2015
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13. Systematic Analysis of Blood Cell Transcriptome in End-Stage Chronic Respiratory Diseases

Author

Julie Chesné, Richard Danger, Karine Botturi, Martine Reynaud-Gaubert, Sacha Mussot, Marc Stern, Isabelle Danner-Boucher, Jean-François Mornex, Christophe Pison, Claire Dromer, Romain Kessler, Marcel Dahan, Olivier Brugière, Jérôme Le Pavec, Frédéric Perros, Marc Humbert, Carine Gomez, Sophie Brouard, Antoine Magnan, COLT Consortium, 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 de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardiopulmonaire, Hôpital Marie Lannelongue, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Foch [Suresnes], Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Service de chirurgie thoracique, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Strasbourg, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), 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 pneumologie [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), UPRES EA220, Lung Transplantation Department, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), ANR-10-IBHU-0005/10-IBHU-0005,CESTI (TSI-IHU),CESTI (TSI-IHU)(2010), Magnan, Antoine, Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), 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), AP-HP - Hôpital Antoine Béclère [Clamart], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre chirurgical Marie Lannelongue, Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique (LOBIP), ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), 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), Hôpital Marie-Lannelongue, Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Lung Diseases, Candidate gene, Pulmonology, Microarrays, [SDV]Life Sciences [q-bio], Pneumologie et système respiratoire, lcsh:Medicine, Lymphocyte Activation, Transcriptome, Pulmonary Disease, Chronic Obstructive, Animal Cells, Medicine and Health Sciences, T Cell Transcription Factor 1, Cluster Analysis, lcsh:Science, Immune Response, Oligonucleotide Array Sequence Analysis, Whole blood, Pulmonary Hypertension, Multidisciplinary, Chronic obstructive pulmonary disease, Middle Aged, Cell Hypoxia, 3. Good health, survie, Blood, Gene ontologies, Cellular Types, medicine.symptom, Transcriptome Analysis, Research Article, Adult, Immune Cells, Hypertension, Pulmonary, Immunology, Médecine humaine et pathologie, Biology, Peripheral blood mononuclear cell, Cystic fibrosis, Immune Deficiency, Respiratory Failure, medicine, Humans, hypertension pulmonaire, RNA, Messenger, Interleukin-7 receptor, Pulmonology and respiratory tract, Blood Cells, Gene Expression Profiling, lcsh:R, Biology and Life Sciences, Computational Biology, Receptors, Interleukin-1, hypoxie, Cell Biology, Hypoxia (medical), Genome Analysis, medicine.disease, Fibrosis, Pulmonary hypertension, infection, Toll-like receptors, Gene expression profiling, Gene Ontology, maladie respiratoire, Case-Control Studies, Clinical Immunology, lcsh:Q, Human health and pathology, cellule sanguine, Gene expression, transcriptome, Metabolic processes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Developmental Biology, thérapie
Abstract

International audience; BackgroundEnd-stage chronic respiratory diseases (CRD) have systemic consequences, such as weight loss and susceptibility to infection. However the mechanisms of such dysfunctions are as yet poorly explained. We hypothesized that the genes putatively involved in these mechanisms would emerge from a systematic analysis of blood mRNA profiles from pre-transplant patients with cystic fibrosis (CF), pulmonary hypertension (PAH), and chronic obstructive pulmonary disease (COPD).MethodsWhole blood was first collected from 13 patients with PAH, 23 patients with CF, and 28 Healthy Controls (HC). Microarray results were validated by quantitative PCR on a second and independent group (7PAH, 9CF, and 11HC). Twelve pre-transplant COPD patients were added to validate the common signature shared by patients with CRD for all causes. To further clarify a role for hypoxia in the candidate gene dysregulation, peripheral blood mononuclear cells from HC were analysed for their mRNA profile under hypoxia.ResultsUnsupervised hierarchical clustering allowed the identification of 3 gene signatures related to CRD. One was common to CF and PAH, another specific to CF, and the final one was specific to PAH. With the common signature, we validated T-Cell Factor 7 (TCF-7) and Interleukin 7 Receptor (IL-7R), two genes related to T lymphocyte activation, as being under-expressed. We showed a strong impact of the hypoxia on modulation of TCF-7 and IL-7R expression in PBMCs from HC under hypoxia or PBMCs from CRD. In addition, we identified and validated genes upregulated in PAH or CF, including Lectin Galactoside-binding Soluble 3 and Toll Like Receptor 4, respectively.ConclusionsSystematic analysis of blood cell transcriptome in CRD patients identified common and specific signatures relevant to the systemic pathologies. TCF-7 and IL-7R were downregulated whatever the cause of CRD and this could play a role in the higher susceptibility to infection of these patients.

