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1. Chest physiotherapy enhances detection of Pseudomonas aeruginosa in nonexpectorating children with cystic fibrosis

Author: Christophe Marguet, Véronique Houdouin, Isabelle Pin, Philippe Reix, Frédéric Huet, Marie Mittaine, Sophie Ramel, Nathalie Wizla-Derambure, Michel Abely, Marie-Laure Dalphin, Michael Fayon, Tiphaine Bihouée, Muriel Le Bourgeois, Eric Deneuville, Harriet Corvol, Muriel Laurans, Laure Couderc, Evelyne Leroux, and Ludovic Lémée
Subjects: Medicine
Abstract: Lung damage in cystic fibrosis (CF) is strongly associated with lower airway infections. Early treatment of Pseudomonas aeruginosa is recommended. Pathogen detection requires sampling of lower airway secretions, which remains a challenge in nonexpectorating patients. Our hypothesis was that chest physiotherapy would improve the quality of airway secretion samples and increase the rates of pathogens detected in nonexpectorating patients. This prospective multicentre study compared three successive methods for sampling airway secretions applied through the same session: 1) an oropharyngeal swab (OP), 2) a chest physiotherapy session followed by a provoked cough to obtain sputum (CP-SP) and 3) a second oropharyngeal swab collected after chest physiotherapy (CP-OP). Haemophilus influenzae, Staphylococcus aureus and P. aeruginosa growth cultures were assessed. Accuracy tests and an equivalence test were performed to compare the three successive methods of collection. 300 nonexpectorating children with CF were included. P. aeruginosa was detected cumulatively in 56 (18.9%) children, and according to the different collection methods in 28 (9.8%), 37 (12.4%) and 44 (14.7%) children by using OP, CP-OP and CP-SP, respectively. Compared with OP, the increased detection rate was +22% for CP-OP (p=0.029) and +57% for CP-SP (p=0.003). CP-SP had the best positive predictive value (86.3%) and negative predictive value (96.0%) for P. aeruginosa compared with the overall detection. The results of this adequately powered study show differences in the rates of pathogens detected according to the sampling method used. Chest physiotherapy enhanced detection of P. aeruginosa in nonexpectorating children with CF.
Published: 2021
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2. Clinical and microbiological characteristics of cystic fibrosis adults never colonized by Pseudomonas aeruginosa: Analysis of the French CF registry.

Author: Réchana Vongthilath, Bénédicte Richaud Thiriez, Clémence Dehillotte, Lydie Lemonnier, Alicia Guillien, Bruno Degano, Marie-Laure Dalphin, Jean-Charles Dalphin, and Patrick Plésiat
Subjects: Medicine, Science
Abstract: Pseudomonas aeruginosa is the main cause of chronic airway infection in cystic fibrosis (CF). However, for unclear reasons some patients are never colonized by P. aeruginosa. The objectives of this study were to better define the clinical, genetic, and microbiological characteristics of such a subpopulation and to identify predictive factors of non-colonization with P. aeruginosa. The French CF patient registry 2013-2014 was used to identify CF patients aged ≥ 20 years. The clinical outcomes, CF Transmembrane conductance Regulator (CFTR) genotypes, and microbiological data of patients reported positive at least once for P. aeruginosa ("Pyo" group, n = 1,827) were compared to those of patients with no history of P. aeruginosa isolation ("Never" group, n = 303). Predictive factors of non-colonization by P. aeruginosa were identified by multivariate logistic regression model with backward selection. Absence of aspergillosis (odds ratio (OR) [95% CI] = 1.64 [1.01-2.66]), absence of diabetes (2.25 [1.21-4.18]), pancreatic sufficiency (1.81 [1.30-2.52]), forced expiratory volume 1 (FEV1) ≥ 80% (3.03 [2.28-4.03]), older age at CF diagnosis (1.03 [1.02-1.04]), and absence of F508del/F508del genotype (2.17 [1.48-3.19]) were predictive clinical factors associated with absence of infection ("Never" group). Microbiologically, this same group was associated with more frequent detection of Haemophilus influenzae and lower rates of Stenotrophomonas maltophilia, Achromobacter xylosoxidans and Aspergillus spp. (all p
Published: 2019
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3. Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

Author: Pierre-Régis Burgel, Isabelle Durieu, Raphaël Chiron, Sophie Ramel, Isabelle Danner-Boucher, Anne Prevotat, Dominique Grenet, Christophe Marguet, Martine Reynaud-Gaubert, Julie Macey, Laurent Mely, Annlyse Fanton, Sébastien Quetant, Lydie Lemonnier, Jean-Louis Paillasseur, Jennifer Da Silva, Clémence Martin, Claire Andrejak, Arnaud Becourt, Julie Mounard, Claire Poulet, Cinthia Rames, Marie Talleux, Marie-Chantal Chevalier, Estelle Darviot, Marie Jouvenot, Caroline Marien, Audrey Paris, Cécile Pelatan, Christine Person, Pascaline Priou, Françoise Troussier, Thierry Urban, Marie-Laure Dalphin, Jean-Charles Dalphin, Alice Ladaurade, Didier Pernet, Bénédicte Richaud-Thiriez, Pauline Roux-Claude, Nathalia Blanc, Vincent Boisserie-Lacroix, Stephanie Bui, Cyrielle Collet, Stéphane Debelleix, Emmanuel Bergot, Jacques Brouard, Karine Campbell, Muriel Laurans, Virginie Ribault, Corinne Borderon, Marie-Christine Heraud, Guillaume Labbe, Sylvie Montcouquiol, Isabelle Petit, Marc Ruivard, Céline Delestrain, Benoit Douvry, Ralph Epaud, Bernard Maitre, Natascha Remus, Guillaume Beltramo, Anne Houzel, Frédéric Huet, Stéphanie Perez, Amale Boldron-Ghaddar, Manuela Scalbert, Rabah Bouzioukh, Charles Simon, Boubou Camara, Rébecca Hamidfar, Catherine Llerena, Isabelle Pin, Antoine Deschildre, Alice Gicquello, Olivier Le Rouzic, Clara Leroy, Nicolas Paris, Thierry Perez, Caroline Thumerelle, Dominique Turck, Nathalie Wizla, Magali Dupuy-Grasset, Jane Languepin, Alexandra Masson-Rouchaud, Céline Menetrey, Stéphane Durupt, Sophie L’Excellent, Raphaele Nove-Josserand, Camille Ohlmann, Phillipe Reix, Quitterie Reynaud, Marie-Christine Werck-Gallois, Mélissandre Baravalle, Bérangère Coltey, Nadine Desmazes-Dufeu, Jean-Christophe Dubus, Clarisse Gautier, Jean-Baptiste Rey, Nathalie Stremler, Davide Caimmi, Margot Devrait, Johan Moreau, Yves Billon, Aurore Blondé, Anne Guillaumot, Sébastien Kiefer, Laura Peretti, Aurélie Tatopoulos, Angélica Tiotiu, Myriam Benhamida, Tiphaine Bihouee, Emmanuel Eschapasse, Adrien Tissot, Marie Giannantonio, Sylvie Leroy, Carole Piccini-Bailly, Johana Pradelli, Jonathan Messika, Véronique Boussaud, Nicolas Carlier, Isabelle Honoré, Dominique Hubert, Reem Kanaan, Céline Bailly-Botuha, Frédérique Chedevergne, Jacques De Blic, Christophe Delacourt, David Drummond, Brigitte Fauroux, Chantal Karila, Muriel Le Bourgeois, Isabelle Sermet, Bertrand Delaisi, Michèle Gerardin, Veronique Houdouin, Laurence Leclainche, Guillaume Aubertin, Laura Berdah, Annick Clement, Harriet Corvol, Nadia Nathan, Blandine Prevost, Nicolas Richard, Aline Tamalet, Jessica Taytard, Guillaume Thouvenin, Barbara Tourniaire, Michel Abely, Katia Bessaci-Kabouya, Sandra Dury, Bruno Ravoninjatovo, Alain Dabadie, Michel Dagorne, Eric Deneuville, Marie Jamin, Mélanie Ribault, Clémentine Vigier, Chantal Belleguic, Graziella Brinchault, Benoit Desrues, Audrey Barzic, Anne Dirou-Prigent, Jean Le Bihan, Krista Revert, Thomas Ropars, Laure Couderc, Stéphane Dominique, Hélène Morisse-Pradier, Stéphanie Pramil, Luc Thiberville, Nathalie Allou, Laurent Enaud, Elsa Gachelin, Eric Huchot, Annabelle Payet, Caroline Perisson, Saguiraly Piyaraly, Sophie Valois, Audrey Herzog, Romain Kessler, Michele Porzio, Laurence Weiss, Laurence Beaumont, Olivier Brugiere, Sylvie Colin, de Verdiere, Elise Cuquemelle, Sandra De Miranda, Adbdul Monem Hamid, François Parquin, Clément Picard, Antoine Roux, Charlotte Roy, François Bremont, Alain Didier, Marion Dupuis, Guillaume Faviez, Géraldine Labouret, Marie Mittaine, Marlène Murris-Espin, Léa Roditis, Laure Cosson, Patrice Diot, Thomas Flament, Charlotte Giraut, Julie Mankikian, Baptiste Arnouat, Gaétane Mousset, Véronique Storni, Philippe Vigneron, Emmanuelle Coirier-Duet, Asma Gabsi, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Université de Lyon, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Fondation ILDYS (ILDYS), Institut du Thorax [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Foch [Suresnes], CHU Rouen, Normandie Université (NU), INSERM-TRANSFERT [Paris] (IT), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), CHU Bordeaux [Bordeaux], Hôpital Renée Sabran [CHU - HCL], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire [Grenoble] (CHU), Vaincre la Mucoviscidose, Association de lutte contre la Mucoviscidose, EFFI-STAT, URC/CIC Paris Descartes Necker Cochin, Hôpital Necker, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Supported by Vaincre la Mucoviscidose, Fondation Sauver la Vie, Universite Paris Descartes, Filiere Maladies Rares Muco-CFTR, and Legs PascalBonnet., Participating Investigators of the FrenchCystic Fibrosis Reference Network StudyGroup:Claire Andrejak, Arnaud Becourt, JulieMounard, Claire Poulet, Cinthia Rames, MarieTalleux (Amiens), Marie-Chantal Chevalier,Estelle Darviot, Marie Jouvenot, Caroline Marien,Audrey Paris, C ecile Pelatan, Christine Person,Pascaline Priou, Franc ̧oise Troussier, ThierryUrban (Angers-Le Mans), Marie-Laure Dalphin,Jean-Charles Dalphin, Alice Ladaurade, DidierPernet, B en edicte Richaud-Thiriez, PaulineRoux-Claude (Besanc ̧on), Nathalia Blanc,Vincent Boisserie-Lacroix, Stephanie Bui,Cyrielle Collet, St ephane Debelleix, Julie Macey(Bordeaux), Emmanuel Bergot, JacquesBrouard, Karine Campbell, Muriel Laurans,Virginie Ribault (Caen), Corinne Borderon,Marie-Christine Heraud, Guillaume Labbe,SylvieMontcouquiol, Isabelle Petit, Marc Ruivard(Clermont-Ferrand), C eline Delestrain, BenoitDouvry, Ralph Epaud, Bernard Maitre, NataschaRemus (Cr eteil), Guillaume Beltramo, AnnlyseFanton, Anne Houzel, Fr ed eric Huet, St ephaniePerez (Dijon), AmaleBoldron-Ghaddar, ManuelaScalbert (Dunkerque), Rabah Bouzioukh,Laurent Mely, Charles Simon (Giens), BoubouCamara, R ebecca Hamidfar, Catherine Llerena,Isabelle Pin, S ebastien Quetant (Grenoble), Antoine Deschildre, Alice Gicquello, Olivier LeRouzic, Clara Leroy, Nicolas Paris, Thierry Perez,Anne Prevotat, Caroline Thumerelle, DominiqueTurck, Nathalie Wizla (Lille), Magali Dupuy-Grasset, Jane Languepin, Alexandra Masson-Rouchaud, C eline Menetrey (Limoges), IsabelleDurieu, St ephane Durupt, Sophie L’Excellent,Raphaele Nove-Josserand, Camille Ohlmann,Phillipe Reix, Quitterie Reynaud, Marie-ChristineWerck-Gallois (Lyon), M elissandre Baravalle,B erang ere Coltey, Nadine Desmazes-Dufeu,Jean-Christophe Dubus, Clarisse Gautier, Jean-Baptiste Rey, Martine Reynaud-Gaubert,Nathalie Stremler (Marseille), Davide Caimmi,Rapha€el Chiron, Margot Devrait, Johan Moreau(Montpellier), Yves Billon, Aurore Blond e, AnneGuillaumot, S ebastien Kiefer, Laura Peretti,Aur elie Tatopoulos, Ang elica Tiotiu (Nancy), Myriam Benhamida, Tiphaine Bihouee, IsabelleDanner-Boucher, Emmanuel Eschapasse,Adrien Tissot (Nantes), Marie Giannantonio,Sylvie Leroy, Carole Piccini-Bailly, JohanaPradelli (Nice), Jonathan Messika (Paris, Bichat), V eronique Boussaud, Pierre-R egis Burgel,Nicolas Carlier, Isabelle Honor e, DominiqueHubert, Reem Kanaan, Cl emence Martin (Paris,Cochin), C eline Bailly-Botuha, Fr ed eriqueChedevergne, Jacques De Blic, ChristopheDelacourt, David Drummond, Brigitte Fauroux,Chantal Karila, Muriel Le Bourgeois, IsabelleSermet (Paris, Necker), Bertrand Delaisi,Mich ele Gerardin, Veronique Houdouin,Laurence Leclainche (Paris, Robert Debr e), Guillaume Aubertin, Laura Berdah, AnnickClement, Harriet Corvol, Nadia Nathan, BlandinePrevost, Nicolas Richard, Aline Tamalet, JessicaTaytard, Guillaume Thouvenin, BarbaraTourniaire (Paris, Trousseau), Michel Abely,Katia Bessaci-Kabouya, Sandra Dury, BrunoRavoninjatovo (Reims), Alain Dabadie, MichelDagorne, Eric Deneuville, Marie Jamin, M elanieRibault, Cl ementine Vigier (Rennes – SaintBrieuc), Chantal Belleguic, Graziella Brinchault,Benoit Desrues (Rennes), Audrey Barzic, AnneDirou-Prigent, Jean Le Bihan, Sophie Ramel,Krista Revert, Thomas Ropars (Roscoff), LaureCouderc, St ephane Dominique, ChristopheMarguet, H el ene Morisse-Pradier, St ephaniePramil, Luc Thiberville (Rouen), Nathalie Allou,Laurent Enaud, Elsa Gachelin, Eric Huchot,Annabelle Payet, Caroline Perisson, SaguiralyPiyaraly, Sophie Valois (La R eunion), AudreyHerzog, Romain Kessler, Michele Porzio,Laurence Weiss (Strasbourg), LaurenceBeaumont, Olivier Brugiere, Sylvie Colin deVerdiere, Elise Cuquemelle, Sandra De Miranda,Dominique Grenet, Adbdul Monem Hamid,Franc ̧ois Parquin, Cl ementPicard, Antoine Roux,Charlotte Roy (Suresnes), Franc ̧ois Bremont,Alain Didier, Marion Dupuis, Guillaume Faviez,G eraldine Labouret, Marie Mittaine, Marl eneMurris-Espin, L ea Roditis (Toulouse), LaureCosson, Patrice Diot, Thomas Flament, CharlotteGiraut, JulieMankikian(Tours), Baptiste Arnouat,Ga etane Mousset, V eronique Storni, PhilippeVigneron (Vannes-Lorient), and Emmanuelle Coirier-Duet, and Asma Gabsi (Versailles)
Subjects: Lung Diseases, Male, elexacaftor, Indoles, Cystic Fibrosis, Pyridines, medicine.medical_treatment, Regulator, Aminophenols, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cystic fibrosis, Gastroenterology, Membrane Potentials, Ivacaftor, 0302 clinical medicine, Prospective Studies, 030212 general & internal medicine, Chloride Channel Agonists, Aged, 80 and over, Middle Aged, Transmembrane protein, Drug Combinations, Quinolines, Female, France, medicine.drug, Adult, Pulmonary and Respiratory Medicine, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, cystic fibrosis transmembrane conductance regulator modulators, Adolescent, Pulmonary disease, Young Adult, 03 medical and health sciences, Internal medicine, lung transplantation, medicine, Humans, Lung transplantation, In patient, Aged, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Editorials, medicine.disease, 030228 respiratory system, Tezacaftor, Pyrazoles, business
Abstract: International audience; Rationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1)
Published: 2021
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4. Protection contre l’allergie par l’environnement de la ferme : en 15 ans, qu’avons-nous appris de la cohorte européenne « PASTURE » ?

