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1. Human Papilloma Virus Vaccination Among Female Patients Attending French Pediatric Cystic Fibrosis Centers

Author: Christine Rousset-Jablonski, Philippe Reix, Isabelle Durieu, M. Perceval, C. Llerena, Angélique Denis, Julie Haesebaert, and S. Touzet
Subjects: Health Knowledge, Attitudes, Practice, Pediatrics, medicine.medical_specialty, Vaccination Coverage, Adolescent, Cystic Fibrosis, Vaccination schedule, Uterine Cervical Neoplasms, Disease, 03 medical and health sciences, 0302 clinical medicine, Health care, medicine, Humans, Papillomavirus Vaccines, 030212 general & internal medicine, Parent-Child Relations, Child, Reproductive health, 030219 obstetrics & reproductive medicine, Cervical screening, business.industry, Papillomavirus Infections, Obstetrics and Gynecology, Professional-Patient Relations, General Medicine, Odds ratio, Hepatitis B, medicine.disease, Vaccination, Cross-Sectional Studies, Pediatrics, Perinatology and Child Health, Female, France, Self Report, business
Abstract: Study Objective To describe human papilloma virus (HPV) vaccination practice among adolescent girls with cystic fibrosis (CF) and to identify reasons for non-vaccination. Design Cross-sectional multicentric study. Setting and Participants Girls aged 9-17 years, attending 7 French pediatric CF centers, and their accompanying adult. Interventions Administration of a self-report questionnaire. Main Outcome Measures The proportion of girls having received or receiving HPV vaccination, compliance with the vaccination schedule, factors associated with vaccination, and reasons for vaccination and for non-vaccination. Results A total of 113 girls and 104 accompanying adults participated. The mean age was 13.6 years (standard deviation 2.5; range 9-17). A total of 34 (30.9%) patients reported having received HPV vaccination. Among the 34 girls aged 15 years or older, 15 (44.1%) were vaccinated. Most patients (58.8%) started vaccination between 11 and 14 years of age (mean age 13.9). Most vaccine prescriptions (67.6%) were made by a CF center health care provider. Factors associated with vaccination were older age (odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.01-1.6, P = .037 for each year older), previous vaccination by the accompanying parent of one of their children for hepatitis B (OR = 8.01, 95% CI = 0.96-67.02), P = .055), and parental influence on decision-making (OR = 2.77, 95% CI = 0.97-7.95, P = .058). Health care providers’ positive advice and fear of HPV-related disease were the main reasons given to justify vaccination decisions. Insufficient knowledge and concerns about potential side effects were the main barriers. Conclusion HPV vaccination remains insufficient among girls with CF. CF health care providers may play a crucial role in HPV vaccination acceptance, and their sensitization to cervical cancer prevention is mandatory.
Published: 2021

2. A formalized transition program for cystic fibrosis: A 10‐year retrospective analysis of 97 patients in Lyon

Author: Isabelle Durieu, Fanny Magne, Raphaele Nove Josserand, Quitterie Reynaud, Philippe Reix, Gaelle Bourgeois, and Stéphane Durupt
Subjects: Adult, Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Cystic Fibrosis, business.industry, Nutritional status, medicine.disease, Cystic fibrosis, 03 medical and health sciences, 0302 clinical medicine, Outpatient visits, 030228 respiratory system, Forced Expiratory Volume, 030225 pediatrics, Pediatrics, Perinatology and Child Health, Retrospective analysis, Humans, Medicine, Child, business, Lung, Body mass index, Lung Transplantation, Retrospective Studies
Abstract: INTRODUCTION The prognosis of people diagnosed with cystic fibrosis (CF) has dramatically improved over the past decade in France, largely due to advances in CF care management, including an emphasis on chronic maintenance medications. Currently, the majority of French CF patients are adults, which means that they went through a transition process from receiving care at a pediatric CF center to receiving care at an adult CF center. To determine the impact of the transfer on clinical evolution, we report the transition procedure of our CF center in Lyon. MATERIALS AND METHODS From January 2006 to December 2016, 97 CF patients underwent a standardized process of transitioning from the pediatric to the adult CF center in Lyon. We compared the clinical evolution of these patients during three periods, starting the year before transition and ending the year after transition. Clinical data taken into account were forced expiratory volume in 1 s (FEV1 in liters), body mass index (BMI in kg/m2 ), pulmonary colonization, number of antibiotic courses, number of days of hospitalization per year, and outpatient visits per year. RESULTS No significant differences were observed between respiratory and nutritional status, respiratory microbiome, number of antibiotic courses, or number of hospitalizations or visits when comparing the threeperiods of observation around transition (the year before, the first year after, and the second year after transfer). CONCLUSION The standardized transition procedure used in Lyon is associated with the clinical stability of our CF patients.
Published: 2021

3. Risk factors for nontuberculous mycobacterial isolation in patients with cystic fibrosis: A meta‐analysis

Author: Raphaele Nove-Josserand, Stéphane Durupt, Pierre-Régis Burgel, Zoe Cavalli, Philippe Reix, Isabelle Durieu, Quitterie Reynaud, and Romain Bricca
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Cystic Fibrosis, Mycobacterium Infections, Nontuberculous, medicine.disease_cause, Azithromycin, Cystic fibrosis, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, 030225 pediatrics, Internal medicine, Humans, Medicine, biology, business.industry, Nontuberculous Mycobacteria, Odds ratio, bacterial infections and mycoses, biology.organism_classification, medicine.disease, Confidence interval, Stenotrophomonas maltophilia, 030228 respiratory system, Staphylococcus aureus, Meta-analysis, Pediatrics, Perinatology and Child Health, Nontuberculous mycobacteria, business, medicine.drug
Abstract: BACKGROUND To better understand the mechanisms of infection with nontuberculous mycobacteria (NTM) in patients with cystic fibrosis (CF), we explore different risk factors associated with NTM positivity in a meta-analysis. METHODS Studies published before 31 July 2019 were selected from MEDLINE. Combined odds ratios (ORs) were calculated by pooling the ORs of each study. The weighted mean difference (WMD) was used for continuous numerical measurements. Summary data were pooled using fixed- or random-effects models according to the presence of heterogeneity (P 50%). RESULTS Nineteen studies with a total of 23 418 patients, of whom 1421 (6%) were diagnosed as NTM positive, were included. Older age was significantly associated with NTM positivity (WMD = 2.12, 95% confidence interval [CI]: 1.11-3.13; P
Published: 2020

4. Long-term safety and efficacy of tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study

Author: Patrick A Flume, Reta Fischer Biner, Damian G Downey, Cynthia Brown, Manu Jain, Rainald Fischer, Kris De Boeck, Gregory S Sawicki, Philip Chang, Hildegarde Paz-Diaz, Jaime L Rubin, Yoojung Yang, Xingdi Hu, David J Pasta, Stefanie J Millar, Daniel Campbell, Xin Wang, Neil Ahluwalia, Caroline A Owen, Claire E Wainwright, Ronald L. Gibson, Steven M. Rowe, Noah Lechtzin, Richard C. Ahrens, Karen S. McCoy, Moira Aitken, Scott H. Donaldson, Kimberly Ann McBennett, Joseph M. Pilewski, Joanne Billings, Carlos Milla, Ronald Rubenstein, Daniel Brian Rosenbluth, Rachel Linnemann, Michael R. Powers, Christopher Fortner, Carla Anne Frederick, Theodore G. Liou, Philip Black, Janice Wang, John L. Colombo, Maria Berdella, Maria Veronica Indihar, Cynthia D. Brown, Michael Anstead, Lara Bilodeau, Leonard Sicilian, James Jerome Tolle, Kathryn Moffett, Samya Nasr, Jennifer Taylor-Cousar, Tara Lynn Barto, Nicholas Antos, John S. Rogers, Bryon Quick, Henry R. Thompson, Gregory Sawicki, Bruce Barnett, Robert L. Zanni, Thomas C. Smith, Karen D. Schultz, Claire Keating, Patrick Flume, Gregory J. Omlor, Alix Ashare, Karen Voter, Nighat Mehdi, Maria Gabriela Tupayachi Ortiz, Tonia E. Gardner, Steven R. Boas, Barbara Messore, Edith Zemanick, Raksha Jain, Michael McCarthy, Dana G. Kissner, Kapilkumar Patel, John McNamara, Julie Philley, Ariel Berlinski, Francisco J. Calimano, Terry Chin, Douglas Conrad, Cori Daines, Hengameh H. Raissy, Thomas G. Keens, Jorge E. Lascano, Bennie McWilliams, Brian Morrissey, Santiago Reyes, Subramanyam Chittivelu, Sabiha Hussain, Arvey Stone, James Wallace, Ross Klingsberg, Julie A. Biller, Stephanie Bui, Olaf Sommerburg, Elisabetta Bignamini, Mirella Collura, Alexander Moller, Donatello Salvatore, Chantal Belleguic, Lea Bentur, Ori Efrati, Eitan Kerem, Dario Prais, Esther Quintana Gallego, Peter Barry, Galit Livnat-Levanon, Jose Ramon Villa Asensi, David Stuart Armstrong, Oscar Asensio de la Cruz, Francis Gilchrist, Diana Elizabeth Tullis, Bradley Quon, Larry C. Lands, Nancy Morrison, Annick Lavoie, Barry Linnane, Okan Elidemir, Felix Ringshausen, Matthias Kappler, Helge Hebestreit, Jochen Mainz, Alexander Kiefer, Cordula Koerner-Rettberg, Doris Staab, Wolfgang Gleiber, Tacjana Pressler, Florian Stehling, Andreas Hector, Sivagurunathan Sutharsan, Lutz Naehrlich, Damian Downey, Jane Carolyn Davies, Robert Ian Ketchell, Mary Patricia Carroll, Simon Doe, Gordon MacGregor, Edward Fairbairn Nash, Nicholas Withers, Daniel Gavin Peckham, Martin James Ledson, Sonal Kansra, Timothy William Rayner Lee, Bertrand Delaisi, Gilles Rault, Jean Le Bihan, Dominique Hubert, Isabelle Fajac, Isabelle Sermet-Gaudelus, Marleen Bakker, Bert Arets, Christiane De Boeck, Raphael Chiron, Philippe Reix, Catherine Mainguy, Eva van Braeckel, Anne Malfroot, Isabelle Durieu, Nadine Desmazes Dufeu, Anne Prevotat, Renske van der Meer, Petrus Merkus, E.J.M. Weersink, Isabel Barrio Gomez-Aguero, Silvia Gartner, Amparo Sole Jover, Antonio Alvarez Fernandez, Desmond William Cox, Edward F. McKone, Barry James Plant, Hiranjan Selvadurai, Simon David Bowler, Claire Elizabeth Wainwright, Daniel Smith, Peter Gordon Middleton, John William Wilson, Sonia Volpi, Carla Colombo, Benedetta Fabrizzi, Vincenzina Lucidi, Federico Cresta, Salvatore Cucchiara, Ernst Eber, Helmut Ellemunter, Isidor Huttegger, Lena Hjelte, Christina Krantz, Marita Gilljam, and Pulmonology
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Indoles, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Quinolones, Aminophenols, Cystic fibrosis, Time, Ivacaftor, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Internal medicine, medicine, Clinical endpoint, Humans, Benzodioxoles, 030212 general & internal medicine, Israel, biology, business.industry, Australia, medicine.disease, Cystic fibrosis transmembrane conductance regulator, Discontinuation, Europe, Drug Combinations, Treatment Outcome, Clinical research, 030228 respiratory system, Tolerability, Mutation, North America, biology.protein, Female, business, medicine.drug
Abstract: Summary Background Tezacaftor–ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8–24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor–ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor–ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation. Methods Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor–ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor–ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov ( NCT02565914 ). Findings Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor–ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor–ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor–ivacaftor-treated F/F participants versus untreated matched historical controls. Interpretation Tezacaftor–ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor–ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor–ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes. Funding Vertex Pharmaceuticals Incorporated.
Published: 2021