Published
2014
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14. Effectiveness of cladribine therapy in patients with pulmonary Langerhans cell histiocytosis

Author

Romain Lazor, Vincent Cottin, Jean-François Cordier, Chahéra Khouatra, Vincent Grobost, 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), Cottin, Vincent, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
Lung Diseases, Male, [SDV]Life Sciences [q-bio], Pneumologie et système respiratoire, Gastroenterology, Langerhans cell granulomatosis, Langerhans cell histiocytosis, Chlorodeoxyadenosine, Genetics(clinical), Pharmacology (medical), Cladribine, Genetics (clinical), Medicine(all), Smoking, Cladribine/*therapeutic use, General Medicine, Middle Aged, Lung Diseases/*diagnosis/*drug therapy/etiology, Smoking/adverse effects/drug therapy, Antineoplastic Agents/*therapeutic use, 3. Good health, Histiocytosis, medicine.anatomical_structure, Treatment Outcome, Female, Langerhans-Cell/complications/*diagnosis/*drug therapy, medicine.drug, Adult, histiocytose X, medicine.medical_specialty, histiocytosis, langerhans cell granulomatosis, cladribine, chlorodeoxyadenosine, pulmonary hypertension, Antineoplastic Agents, Pulmonary hypertension, Internal medicine, medicine, hypertension pulmonaire, Humans, Pulmonology and respiratory tract, Histiocyte, Retrospective Studies, Lung, business.industry, Research, medicine.disease, Histiocytosis, Langerhans-Cell, Pneumonia, Immunology, business, Progressive disease
Abstract

International audience; BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterised by granulomatous proliferation of CD1a-positive histiocytes forming granulomas within lung parenchyma, in strong association with tobacco smoking, and which may result in chronic respiratory failure. Smoking cessation is considered to be critical in management, but has variable effects on outcome. No drug therapy has been validated. Cladribine (chlorodeoxyadenosine, 2-CDA) down-regulates histiocyte proliferation and has been successful in curbing multi-system Langerhans cell histiocytosis and isolated PLCH. METHODS AND PATIENTS: We retrospectively studied 5 patients (aged 37-55 years, 3 females) with PLCH who received 3 to 4 courses of cladribine therapy as a single agent (0.1 mg/kg per day for 5 consecutive days at monthly intervals). One patient was treated twice because of relapse at 1 year. Progressive pulmonary disease with obstructive ventilatory pattern despite smoking cessation and/or corticosteroid therapy were indications for treatment. Patients were administered oral trimethoprim/sulfamethoxazole and valaciclovir to prevent opportunistic infections. They gave written consent to receive off-label cladribine in the absence of validated treatment. RESULTS: Functional class dyspnea improved with cladribine therapy in 4 out of 5 cases, and forced expiratory volume in 1 second (FEV1) increased in all cases by a mean of 387 ml (100-920 ml), contrasting with a steady decline prior to treatment. Chest high-resolution computed tomography (HRCT) features improved with cladribine therapy in 4 patients. Hemodynamic improvement was observed in 1 patient with pre-capillary pulmonary hypertension. The results suggested a greater treatment effect in subjects with nodular lung lesions and/or thick-walled cysts on chest HRCT, with diffuse hypermetabolism of lung lesions on positron emission tomography (PET)-scan, and with progressive disease despite smoking cessation. Infectious pneumonia developed in 1 patient, with later grade 4 neutrocytopenia but without infection. DISCUSSION: Data interpretation was limited by the retrospective, uncontrolled study design and small sample size. CONCLUSION: Cladribine as a single agent may be effective therapy in patients with progressive PLCH.