Author: J.-C. Dalphin, E. von Mutius, D.A. Vuitton, A. Divaret-Chauveau, J.-J. Laplante, Marie-Laure Dalphin, 4e division de l’Académie nationale de médecine, Carcinogenèse associée aux HPV (EA 3181), UFR Santé, Centre collaborateur OMS, Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre collaborateur OMS, Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Département d’allergologie pédiatrique, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Unité de pathologie respiratoire et allergologie, Département de pédiatrie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Association santé, éducation, et prévention sur les territoires, Franche-Comté/Bourgogne, Dr von Hauner Children's Hospital [Munich, Germany], Ludwig-Maximilians-Universität München (LMU), Service de pneumologie, and Oncologie thoracique et allergologie respiratoire
Subjects: 2. Zero hunger, 0301 basic medicine, Farms, Dermatitis, General Medicine, Allergens, Asthma, 3. Good health, 03 medical and health sciences, Milk, 030104 developmental biology, 0302 clinical medicine, 030228 respiratory system, Allergy and immunology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Atopic allergic diseases have become a public health problem because of the marked increase in their incidence along the second half of the 20th century, and their relationship with environmental changes observed in that period of time. Within the "hygiene hypothesis" which associated this increased incidence with a decrease in children's exposure to microbial agents, cross-sectional studies stressed the relationship between dairy farm specific environments with a significant protection against allergy. For the last 15 years, since the last trimester of their mother's pregnancy until now, in the PASTURE cohort 1000 children have been studied in dairy farming regions of 5 European countries (Austria, Finland, France/Franche-Comte, Germany, and Switzerland); 500 lived on a farm and 500 also lived in rural areas, but did not live on a farm. The results of this multidisciplinary endeavor pointed to the role of (1) the diversity of exposure to animals, microbes, and food in early childhood; (2) the consumption of raw milk and milk products; (3) maternal exposure before delivery for the immunological and allergic future of the child; (4) an early orientation/differentiation of dendritic cells, T cells and secreted cytokines towards a "regulatory profile", under the influence of the environmental factors. The PASTURE cohort is a remarkable example of European cooperation to better understand a public health problem, and of the involvement of families in a very demanding clinical research project. Its coordinators now expect to maintain the follow-up of the children until adult age and to work on "farm-like" preventive measures. (C) 2019 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.
Published: 2019
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5. Chest physiotherapy enhances detection of Pseudomonas aeruginosa in nonexpectorating children with cystic fibrosis

Author: Nathalie Wizla-Derambure, Marie Mittaine, E. Deneuville, Michael Fayon, Christophe Marguet, Ludovic Lemée, Véronique Houdouin, Michel Abely, Philippe Reix, S. Ramel, Laure Couderc, Marie-Laure Dalphin, Muriel Le Bourgeois, Evelyne Leroux, Isabelle Pin, F. Huet, Harriet Corvol, Tiphaine Bihouée, Muriel Laurans, Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), 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), Service de pédiatrie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU de Bordeaux Pellegrin [Bordeaux], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pneumologie et d'Allergologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Mucoviscidose: physiopathologie et phénogénomique [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Vaincre la Mucoviscidose, Association de lutte contre la Mucoviscidose, Normandie Université (NU)-Normandie Université (NU), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL-SU, Gestionnaire, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], and Service de Pneumologie pédiatrique [CHU Trousseau]
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, lcsh:Medicine, Chest physiotherapy, medicine.disease_cause, Cystic fibrosis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Haemophilus influenzae, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, 030212 general & internal medicine, Respiratory infections and tuberculosis, CF and non-CF bronchiectasis, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Lung, Paediatric pulmonology, Pseudomonas aeruginosa, business.industry, lcsh:R, medicine.disease, 3. Good health, medicine.anatomical_structure, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Staphylococcus aureus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Sputum, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, Airway
Abstract: Lung damage in cystic fibrosis (CF) is strongly associated with lower airway infections. Early treatment of Pseudomonas aeruginosa is recommended. Pathogen detection requires sampling of lower airway secretions, which remains a challenge in nonexpectorating patients. Our hypothesis was that chest physiotherapy would improve the quality of airway secretion samples and increase the rates of pathogens detected in nonexpectorating patients.This prospective multicentre study compared three successive methods for sampling airway secretions applied through the same session: 1) an oropharyngeal swab (OP), 2) a chest physiotherapy session followed by a provoked cough to obtain sputum (CP-SP) and 3) a second oropharyngeal swab collected after chest physiotherapy (CP-OP). Haemophilus influenzae, Staphylococcus aureus and P. aeruginosa growth cultures were assessed. Accuracy tests and an equivalence test were performed to compare the three successive methods of collection.300 nonexpectorating children with CF were included. P. aeruginosa was detected cumulatively in 56 (18.9%) children, and according to the different collection methods in 28 (9.8%), 37 (12.4%) and 44 (14.7%) children by using OP, CP-OP and CP-SP, respectively. Compared with OP, the increased detection rate was +22% for CP-OP (p=0.029) and +57% for CP-SP (p=0.003). CP-SP had the best positive predictive value (86.3%) and negative predictive value (96.0%) for P. aeruginosa compared with the overall detection.The results of this adequately powered study show differences in the rates of pathogens detected according to the sampling method used. Chest physiotherapy enhanced detection of P. aeruginosa in nonexpectorating children with CF.
Published: 2021
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6. Liste des collaborateurs

Author: Jacques Brouard, Guillaume Lezmi, Guillaume Pouessel, Anna Abecassis, Karine Adel-Patient, Flore Amat, Isabella Annesi Maesano, Annick Barbaud, Étienne Beaudouin, Pascale Beaumont, Nathalia Bellon, Grégoire Benoist, Étienne Bidat, Sibylle Blanc, Christine Bodemer, Marjorie Bonneton, Elena Bradatan, Albanne Branellec, Émilie Capelli, Olivier Carpentier, Laure Couderc, Pierrick Cros, Marie-Laure Dalphin, Jean-Louis Degraix, Christine Delebarre-Sauvage, Antoine Deschildre, Amandine Divaret-Chauveau, Angélique Doc, Guy Dutau, Caroline Faucon, Jean-Luc Fauquert, Agnès Fina, Lea Gaitan, Patrice-Serge Ganga-Zandzou, Lisa Giovannini-Chami, Lydie Guénard-Bilbault, Tamazoust Guiddir, Stéphane Hazebrouck, Luciana Kase Tanno, Alice Ladaurade, Florence Lageix, François Lavaud, Sébastien Lefèvre, Stéphanie Lejeune, Françoise Le Pabic, Carine Metz-Favre, Moïse Michel, Tomas Moraly, Françoise Morel-Codreanu, Ariane Nemni, Nhân Pham Thi, Laura Polivka, Claude Ponvert, Jean-Marc Rame, Jean-Marie Renaudin, Dominique Sabouraud-Leclerc, Adjokè Clarisse Santos, Eva Serrano, Caroline Thumerelle, Joana Vitte, Stéphanie Wanin, and Mathieu Zannotti
Published: 2021
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7. Chest physiotherapy enhances detection of

Author: Christophe, Marguet, Véronique, Houdouin, Isabelle, Pin, Philippe, Reix, Frédéric, Huet, Marie, Mittaine, Sophie, Ramel, Nathalie, Wizla-Derambure, Michel, Abely, Marie-Laure, Dalphin, Michael, Fayon, Tiphaine, Bihouée, Muriel, Le Bourgeois, Eric, Deneuville, Harriet, Corvol, Muriel, Laurans, Laure, Couderc, Evelyne, Leroux, and Ludovic, Lémée
Subjects: Cystic Fibrosis, Original Articles
Abstract: Lung damage in cystic fibrosis (CF) is strongly associated with lower airway infections. Early treatment of Pseudomonas aeruginosa is recommended. Pathogen detection requires sampling of lower airway secretions, which remains a challenge in nonexpectorating patients. Our hypothesis was that chest physiotherapy would improve the quality of airway secretion samples and increase the rates of pathogens detected in nonexpectorating patients. This prospective multicentre study compared three successive methods for sampling airway secretions applied through the same session: 1) an oropharyngeal swab (OP), 2) a chest physiotherapy session followed by a provoked cough to obtain sputum (CP-SP) and 3) a second oropharyngeal swab collected after chest physiotherapy (CP-OP). Haemophilus influenzae, Staphylococcus aureus and P. aeruginosa growth cultures were assessed. Accuracy tests and an equivalence test were performed to compare the three successive methods of collection. 300 nonexpectorating children with CF were included. P. aeruginosa was detected cumulatively in 56 (18.9%) children, and according to the different collection methods in 28 (9.8%), 37 (12.4%) and 44 (14.7%) children by using OP, CP-OP and CP-SP, respectively. Compared with OP, the increased detection rate was +22% for CP-OP (p=0.029) and +57% for CP-SP (p=0.003). CP-SP had the best positive predictive value (86.3%) and negative predictive value (96.0%) for P. aeruginosa compared with the overall detection. The results of this adequately powered study show differences in the rates of pathogens detected according to the sampling method used. Chest physiotherapy enhanced detection of P. aeruginosa in nonexpectorating children with CF., Sputum collection after a chest physiotherapy session strongly enhances the detection of P. aeruginosa in nonexpectorating CF children compared with the commonly used oropharyngeal swab method. Oropharyngeal swab after physiotherapy may be an acceptable alternative. https://bit.ly/3757ewq
Published: 2020

