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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. Measurement properties of the one-minute sit-to-stand test in children and adolescents with cystic fibrosis: A multicenter randomized cross-over trial.

Author

Yann Combret, Fairuz Boujibar, Charlotte Gennari, Clément Medrinal, Sophie Sicinski, Tristan Bonnevie, Francis-Edouard Gravier, Muriel Laurans, Christophe Marguet, Pascal Le Roux, Bouchra Lamia, Guillaume Prieur, and Grégory Reychler

Subjects
Medicine, Science
Abstract

BackgroundFunctional exercise capacity assessment is recommended in children with cystic fibrosis (CF). The six-minute walk test (6MWT) is a valid evaluation of exercise capacity but can be technically complex. Inversely, the sit-to-stand test (STST) is a simple method to evaluate exercise capacity, and is validated in healthy children and adults with CF. This study aimed to evaluate STST measurement properties in children and adolescents with CF.MethodsIn this multicenter study, children with CF (6 to 18 years) performed two iterations of both the STST and the 6MWT in a randomized order. Criterion validity was determined by assessing correlations between STST repetitions and 6MWT distance (6MWD). Intra-rater reliability, test-retest repeatability, mean bias and limits of agreement were also assessed. Relationships with other outcomes (i.e. respiratory and quadriceps muscle strength) and cardio-respiratory responses were analysed for both tests.ResultsThirty-six children with CF were included (mean age 12.0 ±3.5 years and FEV1 95.8 ±25.0%). On average, 39.6 ±10.5 repetitions were performed during the STST and mean 6MWD was 596.0 ±102.6 meters. STST number of repetitions was significantly correlated with 6MWD (r = 0.48; pConclusionsThe STST is an easy-to-use functional test with moderate criterion validity when compared to the 6MWT in children with CF, probably because both tests measure different components of functional exercise capacity. The STST is useful when the 6MWT is unfeasible, however further investigations are required to explore the clinical implications of STST results in children with CF.Clinical trial registrationNCT03069625.

Published
2021
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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. 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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5. 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

6. Le test de lever de chaise pour mesurer la capacité à l’effort des enfants atteints de mucoviscidose : une étude croisée et randomisée multicentrique

Author

Fairuz Boujibar, C. Gennari, Gregory Reychler, Yann Combret, S. Sicinski, Francis Edouard Gravier, C. Medrinal, Guillaume Prieur, Bouchra Lamia, Christophe Marguet, Tristan Bonnevie, Muriel Laurans, and P. Le Roux

Subjects
Pulmonary and Respiratory Medicine
Abstract

Introduction L’evaluation des capacites a l’exercice est recommandee avec la realisation d’une epreuve d’effort incrementale ou d’un test de marche de 6 minutes (TDM6) chez les enfants de plus 10 ans atteints de mucoviscidose. Ces deux evaluations peuvent etre limitees par des contraintes techniques et une incertitude existe pour les enfants plus jeunes. Le test de lever de chaise d’une minute (TLC) est un test de tolerance a l’effort simple et valide chez les patients adultes atteints de mucoviscidose. L’objectif de cette etude etait d’evaluer la performance du TLC comme outil d’evaluation des capacites physiques pour les enfants (de 6 a 18 ans) atteints de mucoviscidose. Methodes Dans cette etude multicentrique, les patients ont realise en cross-over un TLC et un TDM6. L’ordre des tests etait randomise et chaque test a ete realise deux fois pour limiter l’effet d’apprentissage. La distance parcourue au TDM6 et le nombre de repetitions au TLC recueillis a la fin de chaque deuxieme test ont ete utilises pour evaluer les correlations. La force des muscles respiratoires et du quadriceps ont egalement ete mesurees. Les parametres cardiorespiratoires, la dyspnee sur l’echelle de BORG et la fatigue dans les jambes sur l’EVA ont ete recueillis. Resultats Trente-six enfants atteints de mucoviscidose ont ete inclus (âge moyen 12,0 ± 3,5 ans et VEMS 95,8 ± 25,0 %). Une moyenne de 39 ± 10,7 repetitions au TLC et de 590 ± 105,2 metres au TDM6 ont ete realisees. Une correlation significative a ete retrouvee entre les performances au TLC et au TDM6 (r = 0,49 ; p Conclusion Le TLC ne peut pas etre utilise comme une alternative complete au TDM6 mais peut etre envisage de part sa simplicite en cas d’impossibilite de realiser un TDM6. Il peut etre utilise chez les enfants de moins de dix ans comme premiere evaluation a l’effort precoce.