5. Using chest CT scan and unsupervised machine learning for predicting and evaluating response to lumacaftor-ivacaftor in people with cystic fibrosis

Author: Laurent Mely, E. Battistella, Martine Reynaud-Gaubert, Trieu-Nghi Hoang-Thi, Guillaume Chassagnon, Christophe Marguet, Annlyse Fanton, Marie-Pierre Revel, Raphaël Chiron, Chantal Belleguic, Maria Vakalopoulou, Clémence Martin, Stéphanie Bui, Pierre-Régis Burgel, Marlène Murris-Espin, Alienor Campredon, Jennifer Da Silva, Isabelle Durieu, Philippe Reix, OPtimisation Imagerie et Santé (OPIS), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de vision numérique (CVN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-CentraleSupélec-Université Paris-Saclay, Mathématiques et Informatique pour la Complexité et les Systèmes (MICS), and CentraleSupélec-Université Paris-Saclay
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung, biology, business.industry, Lumacaftor, Chest ct, medicine.disease, Cystic fibrosis, Cystic fibrosis transmembrane conductance regulator, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Ivacaftor, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Lung disease, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, biology.protein, Radiology, business, Lung function, medicine.drug
Abstract: ObjectivesLumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). This study aimed to assess lung structural changes after one year of lumacaftor-ivacaftor treatment, and to use unsupervised machine learning to identify morphological phenotypes of lung disease that are associated with response to lumacaftor-ivacaftor.MethodsAdolescents and adults with CF from the French multicenter real-world prospective observational study evaluating the first year of treatment with lumacaftor-ivacaftor were included if they had pretherapeutic and follow-up chest computed tomography (CT)-scans available. CT scans were visually scored using a modified Bhalla score. A k-mean clustering method was performed based on 120 radiomics features extracted from unenhanced pretherapeutic chest CT scans.ResultsA total of 283 patients were included. The Bhalla score significantly decreased after 1 year of lumacaftor-ivacaftor (−1.40±1.53 points compared with pretherapeutic CT; p1) ≥5 under lumacaftor–ivacaftor than those in the other clusters (54% of responders versus 32% and 33%; p=0.01).ConclusionOne year treatment with lumacaftor-ivacaftor was associated with a significant visual improvement of bronchial disease on chest CT. Radiomics features on pretherapeutic CT scan may help in predicting lung function response under lumacaftor-ivacaftor.
Published: 2021

6. Factors Associated with Asthma Severity in Children: Data from the French COBRAPed Cohort

Author: Muriel Le Bourgeois, Guillaume Lezmi, Raphaël Chiron, Marie-Alexandra Alyanakian, Jacques de Blic, Jacques Brouard, Valérie Jolaine, Isabelle Pin, Sylvain Blanchon, Léa Roditis, Christophe Delacourt, C. Mordacq, Emmanuelle Bosdure, Mathieu Pellan, Véronique Houdoin, Graziella Mingardi, David Drummond, Irina Badiu-Decleyre, Patrick Berger, Rola Abou-Taam, V. Jubin, S. Vrielynck, Caroline Tournegros, Sylvie-Anne André Gomez, Julie Mazenq, Marie-Christine Werck Gallois, Stéphanie Wanin, Philippe Reix, Naïm Bouazza, Stephane Debelleix, Camille Ohlmann, Antoine Deschildre, Caroline Thumerelle, Alice Hadchouel-Duvergé, Guillaume Simon, Marie Noelle Lebras, Laurent Béghin, Lucienne Chatennoud, Stéphanie Lejeune, Isabelle Cabon, Patricia El Boustany, Jean-Christophe Dubus, Cecile Bonnel, Valérie Siao, Michael Fayon, Christophe Marguet, Laure Delbecque, Lisa Giovannini-Chami, Marine Servat, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de Pneumologie et d'Allergologie Pédiatriques, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Asthma severity, Disease, Dermatitis, Atopic, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Food allergy, Risk Factors, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, Asthma, Respiratory Sounds, business.industry, Atopic dermatitis, Odds ratio, medicine.disease, 3. Good health, 030228 respiratory system, Child, Preschool, Cohort, Observational study, business, Food Hypersensitivity
Abstract: Background Severe asthma (SA) in children is a complex, heterogeneous disease, associated with a considerable burden. However, factors influencing asthma severity are poorly described and may differ according to age. Objective To determine whether factors associated with asthma severity differ between preschoolers with severe recurrent wheeze (SRW) and school-age children with SA. Methods Data from the French multicenter prospective observational cohort of preschool (3-6 years) children with SRW and nonsevere recurrent wheeze (NSRW) and school-age (7-11 years) children with SA and nonsevere asthma (NSA) (Pediatric Cohort of Bronchial Obstruction and Asthma) were analyzed. Results A total of 131 preschool children (92 SRW and 49 NSRW) and 207 school-age children (92 SA and 115 NSA) were included. In both univariable and multivariable analysis, SRW was associated with second-hand smoke exposure (multivariable analysis: odds ratio [95% CI], 29.8 [3.57-3910]) and exposure to mold/dampness at home (multivariable analysis: odds ratio [95% CI], 4.22 [1.25-18.2]) compared with NSRW. At school-age, history of atopic dermatitis and food allergy was more frequent in children with SA than in those with NSA. Multivariable analysis confirmed that SA was associated with a history of food allergy (odds ratio [95% CI], 5.01 [2.23-11.9]). Conclusions Our data suggest that factors influencing asthma severity may differ according to age. In preschool children with SRW, second-hand smoke and exposure to mold are predominant, whereas associated allergic disorders are mainly involved in SA at school-age.
Published: 2021