8. The protective effect of cheese consumption at 18 months on allergic diseases in the first 6 years

Author: Erika von Mutius, Dominique A. Vuitton, Charlotte Braun-Fahrländer, Jean-Charles Dalphin, Roger Lauener, Eléa Ksiazek, Elisabeth Schmausser-Hechfellner, Sophie Nicklaus, Caroline Roduit, Harald Renz, Marie-Laure Chardon, Marie-Laure Dalphin, Pirkka V. Kirjavainen, Anne M. Karvonen, Juha Pekkanen, Amandine Divaret-Chauveau, Vincent Kaulek, Josef Riedler, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Christine Kühne Center, Partenaires INRAE, University Children’s Hospital Zurich, Laboratoire Chrono-environnement - CNRS - UBFC (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), National Institute of Health and Welfare, University of Helsinki, Children's Hospital of Eastern Switzerland St.Gallen, Department of Pediatric Immunology and Rheumatology, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität (LMU), Munich, Philipps University of Marburg, German Centre for Lung Research, Swiss Tropical and Public Health Institute [Basel], University of Basel (Unibas), Schwarzach Hospital Kardinal Schwarzenberg'sches Krankenhaus, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), German Research Center for Environmental Health - Helmholtz Center München (GmbH), and the French national program for hospital research (PHRC IR 2012 DIRC EST PATUREIV).
Subjects: Male, 0301 basic medicine, Immunology, Gut flora, complementary feeding, Dermatitis, Atopic, cheese, Atopy, Toxicology, 03 medical and health sciences, 0302 clinical medicine, Food allergy, Surveys and Questionnaires, Hypersensitivity, medicine, Humans, Immunology and Allergy, Child, Asthma, 2. Zero hunger, food allergy, atopic dermatisis, biology, business.industry, Confounding, Infant, Atopic dermatitis, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, biology.organism_classification, medicine.disease, allergic disease, 030104 developmental biology, 030228 respiratory system, Child, Preschool, Regression Analysis, Hay fever, Allergic Disease, Atopic Dermatitis, Cheese, Complementary Feeding, Food Allergy, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Hypersensitivity, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Cohort study
Abstract: International audience; Background The effect of exposure to micro-organisms on allergic diseases has been well studied. The protective effect of early food diversity against allergic diseases was previously shown in the PASTURE cohort study. The consumption of cheese, a food potentially rich in microbial diversity, deserves further examination. We aimed to evaluate whether cheese consumption is associated with allergic diseases. Methods In the PASTURE study (birth cohort in 5 European countries), data on feeding practices, environmental factors and allergic diseases were collected by questionnaires from birth to 6 years (N=931). Cheese consumption at 18 months of age was quantified in terms of frequency and diversity (i.e., number of consumed types among 6 types: hard pressed, semi-pressed, soft, blue, fresh cheese, from the farm). Multiple logistic regressions were performed to evaluate the effect of cheese consumption on atopic dermatitis (AD), food allergy (FA), allergic rhinitis, asthma and atopic sensitization at 6 years after adjustment for confounders of atopy. Results Cheese consumption (vs. non-consumption) had a significant protective effect on AD (OR=0.51 [0.29-0.90], p=0.02) and FA (OR=0.32, [0.15-0.71], p=0.004), but no effect on atopic sensitization, allergic rhinitis and asthma at 6 years. This effect on AD and FA may be related to the diversity of consumed cheeses (OR=0.64 [0.48-0.85] per cheese type, p=0.002; OR=0.55 [0.33-0.92], p=0.02, respectively). Conclusions Although reverse causality cannot totally be ruled out, cheese diversity at 18 months had a protective effect against AD and FA at 6 years in addition to the protective effect of diversity of other foods.
Published: 2018
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9. Palivizumab prophylaxis in infants with cystic fibrosis does not delay first isolation of Pseudomonas aeruginosa or Staphylococcus aureus

Author: Stéphane Sanchez, Behrouz Kassai-Koupai, Marie-Laure Dalphin, Philippe Reix, Laurianne Coutier, Clélia Buchs, Catherine Mainguy, and M. Perceval
Subjects: Male, Palivizumab, Staphylococcus aureus, medicine.medical_specialty, Pediatrics, Cystic Fibrosis, Respiratory Syncytial Virus Infections, medicine.disease_cause, Staphylococcal infections, Antiviral Agents, Injections, Intramuscular, Cystic fibrosis, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Internal medicine, medicine, Humans, Pseudomonas Infections, Respiratory system, Retrospective Studies, Pseudomonas aeruginosa, business.industry, Age Factors, Case-control study, Infant, Retrospective cohort study, Staphylococcal Infections, medicine.disease, Treatment Outcome, 030228 respiratory system, Case-Control Studies, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, business, Follow-Up Studies, medicine.drug
Abstract: Respiratory syncytial virus (RSV) infections may worsen cystic fibrosis (CF) lung disease and favor Pseudomonas aeruginosa (Pa) or Staphylococcus aureus (Sa) acquisition, which is of particular importance in the youngest patients. We aimed to determine the effectiveness of PVZ on microbiological outcomes in young children with CF. We conducted a retrospective case-control study to compare these outcomes in children who systematically received PVZ (PVZ+; n = 40) or not (PVZ-; n = 140). One case was matched with at least three same-gender controls born the same year and month. Median (range) age at first Pa isolation was not statistically different between PVZ- (12.3 [3.8-32.6] months) and PVZ+ (10.4 [1.2-33.0] months; p = 0.953) patients. A similar trend was found for Sa (PVZ+: 6.4 [2.0-59.0] months; PVZ-: 3.8 [0.1-74.1] months; p = 0.191). The proportion of Pa isolations by 3 years of age did not differ between groups (PVZ+ 40% vs. PVZ- 41.4%), but this proportion was higher for Sa in the PVZ+ group (97%) than in the PVZ- group (85%; p = 0.001). Healthcare consumption and growth outcomes did not significantly differ between groups.Systematic PVZ use did not delay key pathogen acquisition in young children with CF. What is known: • Palivizumab is the only available monoclonal antibody against respiratory syncytial virus infection. • Whether or not it is useful in infants with cystic fibrosis remains controversial. What is new: • Palivizumab does not delay key pathogens (Pseudomonas aeruginosa, Staphylococcus aureus) first isolation in young children with cystic fibrosis. • Palivizumab does not reduce healthcare consumption or improve growth during the first 3 years of life of young children with cystic fibrosis.
Published: 2017
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10. Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis

Author: Pierre-Régis Burgel, Anne Munck, Isabelle Durieu, Raphaël Chiron, Laurent Mely, Anne Prevotat, Marlene Murris-Espin, Michele Porzio, Michel Abely, Philippe Reix, Christophe Marguet, Julie Macey, Isabelle Sermet-Gaudelus, Harriet Corvol, Stéphanie Bui, Lydie Lemonnier, Clémence Dehillotte, Jennifer Da Silva, Jean-Louis Paillasseur, Dominique Hubert, Julie Mounard, Claire Poulet, Cinthia Rames, Christine Person, Françoise Troussier, Thierry Urban, Marie-Laure Dalphin, Jean-Claude Dalphin, Didier Pernet, Bénédicte Richaud-Thiriez, Mickael Fayon, Julie Macey-Caro, Karine Campbell, Muriel Laurans, Corinne Borderon, Marie-Christine Heraud, André Labbé, Sylvie Montcouquiol, Laurence Bassinet, Natascha Remus, Annlyse Fanton, Anne Houzel-Charavel, Frédéric Huet, Stéphanie Perez-Martin, Amale Boldron-Ghaddar, Manuela Scalbert, Boubou Camara, Catherine Llerena, Isabelle Pin, Sébastien Quétant, Aurélie Cottereau, Antoine Deschildre, Alice Gicquello, Thierry Perez, Lidwine Stervinou-Wemeau, Caroline Thumerelle, Benoit Wallaert, Nathalie Wizla, Jane Languepin, Céline Ménétrey, Magalie Dupuy-Grasset, Lucie Bazus, Clelia Buchs, Virginie Jubin, Marie-Christine Werck-Gallois, Catherine Mainguy, Thomas Perrin, Agnès Toutain-Rigolet, Stéphane Durupt, Quitterie Reynaud, Raphaele Nove-Josserand, Melisande Baravalle-Einaudi, Bérangère Coltey, Nadine Dufeu, Jean-Christophe Dubus, Nathalie Stremler, Davide Caimmi, Yves Billon, Jocelyne Derelle, Sébastien Kieffer, Anne-Sophie Pichon, Cyril Schweitzer, Aurélie Tatopoulos, Sarah Abbes, Tiphaine Bihouée, Isabelle Danner-Boucher, Valérie David, Alain Haloun, Adrien Tissot, Sylvie Leroy, Carole Bailly-Piccini, Annick Clément, Aline Tamalet, Isabelle Honoré, Reem Kanaan, Clémence Martin, Cécile Bailly, Frédérique Chédevergne, Jacques De Blic, Brigitte Fauroux, Murielle Le Bourgeois, Bertrand Delaisi, Michèle Gérardin, Michel Abély, Bruno Ravoninjatovo, Chantal Belleguic, Benoit Desrues, Graziella Brinchault, Michel Dagorne, Eric Deneuville, Sylvaine Lefeuvre, Anne Dirou, Jean Le Bihan, Sophie Ramel, Stéphane Dominique, Annabelle Payet, Romain Kessler, Vincent Rosner, Laurence Weiss, Sandra de Miranda, Dominique Grenet, Abdoul Hamid, Clément Picard, François Brémont, Alain Didier, Géraldine Labouret, Marie Mittaine, Marlène Murris-Espin, Laurent Têtu, Laure Cosson, Charlotte Giraut, Anne-Cécile Henriet, Julie Mankikian, Sophie Marchand, Sandrine Hugé, Véronique Storni, Emmanuelle Coirier-Duet, CHU Cochin [AP-HP], Service de Médecine Interne - Centre Hospitalier Lyon Sud, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Ressources et de Compétences en Mucoviscidose [Lyon] (CRCM [Lyon]), Hospices Civils de Lyon (HCL)-CHU Lyon-Hôpital Renée Sabran [CHU - HCL], Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Toulouse [Toulouse], 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), Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Ressources et de Compétences de la Mucoviscidose (CRCM), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Association Vaincre La Mucoviscidose, Institut Cochin (IC UM3 (UMR 8104 / U1016)), EFFI-STAT, CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Mucoviscidose: physiopathologie et phénogénomique [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre de Ressources et de Compétences en Mucoviscidose [CHU Toulouse] (CRCM Toulouse), Service Pneumologie et allergologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe hospitalier Broca-Université Paris Descartes - Paris 5 (UPD5)-Hôtel-Dieu-Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Cystic Fibrosis, Gastrointestinal Diseases, [SDV]Life Sciences [q-bio], Aminopyridines, Quinolones, Critical Care and Intensive Care Medicine, Logistic regression, Aminophenols, Cystic fibrosis, Body Mass Index, Ivacaftor, chemistry.chemical_compound, 0302 clinical medicine, Deprescriptions, Forced Expiratory Volume, Medicine, 030212 general & internal medicine, Fatigue, 2. Zero hunger, biology, Lumacaftor, Headache, lumacaftor–ivacaftor, Cystic fibrosis transmembrane conductance regulator, 3. Good health, Anti-Bacterial Agents, Drug Combinations, Treatment Outcome, Administration, Intravenous, Female, France, medicine.drug, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Metrorrhagia, Adolescent, Nutritional Status, 03 medical and health sciences, Young Adult, Internal medicine, Product Surveillance, Postmarketing, Humans, Benzodioxoles, Adverse effect, Bronchial Spasm, business.industry, Editorials, Myalgia, medicine.disease, Discontinuation, Dyspnea, Logistic Models, 030228 respiratory system, chemistry, Cough, Multivariate Analysis, biology.protein, postmarketing study, business, Body mass index
Abstract: International audience; Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting.Methods: The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations.Measurements and Main Results: Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV1 (ppFEV1) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftor-ivacaftor initiation. Patients with continuous exposure to lumacaftor-ivacaftor showed an absolute increase in ppFEV1 (+3.67%), an increase in body mass index (+0.73 kg/m2), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV1, without improvement in body mass index or decrease in intravenous antibiotic courses.Conclusions: Lumacaftor-ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.
Published: 2019
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11. Health-related quality of life in children interstitial lung disease