Published
2014
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15. Impact de la ventilation mécanique sur la réponse inflammatoire médiée par les Toll-like receptors 2 et 4 dans un modèle de pneumopathie bactérienne

Author

Barbar, Saber Davide

Subjects
SDV:BC, Pneumologie et système respiratoire, Pulmonology and respiratory tract, Prone position, Staphylococcus aureus, Toll-­Like Receptor 2, Ventilator associated pneumonia, Ventilator induced lung injury, Mechanical ventilation, Stretch, Pneumonie associées à la ventilation, Toll-like Receptor 2, Enterobacter aerogenes, Decubitus ventral, Lésion pulmonaire induite par la ventilation, Ventilation mécanique, Étirement
Abstract

Introduction: La pneumonie associée à la ventilation mécanique (VM) est fréquente chez les patients ventilés. L’étirement cyclique (EC) induit par la VM pourrait amorcer le poumon vers une réponse inflammatoire en cas d'exposition à des bactéries. Les Toll-like Receptors (TLR) reconnaissent les bactéries et déclenchent l'immunité. La VM pourrait moduler l'expression des TLR et leur réactivité aux agonistes. Le décubitus ventral (DV) réduit l’étirement du poumon. Méthodes: Les niveaux de TLR2 et la réponse à ses agonistes ont été mesures dans des cellules pulmonaires soumises à un EC, et dans un modèle de lapin ventilé. Une stimulation ex vivo du sang total prélevé sur lapins ventilés a été réalisée. Une pneumonie a été induite chez des lapins soumis à VM et maintenus en décubitus dorsal ou tournés en DV. Résultats: L’EC des cellules ainsi que des poumons de lapins augmente les niveaux de TLR2 et la réponse inflammatoire à ses agonistes. La VM et l’exposition du poumon à des agonistes TLR2 induisent synergiquement des lésions. Chez des lapins avec pneumonie sous VM la clairance bactérienne pulmonaire est réduite, la probabilité de bactériémie et le taux des cytokines circulantes augmentés. Le sang total provenant d'animaux sous VM libère de grandes quantités de cytokines après stimulation. Le DV est associe à des niveaux plus faibles de concentrations bactériennes et d'inflammation. Conclusions: La VM sensibilise le poumon aux ligands bactériens de TLR2, modifie la clairance bactérienne pulmonaire, favorise les lésions pulmonaires et de l'inflammation. La surexpression de TLR2 induite par l’EC pourrait expliquer ces différences. Le DV pourrait avoir un effet protecteur., Introduction: Ventilator-associated pneumonia is common in patients subjected to mechanical ventilation (MV). Cyclic stretch subsequent to MV could prime the lung toward an inflammatory response if exposed to bacteria. Toll-like receptors (TLRs) recognize pathogens thus triggering immunity. MV could modulate TLRs expression and responsiveness to agonists. The prone position (PP) reduces lung stretch.Methods:TLR2 levels and response to the TLR2 ligands were measured in human pulmonary cells submitted to cyclic stretch, and either spontaneously breathing (SB) or MV rabbits. Ex vivo stimulation of whole blood taken from SB or MV rabbits was performed.Enterobacter aerogenes pneumonia was induced in rabbits subjected to MV and kept supine or turned to the PP. Results: Cyclic stretch of human cells as well as rabbitsÕ lung increased both TLR2 levels and inflammatory response to its agonist. MV and airways exposure to TLR2 ligands acted synergistically in causing lung injury.A decrease of lung bacterial clearance and a greater likelihood of bacteremia were observed in MV rabbits with S. aureus pneumonia. Circulating cytokines rose significantly only in these animals. MV induced TLR2 spleen overexpression. Whole blood obtained from MV animals released larger amounts of cytokines after stimulation. PP was associated with lower levels of bacterial concentrations and inflammation. Conclusions: MV sensitizes the lung to bacterial TLR2 ligands, alters lung bacterial clearance, promotes lung injury and inflammation. Both pulmonary and peripheral blood stretch-induced TLR2 overexpression could account at least in part for such differences. The PP could be protective.

Published
2014

16. Lung neonatal responses to respiratory syncytial virus reveal deficiencies in dendritic cells and type I interferon in a mouse model of airway enhanced disease

Author

Jouneau, Luc, Descamps, Delphyne, Dubuquoy, Catherine, Bouet, Stephan, Lecardonnel, Jerôme, Rebours, Emmanuelle, Cherbuy, Claire, Petit-Camurdan, Agnes, Riffault, Sabine, and Remot, Aude

Subjects
animal nouveau né, maladie respiratoire, Pneumologie et système respiratoire, cellule dendritique, interferon, Pulmonology and respiratory tract, modèle murin, virus respiratoire syncytial
Published
2014

17. Pirfenidone in idiopathic pulmonary fibrosis: expert panel discussion on the management of drug-related adverse events

Author

James Ferguson, Pieter Dewint, Richard Groves, Alexandre Sarafidis, Carlo Vancheri, Jim J. Egan, Per M. Hellström, Michael Kreuter, Maria Molina-Molina, Toby M. Maher, Vincent Cottin, Klas Nordlind, Ulrich Costabel, Elisabeth Bendstrup, Costabel, Ulrich, University of Duisburg-Essen, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital [Gothenburg], Rétrovirus et Pathologie Comparée, 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)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Erasmus University Rotterdam, Mater Misericordiae University Hospital, Ninewells Hospital, King‘s College London, Uppsala University, Heidelberg University, Respiratory Critical Care Medicine Heidelberg, Partenaires INRAE, Royal Brompton Hospital, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University Hospital, Centre Hospitalier Interrégional Edith Cavell (CHIREC), Università degli Studi di Catania (UniCT), and InterMune International AG, Basel, Switzerland.