7. Real-world assessment of LCI following lumacaftor-ivacaftor initiation in adolescents and adults with cystic fibrosis

Author: Aurélie Tatopoulos, Philippe Reix, Marie Luce Choukroun, Pierre-Régis Burgel, Katia Bessaci-Kabouya, Iulia Ioan, Jennifer Da Silva, Muriel Le Bourgeois, Plamen Bokov, M. Gerardin, Jean-Louis Paillasseur, Stéphanie Bui, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), and Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Adolescent, Cystic Fibrosis, [SDV]Life Sciences [q-bio], Aminopyridines, Cystic Fibrosis Transmembrane Conductance Regulator, Quinolones, Aminophenols, Cystic fibrosis, Ivacaftor, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Daily practice, Medicine, Humans, Benzodioxoles, Young adult, 10. No inequality, Chloride Channel Agonists, ComputingMilieux_MISCELLANEOUS, business.industry, Lumacaftor, medicine.disease, 3. Good health, Respiratory Function Tests, Drug Combinations, 030104 developmental biology, 030228 respiratory system, chemistry, Lung disease, Pediatrics, Perinatology and Child Health, Biomarker (medicine), Observational study, business, medicine.drug
Abstract: Lung clearance index (LCI) is a biomarker of ventilation inhomogeneity. Data are scarce on its usefulness in daily practice for monitoring the effects of treatments in older children and adults with CF. In this French observational study of lumacaftor-ivacaftor, 63 of 845 patients (7.5%) had available LCI performed at baseline and at six (M6; n=34) or 12 months (M12; n=46) after lumacaftor-ivacaftor initiation. At inclusion, median [IQR] age was 16 years [13-17], ppFEV1 was 72.8 [59.6-80.7], and LCI was 12.3 [10.3-15.0]. At both M6 and M12, no statistically significant LCI increases of 0.13 units or 1.34% (95% CI: -4.85-7.53) and 0.6 units or 6.66% (95% CI: -0.03-13.5) were observed. Discordant results between LCI and ppFEV1 were observed in one-third of the patients. In daily practice, LCI monitoring in adolescents and young adults with moderate lung disease gives results that are more heterogenous than those reported in children with milder disease.
Published: 2021

8. 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

9. HOMA indices as screening tests for cystic fibrosis-related diabetes

Author: Catherine Mainguy, Isabelle Durieu, S. Touzet, Quitterie Reynaud, Angélique Denis, Philippe Reix, Catherine Llerena, Tom Toin, and Isabelle Pin
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Adult, Blood Glucose, Male, medicine.medical_specialty, endocrine system diseases, Screening test, Adolescent, Cystic Fibrosis, Cystic fibrosis-related diabetes, Cystic fibrosis, Gastroenterology, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Insulin resistance, Age groups, Predictive Value of Tests, Positive predicative value, Diabetes mellitus, Internal medicine, Insulin-Secreting Cells, medicine, Diabetes Mellitus, Humans, Insulin, Prospective Studies, Prospective cohort study, Child, business.industry, nutritional and metabolic diseases, Glucose Tolerance Test, medicine.disease, 030104 developmental biology, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Female, Insulin Resistance, business, hormones, hormone substitutes, and hormone antagonists, Biomarkers
Abstract: We assessed the diagnostic performances of homeostasis model assessment indices (HOMA) of β-cell function (HOMA-%β) and of insulin resistance (HOMA-IR) for cystic fibrosis related diabetes (CFRD) screening.Data were collected from a prospective cohort of 228 patients with CF (117 adults and 111 children). Fasting insulin and glucose levels were measured to calculate HOMA-%β and HOMA-IR. HOMA-%β100 indicated insulin secretion deficiency and HOMA-IR1 insulin resistance. Both were used to calculate sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Two-hour oral glucose tolerance tests (2h-OGTT) defined CFRD. Analyses were conducted separately for children and adults. Performances of HOMA-%β and HOMA-IR were calculated at inclusion, for each year of follow-up and for pooled data over the follow-up period.Sensitivity, specificity, NPV and PPV were respectively: 88%, 45%, 98% and 11% for HOMA-%β and 42%, 48%, 91% and 6% for HOMA-IR in the pooled data of children; and 83%, 18%, 90% and 10% for HOMA-%β, and 39%, 80%, 92% and 18% for HOMA-IR in the pooled data of adults. Combining HOMA-%β and HOMA-IR did not improve performances.Within both age groups, HOMA-%β100 provided good sensitivity and NPV. HOMA-IR1 had low sensitivity. Calculation of the HOMA-%β could be an interesting first-line screening approach to exclude CFRD and thus avoid unnecessary OGTT in patients for whom value is ≥100. However, HOMA-%β100 does not support the diagnosis of CFRD and should be complemented by OGTT.
Published: 2021

10. Clinical response to lumacaftor-ivacaftor in patients with cystic fibrosis according to baseline lung function

Author: Marlène Murris-Espin, Christophe Marguet, Anne Munck, Michel Abely, Harriet Corvol, Philippe Reix, Laurent Mely, Clémence Martin, Tiphaine Biouhee, Julie Macey, Michele Porzio, A. Prevotat, Stéphanie Bui, Dominique Hubert, Isabelle Sermet-Gaudelus, Jennifer Da Silva, Clémence Dehillotte, Isabelle Durieu, Lydie Lemonnier, Raphaël Chiron, Pierre-Régis Burgel, Jean-Louis Paillasseur, 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), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital Renée Sabran [CHU - HCL], Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Strasbourg, American Memorial Hospital (Hôpital des enfants) [Reims], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Rouen, Normandie Université (NU), CHU Bordeaux [Bordeaux], CHU Necker - Enfants Malades [AP-HP], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), 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), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Robert Debré, Vaincre la Mucoviscidose, Association de lutte contre la Mucoviscidose, EFFI-STAT, and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Adolescent, Cystic Fibrosis, [SDV]Life Sciences [q-bio], Aminopyridines, Quinolones, Aminophenols, Cystic fibrosis, Ivacaftor, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, In patient, Benzodioxoles, Chloride Channel Agonists, Lung function, ComputingMilieux_MISCELLANEOUS, business.industry, Lumacaftor, Authorization, medicine.disease, 3. Good health, Respiratory Function Tests, Drug Combinations, 030104 developmental biology, Cftr mutation, 030228 respiratory system, chemistry, Pediatrics, Perinatology and Child Health, Disease Progression, Female, France, business, medicine.drug
Abstract: International audience; Background: Phase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV1) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV1.Methods: To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV1
Published: 2020

11. Real-life acute lung function changes after lumacaftor/ivacaftor first administration in pediatric patients with cystic fibrosis

Author: Laurianne Coutier, Camille Ohlmann, Catherine Mainguy, M. Perceval, Aurélie Labaste, Philippe Reix, and V. Jubin
Subjects: Male, Pulmonary and Respiratory Medicine, Adolescent, Cystic Fibrosis, Aminopyridines, Quinolones, Aminophenols, Cystic fibrosis, Ivacaftor, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Forced Expiratory Volume, medicine, Humans, Benzodioxoles, 030212 general & internal medicine, Respiratory system, Chloride Channel Agonists, Inhalation, business.industry, Lumacaftor, respiratory system, Airway obstruction, medicine.disease, Respiratory Function Tests, respiratory tract diseases, Drug Combinations, Treatment Outcome, 030228 respiratory system, chemistry, Anesthesia, Pediatrics, Perinatology and Child Health, Salbutamol, Female, Bronchoconstriction, France, Drug Monitoring, Symptom Assessment, medicine.symptom, business, circulatory and respiratory physiology, medicine.drug
Abstract: The combination of lumacaftor and ivacaftor (LUM/IVA) has been reported to induce a mean acute absolute drop of -4.1% predicted forced expiratory volume in 1s (FEV1) after a unique administration in healthy subjects. The aim of the present study was to assess acute FEV1 changes after the first dose of LUM/IVA in CF patients. A total of 32 pediatric patients were included. Respiratory manifestations occurred in only 3 patients (9.4%), but FEV1 consistently decreased (-10.4±4.6%, range: -1.5; -21.8%). FEV1 only partially resumed after salbutamol inhalation. Patients with previously known significant reversible airway obstruction and low FEV1 were more at risk of FEV1 decrease.
Published: 2017

12. 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

13. Actinomycose disséminée traitée par clindamycine

Author: Philippe Reix, Gaud Catho, Frédérique Dijoud, Philippe Thiesse, A. Tristan, S. Bouttefroy, Thomas Perpoint, C. Faure Conter, and Florent Valour
Subjects: 0301 basic medicine, medicine.medical_specialty, 030106 microbiology, Population, 03 medical and health sciences, 0302 clinical medicine, Medicine, 030212 general & internal medicine, education, education.field_of_study, Bacterial disease, biology, business.industry, Clindamycin, Actinomyces israelii, biology.organism_classification, medicine.disease, Dermatology, 3. Good health, Histiocytosis, Pediatrics, Perinatology and Child Health, Actinomycosis, Anaerobic bacteria, business, Actinomyces, medicine.drug
Abstract: Actinomycosis is a rare bacterial disease caused by Actinomyces spp., an anaerobic bacteria from the oropharynx, digestive, and female genital tracts. Initial clinical presentation often mimics malignancy, which can lead to a delay in diagnosis. Cervico-facial, genitourinary, digestive, and respiratory features are the most frequent. Few cases are reported in children and risk factors are not well known in this population. We report on the case of an 8-year-old boy with disseminated actinomycosis with cervico-facial, pulmonary, and bone involvement caused by Actinomyces israelii. The infiltrative appearance initially suggested malignancy and the patient was started on chemotherapy for presumed histiocytosis. Evaluation of subsequent tissue samples demonstrated the presence of filamentous structures consistent with fungal or filamentous bacterial infection. Prolonged culture yielded the correct diagnosis. The patient had a severe allergic reaction to piperacillin/tazobactam and was therefore transitioned to clindamycin to complete a 9-month course. This treatment, which has not been reported in children, led to a favorable clinical, biological, and radiological response, with a good clinical tolerance.
Published: 2017