Author: Clara Lauby, Marie-Catherine Renoux, Pierre-Yves Boëlle, Isabelle Pin, Jean-Christophe Dubus, Michael Fayon, Christophe Marguet, Antoine Deschildre, Anne Houzel, Christophe Delacourt, Nadia Nathan, Laurence Weiss, Céline Delestrain, Cyril Schweitzer, Annick Clement, Lisa Giovannini-Chami, Ralph Epaud, Marie-Laure Dalphin, Véronique Houdouin, Jacques Brouard, Rola Abou Taam, Katia Bessaci, Aurélie Tatopoulos, Caroline Thumerelle, Philippe Reix, Françoise Troussier, and Stéphanie Wanin
Subjects: Health related quality of life, Pediatrics, medicine.medical_specialty, Quality of life, business.industry, Healthy population, Interstitial lung disease, Medicine, Disease, business, medicine.disease, humanities, Lung function
Abstract: Introduction: Health-related quality of life (HR-QoL) is an understudied area in rare diseases. Interstitial lung diseases in children (chILD) are heterogeneous disorders that are associated with a high morbidity and mortality. The impaired lung function, the nutritional impact and the burden of the treatments can impair the HR-QoL of these children. The aim of this study was to compare the HR-QoL in chILD to an aged-matched healthy population and to identify the factors that were associated to an altered QoL. Methods: Patients were recruited in the French RespiRare network. Patients with chILD of all causes, aged 1 month to 18 years were prospectively included. The children over 8 years old and the 2 parents of all children were asked to complete the PedsQLTM 4.0 Generic Core Scale (0 to 100 points). Results: A total of 78 children were included in the RespiRare centres. Total mean scores appeared to be significantly reduced in child self-report and in parent proxy-report (11.94 points (p=0.0003) and 14.08 points (p Conclusion: The study shows that HR-QoL is significantly impaired in chILD compared to a healthy population, using a validated generic QoL scale. Factors altering QoL score are easy to recognize and could help identify children at a heightened risk of low QoL. A longitudinal follow-up of HR-QoL in chILD is necessary to follow the impact of the disease and the treatments. To better appreciate chILD QoL, a specific scale is currently under study by the chILD-EU group.
Published: 2019
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12. Pneumopathie d’hypersensibilité de l’enfant

Author: T. Soumagne, Marie-Laure Dalphin, J.-C. Dalphin, Service de Pneumologie, oncologie thoracique et allergologie respiratoire [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), and Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Interstitial lung disease, Hypoxia (medical), medicine.disease, Dermatology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Immune system, 030228 respiratory system, Antigen, medicine, 030212 general & internal medicine, Exertion, medicine.symptom, Respiratory system, business, Hypersensitivity pneumonitis, Rare disease
Abstract: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by an immune response to a variety of antigens to which patients have been previously sensitised. It can occur at any age. In children, it is a rare disease, probably under-diagnosed, with an estimated prevalence of 4 per million. The paediatric forms are not really different from those of adults but present some particularities. Avian exposure is by far the most frequent cause of HP, accounting for nearly two-thirds of cases. Although there is no current recommendation for the diagnosis of HP, it is commonly considered that the diagnosis can be made with confidence on the combination of (1) compatible respiratory symptoms, (2) exposure to a known offending antigen, (3) lymphocytic alveolitis, (4) decreased transfer factor for carbon monoxide or hypoxia on exertion and (5) compatible radiologic features. The treatment is based on antigen avoidance that must be complete and definitive. Corticosteroids can be necessary in severe forms. The prognosis of HP in children is better than in adults, with a full clinical and functional recovery in the majority of cases after complete antigenic withdrawal.
Published: 2019
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13. Health‐related quality of life in infants and children with interstitial lung disease

Author: Aurélie Tatopoulos, Philippe Reix, Ralph Epaud, Jean-Christophe Dubus, Antoine Deschildre, Caroline Thumerelle, Christophe Delacourt, Lisa Giovannini-Chami, Katia Bessaci, Marie-Laure Dalphin, Nadia Nathan, Céline Delestrain, Pierre-Yves Boëlle, Stéphanie Wanin, Rola Abou Taam, Laurence Weiss, Annick Clement, Michael Fayon, Christophe Marguet, Cyril Schweitzer, Véronique Houdouin, Jacques Brouard, Françoise Troussier, Marie-Catherine Renoux, Anne Houzel, Isabelle Pin, Clara Lauby, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte [CHU Necker] (MaMEA Necker), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital universitaire Robert Debré [Reims], Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire de Sciences de la Terre (LST), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pédiatrie spécialisée et médecine infantile (neurologie, pneumologie, maladies héréditaires du métabolisme) [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Nice (CHU Nice), AP-HP Hôpital universitaire Robert-Debré [Paris], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, CHU Grenoble, Inflammatory Responses and Transcriptomic Networks in diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hospices Civils de Lyon (HCL), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 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), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et la Recherche Médicale (INSERM), the European Union's Seventh Framework Program, Grant/Award Number: FP7‐ChILD‐EU 2007‐2013, Respirer c'est Grandir and Belleherbe Association, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Service de Pneumologie pédiatrique [CHU Trousseau], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Mzembaba, Sandy, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Physiologie, biologie des organismes, populations, interactions, and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pulmonary and Respiratory Medicine, Male, Parents, Pediatrics, medicine.medical_specialty, chILD, Adolescent, medicine.medical_treatment, Disease, Severity of Illness Index, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, scale, 03 medical and health sciences, 0302 clinical medicine, Quality of life, children, 030225 pediatrics, Oxygen therapy, medicine, Humans, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS, Health related quality of life, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, interstitial lung disease, Heterogeneous group, business.industry, Nutritional Support, Healthy population, Interstitial lung disease, Infant, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, humanities, Proxy, 3. Good health, Oxygen, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030228 respiratory system, quality of life, Child, Preschool, Pediatrics, Perinatology and Child Health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Etiology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Lung Diseases, Interstitial
Abstract: International audience; Introduction: Interstitial lung disease in children (chILD) is a highly heterogeneous group of rare and severe respiratory disorders. The disease by itself, the burden of the treatments (oxygen therapy, corticosteroid pulses, nutritional support) and recurrent hospitalizations may impair the quality of life (QoL) of these children. The aim of the study was to compare the health-related QoL (HR-QoL) in chILD compared to a healthy population and to find out the predictive factors of an altered QoL.Methods: Patients aged 1 month to 18 years with ILD of known or unknown etiology were prospectively included. Parents and children over 8 years old were asked to fill the PedsQL 4.0 Generic Core Scale ranging from 0 to 100 points.Results: A total of 78 children were recruited in 13 French pediatric centers. Total scores were 11.94 points (P = 0.0003) less for child self-report and 14.08 points ( P < 0.0001) less for parent proxy-report with respect to the healthy population. The clinical factors associated with a lower total score were: extrapulmonary expression of the disease, higher Fan severity score, long-term oxygen therapy, nutritional support, and a number of oral treatments.Conclusion: Using a validated quality of life (QoL) scale, we showed that health-related-QoL is significantly impaired in chILD compared with a healthy population. Factors altering QoL score are easy to recognize and could help identify children at a heightened risk of low QoL
Published: 2019
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14. Clinical and microbiological characteristics of cystic fibrosis adults never colonized by Pseudomonas aeruginosa: Analysis of the French CF registry

Author: Bénédicte Richaud Thiriez, Lydie Lemonnier, Clémence Dehillotte, Patrick Plésiat, Alicia Guillien, Jean-Charles Dalphin, Rechana Vongthilath, Marie-Laure Dalphin, Bruno Degano, 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 bactériologie [Besançon], and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: Male, Cystic Fibrosis, Pulmonology, Cystic Fibrosis Transmembrane Conductance Regulator, Pathology and Laboratory Medicine, Aspergillosis, medicine.disease_cause, Cystic fibrosis, Gastroenterology, Haemophilus influenzae, Endocrinology, 0302 clinical medicine, Stenotrophomonas Maltophilia, Forced Expiratory Volume, Medicine and Health Sciences, Registries, 030212 general & internal medicine, Lung, ComputingMilieux_MISCELLANEOUS, Disease Resistance, Haemophilus Influenzae, Multidisciplinary, biology, Age Factors, Fungal Diseases, Pseudomonas Aeruginosa, Achromobacter xylosoxidans, Middle Aged, Bacterial Pathogens, 3. Good health, Stenotrophomonas maltophilia, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Medical Microbiology, Genetic Diseases, Medicine, Female, France, Pathogens, medicine.symptom, Research Article, Adult, medicine.medical_specialty, Clinical Pathology, Endocrine Disorders, Science, Haemophilus, Microbiology, Young Adult, 03 medical and health sciences, Autosomal Recessive Diseases, Pseudomonas, Internal medicine, Diabetes Mellitus, medicine, Humans, Pseudomonas Infections, Microbial Pathogens, Retrospective Studies, Clinical Genetics, Bacteria, Pseudomonas aeruginosa, business.industry, Sputum, Organisms, Biology and Life Sciences, Odds ratio, medicine.disease, biology.organism_classification, Fibrosis, Clinical Microbiology, 030228 respiratory system, Metabolic Disorders, Respiratory Infections, business, Follow-Up Studies, Developmental Biology
Abstract: Pseudomonas aeruginosa is the main cause of chronic airway infection in cystic fibrosis (CF). However, for unclear reasons some patients are never colonized by P. aeruginosa. The objectives of this study were to better define the clinical, genetic, and microbiological characteristics of such a subpopulation and to identify predictive factors of non-colonization with P. aeruginosa. The French CF patient registry 2013–2014 was used to identify CF patients aged ≥ 20 years. The clinical outcomes, CF Transmembrane conductance Regulator (CFTR) genotypes, and microbiological data of patients reported positive at least once for P. aeruginosa (“Pyo” group, n = 1,827) were compared to those of patients with no history of P. aeruginosa isolation (“Never” group, n = 303). Predictive factors of non-colonization by P. aeruginosa were identified by multivariate logistic regression model with backward selection. Absence of aspergillosis (odds ratio (OR) [95% CI] = 1.64 [1.01–2.66]), absence of diabetes (2.25 [1.21–4.18]), pancreatic sufficiency (1.81 [1.30–2.52]), forced expiratory volume 1 (FEV1) ≥ 80% (3.03 [2.28–4.03]), older age at CF diagnosis (1.03 [1.02–1.04]), and absence of F508del/F508del genotype (2.17 [1.48–3.19]) were predictive clinical factors associated with absence of infection (“Never” group). Microbiologically, this same group was associated with more frequent detection of Haemophilus influenzae and lower rates of Stenotrophomonas maltophilia, Achromobacter xylosoxidans and Aspergillus spp. (all p
Published: 2019
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15. Real-World Long-Term Ivacaftor for Cystic Fibrosis in France: Clinical Effectiveness and Healthcare Resource Utilization.