Published
2020
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7. 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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8. Measurement properties of the one-minute sit-to-stand test in children and adolescents with cystic fibrosis: A multicenter randomized cross-over trial

Author

Gregory Reychler, Guillaume Prieur, Yann Combret, Clément Medrinal, Fairuz Boujibar, Tristan Bonnevie, Sophie Sicinski, Christophe Marguet, Pascal Roux, Bouchra Lamia, Charlotte Gennari, Francis-Edouard Gravier, Muriel Laurans, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, and UCL - (SLuc) Service de pneumologie

Subjects
Male, Pulmonology, Cystic Fibrosis, Physiology, Pulmonary Function, Walking, Cystic fibrosis, Quadriceps Muscle, Pulmonary function testing, Families, Medical Conditions, 0302 clinical medicine, Medicine and Health Sciences, Medicine, Public and Occupational Health, 030212 general & internal medicine, Child, Children, Cross-Over Studies, Exercise Tolerance, Multidisciplinary, Muscle Analysis, Repeatability, Sports Science, Respiratory Function Tests, Bioassays and Physiological Analysis, Genetic Diseases, Strength Training, Legs, Female, Anatomy, Research Article, medicine.medical_specialty, Adolescent, Science, Walk Test, Research and Analysis Methods, 03 medical and health sciences, Autosomal Recessive Diseases, Criterion validity, Respiratory muscle, Humans, Muscle Strength, Sports and Exercise Medicine, Exercise, Clinical Genetics, Biological Locomotion, business.industry, Sit to stand test, Biology and Life Sciences, Reproducibility of Results, Physical Activity, medicine.disease, Fibrosis, Crossover study, Clinical trial, 030228 respiratory system, Physical Fitness, Age Groups, Body Limbs, People and Places, Exercise Test, Physical therapy, Population Groupings, business, Developmental Biology
Abstract

Background Functional exercise capacity assessment is recommended in children with cystic fibrosis (CF). The six-minute walk test (6MWT) is a valid evaluation of exercise capacity but can be technically complex. Inversely, the sit-to-stand test (STST) is a simple method to evaluate exercise capacity, and is validated in healthy children and adults with CF. This study aimed to evaluate STST measurement properties in children and adolescents with CF. Methods In this multicenter study, children with CF (6 to 18 years) performed two iterations of both the STST and the 6MWT in a randomized order. Criterion validity was determined by assessing correlations between STST repetitions and 6MWT distance (6MWD). Intra-rater reliability, test-retest repeatability, mean bias and limits of agreement were also assessed. Relationships with other outcomes (i.e. respiratory and quadriceps muscle strength) and cardio-respiratory responses were analysed for both tests. Results Thirty-six children with CF were included (mean age 12.0 ±3.5 years and FEV1 95.8 ±25.0%). On average, 39.6 ±10.5 repetitions were performed during the STST and mean 6MWD was 596.0 ±102.6 meters. STST number of repetitions was significantly correlated with 6MWD (r = 0.48; pSTST = 0.91 (95%CI 0.76–0.96) and ICC6MWT = 0.94 (95%CI 0.85–0.97)), and a significant test-retest learning effect. The number of STST repetitions was not correlated with quadriceps or respiratory muscle strength test, and the STST induced fewer cardio-respiratory responses than the 6MWT. Conclusions The STST is an easy-to-use functional test with moderate criterion validity when compared to the 6MWT in children with CF, probably because both tests measure different components of functional exercise capacity. The STST is useful when the 6MWT is unfeasible, however further investigations are required to explore the clinical implications of STST results in children with CF. Clinical trial registration NCT03069625.

Published
2021
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9. High rate of macrolide resistance in Staphylococcus aureus strains from patients with cystic fibrosis reveals high proportions of hypermutable strains

Author

Muriel Laurans, Jean-Francois Duhamel, Roland Leclercq, Anne-Laure Prunier, Jacques Brouard, and Brigitte Malbruny

Subjects
Adult, Male, Staphylococcus aureus, Cystic Fibrosis, Erythromycin, Drug resistance, Biology, medicine.disease_cause, DNA, Ribosomal, law.invention, Microbiology, Bacterial Proteins, law, 23S ribosomal RNA, Drug Resistance, Multiple, Bacterial, medicine, Immunology and Allergy, Humans, Polymerase chain reaction, Adenosine Triphosphatases, Escherichia coli Proteins, Ribosomal RNA, Staphylococcal Infections, Virology, MutS DNA Mismatch-Binding Protein, Anti-Bacterial Agents, DNA-Binding Proteins, Infectious Diseases, Phenotype, Streptomycin, Mutation, Female, Macrolides, Staphylococcus, medicine.drug
Abstract

Incidence of resistance to erythromycin at our institution reached 53% in 122 Staphylococcus aureus isolates obtained from patients with cystic fibrosis (CF) from 1997 to 1999. Macrolide-resistance genes were sought for in 20 erythromycin-resistant isolates from 9 patients with CF by use of polymerase chain reaction; 13 strains did not contain any known macrolide-resistance genes. Sequence of ribosomal genes rrl (23S rRNA), rplD (L4 protein), and rplV (L22 protein) revealed the presence of mutations in the target site of macrolides in 15 of the 20 isolates. A higher proportion of hypermutator strains was observed in a group of 89 CF staphylococcal isolates, compared with that in the 74 non-CF control isolates (13/89 vs. 1/74 with resistance to rifampin [P=.0045]; 9/89 vs. 1/74 with resistance to streptomycin [P=.04]). Various mutations or deletions of the mutator mutS gene were found not only in 5 of 11 hypermutable strains but also in 3 nonhypermutable strains harboring a large number of ribosomal mutations. The presence of a high proportion of hypermutable strains might explain the adaptation of certain strains in the patients, as well as the emergence of macrolide resistance as a result of antibiotic selective pressure in CF.

Published
2002

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