14. WS15.3 HOMA indexes diagnosis performance for Cystic Fibrosis-Related Diabetes

Author: Catherine Mainguy, S. Touzet, T. Toin, Isabelle Durieu, Quitterie Reynaud, Philippe Reix, and Angélique Denis
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, Internal medicine, Pediatrics, Perinatology and Child Health, Cystic fibrosis-related diabetes, medicine, medicine.disease, business, Cystic fibrosis, Gastroenterology
Published: 2020

15. 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

16. Do patients with cystic fibrosis participating in clinical trials demonstrate placebo response ? A meta-analysis

Author: François Gueyffier, Behrouz Kassai-Koupai, Perrine Janiaud, Julie Coton, Michel Cucherat, Ha-Hai Le, and Philippe Reix
Subjects: Clinical trial, medicine.medical_specialty, Placebo response, business.industry, Internal medicine, Meta-analysis, Medicine, business, medicine.disease, Cystic fibrosis
Published: 2019

17. 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

18. Viral respiratory tract infections in young children with cystic fibrosis: a prospective full-year seasonal study

Author: Camille Ohlmann, Catherine Mainguy, Mathilde Eymery, Anne Doléans-Jordheim, Philippe Reix, M. Perceval, Florence Morfin, Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, viruses, [SDV]Life Sciences [q-bio], Population, Respiratory Syncytial Virus Infections, Respiratory virus, Biology, medicine.disease_cause, Severity of Illness Index, Cystic fibrosis, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Virology, medicine, Humans, lcsh:RC109-216, Prospective Studies, Respiratory system, education, Respiratory Tract Infections, Children, Coronavirus, education.field_of_study, Picornaviridae Infections, Respiratory tract infections, Coinfection, Research, Infant, medicine.disease, 3. Good health, 030104 developmental biology, Infectious Diseases, Viruses, Enterovirus, Female, 030211 gastroenterology & hepatology, France, Seasons, Rhinovirus, Coronavirus Infections
Abstract: Viral respiratory tract infections are common during early childhood. How they impact cystic fibrosis lung disease history in young children is poorly known. The principal aim of our study was to determinate respiratory tract infections frequency in this cystic fibrosis young population. Secondary outcomes were nature of viral agents recovered and impact of such infections. We conducted a prospective cohort study of 25 children affected by cystic fibrosis and aged less than 2 years. Nasal samplings were taken systematically monthly or bimonthly with additional samples taken during respiratory tract infections episodes. Ten pathogens were tested by a combination of five duplex RT-PCRs or PCRs: influenza A and B, respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus/enterovirus (RV/EV)), coronavirus (HKU1, NL63, 229E and OC43), parainfluenza virus (1–4), adenovirus and bocavirus (Respiratory Multi-Well System MWS r-gene®, BioMerieux, Marcy l’Etoile, France). Cycle thresholds (CTs) were reported for all positive samples and considered positive for values below 40. Quantitative variables were compared using a nonparametric statistical test (Wilcoxon signed rank for paired comparisons). Pearson’s correlation coefficient (r) was used to assess relationships between two variables. Statistical analyses were performed using SAS v9.4 (SAS Institute, Cary, NC, USA) or GraphPad Prism V6.00 (GraphPad Software, La Jolla, CA, USA). The significance level was set at 0.05. The mean age at inclusion was 9.6 ± 6.7 months. The patients had 3.4 ± 1.7 respiratory tract infections episodes per child per year. Forty-four respiratory tract infections (69%) were associated with virus: rhinovirus and enterovirus (RV/EV) were implied in 61% of them and respiratory syncytial virus (RSV) in 14%. Only one patient required hospitalization for lower respiratory tract infections. 86% of the patients were treated by antibiotics for a mean of 13.8 ± 6.2 days. RSV infections (n = 6) were usually of mild severity. Respiratory tract infections in young children with cystic fibrosis were of mild severity, rarely requiring hospitalization. Unsurprisingly, RV/EV were the most frequent agents. RSV-related morbidity seems low in this population. This raises the question of the usefulness of RSV preventive medication in this young population.
Published: 2019
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19. Usefulness of bronchoalveolar lavage in a French pediatric cohort with hypersensitivity pneumonitis

Author: Philippe Reix, Stéphanie Wanin, Antoine Deschildre, Gabriel Reboux, Véronique Houdouin, Jacques de Blic, Nadia Nathan, and Clara Malka-Ruimy
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Adolescent, Lymphocyte, CD4-CD8 Ratio, Lung biopsy, Gastroenterology, Serology, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Internal medicine, medicine, Humans, Exertion, Child, Lung, medicine.diagnostic_test, business.industry, Interstitial lung disease, medicine.disease, respiratory tract diseases, Respiratory Function Tests, Bronchoalveolar lavage, medicine.anatomical_structure, Dyspnea, 030228 respiratory system, Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Female, business, Tomography, X-Ray Computed, Bronchoalveolar Lavage Fluid, Hypersensitivity pneumonitis, Alveolitis, Extrinsic Allergic
Abstract: Background Hypersensitivity pneumonitis (HP) is a rare interstitial lung disease in children, and very little data are available on the frequency, diagnosis, and outcomes of HP. In a pediatric cohort with HP, the characteristics of the CD4/CD8 lymphocyte ratio are often described as nonspecific. Methods We used the National French Database (RespiRare) to collect data from the last decade on HP. The diagnosis of HP was defined by the presence of a relevant exposure, clinical symptoms, and compatible lung imaging radiology and was usually defined by positive precipitins antibodies. Results A total of 16 children with a mean age of 10 years (4-13) presented with HP. All children presented with dyspnea on exertion. Diffuse ground-glass opacity was present in all computed tomography (CT) scans. Research guided by a questionnaire and precipitins antibodies against the corresponding antigens showed that patients were positive for contact with birds with or without fungi. Bronchoalveolar lavage (BAL) was performed in 12 children. The total cell counts were elevated in BAL fluid, with a mean value of 36% lymphocytes. The CD4/CD8 lymphocyte ratio was below one for all children. Conclusion BAL in our pediatric cohort with HP had the same characteristics as that of adults with HP. An HP diagnosis must be considered when dyspnea on exertion and diffuse ground-glass opacity are observed. Carrying out BAL and serological tests can help diagnose and avoid lung biopsy.
Published: 2019

20. Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis

Author: Diana Bilton, Tacjana Pressler, Isabelle Fajac, John Paul Clancy, Dorota Sands, Predrag Minic, Marco Cipolli, Ivanka Galeva, Amparo Solé, Alexandra L. Quittner, Keith Liu, John P. McGinnis, Gina Eagle, Renu Gupta, Michael W. Konstan, Sabine Renner, Christiane Knoop, Anne Malfroot, Lieven Dupont, Kristine Desager, Frans De Baets, Miroslava Bosheva, Vania Nedkova, Ivan Galabov, Andreas Freitag, Nancy Morrison, Pearce Wilcox, Tanja Pressler, Yves Martinet, Raphael Chiron, Stephan Dominique, Philippe Reix, Anne Prevotat, Isabelle Sermet, Isabelle Durieu, Rainald Fischer, Rudolf Huber, Doris Staab, Uwe Mellies, Wolfgang Sextro, Tobias Welte, Heinrike Wilkens, Urte Sommerwerk, Burkhard Bewig, Ilias Inglezos, Stavros-Eleftherios Doudounakis, Olga Bede, Ferenc Gönczi, Rita Újhelyi, Edward McKone, Paul McNally, Vincenzina Lucidi, Mario La Rosa, Laura Minicucci, Rita Padoan, Giovanna Pisi, Rolando Gagliardini, Carla Colombo, Inez Bronsveld, Ewa Sapiejka, Henryk Mazurek, Grażyna Górnicka, Iwona Stelmach, Halina Batura-Gabryel, Marta Rachel, Jaroslava Orosova, Branko Takac, Anna Feketova, Carmen Martinez, Gloria Garcia Hernandez, Jose Ramon Villa-Asensi, Silvia Gartner, Amparo Sole, Anders Lindblad, Martin Ledson, Joanna Whitehouse, Alan Smyth, Ian Ketchell, Timothy Lee, and Gordon MacGregor
Subjects: 0301 basic medicine, Male, Cystic Fibrosis, Gastroenterology, Cystic fibrosis, 0302 clinical medicine, Surveys and Questionnaires, Tobramycin, education.field_of_study, Inhalation, Symptom Flare Up, 3. Good health, Anti-Bacterial Agents, Respiratory Function Tests, Hospitalization, medicine.anatomical_structure, Treatment Outcome, Amikacin, Pseudomonas aeruginosa, Female, medicine.symptom, Symptom Assessment, medicine.drug, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Population, Article, 03 medical and health sciences, Internal medicine, Administration, Inhalation, medicine, Humans, Pseudomonas Infections, education, Adverse effect, Lung, Dose-Response Relationship, Drug, business.industry, Sputum, medicine.disease, respiratory tract diseases, 030104 developmental biology, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Liposomes, business
Abstract: Background Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung. Methods Eligible patients with forced expiratory volume in 1 s (FEV1) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV1 (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results The study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, −4.95 to 2.34) for relative change in FEV1 (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF. Conclusions Cyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function. ClinicalTrials.gov Identifier: NCT01315678
Published: 2019