Author: Hubert, Dominique, Marguet, Christophe, Benichou, Jacques, DeSouza, Cynthia, Payen-Champenois, Catherine, Kinnman, Nils, Chandarana, Keval, Munck, Anne, Fajac, Isabelle, the BRIO Study Group, Ramel, Sophie, Vigneron, Philippe, Storni, Veronique, Remus, Natacha, Durieu, Laurence Bassinet Isabelle, Laurans, Muriel, Troussier, Cinthia Rames Françoise, Huet, Marie-Laure Dalphin Frédéric, Pin, Isabelle, and Payet, Boubou Camara Annabelle
Subjects: CYSTIC fibrosis transmembrane conductance regulator, CYSTIC fibrosis, FORCED expiratory volume, MEDICAL care, TREATMENT effectiveness
Abstract: Introduction: Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that has demonstrated clinical benefits in phase 3 trials. We report results from a real-world study (BRIO) to assess the effectiveness of ivacaftor in people with cystic fibrosis (pwCF) in France. Methods: BRIO was an observational study conducted at 35 centers in France. Both pwCF initiating ivacaftor treatment and those already taking ivacaftor were included and prospectively followed for 24 months. The primary objective was to evaluate the effect of ivacaftor on percent predicted forced expiratory volume in 1 s (ppFEV1); secondary objectives were evaluating the effect of ivacaftor on clinical effectiveness, healthcare resource utilization (HCRU), and safety. Results: A total of 129 pwCF were enrolled; 58.9% were aged < 18 years; 64.3% had a G551D-CFTR allele. Mean age at ivacaftor initiation was 19.1 years (range, 2–64 years); ppFEV1 increased by a least squares mean of 8.49 percentage points in the first 6 months and was sustained through 36 months of ivacaftor use. Growth metrics increased during the first 12 months post-ivacaftor and remained stable. The rate of pulmonary exacerbations (PEx) decreased during the 12 months post-ivacaftor compared with the 12 months pre-ivacaftor; estimated rate ratios (95% CI) were 0.57 (0.43–0.75) for PEx events and 0.25 (0.13–0.48) for PEx requiring hospitalization. No new safety concerns were identified; no deaths occurred. Conclusions: The results from this real-world study of ivacaftor usage in France were consistent with prior clinical trial outcomes, confirming the clinical effectiveness of ivacaftor, as well as an associated reduction in HCRU. [ABSTRACT FROM AUTHOR]
Published: 2021
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16. First Wave of COVID-19 in French Patients with Cystic Fibrosis

Author: S. Ramel, Martine Reynaud Gaubert, Astrid Kemgang, Harriet Corvol, Véronique Houdouin, Isabelle Durieu, Pierre-Régis Burgel, Marine Revillion, Lydie Lemonnier, Laurence Weiss, Sandra de Miranda, Raphaël Chiron, Marie-Laure Dalphin, A. Prevotat, Pierre-Yves Boëlle, Jean-Christophe Dubus, Loïc Guillot, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Mucoviscidose: physiopathologie et phénogénomique [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Hôpital Foch [Suresnes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Pneumologie et Allergie - Hôpital Nord [Marseille], Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Robert Debré Paris, Hôpital Robert Debré, Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département des maladies respiratoires [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Gestionnaire, Hal Sorbonne Université
Subjects: medicine.medical_specialty, Cystic Fibrosis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, lcsh:Medicine, Cystic fibrosis, Asymptomatic, Article, law.invention, Serology, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Diabetes mellitus, Oxygen therapy, Medicine, 030212 general & internal medicine, education, education.field_of_study, Lung, SARS-CoV-2, business.industry, lcsh:R, COVID-19, General Medicine, acute respiratory distress syndrome, medicine.disease, lung transplant, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030228 respiratory system, medicine.symptom, business
Abstract: Viral infections are known to lead to serious respiratory complications in cystic fibrosis (CF) patients. Hypothesizing that CF patients were a population at high risk for severe respiratory complications from SARS-CoV-2 infection, we conducted a national study to describe the clinical expression of COVID-19 in French CF patients. This prospective observational study involves all 47 French CF centers caring for approximately 7500 CF patients. Between March 1st and June 30th 2020, 31 patients were diagnosed with COVID-19: 19 had positive SARS-CoV-2 RT-PCR in nasopharyngeal swabs, 1 had negative RT-PCR but typical COVID-19 signs on a CT scan, and 11 had positive SARS-CoV-2 serology. Fifteen were males, median (range) age was 31 (9&ndash, 60) years, and 12 patients were living with a lung transplant. The majority of the patients had CF-related diabetes (n = 19, 61.3%), and a mild lung disease (n = 19, 65%, with percent-predicted forced expiratory volume in 1 s (ppFEV1) &gt, 70). Three (10%) patients remained asymptomatic. For the 28 (90%) patients who displayed symptoms, most common symptoms at admission were fever (n = 22, 78.6%), fatigue (n = 14, 50%), and increased cough (n = 14, 50%). Nineteen were hospitalized (including 11 out of the 12 post-lung transplant patients), seven required oxygen therapy, and four (3 post-lung transplant patients) were admitted to an Intensive Care Unit (ICU). Ten developed complications (including acute respiratory distress syndrome in two post-lung transplant patients), but all recovered and were discharged home without noticeable short-term sequelae. Overall, French CF patients were rarely diagnosed with COVID-19. Further research should establish whether they were not infected or remained asymptomatic upon infection. In diagnosed cases, the short-term evolution was favorable with rare acute respiratory distress syndrome and no death. Post-lung transplant patients had more severe outcomes and should be monitored more closely.
Published: 2020
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17. Central venous thrombosis and thrombophilia in cystic fibrosis: A prospective study

Author: Isabelle Durieu, E. Darviot, J.-L. Giniès, Raphaele Nove-Josserand, Charlotte Giraut, Anne Munck, Marie-Francoise Hurtaud, Michael Fayon, Muriel Le Bourgeois, A. Sardet, Raphaël Chiron, Marlène Murris-Epin, Annelyse Fanton, B. Delaisi, Dominique Hubert, Laure Couderc, Corinne Alberti, Dominique Grenet, Frédéric Huet, Marie Laure Dalphin, Stéphanie Wanin, François Bremont, Stéphane Dominique, Françoise Varaigne, Reynaud-Gaubert Martine, Marcel Guillot, S. Ramel, Laurence Weiss, M. Gerardin, Ahmed Kheniche, Isabelle Pin, and Isabelle Sermet-Gaudelus
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, Cystic Fibrosis, Comorbidity, Thrombophilia, Severity of Illness Index, Asymptomatic, Cohort Studies, Young Adult, Age Distribution, Catheters, Indwelling, Prevalence, medicine, Humans, Medical history, Prospective Studies, Pediatrics, Perinatology, and Child Health, Sex Distribution, Child, Prospective cohort study, Venous Thrombosis, Catheter insertion, business.industry, Thrombosis, Ultrasonography, Doppler, Prognosis, medicine.disease, 3. Good health, Surgery, Venous thrombosis, Catheter, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, business
Abstract: Background and Aims Catheter venous thrombosis may result in life-threatening embolic complications. Recently, a thrombophilic tendency was described in cystic fibrosis (CF), the significance of which remains unclear. The aims of this study were to (1) document the frequency of catheter venous thrombosis detected by colour-Doppler-ultrasound (Doppler-US), (2) assess genetic and acquired thrombophilia risk factors for catheter venous thrombosis and hypercoagulability status and (3) provide recommendations on laboratory screening when considering insertion of a totally implantable vascular access device (TIVAD) in CF patients. Methods We designed a multicentre prospective study in patients selected at the time of catheter insertion. Doppler-US was scheduled at 1 and 6months after insertion and before insertion in case of a previous central line. Blood samplings were drawn at insertion and at 1 and 6months later. Results One-hundred patients received a TIVAD and 90 completed the 6-month study. Prevalence of thrombophilia abnormalities and hypercoagulability was found in 50% of the cohorts. Conversely, catheter venous thrombosis frequency was low (6.6%). Conclusion Our data do not support biological screening at the time of a TIVAD insertion. We emphasise the contribution of a medical history of venous thromboembolism and prospective Doppler-US for identifying asymptomatic catheter venous thrombosis to select patients who may benefit from biological screening and possible anticoagulant therapy.
Published: 2015
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18. Asthmatic farm children show increased CD3

Author: Monika, Twardziok, Paul C, Schröder, Johanna, Krusche, Vera I, Casaca, Sabina, Illi, Andreas, Böck, Georg J, Loss, Michael, Kabesch, Antoaneta A, Toncheva, Caroline, Roduit, Martin, Depner, Jon, Genuneit, Harald, Renz, Marjut, Roponen, Juliane, Weber, Charlotte, Braun-Fahrländer, Josef, Riedler, Roger, Lauener, Dominique Angèle, Vuitton, Jean-Charles, Dalphin, Juha, Pekkanen, Erika, von Mutius, Bianca, Schaub, Anne, Hyvärinen, Anne M, Karvonen, Pirkka V, Kirjavainen, Sami, Remes, Vincent, Kaulek, Marie-Laure, Dalphin, Markus, Ege, Petra I, Pfefferle, and Gert, Doekes
Subjects: Male, Farms, CD3 Complex, Membrane Proteins, CD8-Positive T-Lymphocytes, Polymorphism, Single Nucleotide, Asthma, Neoplasm Proteins, Cohort Studies, Interferon-gamma, Germany, Humans, Female, Child
Published: 2017

19. TNF-α–induced protein 3 is a key player in childhood asthma development and environment-mediated protection

Author: Sabina Illi, Anne Hyvärinen, Josef Riedler, Martin Depner, Bianca Schaub, Harald Renz, Marie-Laure Dalphin, Charlotte Braun-Fahrländer, R. Frei, Yuhan Xing, Jing Li, Monika Twardziok, Andreas Böck, P. C. Schröder, Gert Doekes, Gary W.K. Wong, Jon Genuneit, Jean-Charles Dalphin, Marjut Roponen, Anne M. Karvonen, Miranda S. Tsang, Pirkka Kirjavainen, Caroline Roduit, Jörg Kumbrink, Vincent Kaulek, Johanna Krusche, P. Pfefferle, Thomas Kirchner, Markus J. Ege, Sami Remes, Roger Lauener, Katharina Rehbach, Juha Pekkanen, Michael Kabesch, G. Loss, Amandine Divaret-Chauveau, Chun K. Wong, Department of Public Health, and University of Helsinki
Subjects: Male, 0301 basic medicine, Allergy, DUST, TNFAIP3, 0302 clinical medicine, Immunology and Allergy, Longitudinal Studies, Prospective Studies, Child, RISK, INDUCTION, IRAK1, protection, 3. Good health, ALLERGY, A20, Child, Preschool, Cord blood, Female, environment, LPS, Immunology, inflammatory, farming, Proinflammatory cytokine, EARLY-LIFE, 03 medical and health sciences, medicine, Humans, EXPOSURE, Tumor Necrosis Factor alpha-Induced Protein 3, childhood, Asthma, business.industry, Infant, Newborn, Infant, Environmental Exposure, Dendritic cell, medicine.disease, Toll-Like Receptor 4, Cross-Sectional Studies, 030104 developmental biology, Gene Expression Regulation, 030228 respiratory system, immune development, 3121 General medicine, internal medicine and other clinical medicine, TLR4, ENDOTOXIN, business, Biomarkers
Abstract: Background: Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-alpha-induced protein 3 (TNFAIP3; A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) signaling, mediates environmentally induced asthma protection. Objective: We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors. Methods: In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from "asthma-protective'' farms or LPS. NF-kappa B signaling-related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns. Results: Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P
Published: 2019
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20. Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts

Author: Josef Riedler, Alexander J. Hose, Pekka Tiittanen, Ulrich Wahn, Oliver Fuchs, Markus J. Ege, Jean-Charles Dalphin, Susanne Lau, Petra Ina Pfefferle, Juha Pekkanen, Renate L. Bergmann, Sami Remes, Andreas Reich, Linus Grabenhenrich, Roger Lauener, V. Wahn, Jon Genuneit, Marjut Roponen, Remo Frei, Thomas Keil, Nicole Blümer, Michael Kabesch, G. Loss, Sabina Illi, Harald Renz, Fred Zepp, Anne M. Karvonen, Erika von Mutius, Vincent Kaulek, Caroline Roduit, Karl E. Bergmann, Antje Schuster, Elisabeth Schmaußer-Hechfellner, Carl Peter Bauer, Marie-Laure Dalphin, Johannes Forster, Urs Frey, Gert Doekes, Martin Depner, Anne Hyvärinen, Bianca Schaub, Charlotte Braun-Fahrländer, University of Zurich, Hose, Alexander J, Clinicum, Department of Public Health, and University of Helsinki
Subjects: Male, Allergy, CHILDHOOD, CHILDREN, medicine.disease_cause, sensitization, Atopy, Cohort Studies, 0302 clinical medicine, Allergen, Forced Expiratory Volume, Immunology and Allergy, 030212 general & internal medicine, Child, Sensitization, RISK, Ige, Asthma, Lung Function, Cytokines, Severe Atopy, Atopic Diseases, Latent Class Analysis, Unsupervised Clustering, Path Analysis, Epidemiology, 3142 Public health care science, environmental and occupational health, Latent class model, 3. Good health, RESPIRATORY SYMPTOMS, medicine.anatomical_structure, Phenotype, Child, Preschool, Cohort, 2723 Immunology and Allergy, Hay fever, epidemiology, Female, SKIN-TEST, Immunology, 610 Medicine & health, unsupervised clustering, 03 medical and health sciences, latent class analysis, medicine, Hypersensitivity, path analysis, Humans, IGE, 2403 Immunology, business.industry, Infant, lung function, asthma, Allergens, Immunoglobulin E, medicine.disease, INHALANT ALLERGENS, LIFE, 030228 respiratory system, 10036 Medical Clinic, 3121 General medicine, internal medicine and other clinical medicine, severe atopy, atopic diseases, business
Abstract: Background: Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear. Objective: We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE). Methods: Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort. Results: The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-gamma ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk. Conclusions: LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function.
Published: 2016

21. Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis

Author: Remo Frei, Ruth Ferstl, Caroline Roduit, Mario Ziegler, Elisa Schiavi, Weronika Barcik, Noelia Rodriguez-Perez, Oliver F. Wirz, Marcin Wawrzyniak, Benoit Pugin, Dirk Nehrbass, Marek Jutel, Sylwia Smolinska, Patrycja Konieczna, Christian Bieli, Susanne Loeliger, Marco Waser, Göran Pershagen, Josef Riedler, Martin Depner, Bianca Schaub, Jon Genuneit, Harald Renz, Juha Pekkanen, Anne M. Karvonen, Jean-Charles Dalphin, Marianne van Hage, Gert Doekes, Mübeccel Akdis, Charlotte Braun-Fahrländer, Cezmi A. Akdis, Erika von Mutius, Liam O’Mahony, Roger P. Lauener, Tobias Alfvén, Johan Alm, Anna Bergström, Lars Engstrand, Helen Rosenlund, Niclas Hakansson, Gunnar Lilja, Frederik Nyberg, Jackie Swartz, Magnus Wickman, Johannes Wildhaber, Alex Möller, Bert Brunekreef, Mirian Boeve, Jeroen Douwes, Machteld Huber, Mirjam Matze Gertraud Weiss, Mynda Schreue, Karin B. Michles, Felix Sennhauser, Annika Scheynius, Maija-Riitta Hirvonen, Sami Remes, Marjut Roponen, Pekka Tiittanen, Marie-Laure Dalphin, Vincent Kaulek Gisela Buchele, Markus Ege, Michael Kabesch, Petra Pfefferle, Georg Loss, Anne Hyvärinen, Ympäristö- ja biotieteiden laitos / Toiminta, School of Medicine / Public Health, dIRAS RA-2, LS IRAS EEPI GRA (Gezh.risico-analyse), Department of Public Health, Clinicum, University of Helsinki, and University of Zurich
Subjects: HAY-FEVER, 0301 basic medicine, Allergy, colitis, Respiratory Tract Diseases, airway inflammation, Severity of Illness Index, Inflammatory bowel disease, 0302 clinical medicine, ALLERGIC DISEASES, 10183 Swiss Institute of Allergy and Asthma Research, T-Lymphocyte Subsets, Immunology and Allergy, Lymphocytes, Child, Sensitization, anti-inflammatory, Mice, Knockout, RISK, Farmers, farmer's children, Age Factors, FOXP3, 3142 Public health care science, environmental and occupational health, 3. Good health, ATOPIC SENSITIZATION, medicine.anatomical_structure, Child, Preschool, Population Surveillance, 030220 oncology & carcinogenesis, 2723 Immunology and Allergy, Hay fever, medicine.symptom, Farmers' children, N-glycolylneuraminic acid, Immunology, 610 Medicine & health, EARLY-LIFE, 03 medical and health sciences, Wheeze, medicine, Animals, Humans, Colitis, Asthma, Inflammation, 2403 Immunology, NONHUMAN SIALIC-ACID, business.industry, Infant, nonmicrobial, Environmental Exposure, SCHOOL-AGE-CHILDREN, Allergens, Immunoglobulin E, medicine.disease, Disease Models, Animal, MICE, Cross-Sectional Studies, 030104 developmental biology, Immunoglobulin G, 3121 General medicine, internal medicine and other clinical medicine, INNATE IMMUNITY, ASTHMA, Neuraminic Acids, business, Biomarkers
Abstract: Background Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. Objective We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. Methods Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. Results In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells. Conclusions In addition to microbial exposure, increased exposure to non–microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment., published version, peerReviewed
Published: 2018
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22. Disagreement between Skin Prick Tests and Specific IgE in Early Childhood

Author: Dominique A. Vuitton, Aurore Pugin, A. Chauveau, Erika von Mutius, Marie-Laure Dalphin, Jean-Charles Dalphin, Caroline Roduit, Vincent Kaulek, Etude du Polymorphisme des Génomes Végétaux (EPGV), Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université de Franche-Comté (UFC), Children's Hospital, University hospital of Zurich [Zurich], Christine Kühne – Centre for Allergy Research and Education (CK-CARE), University of Munich, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (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), Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), University of Zurich, Chauveau, Amandine, Etude du Polymorphisme des Génomes Végétaux ( EPGV ), Institut National de la Recherche Agronomique ( INRA ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Université de Franche-Comté ( UFC ), Christine Kühne – Centre for Allergy Research and Education ( CK-CARE ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), and Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC )
Subjects: Male, Allergy, medicine.medical_specialty, Immunology, 610 Medicine & health, Immunoglobulin E, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, Dermatitis, Atopic, Allergic sensitization, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Hypersensitivity, Prevalence, medicine, Humans, Immunology and Allergy, Early childhood, Child, Sensitization, Skin Tests, 2. Zero hunger, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, 2403 Immunology, biology, business.industry, Infant, Reproducibility of Results, General Medicine, Atopic dermatitis, Allergens, medicine.disease, Dermatology, Rural environment, medicine.anatomical_structure, 030228 respiratory system, 10036 Medical Clinic, Child, Preschool, Cohort, 2723 Immunology and Allergy, biology.protein, Female, Immunization, business
Abstract: Background: Accurate diagnosis of allergic sensitization is essential in clinical practice and allergy research, and the choice of assessment method may have an important impact. The PASTURE study (Protection against Allergy: Study of Rural Environment) examines the influence of exposure to a dairy farm environment on the occurrence of allergy in a cohort of rural European children from birth to 10 years. The aim of our study was to analyze agreement between skin prick tests (SPTs), to aeroallergens and food allergens, and specific IgE and to evaluate the association of SPT with atopic dermatitis in the 204 French children of the PASTURE study. Methods: SPT, atopic dermatitis assessment, and specific IgE measurements were performed at 1, 4.5, and 6 years. Results: A total of 137 children attended all three visits. The agreement between SPTs and specific IgE was poor except for perennial aeroallergens at 6 years and for an IgE cutoff greater than 0.7 IU/ml (κ = 0.69, 0.5202 - 0.8621). The prevalence of positive SPTs increased with age. Positive SPTs were transient at 1 year, whereas they were persistent between 4.5 and 6 years. Positive SPTs at 1 year were predictive of the occurrence of atopic dermatitis during follow-up. Conclusion: SPTs did not have good agreement with serum-specific IgE in early childhood. Both tests (SPT and specific IgE) should be used. Skin allergenic reactivity increased with age and was transient at 1 year but associated with the occurrence of atopic dermatitis.
Published: 2015

23. Genetic testing in idiopathic interstitial pneumonia

Author: Caroline Thumerelle, Florence Dastot-Le Moal, Guillaume Lezmi, Martine Reynaud-Gaubert, Christophe Delacourt, Caroline Kannengiesser, Marie Legendre, Violaine Giraud, Sylvain Marchand-Adam, S. Amselem, Antoine Deschildre, Grégoire Prévot, Jean-Marc Naccache, Philippe Reix, Claire Dromer, Anne Gondouin, Bruno Crestani, Vincent Cottin, Marie-Laure Dalphin, Dominique Israel Biet, Raphael Borie, Clément Picard, Hilario Nunes, Nadia Nathan, Dominique Valeyre, Annick Clement, Christophe Marguet, and Laurent Gouya
Subjects: education.field_of_study, Pediatrics, medicine.medical_specialty, medicine.diagnostic_test, biology, business.industry, Population, ABCA3, Gene mutation, medicine.disease, Compound heterozygosity, Mutation (genetic algorithm), medicine, Etiology, biology.protein, education, business, Idiopathic interstitial pneumonia, Genetic testing
Abstract: Background: Idiopathic interstitial pneumonia (IIP)s are severe diseases that can occur from neonates to elderly. A genetic cause is identified in around 2% cases in sporadic cases, and up to 20% in familial cases, telomerase genes mutations being the first etiology. We aimed to identify the relevance of a systematic surfactant genetic testing in familial or sporadic early cases (before 50 years-old) of IIP with no telomerase gene mutations. Methods: Patients were recruited through the French national network for rare lung diseases. All the surfactant system genes in which mutations has been involved in IIP were sequenced by Sanger method: genes encoding the surfactant proteins A2, B and C ( SFTPA2 , SFTPB , SFTPC) , and their transporter, the ATP-binding cassette family A member 3 ( ABCA3 ). A signed informed consent and a clinical form were obtained for each patient. Results: A population of 227 patients (203 unrelated families) was included. Forty-two cases (20%) were familial, 89 were children at the time of the diagnosis. A genetic cause was identified for 15 unrelated patients (7.4% of the families): 7 children aged 0 to 1.5 years, and 8 adults aged 28 to 64 years, including 3 familial cases. In children, 4 had a SFTPC mutation, 3 had a homozygous or compound heterozygous ABCA3 mutation. In adults, 2 had a SFTPA2 mutation, 4 a SFTPC mutation and 2 an ABCA3 mutation. In addition, 8 patients had a heterozygous ABCA3 mutation. Discussion: A genetic cause of IIP has been identified in a number of IIP, not only in familial cases (7%), but also in sporadic cases (7%), in children (7.9%) and in adult cases (7%). These results suggest that surfactant testing is of importance in the diagnosis of IIP in children, but also in adults.
Published: 2015
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24. Dans la mucoviscidose, un indice de clairance pulmonaire élevé est associé à des anomalies de fonction pulmonaire à l’exercice chez des adolescents avec spirométrie normale

Author: G. Eberst, R. Vieux, J.-C. Dalphin, A. Guillien, Bruno Degano, R. Chelabi, T. Soumagne, Marc Puyraveau, and Marie-Laure Dalphin
Subjects: Pulmonary and Respiratory Medicine, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, 030212 general & internal medicine
Abstract: Introduction Grâce a l’amelioration de leur prise en charge, certains patients atteints de mucoviscidose atteignent desormais l’adolescence avec une spirometrie normale. Neanmoins, certains d’entre eux ont une atteinte bronchique distale, de distribution heterogene, qu’il est possible d’identifier grâce a la mesure de l’indice de clairance pulmonaire ou « LCI ». Dans la mucoviscidose, un LCI eleve est associe a un plus mauvais ressenti de la maladie evalue par le CF questionnaire-revised (CFQ-R). Les consequences de l’atteinte bronchique distale sur la fonction pulmonaire a l’exercice ne sont pas connues. Methodes Dans ce travail exploratoire, 12 patients atteints de mucoviscidose âges de 12 a 18 ans, tous avec un VEMS normal (> limite inferieure de la normale ; equations GLI 2012) ont ete etudies. Le questionnaire CFQ-R a ete renseigne. Le LCI a ete mesure par rincage de l’azote. Les patients ont ete consideres comme ayant une ventilation homogene si leur LCI etait inferieur a la limite superieure de la normale (LSN) et une ventilation inhomogene si LCI > LSN. Une epreuve d’effort incrementale maximale sur cycloergometre avec une mesure continue des gaz inspires et expires, et mesure iterative de la capacite inspiratoire (IC), du score de Borg et des gaz du sang a ete realisee. Resultats Six patients avaient une ventilation homogene et 6 une ventilation inhomogene. La composante « respiratoire » du CRQ etait plus alteree dans le groupe avec ventilation inhomogene. Les patients des deux groupes avaient des capacites aerobies et des puissances maximales similaires (V’O2 au pic d’exercice : 100 ± 13 % et 99 ± 15 % des valeurs predites [% pred], p = 0,92 ; puissance au pic d’exercice : 80 ± 11 et 86 ± 14 % pred, p = 0,76 dans les groupes avec ventilation homogene et inhomogene, respectivement). Un seul patient (avec ventilation inhomogene) a developpe une distension dynamique. Neanmoins, les patients avec ventilation inhomogene avaient un score de Borg plus eleve au pic de l’effort que ceux avec LCI normal (9,0 ± 0,9 vs. 6,8 ± 1,9 ; p = 0,04). De plus, la difference alveolo-arterielle en oxygene au pic de l’effort etait significativement plus elevee chez les patients avec LCI eleve (17,1 ± 3,3 vs. 10,1 ± 2,8 mmHg, p = 0,01). Conclusion En plus d’avoir un impact sur le CFQ-R, la presence d’une ventilation pulmonaire inhomogene mesuree par le LCI est associee a une dyspnee plus intense et a des anomalies des echanges gazeux lors de l’exercice chez des adolescents avec VEMS normal.
Published: 2017
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25. Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood

Author: Roger Lauener, Vera Isabel Casaca, Caroline Roduit, R. Frei, Juha Pekkanen, Anna Lluis, Josef Riedler, Jean-Charles Dalphin, Harald Renz, Marie-Laure Dalphin, S. Remes, Michael Kabesch, Maija-Riitta Hirvonen, Béatrice Gaugler, Dominique A. Vuitton, Jon Genuneit, Jörg Tost, Juliane Weber, Georg Loss, Diana Raedler, Marjut Roponen, Philippe Saas, Vincent Kaulek, Gisela Büchele, Anne Hyvärinen, Charlotte Braun-Fahrländer, Jing Liu, Martin Depner, Bianca Schaub, Pekka Tiittanen, Erika von Mutius, Gert Doekes, S. Bitter, Petra Ina Pfefferle, Sven Michel, Anne M. Karvonen, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Xi'an Jiaotong University ( Xjtu ), Institute of Epidemiology, Universität Ulm, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Asthma and Allergy Department, University Children's Hospital-Ludwig Maximilians University, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Xi'an Jiaotong University (Xjtu), Universität Ulm - Ulm University [Ulm, Allemagne], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Laboratoire Chrono-environnement (UMR 6249) (LCE), and University Children's Hospital-Ludwig-Maximilians University [Munich] (LMU)
Subjects: Hypersensitivity, Immediate, Male, Allergy, MESH: Asthma, MESH: CD4 Lymphocyte Count, MESH : Prospective Studies, MESH : Child, Preschool, Immunoglobulin E, MESH : Agriculture, MESH : Hypersensitivity, Immediate, T-Lymphocytes, Regulatory, Atopy, MESH : T-Lymphocytes, Regulatory, MESH: Pregnancy, MESH: DNA Methylation, Pregnancy, Immunology and Allergy, MESH: Animals, MESH : Female, IL-2 receptor, Prospective Studies, Sensitization, 2. Zero hunger, biology, MESH: Immunoglobulin E, FOXP3, Agriculture, Forkhead Transcription Factors, hemic and immune systems, MESH : Infant, MESH: Infant, 3. Good health, Europe, MESH : Forkhead Transcription Factors, medicine.anatomical_structure, Milk, Child, Preschool, Female, MESH: Hypersensitivity, Immediate, MESH: Agriculture, Regulatory T cell, MESH : Male, Immunology, MESH : Europe, chemical and pharmacologic phenomena, MESH : Asthma, MESH : Immunoglobulin E, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, MESH: Forkhead Transcription Factors, medicine, MESH : CD4 Lymphocyte Count, Animals, Humans, Asthma, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, business.industry, MESH: T-Lymphocytes, Regulatory, MESH: Child, Preschool, MESH : Humans, Infant, DNA Methylation, medicine.disease, MESH: Male, MESH: Prospective Studies, CD4 Lymphocyte Count, MESH: Milk, MESH : Pregnancy, MESH : Milk, biology.protein, MESH: Europe, MESH : Animals, business, MESH: Female, MESH : DNA Methylation
Abstract: International audience; BACKGROUND: European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. OBJECTIVE: We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. METHODS: From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4(+)CD25(+) forkhead box protein 3 (FOXP3)(+) (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. RESULTS: Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4(+)CD25(+), FOXP3(+) T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. CONCLUSIONS: Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.
Published: 2014
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26. La diversité de consommation de fromages dans la petite enfance : un facteur protecteur des maladies allergiques ?

Author: Sophie Nicklaus, E. von Mutius, Jean-Charles Dalphin, J. Pekannen, A. Chauveau, J. Riedler, Marie-Laure Chardon, Marie-Laure Dalphin, Dominique A. Vuitton, Caroline Roduit, Charlotte Braun-Fahrländer, Vincent Kaulek, ProdInra, Migration, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre des Sciences du Goût et de l'Alimentation (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Christine Kühne Center, Partenaires INRAE, National Institute of Health and Welfare, Swiss Tropical and Public Health Institute [Basel], Children's Hospital, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Ludwig Maximilians University of Munich, Projet PHRC Pature 4, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Christine Kühne-Center for Allergy research and Education, University of Zurich, Laboratoire Chrono-environnement - CNRS - UBFC (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), Centre National de la Recherche Scientifique (CNRS), National Institute for Health and Welfare [Helsinki], University of Basel (Unibas), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), UMR 6249, Université de Franche-Comté ( UFC ), Centre National de la Recherche Scientifique ( CNRS ), National Institute for Health and Welfare, University of Basel ( Unibas ), Swiss Tropical and Public Health Institute ( Swiss TPH ), EA3181, Université Bourgogne Franche-Comté ( UBFC ), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: child, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, cheese consumption, PaTURE cohort, allergy, 030207 dermatology & venereal diseases, 03 medical and health sciences, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 0302 clinical medicine, 030228 respiratory system, food diversity, Immunology and Allergy, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract: Introduction et but de l’étudeUne diversité alimentaire importante et précoce a été montrée protectrice contre des maladies allergiques (Roduit C. et al, JACI2012 Jul;130(1): 130-6). L’effet de la diversité de consommation de fromages, riches en microorganismes, n’a pas été étudié. Or l’exposition aux microorganismes est suspectée pour son rôle protecteur contre la survenue de maladies allergiques. Le but de notre étude était d’évaluer l’effet protecteur de la diversité de consommation de fromages contre des maladies allergiques (MA) : allergie alimentaire (AA), dermatite atopique (DA), asthme (AS), rhinite allergique (RA) et bronchite (BR).Matériel et méthodesL’étude a porté sur 941 enfants de la cohorte PATURE (Protection contre l’Allergie : étude du milieu Rural et de son Environnement) qui étudie l’influence de l’exposition à l’environnement fermier sur le développement des maladies allergiques dans 5 pays européens (France, Allemagne, Autriche, Suisse et Finlande). Les données concernant les habitudes alimentaires, l’atopie parentale et les facteurs environnementaux ont été colligées par questionnaire de la naissance à 6 ans. Les MA ont été définies par un diagnostic médical rapporté par les parents. Les fromages ont été classés en 6 catégories (à pâte dure pressée, semi-pressée, molle, bleu, frais, de la ferme). La diversité de consommation de fromages à 18 mois (DC18) a été définie par le nombre de différentes catégories de fromages consommées. L’effet de la diversité de consommation de fromages contre chaque MA à l’âge de 6 ans a été analysé par régressions logistiques linéaires multiples ajustées pour la diversité alimentaire à 6 mois, le pays, l’environnement fermier et les facteurs confondants d’atopie, comme l’atopie parentale.Résultats et Analyse statistiqueDC18 n’était pas corrélée à la diversité alimentaire à 6 ou 12 mois (P < 0,001). Une diversité élevée de fromages consommés avait un effet significativement protecteur contre la DA à 6 ans (P < 0,0007 ; OR = 0,60; IC[0,44;0,81]) et les AA à 6 ans (P < 0,041 ; OR = 0,57; IC[0,33;0,98]), mais pas contre les autres MA à 6 ans (AS, RA, BR).ConclusionLa consommation d’une diversité de fromages à 18 mois semble avoir un effet protecteur contre la DA et les A A à 6 ans, indépendamment de la diversité de consommation des autres groupes d’aliments.
Published: 2014
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27. 116 Effect of Staphylococcus aureus supernatant on airway epithelium functionality in infants with cystic fibrosis

Author: P. Mauran, J.M. Zahm, Laurence Weiss, Marie Laure Dalphin, J. Derelle, Christelle Coraux, Philippe Birembaut, Katia Bessaci-Kabouya, B. Gaultier, Frédéric Huet, Aurélie Tatopoulos, S. Perez-Martin, and M. Abely
Subjects: Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, business.industry, medicine.disease_cause, medicine.disease, Cystic fibrosis, Microbiology, Staphylococcus aureus, Pediatrics, Perinatology and Child Health, Medicine, Respiratory epithelium, Pediatrics, Perinatology, and Child Health, business
Published: 2013
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28. ω-3 fatty acids contribute to the asthma-protective effect of unprocessed cow's milk

Author: G. Loss, Erika von Mutius, M. Kabesch, Jean-Charles Dalphin, Roger Lauener, Tabea Brick, M. Depner, Harald Renz, Juha Pekkanen, Josef Riedler, Wolfgang Andreas Nockher, Bianca Schaub, Sabina Illi, Markus J. Ege, Christian Böcking, Charlotte Braun-Fahrländer, Petra Ina Pfefferle, Jon Genuneit, Pekka Tiittanen, Anne M. Karvonen, Outi Vaarala, Yvonne Schober, Marie-Laure Dalphin, and Clinicum
Subjects: Male, 0301 basic medicine, Allergy, Allergy protection, FARM, FISH-OIL SUPPLEMENTATION, farm milk effect, 0302 clinical medicine, Surveys and Questionnaires, Odds Ratio, Immunology and Allergy, Medicine, Food science, Child, LIPID OXIDATION, HIGH-PRESSURE HOMOGENIZATION, POLYUNSATURATED FATTY-ACIDS, 2. Zero hunger, chemistry.chemical_classification, omega-3 fatty acid, food and beverages, RANDOMIZED CONTROLLED-TRIAL, 3. Good health, Milk, Child, Preschool, Female, Polyunsaturated fatty acid, Immunology, Article, 03 medical and health sciences, Animal science, Lipid oxidation, Fatty Acids, Omega-3, Animals, Humans, Omega 3 fatty acid, Asthma, business.industry, Infant, Newborn, Case-control study, CHILDHOOD ASTHMA, Infant, Fatty acid, ALLERGIC SENSITIZATION, Odds ratio, medicine.disease, HIGH-RISK, 030104 developmental biology, 030228 respiratory system, chemistry, INVERSE ASSOCIATION, 3121 General medicine, internal medicine and other clinical medicine, Case-Control Studies, Cattle, Immunization, business
Abstract: Background: Living on a farm has repeatedly been shown to protect children from asthma and allergies. A major factor involved in this effect is consumption of unprocessed cow's milk obtained directly from a farm. However, this phenomenon has never been shown in a longitudinal design, and the responsible milk components are still unknown. Objectives: We sought to assess the asthma-protective effect of unprocessed cow's milk consumption in a birth cohort and to determine whether the differences in the fatty acid (FA) composition of unprocessed farm milk and industrially processed milk contributed to this effect. Methods: The Protection Against Allergy-Study in Rural Environments (PASTURE) study followed 1133 children living in rural areas in 5 European countries from birth to age 6 years. In 934 children milk consumption was assessed by using yearly questionnaires, and samples of the ``usually'' consumed milk and serum samples of the children were collected at age 4 years. Doctor-diagnosed asthma was parent reported at age 6 years. In a nested case-control study of 35 asthmatic and 49 nonasthmatic children, 42 FAs were quantified in milk samples. Results: The risk of asthma at 6 years of age was reduced by previous consumption of unprocessed farm milk compared with shop milk (adjusted odds ratio for consumption at 4 years, 0.26; 95% CI,0.10-0.67). Part of the effect was explained by the higher fat content of farm milk, particularly the higher levels of omega-3 polyunsaturated FAs (adjusted odds ratio, 0.29; 95% CI,0.11-0.81). Conclusion: Continuous farm milk consumption in childhood protects against asthma at school age partially by means of higher intake of omega-3 polyunsaturated FAs, which are precursors of anti-inflammatory mediators.
Published: 2016
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29. Development of atopic dermatitis according to age of onset and association with early-life exposures

Author: Martin Depner, Josef Riedler, Juha Pekkanen, Jean-Charles Dalphin, Juliane Weber, Gisela Büchele, Marjut Roponen, Susanne Loeliger, Roger Lauener, Remo Frei, Anne Hyvärinen, Georg Loss, Caroline Roduit, Marie-Laure Dalphin, Erika von Mutius, Charlotte Braun-Fahrländer, Institute of Epidemiology, Universität Ulm, Service Pédiatrie, Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Asthma and Allergy Department, University Children's Hospital-Ludwig Maximilians University, Universität Ulm - Ulm University [Ulm, Allemagne], Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), and Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: Male, Rural Population, Pediatrics, Disease, MESH : Child, Preschool, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cohort Studies, 0302 clinical medicine, MESH: Pregnancy, MESH: Rural Population, Pregnancy, Risk Factors, MESH: Risk Factors, MESH : Dermatitis, Atopic, Immunology and Allergy, MESH: Animals, MESH : Female, 030212 general & internal medicine, SCORAD, Age of Onset, MESH: Cohort Studies, 2. Zero hunger, medicine.diagnostic_test, MESH : Infant, Atopic dermatitis, Yogurt, MESH: Infant, MESH : Risk Factors, 3. Good health, MESH : Age of Onset, Europe, Breast Feeding, Milk, Child, Preschool, MESH: Breast Feeding, Female, Infant Food, Cohort study, medicine.medical_specialty, MESH: Age of Onset, MESH : Male, Immunology, MESH : Europe, MESH : Cohort Studies, Dermatitis, Atopic, 03 medical and health sciences, MESH: Dermatitis, Atopic, medicine, Animals, Humans, MESH: Infant Food, MESH: Humans, business.industry, MESH: Child, Preschool, MESH : Humans, Infant, Odds ratio, MESH : Infant Food, MESH : Yogurt, medicine.disease, MESH: Male, MESH: Yogurt, MESH: Milk, body regions, MESH : Rural Population, MESH : Pregnancy, 030228 respiratory system, MESH : Milk, MESH : Breast Feeding, MESH: Europe, MESH : Animals, Age of onset, business, Breast feeding, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract: International audience; BACKGROUND: Environmental factors can affect the development of atopic dermatitis, and this was described to be already effective during pregnancy and in early life. An important early postnatal exposure is nutrition, although its association with allergic disease remains unclear. OBJECTIVE: We sought to determine prospectively whether early postnatal exposures, such as the introduction to complementary food in the first year of life, are associated with the development of atopic dermatitis, taking into account the reverse causality. METHODS: One thousand forty-one children who participated in the Protection Against Allergy-Study in Rural Environments birth cohort study were included in the current study. Atopic dermatitis was defined by a doctor's diagnosis reported by the parents of children up to 4 years of age, by questionnaires, and/or by positive SCORAD scores from 1 year of age and according to the age of onset within or after the first year of life. Feeding practices were reported by parents in monthly diaries between the 3rd and 12th months of life. RESULTS: The diversity of introduction of complementary food in the first year of life was associated with a reduction in the risk of having atopic dermatitis with onset after the first year of life (adjusted odds ratio for atopic dermatitis with each additional major food item introduced, 0.76; 95% CI, 0.65-0.88). The introduction of yogurt in the first year of life also reduced the risk for atopic dermatitis (adjusted odds ratio, 0.41; 95% CI, 0.23-0.73). CONCLUSION: As early-life exposure, the introduction of yogurt and the diversity of food introduced in the first year of life might have a protective effect against atopic dermatitis.
Published: 2012
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30. Prenatal and early-life exposures alter expression of innate immunity genes: the PASTURE cohort study