Subjects
photosensibilité, Alternative medicine, Medizin, Pneumologie et système respiratoire, Review, Pharmacology, Pharmacologie, Pirfenidone, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Adverse event management, Photosensitivity, Medicine, Pharmacology (medical), 030212 general & internal medicine, Disease management (health), General Clinical Medicine, media_common, Medicine(all), Anti-Inflammatory Agents, Non-Steroidal, adverse event management, Disease Management, General Medicine, Farmakologi och toxikologi, idiopathic pulmonary fibrosis, 3. Good health, Respiratory Function Tests, expert opinion, Expert opinion, Respiratory, expertise, Safety, medicine.drug, Drug, safety, medicine.medical_specialty, fibrose pulmonaire, Drug-Related Side Effects and Adverse Reactions, Pyridones, media_common.quotation_subject, MEDLINE, photosensitivity, Pharmacology and Toxicology, Disease-Free Survival, 03 medical and health sciences, Humans, gastrointestinal events, Intensive care medicine, Adverse effect, Pulmonology and respiratory tract, Panel discussion, business.industry, Tumor Necrosis Factor-alpha, Gastrointestinal events, Skin-related events, medicine.disease, respiratory, 030228 respiratory system, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, pirfenidone, skin-related events, 1115 Pharmacology And Pharmaceutical Sciences, business
Abstract

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose. Electronic supplementary material The online version of this article (doi:10.1007/s12325-014-0112-1) contains supplementary material, which is available to authorized users.

Published
2014
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18. Impact of lung microbiota on neonatal immunity

Author

Thomas, Muriel, Hammad, Hamida, and Remot, Aude

Subjects
microbiote, Immunologie, Immunology, poumon, Pneumologie et système respiratoire, nouveau né, Pulmonology and respiratory tract, immunité
Published
2013

19. Combined modalities treatment of pulmonary metastasis from an urachal adenocarcinoma

Author

Fabrice Piegay, Jean-François Mornex, Hospices Civils de Lyon (HCL), Université de Lyon (COMUE), Rétrovirus et Pathologie Comparée, 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)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), and Mornex, Jean-Francois

Subjects
Pathology, medicine.medical_specialty, bladder, lung, urachus, Histology, Umbilicus (mollusc), adénocarcinome, Lung metastasis, 030232 urology & nephrology, Pneumologie et système respiratoire, Case Report, vessie, métastase, lcsh:RC254-282, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, medicine, Neoplasm, Pulmonary metastasis, Pulmonology and respiratory tract, Urachus, Lung, business.industry, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Urachal adenocarcinoma, 3. Good health, body regions, urachus, bladder, lung, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, poumon, Lymph, business
Abstract

International audience; Urachal adenocarcinoma is a rare neoplasm of the bladder. Most of these tumors arise from urachal remnants in the dome of the bladder and extend into the umbilicus. These tumors can recur and most commonly metastasize to lymph nodes, retroperitoneum, lungs, liver and bone. Here we report a case of an urachal adenocarcinoma followed for seven years with lung metastasis for three years.

Published
2013
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20. Interplay between JSRV, an oncogenic retrovirus and the pulmonary epithelium

Author

Mornex, Jean-Francois, Leroux, Caroline, and Archer, Fabienne

Subjects
épithélium branchial, mouton, adénocarcinome, réponse immunitaire, Pneumologie et système respiratoire, cancer du poumon, Pulmonology and respiratory tract, JSRV, lung, immune response, adenocarcinoma, alveolar type II cells, rétrovirus Jaagsiekte du mouton
Published
2012

21. Neonatal Nasal Vaccination with the Nucleoprotein of the Respiratory Syncytial Virus Elicits Virus-protective but Airway-pathogenic Th2-biased Immunity that can be Modulated by the Choice of Adjuvants

Author

Remot, Aude, Roux, Xavier, Dubuquoy, Catherine, Bernard, Julie, Moudjou, Mohammed, Eleouet, Jean Francois, Riffault, Sabine, Petit-Camurdan, Agnes, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), and Society for Mucosal Immunology.