21. 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

22. Do patients with cystic fibrosis participating in clinical trials demonstrate placebo response? A meta-analysis

Author: Perrine Janiaud, Philippe Reix, Julie Coton, Michel Cucherat, Ha-Hai Le, Behrouz Kassai-Koupai, Victor Veuillet, François Gueyffier, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie Pédiatrique [Hôpital Femme Mère Enfant - CHU de Lyon], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), and Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-lyon
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Vital capacity, Cystic Fibrosis, Cystic fibrosis, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Internal medicine, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, Clinical Trials as Topic, Placebo response, business.industry, Placebo Effect, medicine.disease, Confidence interval, 3. Good health, Clinical trial, Treatment Outcome, 030104 developmental biology, 030228 respiratory system, Meta-analysis, Pediatrics, Perinatology and Child Health, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, Body mass index
Abstract: Background Patients' and families' expectation that a cure for cystic fibrosis (CF) will be found is high. In other debilitating conditions, high expectation has been shown to drive a strong placebo response (PR). Therefore, our goal was to evaluate PR on objective continuous outcomes (FEV1, BMI) and the CF Questionnaire Revised-Respiratory Domain (CFQR-RD) monitored during randomised clinical trials (RCTs) for CF. Methods We conducted a meta-analysis after a systematic review of the literature carried out to identify RCTs with FEV1, CFQR-RD and BMI as outcome measures. The standardised mean difference (SMD) was calculated to estimate the PR. A meta-regression analysis was conducted to assess other contributing factors on PR such as study design, trial duration, patient age and disease severity. Results Out of 289 RCTs found in the search, we identified 61 articles (published from 1987 to 2017) with respectively 59, 17 and 9 reporting FEV1, CFQR-RD and BMI at the start and at the end of the RCTs. No significant PR was found on FEV1 or CFQR-RD. However, a small but significant PR was found on BMI SMD, 0.09 (95% CI (0.01; 0.17); p = 0.03). Conclusion The PR seems higher when measuring BMI. However, it is not clear whether this improvement can be explained by a PR alone.
Published: 2019

23. Case series of omalizumab for allergic bronchopulmonary aspergillosis in cystic fibrosis patients

Author: Isabelle Durieu, Soazic Grard, Benyebka Mammar, Dominique Hubert, Raphaele Nove-Josserand, Philippe Reix, Lila Auzou, Laurent Mely, Marlène Murris-Espin, Pierre-Régis Burgel, and François Bremont
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, biology, business.industry, Context (language use), Omalizumab, Immunoglobulin E, medicine.disease, Cystic fibrosis, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, Concomitant, Pediatrics, Perinatology and Child Health, medicine, biology.protein, 030212 general & internal medicine, Allergic bronchopulmonary aspergillosis, Adverse effect, business, Body mass index, medicine.drug
Abstract: Allergic bronchopulmonary aspergillosis (ABPA) affects up to 15% of patients with cystic fibrosis (CF). Corticosteroids are used as first-line therapy, but relapse and adverse effects commonly occur. Case reports have suggested the efficacy of the anti-IgE recombinant humanized monoclonal antibody omalizumab. A retrospective multicenter observational French study retrieved 32 CF patients (11 children and 21 adults) who have received omalizumab for more than 3 months in the context of ABPA. Clinical characteristics, concomitant medications (inhaled and oral corticosteroids, antifungal drugs), lung function, body mass index (BMI), and serum IgE were compared at the start and during the first year of omalizumab therapy. Omalizumab-related adverse effects and costs were also evaluated. No significant difference with omalizumab could be demonstrated with regard to lung function, BMI, or the number of patients receiving oral corticosteroids. At the time of initiation of omalizumab, 56% of patients were receiving oral corticosteroids. Five patients were able to discontinue corticosteroids during follow-up and nine patients were able to reduce their daily dose. A total of 78% of the patients had received antifungal therapy at the time of the initiation of omalizumab. Treatment tolerance was good (12.5% of patients experienced side effects). The median cost of omalizumab treatment was €3,620 per patient per month. Omalizumab may represent a steroid-sparing therapy in CF patients with ABPA. A randomized-controlled trial is urgently required to provide higher level of evidence regarding the efficacy and cost-effectiveness of omalizumab in CF patients with ABPA. Pediatr Pulmonol. 2017;52:190-197. © 2016 Wiley Periodicals, Inc.
Published: 2016

24. Maladie osseuse liée à la mucoviscidose : mise au point

Author: Philippe Reix, Justine Bacchetta, and C. Braun
Subjects: medicine.medical_specialty, Bone disease, Bone density, medicine.diagnostic_test, business.industry, Bone fracture, medicine.disease, Gastroenterology, Asymptomatic, Cystic fibrosis, Bone remodeling, 03 medical and health sciences, Bone Density Conservation Agents, 0302 clinical medicine, 030228 respiratory system, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, 030212 general & internal medicine, medicine.symptom, Quantitative computed tomography, business
Abstract: With the increasing life expectancy of patients with cystic fibrosis (CF), prevalence of late complications such as CF-related bone disease (CFBD) has increased. It was initially described in 24% of the adult population with CF and has also been reported in the pediatric population. CFBD is multifactorial and progresses in different steps. Both decreased bone formation and increased bone resorption (in different amounts) are observed. CFBD is likely primitive (directly related to the CFTR defect itself), but is also worsened by acquired secondary factors such as lung infections, chronic inflammation, denutrition, vitamin deficiency, and decreased physical activity. CFBD may be clinically apparent (i.e., mainly vertebral and costal fractures), or clinically asymptomatic (therefore corresponding to abnormalities in bone density and architecture). CFBD management mainly aims to prevent the occurrence of fractures. Prevention and regular monitoring of bone disease as early as 8 years of age is of the utmost importance, as is the control of possible secondary deleterious CFBD factors. New radiological tools, such as high-resolution peripheral quantitative computed tomography, allow an accurate evaluation of cortical and trabecular bone micro-architecture in addition to compartmental density; as such, they will likely improve the assessment of the bone fracture threat in CF patients in the near future.
Published: 2016

25. Effectiveness of palivizumab in children with childhood interstitial lung disease: The French experience

Author: Christophe Delacourt, Philippe Reix, M. Fayon, Delphine Habouria, Caroline Thumerelle, David Drummond, Annick Clement, Alice Hadchouel, Malika Mahloul, and Ralph Epaud
Subjects: Pulmonary and Respiratory Medicine, Palivizumab, education.field_of_study, Pediatrics, medicine.medical_specialty, business.industry, Population, Corticosteroid treatment, Interstitial lung disease, Retrospective cohort study, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Bronchiolitis, 030225 pediatrics, Pediatrics, Perinatology and Child Health, National study, medicine, Etiology, education, business, medicine.drug
Abstract: Summary Introduction There is a lack of evidence concerning the effectiveness of immunoprophylaxis with palivizumab in children with childhood interstitial lung disease (chILD). In this retrospective study, we evaluated the effectiveness of palivizumab for decreasing the rate of RSV-related hospitalizations in children under the age of 24 months with chILD treated with corticosteroids. Methods A retrospective national study was conducted in France. Patients born between 2007 and 2013, diagnosed with chILD and on corticosteroid treatment were identified through the French online database for pediatric interstitial lung disease (Respirare®). Data were collected for the etiology and severity of chILD, risk factors and preventive measures for bronchiolitis, palivizumab immunoprophylaxis, and hospitalizations for bronchiolitis and RSV-bronchiolitis. Results We included and evaluated 24 children during their first two RSV seasons, corresponding to 36 patient-seasons. The observed rate of RSV-related hospitalization (305/1000 patient-seasons), and the median length of stay (7 days), were higher than those for the general population. RSV-related hospitalization rates did not differ significantly between children with and without palivizumab prophylaxis (5/16 vs. 4/18, respectively, P = 0.70). Conclusion Children with chILD on corticosteroid treatment are at high risk of hospitalization for RSV-bronchiolitis, which tends to be more severe in these children than in the general population. The effectiveness of palivizumab prophylaxis in this population remains to be demonstrated. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.
Published: 2015

26. P153 Population PK analysis and dosing simulation of tobramycin in paediatric patients with cystic fibrosis

Author: S. Goutelle, Philippe Reix, A. Praet, Anne Doléans-Jordheim, L. Bourguignon, V. Bréant, Oana Dumitrescu, and F. Vételé
Subjects: Pulmonary and Respiratory Medicine, education.field_of_study, medicine.medical_specialty, business.industry, Population, medicine.disease, Cystic fibrosis, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, Tobramycin, Dosing, education, business, Paediatric patients, medicine.drug
Published: 2020

27. WS01.1 Low frequency of confirmed hypersensitivity to antibiotics in cystic fibrosis patients

Author: V. Jubin, Isabelle Durieu, C. Braun, Camille Ohlmann, A. Nosbaum, Catherine Mainguy, Philippe Reix, Raphaele Nove-Josserand, Stéphane Durupt, and J.-F. Nicolas
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, medicine.drug_class, Internal medicine, Pediatrics, Perinatology and Child Health, Antibiotics, Medicine, business, medicine.disease, Gastroenterology, Cystic fibrosis
Published: 2020