Author: Charlotte Braun-Fahrländer, S. Bitter, Juha Pekkanen, Juliane Weber, Jon Genuneit, Jean-Charles Dalphin, Remo Frei, Josef Riedler, Johanna Wohlgensinger, Caroline Roduit, Sven Michel, Maija-Riitta Hirvonen, Erika von Mutius, Marie Laure Dalphin, Roger Lauener, Marjut Roponen, Georg Loss, Michael Kabesch, Institute of Epidemiology, Universität Ulm - Ulm University [Ulm, Allemagne], Laboratoire Chrono-environnement - CNRS - UBFC (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), Service Pédiatrie, Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Asthma and Allergy Department, University Children's Hospital-Ludwig Maximilians University, Universität Ulm, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), and Hôpital Saint-Jacques-Université de Franche-Comté ( UFC )
Subjects: Hypersensitivity, Immediate, Male, Rural Population, MESH : RNA, Messenger, MESH : Prenatal Exposure Delayed Effects, MESH : Prospective Studies, Lipopolysaccharide Receptors, Gene Expression, MESH : Agriculture, MESH : Hypersensitivity, Immediate, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, MESH: Pregnancy, MESH: Rural Population, Pregnancy, Surveys and Questionnaires, Immunology and Allergy, MESH : Female, MESH: Animals, Prospective Studies, MESH: Maternal Exposure, 2. Zero hunger, 0303 health sciences, MESH: Antigens, CD14, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Toll-Like Receptors, MESH : Questionnaires, MESH : Infant, MESH : Maternal Exposure, Agriculture, MESH : Adult, MESH : Immunity, Innate, Fetal Blood, MESH: Infant, Milk, Maternal Exposure, Prenatal Exposure Delayed Effects, MESH: Immunity, Innate, Female, MESH: Cats, MESH: Hypersensitivity, Immediate, MESH : Cats, MESH: Agriculture, MESH: Toll-Like Receptors, Adult, MESH: Gene Expression, CD14, MESH : Male, Immunology, Biology, Polymorphism, Single Nucleotide, MESH: Prenatal Exposure Delayed Effects, 03 medical and health sciences, Immunity, Animals, Humans, MESH: Fetal Blood, RNA, Messenger, 030304 developmental biology, MESH: RNA, Messenger, MESH : Fetal Blood, Innate immune system, MESH: Humans, MESH: Questionnaires, MESH : Humans, TLR9, Infant, MESH: Adult, TLR7, TLR8, MESH: Male, MESH: Prospective Studies, Immunity, Innate, MESH : Rural Population, MESH : Gene Expression, MESH: Milk, MESH : Pregnancy, MESH : Antigens, CD14, 030228 respiratory system, MESH : Milk, TLR6, MESH : Toll-Like Receptors, TLR4, Cats, MESH : Animals, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract: International audience; BACKGROUND: There is evidence that gene expression of innate immunity receptors is upregulated by farming-related exposures. OBJECTIVE: We sought to determine environmental and nutritional exposures associated with the gene expression of innate immunity receptors during pregnancy and the first year of a child's life. METHODS: For the Protection Against Allergy: Study in Rural Environments (PASTURE) birth cohort study, 1133 pregnant women were recruited in rural areas of Austria, Finland, France, Germany, and Switzerland. mRNA expression of the Toll-like receptor (TLR) 1 through TLR9 and CD14 was assessed in blood samples at birth (n= 938) and year 1 (n= 752). Environmental exposures, as assessed by using questionnaires and a diary kept during year 1, and polymorphisms in innate receptor genes were related to gene expression of innate immunity receptors by using ANOVA and multivariate regression analysis. RESULTS: Gene expression of innate immunity receptors in cord blood was overall higher in neonates of farmers (P for multifactorial multivariate ANOVA= .041), significantly so for TLR7 (adjusted geometric means ratio [aGMR], 1.15; 95% CI, 1.02-1.30) and TLR8 (aGMR, 1.15; 95% CI, 1.04-1.26). Unboiled farm milk consumption during the first year of life showed the strongest association with mRNA expression at year 1, taking the diversity of other foods introduced during that period into account: TLR4 (aGMR, 1.22; 95% CI, 1.03-1.45), TLR5 (aGMR, 1.19; 95% CI, 1.01-1.41), and TLR6 (aGMR, 1.20; 95% CI, 1.04-1.38). A previously described modification of the association between farm milk consumption and CD14 gene expression by the single nucleotide polymorphism CD14/C-1721T was not found. CONCLUSION: Farming-related exposures, such as raw farm milk consumption, that were previously reported to decrease the risk for allergic outcomes were associated with a change in gene expression of innate immunity receptors in early life.
Published: 2012
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31. O58: La diversité de consommation de fromages dans la petite enfance : un facteur protecteur des maladies allergiques ?

Author: Marie-Laure Dalphin, J. Pekannen, Dominique A. Vuitton, Caroline Roduit, J. Riedler, Marie-Laure Chardon, Charlotte Braun-Fahrländer, E. Von Mutiu, Vincent Kaulek, Jean-Charles Dalphin, Sophie Nicklaus, and A. Chauveau
Subjects: 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, Nutrition and Dietetics, 030309 nutrition & dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, 030209 endocrinology & metabolism
Abstract: Introduction et but de l’etude Une diversite alimentaire importante et precoce a ete montree protectrice contre des maladies allergiques (Roduit C. et al, JACI2012 Jul;130(1): 130-6). L’effet de la diversite de consommation de fromages, riches en microorganismes, n’a pas ete etudie. Or l’exposition aux microorganismes est suspectee pour son role protecteur contre la survenue de maladies allergiques. Le but de notre etude etait d’evaluer l’effet protecteur de la diversite de consommation de fromages contre des maladies allergiques (MA) : allergie alimentaire (AA), dermatite atopique (DA), asthme (AS), rhinite allergique (RA) et bronchite (BR). Materiel et methodes L’etude a porte sur 941 enfants de la cohorte PATURE (Protection contre l’Allergie : etude du milieu Rural et de son Environnement) qui etudie l’influence de l’exposition a l’environnement fermier sur le developpement des maladies allergiques dans 5 pays europeens (France, Allemagne, Autriche, Suisse et Finlande). Les donnees concernant les habitudes alimentaires, l’atopie parentale et les facteurs environnementaux ont ete colligees par questionnaire de la naissance a 6 ans. Les MA ont ete definies par un diagnostic medical rapporte par les parents. Les fromages ont ete classes en 6 categories (a pâte dure pressee, semi-pressee, molle, bleu, frais, de la ferme). La diversite de consommation de fromages a 18 mois (DC18) a ete definie par le nombre de differentes categories de fromages consommees. L’effet de la diversite de consommation de fromages contre chaque MA a l’âge de 6 ans a ete analyse par regressions logistiques lineaires multiples ajustees pour la diversite alimentaire a 6 mois, le pays, l’environnement fermier et les facteurs confondants d’atopie, comme l’atopie parentale. Resultats et Analyse statistique DC18 n’etait pas correlee a la diversite alimentaire a 6 ou 12 mois (P Conclusion La consommation d’une diversite de fromages a 18 mois semble avoir un effet protecteur contre la DA et les A A a 6 ans, independamment de la diversite de consommation des autres groupes d’aliments.
Published: 2014
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32. Évolution des tests cutanés (TC) de l’âge de 1 à 6ans et relation avec la dermatite atopique (DA) et les IgE spécifiques : cohorte française de l’étude européenne PATURE

Author: S. Drillon, Caroline Roduit, E. von Mutius, J. Dalphin, A. Chauveau, Anne Leydier, Vincent Kaulek, and Marie-Laure Dalphin
Subjects: Pulmonary and Respiratory Medicine
Published: 2013
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33. Some Risk Factors for Cerebral Palsy in Extremely Premature Infants : Importance of Premature Rupture of Membranes and Monochorionic-Twin Placentation 1199

Author: Antoine, Burguet, primary, Elisabeth, Monnet, additional, Jean-Yves, Pauchard, additional, Philippe, Roth, additional, Christine, Fromentin, additional, Marie-Laure, Dalphin, additional, Hubert, Allemand, additional, Robert, Maillet, additional, and Alain, Menget, additional
Published: 1998
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33 results on '"Marie-Laure Dalphin"'

1. Chest physiotherapy enhances detection of Pseudomonas aeruginosa in nonexpectorating children with cystic fibrosis

2. Clinical and microbiological characteristics of cystic fibrosis adults never colonized by Pseudomonas aeruginosa: Analysis of the French CF registry.

3. Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

4. Protection contre l’allergie par l’environnement de la ferme : en 15 ans, qu’avons-nous appris de la cohorte européenne « PASTURE » ?

5. Chest physiotherapy enhances detection of Pseudomonas aeruginosa in nonexpectorating children with cystic fibrosis

6. Liste des collaborateurs

7. Chest physiotherapy enhances detection of

8. The protective effect of cheese consumption at 18 months on allergic diseases in the first 6 years

9. Palivizumab prophylaxis in infants with cystic fibrosis does not delay first isolation of Pseudomonas aeruginosa or Staphylococcus aureus

10. Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis

11. Health-related quality of life in children interstitial lung disease

12. Pneumopathie d’hypersensibilité de l’enfant

13. Health‐related quality of life in infants and children with interstitial lung disease

14. Clinical and microbiological characteristics of cystic fibrosis adults never colonized by Pseudomonas aeruginosa: Analysis of the French CF registry

15. Real-World Long-Term Ivacaftor for Cystic Fibrosis in France: Clinical Effectiveness and Healthcare Resource Utilization.

16. First Wave of COVID-19 in French Patients with Cystic Fibrosis

17. Central venous thrombosis and thrombophilia in cystic fibrosis: A prospective study

18. Asthmatic farm children show increased CD3

19. TNF-α–induced protein 3 is a key player in childhood asthma development and environment-mediated protection

20. Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts

21. Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis

22. Disagreement between Skin Prick Tests and Specific IgE in Early Childhood

23. Genetic testing in idiopathic interstitial pneumonia

24. Dans la mucoviscidose, un indice de clairance pulmonaire élevé est associé à des anomalies de fonction pulmonaire à l’exercice chez des adolescents avec spirométrie normale

25. Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood

26. La diversité de consommation de fromages dans la petite enfance : un facteur protecteur des maladies allergiques ?

27. 116 Effect of Staphylococcus aureus supernatant on airway epithelium functionality in infants with cystic fibrosis

28. ω-3 fatty acids contribute to the asthma-protective effect of unprocessed cow's milk

29. Development of atopic dermatitis according to age of onset and association with early-life exposures

30. Prenatal and early-life exposures alter expression of innate immunity genes: the PASTURE cohort study

31. O58: La diversité de consommation de fromages dans la petite enfance : un facteur protecteur des maladies allergiques ?

32. Évolution des tests cutanés (TC) de l’âge de 1 à 6ans et relation avec la dermatite atopique (DA) et les IgE spécifiques : cohorte française de l’étude européenne PATURE

33. Some Risk Factors for Cerebral Palsy in Extremely Premature Infants : Importance of Premature Rupture of Membranes and Monochorionic-Twin Placentation 1199

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33 results on '"Marie-Laure Dalphin"'

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