Subjects
administration intra nasal, viruses, Pneumologie et système respiratoire, nouveau né, nucléoprotéine, respiratory system, vaccination, Pulmonology and respiratory tract, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, virus respiratoire syncytial
Abstract

National audience; There is still no licensed vaccine against human respiratory syncytial virus (RSV) which causes severe bronchiolitis in yound children. The nucleoprotein N, a major component of the RSV nucleocapsid, is remarkably conserved among RSV subtypes and is recognized as a target of protective T cell responses. We reported a method to produce recombinant N assembling in homogenous rings composed of 10-11 N subunits.Intranasal vaccination of adult BALB/c mice with N-rings and detoxified E.coli enterotoxin LT(R192G) as adjuvant (provided by J. Clements, USA), proved protective against an RSV challenge, without causing significant lung inflammatory reactions. In the present study, we evaluated the vaccine potential of N-rings in 5 to 7 day-old BALB/c pups: a single intranasal administration of N-rings with LT(R192G) provided a significant reduction of the viral load after an RSV challenge at five weeks of age. However, neonatal vaccination also generated an enhanced lung infiltration by eosinophils following the RSV challenge. Analysis of antibody subclasses and cytokines produced after an RSV challenge or a boost administration of the vaccine suggested that neonatal vaccination induced a long lasting Th2 biased local immune memory. This early Th2 bias could be prevented by adding CpG-ODN to the vaccine formulation, but then the protection against virus replication was also reduced. In conclusion, protective vaccination against RSV can be achieve in neonates but requires an appropriate combinations of adjuvant.

Published
2011

22. Centrilobular emphysema combined with pulmonary fibrosis results in improved survival: a response

Author

Athol U. Wells, Vincent Cottin, Jean-François Cordier, Rétrovirus et Pathologie Comparée, 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)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Hôpital Louis Pradel, Service de Pneumologie, Centre de Référence National des Maladies Pulmonaires Rares, Hospices Civils de Lyon (HCL), and Royal Brompton Hospital

Subjects
fibrose pulmonaire, emphysème pulmonaire, Pathology, medicine.medical_specialty, Pneumologie et système respiratoire, Medicine (miscellaneous), Improved survival, Dermatology, Letter to the Editors, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Pulmonary fibrosis, Centrilobular emphysema, Medicine, 030212 general & internal medicine, Pulmonology and respiratory tract, capacité de survie, Hepatology, business.industry, Gastroenterology, respiratory system, Tissue repair, medicine.disease, Combined pulmonary fibrosis and emphysema, respiratory tract diseases, 3. Good health, 030228 respiratory system, business
Abstract

International audience; Better survival in combined pulmonary fibrosis and emphysema than in lone pulmonary fibrosis: bias or reality? A response to Centrilobular emphysema combined with pulmonary fibrosis results in improved survival by Todd et al., Fibrogenesis & Tissue Repair 2011, 4:6. Please see related letter http://fibrogenesis.com/content/4/1/17.

Published
2011
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23. Nucleoprotein nanostructures: a mucosal subunit vaccine candidate for neonates protective against the respiratory syncytial virus

Author

Roux, Xavier, Dubuquoy, Catherine, Bernard Theron, Julie, fix, Jenna, Moudjou, Mohammed, Eleouet, Jean Francois, Petit-Camurdan, Agnes, Riffault, Sabine, and Remot, Aude

Subjects
maladie respiratoire, Pneumologie et système respiratoire, nouveau né, nucléoprotéine, vaccination, immunisation intranasale, Pulmonology and respiratory tract, virus respiratoire syncytial
Published
2011

24. Rôle des récepteurs PAR et TLR pulmonaires dans les réponses néonatales aux infections virales respiratoires

Author

Djavidi, Azadeh, Petit-Camurdan, Agnes, Dubuquoy, Catherine, Schwartz, Isabelle, Laurent, Fabrice, Morel, Olivier, Chavatte-Palmer, Pascale, Parez, Nathalie, Riffault, Sabine, and Remot, Aude

Subjects
modèle animal, inflammation, Bronchiolite, Nouveau-né, Poumon, PAR, TLR, poumon, agneau, Pneumologie et système respiratoire, Médecine humaine et pathologie, nouveau né, Human health and pathology, protéase, Pulmonology and respiratory tract
Published
2010

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