28. P131 Most of Staphylococcus aureus and Pseudomonas aeruginosa coinfecting isolates coexist, a condition that may impact clinical outcomes in cystic fibrosis patients

Author: Philippe Reix, Anne Doléans-Jordheim, Karen Moreau, Paul Briaud, Laura Camus, S. Bastien, François Vandenesch, M. Boyadjian, and Catherine Mainguy
Subjects: Pulmonary and Respiratory Medicine, business.industry, Staphylococcus aureus, Pseudomonas aeruginosa, Pediatrics, Perinatology and Child Health, Medicine, business, medicine.disease_cause, medicine.disease, Cystic fibrosis, Microbiology
Published: 2020

29. Down syndrome and pulmonary hemosiderosis: an under-recognized association

Author: Sophie Leyronnas, Pierrick Cros, Philippe Reix, Antoine Deschildre, Caroline Thumerelle, Harriet Corvol, Françoise Troussier, Annick Clement, Sylvie Roullaud, Jessica Taytard, Michael Fayon, Marie-Catherine Renoux, Jacques de Blic, Guillaume Thouvenin, Caroline Perisson, Isabelle Gibertini, Rola Abou Taam, Aude Forgeron, Marc Lubrano Lavadera, Ralph Epaud, Véronique Houdouin, Aurelia Alimi, Jocelyne Derelle, Nadia Nathan, and Aimé Ravel
Subjects: Autoimmune disease, medicine.medical_specialty, Down syndrome, Lung, business.industry, Interstitial lung disease, Pulmonary hemosiderosis, Hemosiderosis, Disease, medicine.disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030228 respiratory system, Internal medicine, medicine, 030212 general & internal medicine, Risk factor, business
Abstract: Introduction: Pulmonary hemosiderosis is a rare cause of interstitial lung disease in children. The French experience had previously highlighted that 20% of the 25 included children also had Down syndrome (DS). In this study populations, the main features of the patients with hemosiderosis were unspecific stigmata of autoimmune disease. This study aims to investigate the relationships between pulmonary hemosiderosis and DS. Material and methods: Patients with pulmonary hemosiderosis followed is one of RespiRare network and younger than 20 years old at diagnosis were selected. The following data were collected : DS status, clinical, biological, functional, and radiological findings. Results: Nine of the 34 included patients (26%) had DS. They were a girl predominance (72%) in the non-DS group, and a male predominance in the DS group (56%). The mean age at the diagnosis was 3.80±3.30 with no significant difference between DS and non-DS patients. DS patients tended to present a more severe form of the disease with more dyspnoea (p=0.03) and more pulmonary arterial hypertension (PAH) (p=0.0003). The 3 (9%) patients who died were DS patients (p=0.0003). Discussion and conclusions: DS seem to be a risk factor for hemosiderosis. Hemosiderosis in DS patients is more severe at presentation, and at follow-up. Several hypotheses can be proposed for such association: an increased fragility of the lung capillary, a higher susceptibility to autoimmune lesions, and a higher risk of chronic hypoxia, leading to PAH. In DS, hemosiderosis should be considered in patients with anaemia of unknown origin.
Published: 2018

30. Functional assessment of newly identified SFTPA1 and SFTPA2 mutations in patients with idiopathic interstitial pneumonia (IIP) and lung cancer

Author: Valérie Nau, Emilie Filhol-Blin, Violaine Giraud, Laurent Gouya, Philippe Duquesnoy, Christophe Delacourt, Afifaa Butt, Jean-Charles Dalphin, Julie Traclet, Philippe Reix, Hilario Nunes, Bruno Crestani, Juliette Albuisson, Serge Amselem, Paul De Vuyst, Bruno Copin, Marie Legendre, Carine Gomez, Grégoire Prévot, Diane Bouvry, Raphael Borie, Clément Picard, Florence Dastot-Le Moal, Vincent Cottin, Caroline Kannengiesser, Nadia Nathan, Keren Borensztajn, Aurore Coulomb L'Hermine, Annick Clement, Kais Ahmad, Nathalie Allou, and Martine-Louise Reynaud-Gaubert
Subjects: Pathology, medicine.medical_specialty, Lung, business.industry, medicine.disease, Penetrance, 3. Good health, Alveolar cells, medicine.anatomical_structure, SFTPA2, medicine, Adenocarcinoma, Secretion, Lung cancer, business, Idiopathic interstitial pneumonia
Abstract: Background: Heterozygous mutations in the SFTPA1 and SFTPA2 genes, encoding the surfactant protein SP-A1 and SP-A2 have been associated with rare forms of familial IIP and lung adenocarcinoma. We previously described 11 new heterozygous SFTPA1 and SFTPA2 variations in 13 unrelated patients including one newborn. The study aims to analyze the pathogenicity of those variations. Methods: We first analyzed the intrafamilial segregation of the identified variations with IIP and lung cancer. The production and the secretion of the mutant proteins were subsequently studied in HEK293T cells transiently expressing the SP-A proteins carrying the variations. Finally, SP-A expression was assessed on lung tissues of the patients. Results: In the studied families (38 adults, 3 children), the variations segregated with either IIP and/or lung cancer (37%) with an incomplete penetrance of the disease phenotype. The mean age at onset of the IIP was 45 years (0-68). Nine of the variations were located in the highly conserved carbohydrate recognition domain of the protein. In vitro, the mutant proteins were produced but their secretion was absent (n=9) or altered (n=2). The lung expression of SP-A studied in 3 unrelated patients showed an increased expression of SP-A in the cytoplasm of hypertrophic type 2 alveolar cells. Discussion and conclusion: The 11 identified SFTPA1 and SFTPA2 variations are pathogenic. They are associated with IIP and with an increased risk of lung cancer. They were identified mainly in adults but also in children. The pathophysiological consequences of their abnormal secretion/expression remain to be elucidated.
Published: 2018

31. Glucose trajectories in cystic fibrosis and their association with pulmonary function

Author: Sylvain Roche, Muriel Rabilloud, C. Llerena, Jean Iwaz, Philippe Reix, Raphaele Nove-Josserand, Isabelle Durieu, Emilie Blond, S. Poupon-Bourdy, Martine Laville, Quitterie Reynaud, Sébastien Quétant, Sandrine Touzet, Hospices Civils de Lyon (HCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de Biostatistiques [Lyon], Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Pôle Information Médicale Evaluation Recherche (IMER), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Blood Glucose, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pediatrics, Cystic Fibrosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Cystic fibrosis-related diabetes, 030209 endocrinology & metabolism, Cystic fibrosis, Body Mass Index, Pulmonary function testing, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Glucose Intolerance, Diabetes Mellitus, medicine, Humans, Respiratory system, Child, Correlation of Data, ComputingMilieux_MISCELLANEOUS, business.industry, Insulin, Glucose Tolerance Test, medicine.disease, Respiratory Function Tests, 3. Good health, Endocrinology, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Disease Progression, Female, France, Abnormality, business, Body mass index
Abstract: Background The prevalence of cystic fibrosis-related diabetes is increasing. This condition is potentially responsible for respiratory decline. Methods At inclusion, then yearly (over three years), 111 children and 117 adults with cystic fibrosis had oral glucose tolerance and insulin tests at one (G1) and 2h (G2). KmL analysis identified homogeneous G1 and G2 glucose trajectories. A linear mixed model quantified the relationships between trajectories and FEV1 changes. Results In children, there were three G1 and four G2 trajectories and FEV1 decrease was not significantly different between G1 or G2 trajectories. In adults, two G1 and four G2 trajectories were identified and FEV1 change was estimated at −0.85/year (95% CI: [−1.54; −0.17], p=0.01) whatever the G1 trajectory and found significantly faster in the high and increasing G2 trajectory (−2.1/year, [−3.9; −0.2], p=0.03). Conclusions In case of persistent G2 abnormality, physicians should be alert for clinical deterioration and intensify patient surveillance.
Published: 2018

32. Nutritional Status in the First 2 Years of Life in Cystic Fibrosis Diagnosed by Newborn Screening

Author: Anne, Munck, Rym, Boulkedid, Laurence, Weiss, Pierre, Foucaud, Nathalie, Wizla-Derambure, Philippe, Reix, François, Bremont, Jocelyne, Derelle, Julien, Schroedt, Corinne, Alberti, and Laure, Couderc
Subjects: Male, Pediatrics, medicine.medical_specialty, Staphylococcus aureus, Cystic Fibrosis, Body height, Enzyme Therapy, Nutritional Status, Cystic fibrosis, 03 medical and health sciences, 0302 clinical medicine, Neonatal Screening, 030225 pediatrics, Medicine, Humans, 030212 general & internal medicine, Longitudinal Studies, Prospective Studies, Prospective cohort study, Respiratory Tract Infections, Growth Disorders, Newborn screening, business.industry, Nutritional Support, Body Weight, Malnutrition, Gastroenterology, Infant, Newborn, Infant, Nutritional status, Avitaminosis, Proton Pump Inhibitors, Vitamins, medicine.disease, Body Height, Breast Feeding, Multicenter study, Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Carrier State, Pseudomonas aeruginosa, Exocrine Pancreatic Insufficiency, Female, business, Breast feeding
Abstract: To evaluate nutritional status and associated factors in a cystic fibrosis (CF) cohort diagnosed by newborn screening and followed up to month 24.A prospective longitudinal multicenter study assessing nutritional status according to pancreatic status, feeding modalities, prescriptions, pulmonary outcome, and biological nutritional parameters.One hundred and five infants were recruited and 99 completed the study. Nutritional care management prevented undernutrition and stunting in those with exocrine pancreatic sufficiency (EPS), but affected (13/87) 15% and (21/86) 24%, respectively, of infants with exocrine pancreatic insufficiency (EPI). The logistic regression model found a positive association between both weight and length z scores "at risk" at month 24, and initial pulmonary symptoms (odds ratio [OR] 0.06, P 0.01 and OR 0.08, P 0.01, respectively); these symptoms were less frequent when age at first visit was earlier than 1.2 months (33% vs 67%, P = 0.02); stunting was also associated with high-calorie density intake and Staphylococcus aureus (OR 0.05, P = 0.01 and OR 0.17, P 0.01). Pulmonary outcome did not differ according to pancreatic status; breast-feeding for at least 3 months delayed first acquisition of Pseudomonas aeruginosa. Despite sodium and fat-soluble vitamin supplementation, half of both cohorts had low urinary sodium output and half of the EPI cohort had low vitamin D levels.Our data shed light on the fact that stunting was more frequent than undernutrition, while both parameters involved only patients with pancreatic insufficiency. Modalities of feeding were not associated with nutritional status; breast-feeding may provide some protection against acquisition of P aeruginosa.
Published: 2018

33. Eosinophilic granulomatosis with polyangiitis in children: Data from the French RespiRare (R) cohort

Author: Antoine Tran, Laure Couderc, Nathalie Faure, Marie-Dominique Donnou, Anne Pagnier, Jean-Christophe Dubus, Sylvain Blanchon, Jocelyne Derelle, Laurent Mely, Philippe Reix, Lisa Giovannini-Chami, Michael Fayon, Agnès Fina, M. Albertini, Jacques de Blic, Microbes évolution phylogénie et infections (MEPHI), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, Adrenal Cortex Hormones, Recurrence, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intensive care, Internal medicine, Eosinophilic, Necrotizing Vasculitis, Eosinophilia, medicine, Humans, 030212 general & internal medicine, Age of Onset, Child, Anti-neutrophil cytoplasmic antibody, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, Granulomatosis with Polyangiitis, medicine.disease, Rheumatology, Asthma, 3. Good health, Treatment Outcome, Pediatrics, Perinatology and Child Health, Cohort, Female, Granulomatosis with polyangiitis, business, Vasculitis
Abstract: International audience; Objectives To describe the characteristics of pediatric cases of eosinophilic granulomatosis with polyangiitis (EGPA), a systemic necrotizing vasculitis rarely diagnosed in children, retrieved from the French Reference Center for rare pediatric lung diseases and compared with adult cases included in the French Vasculitis Study Group cohort. Methods Results We collected information on pediatric EGPA disease presentation, management, and outcome. Cases met the Lanham criteria and/or American College of Rheumatology classification criteria. Fourteen cases of pediatric EGPA were included, from 1980 to 2012, with a median follow-up of 58.5 months. Median age at diagnosis was 12.3 years. All cases had respiratory involvement. The organ systems most frequently involved were the upper airway (85%), skin (71%), digestive tract (64%), and heart (57%). Neurological and renal involvement were rare. Four of the fourteen children were positive for ANCA (30.7%). During follow-up, three children required intensive care and one child died. The relapse rate was 64%. In comparison with an adult cohort, we found more ENT, heart, and digestive-tract involvement, and fewer neurological manifestations. In children, the delay between asthma onset and diagnosis was shorter, and biopsies showed fewer features of vasculitis. Conclusion This French cohort is the biggest pediatric EGPA series described to date, with a long follow-up period. The findings confirm that pediatric EGPA has specific clinical, radiological, and histological characteristics that differ from adult EGPA. Development of systemic symptoms, and consequently diagnosis, occur with a shorter delay in children, mainly during the eosinophilic phase and leading to a specific presentation.
Published: 2018

34. Pulmonary hemosiderosis in children with Down syndrome: a national experience

Author: Aurelia Alimi, Jessica Taytard, Rola Abou Taam, Véronique Houdouin, Aude Forgeron, Marc Lubrano Lavadera, Pierrick Cros, Isabelle Gibertini, Jocelyne Derelle, Antoine Deschildre, Caroline Thumerelle, Ralph Epaud, Philippe Reix, Michael Fayon, Sylvie Roullaud, Françoise Troussier, Marie-Catherine Renoux, Jacques de Blic, Sophie Leyronnas, Guillaume Thouvenin, Caroline Perisson, Aimé Ravel, Annick Clement, Harriet Corvol, Nadia Nathan, for the French RespiRare® group, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte [CHU Necker] (MaMEA Necker), 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 sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), RespiRare - Centre pédiatrique de pneumologie et de référence pour les maladies pulmonaires rares [AP-HP Hôpital Robert Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Ingénierie de la vectorisation particulaire, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pédiatrie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Département de pneumologie pédiatrique [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Département de pneumologie pédiatrique [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pédiatrie [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département de pédiatrie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de pneumologie pédiatrique [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Département de pneumologie pédiatrique [CHU Créteil] (RespiRare), Centre Hospitalier Universitaire de Lille (CHU de Lille), 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), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Département de pneumologie pédiatrique [CHU Lyon], Centre Hospitalier Universitaire de Lyon (CHU Lyon), Département de pneumologie pédiatrique [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pneumologie pédiatrique [CH Angoulême], Centre Hospitalier d'Angoulême (CH Angoulême), Département de pneumologie pédiatrique [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Sorbonne Université (SU), Institut Jérôme Lejeune, Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), French RespiRare® group, ANR-10-COHO-0003,RADICO,Cohorte nationale maladies rares(2010), European Project: 305653,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,CHILD-EU(2012), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), 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), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Bernardo, Elizabeth, Cohortes - Cohorte nationale maladies rares - - RADICO2010 - ANR-10-COHO-0003 - COHO - VALID, Orphans Unite: chILD better together –European Management Platform for Childhood Interstitial Lung Diseases - CHILD-EU - - EC:FP7:HEALTH2012-12-01 - 2016-11-30 - 305653 - VALID, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Maladies génétiques d'expression pédiatrique (U933), RespiRare - Centre pédiatrique de pneumologie et de référence pour les maladies pulmonaires rares [AP-HP Hôpital Armand-Trousseau], AP-HP Hôpital Armand-Trousseau [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Département de Pédiatrie [CH Le Mans], Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier d'Angoulême, Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Sorbonne Universités, Physiopathologie des maladies génétiques d'expression pédiatrique, and ANR-10-COHO-03/10-COHO-0003,RADICO,Cohorte nationale maladies rares(2010)
Subjects: Lung Diseases, Male, Pediatrics, Down syndrome, lcsh:Medicine, Autoimmunity, 0302 clinical medicine, Medicine, Celiac disease, Pharmacology (medical), Young adult, Child, Children, Genetics (clinical), education.field_of_study, Interstitial lung disease, General Medicine, 3. Good health, medicine.anatomical_structure, Child, Preschool, Female, medicine.symptom, Vasculitis, Adult, medicine.medical_specialty, Hemosiderosis, Adolescent, Hypertension, Pulmonary, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pulmonary hypertension, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, 030225 pediatrics, Humans, education, Lung, business.industry, Research, lcsh:R, Infant, Newborn, Infant, Hypoxia (medical), medicine.disease, Pulmonary hemosiderosis, 030228 respiratory system, business, Lung Diseases, Interstitial
Abstract: Background Pulmonary hemosiderosis is a rare and complex disease in children. A previous study from the French RespiRare® network led to two important findings: 20% of the children presented with both pulmonary hemosiderosis and Down syndrome (DS), and at least one tested autoantibody was found positive in 50%. This study investigates the relationships between pulmonary hemosiderosis and DS. Methods Patients younger than 20 years old and followed for pulmonary hemosiderosis were retrieved from the RespiRare® database. Clinical, biological, functional, and radiological findings were collected, and DS and non-DS patients’ data were compared. Results A total of 34 patients (22 girls and 12 boys) were included, among whom nine (26%) presented with DS. The mean age at diagnosis was 4.1 ± 3.27 years old for non-DS and 2.9 ± 3.45 years old for DS patients. DS patients tended to present a more severe form of the disease with an earlier onset, more dyspnoea at diagnosis, more frequent secondary pulmonary hypertension, and an increased risk of fatal evolution. Conclusions DS patients have a higher risk of developing pulmonary hemosiderosis, and the disease seems to be more severe in this population. This could be due to the combination of an abnormal lung capillary bed with fragile vessels, a higher susceptibility to autoimmune lesions, and a higher risk of evolution toward pulmonary hypertension. A better screening for pulmonary hemosiderosis and a better prevention of hypoxia in DS paediatric patients may prevent a severe evolution of the disease. Electronic supplementary material The online version of this article (10.1186/s13023-018-0806-6) contains supplementary material, which is available to authorized users.
Published: 2018

35. Syndrome d’Allgrove

Author: A. L. Souillet, M. Rossi, Denis Jullien, Philippe Reix, C. Raynaud, and A. Alakeel
Subjects: Gynecology, medicine.medical_specialty, business.industry, medicine, Adrenal insufficiency, Dermatology, medicine.disease, business, Alacrima
Abstract: Resume Introduction Le syndrome d’Allgrove ou « syndrome Triple A » comporte une insuffisance surrenalienne (Adrenal Insufficiency) par resistance a l’hormone adrenocorticotrope (ACTH), une achalasie et une alacrymie, souvent associees a des signes neurologiques. Nous rapportons un nouveau cas de cette maladie genetique rare, interessant par son mode de decouverte dermatologique. Observation Une enfant de 4 ans, nee de parents consanguins au premier degre, presentait une hyperpigmentation buccale et une melanodermie diffuse acquise, ainsi qu’un syndrome sec oculaire ancien. Une insuffisance surrenalienne basse etait confirmee biologiquement. L’association alacrymie-insuffisance surrenalienne faisait rechercher un syndrome d’Allgrove, confirme par l’analyse genetique mettant en evidence une mutation c.1331 + 1G > A a l’etat homozygote dans l’intron 14 du gene de la proteine ALADIN. Les deux parents etaient heterozygotes pour la meme mutation. Deux ans plus tard, l’apparition de vomissements faisait suspecter une achalasie, confirmee par la manometrie œsophagienne. L’enfant etait traitee symptomatiquement par supplementation en hydrocortisone et dilatations œsophagiennes. Discussion Cette observation rappelle que le dermatologue peut etre amene a diagnostiquer un syndrome d’Allgrove. La prise en charge des patients est multidisciplinaire, reposant sur le traitement medical de l’insuffisance surrenalienne et les larmes artificielles en cas d’alacrymie. L’achalasie est traitee par la dilatation œsophagienne ou par chirurgie.
Published: 2015

36. Acute chest pain in an adolescent with cystic fibrosis in September: Would you have thought about this?

Author: Philippe Reix, Florence Morfin-Sherpa, Hiba Dowaikh, 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), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [GH Nord HCL, Lyon] (CNR des virus influenza), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Groupement Hospitalier Nord des HCL [Lyon], Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Groupement Hospitalier Nord des HCL [Lyon]-Institut des Agents Infectieux [Lyon] (IAI), and Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Chest Pain, Adolescent, Cystic Fibrosis, education, Acute abdominal pain, Coxsackievirus Infections, Chest pain, medicine.disease_cause, Cystic fibrosis, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Internal medicine, medicine, Acute chest pain, Humans, In patient, Myositis, Bornholm, business.industry, enterovirus, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bornholm disease, Enterovirus B, Human, 3. Good health, Surgery, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Acute Disease, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Enterovirus, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, Enterovirus B, business, myositis, Human
Abstract: International audience; Acute chest pain is common in patients with cystic fibrosis (CF). Here we report the case of an adolescent who suffered acute chest pain in September after an history of acute abdominal pain and fever. The reason for this clinical sceneriao was found to be Coxsackievirus B3, known to be responsible of Bornholm disease, a frequent but under recognized viral myositis. The diagnosis is mainly clinical, but evocating this diagnosis may avoid unnecessary exam.
Published: 2017

37. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial

Author: Laura A. Sass, Thomas Lahiri, Alicia Casey, Carlos Milla, James F. Chmiel, Fadi Asfour, Seth Walker, Alastair Reid, Jane C. Davies, Michael J. Rock, Xiaohong Huang, Barry Clements, Ronald C. Rubenstein, Tacjana Pressler, Philippe Reix, Anne Munck, Howard Schmidt, Timothy D. Starner, Doris Staab, Stephanie Bui, Christiane De Boeck, Melinda Solomon, Don S. Urquhart, Diana Quintero, Tim Lee, Gautham Marigowda, Fadel Ruiz, Margaret Rosenfeld, Floyd Livingston, Sanja Stanojevic, Matthias Griese, Anne Malfroot, Deborah Froh, Mark A. Chilvers, Isabelle Sermet Gaudelus, John McNamara, Sibylle Junge, Thomas G. Keens, Aaron Chidekel, Ian M. Balfour-Lynn, S. Tian, Claire E. Wainwright, Brian O'Sullivan, Susanna A. McColley, Christopher Hug, Philip Black, Lutz Naehrlich, Silke van Koningsburggen-Rietschel, Philip Robinson, John L. Colombo, Hiranjan Selvadurai, Felix Ratjen, George Z. Retsch-Bogart, Carlos E Milla, David M. Orenstein, David Schaeffer, Lena Hjelte, David Waltz, Alexandra G Cornell, Jodi Hilton, Larry C. Lands, Paul Robinson, Patrick A. Flume, Gary Mueller, Clinical sciences, and Growth and Development
Subjects: Male, Pediatrics, Cystic Fibrosis, Respiratory System, Aminopyridines, Cystic Fibrosis Transmembrane Conductance Regulator, Quinolones, Aminophenols, Cystic fibrosis, DISEASE, law.invention, Ivacaftor, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Forced Expiratory Volume, Surveys and Questionnaires, Clinical endpoint, 030212 general & internal medicine, Child, Chloride Channel Agonists, Sweat, Lung, ABNORMALITIES, Lumacaftor, INERT-GAS WASHOUT, Drug Combinations, Mucociliary Clearance, Female, Life Sciences & Biomedicine, CLINICAL-TRIALS, medicine.drug, Pulmonary and Respiratory Medicine, medicine.medical_specialty, YOUNG-CHILDREN, Placebo, LUNG CLEARANCE INDEX, 1117 Public Health and Health Services, 03 medical and health sciences, Critical Care Medicine, Double-Blind Method, General & Internal Medicine, medicine, Humans, Benzodioxoles, Adverse effect, Science & Technology, business.industry, 1103 Clinical Sciences, IN-VITRO, medicine.disease, PHE508DEL CFTR, CFTR POTENTIATOR, Clinical trial, 030228 respiratory system, chemistry, Mutation, VX14-809-109 investigator group, business, 1199 Other Medical and Health Sciences
Abstract: Background Lumacaftor and ivacaftor combination treatment showed efficacy in patients aged 12 years or older with cystic fibrosis homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR) in placebo-controlled studies and patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR in an open-label study. We report efficacy and safety of lumacaftor and ivacaftor in patients with cystic fibrosis aged 6–11 years homozygous for F508del-CFTR. Methods In this phase 3, randomised, double-blind, placebo-controlled, multicentre study, patients were enrolled at 54 hospitals and medical centres in nine countries (the USA, Australia, Belgium, Canada, Denmark, France, Germany, Sweden, and the UK). Eligible patients weighed at least 15 kg, with a confirmed diagnosis of cystic fibrosis, percent predicted forced expiratory volume in 1 s (FEV 1) of 70 or more, and lung clearance index 2·5 (LCI 2·5) of 7·5 or more at screening (values less than these thresholds were permitted at day 1). All patients were tested for CFTR genotype at screening; eligible patients had to have the F508del-CFTR mutation on both alleles. Exclusion criteria included any comorbidity or laboratory abnormality that might confound the study results or pose additional risk to the patient. Patients were stratified by weight (
Published: 2017

38. 164 Are viral respiratory infections a real issue in infants with cystic fibrosis: preliminary results of a prospective cohort study

Author: Philippe Reix, S. Vrielynck, M. Perceval, F. Morfin, V. Jubin, Anne Doléans-Jordheim, M. Eymery, Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), and Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pulmonary and Respiratory Medicine, 0303 health sciences, Pediatrics, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], medicine.disease, Cystic fibrosis, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Pediatrics, Perinatology and Child Health, medicine, Respiratory system, Prospective cohort study, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2017

39. Sensitivity and specificity of different methods for cystic fibrosis-related diabetes screening: is the oral glucose tolerance test still the standard?

Author: Laurent Remontet, Muriel Rabilloud, Behrouz Kassai-Koupai, Véronique Delaup, Philippe Reix, Stéphane Mazur, Gabriel Bellon, Catherine Mainguy, Tiphanie Ginoux, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and 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)
Subjects: Blood Glucose, Male, medicine.medical_specialty, Adolescent, Cystic Fibrosis, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Cystic fibrosis-related diabetes, 030209 endocrinology & metabolism, Comorbidity, Carbohydrate metabolism, Cystic fibrosis, Gastroenterology, Sensitivity and Specificity, Impaired glucose tolerance, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, Internal medicine, Diabetes mellitus, Glucose Intolerance, medicine, Diabetes Mellitus, Prevalence, Humans, Mass Screening, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Child, ComputingMilieux_MISCELLANEOUS, Glycated Hemoglobin, business.industry, Glucose Tolerance Test, medicine.disease, Prognosis, 3. Good health, Pediatrics, Perinatology and Child Health, Female, France, Insulin Resistance, business, Biomarkers, Follow-Up Studies
Abstract: Background:Cystic fibrosis-related diabetes (CFRD) is a late cystic fibrosis (CF)-associated comorbidity whose prevalence is increasing sharply lifelong. Guidelines for glucose metabolism (GM) monitoring rely on the oral glucose tolerance test (OGTT). However, this test is neither sensitive nor specific. The aim of this study was to compare sensitivity and specificity of different methods for GM monitoring in children and adolescents with CF.Methods:Continuous glucose monitoring system (CGMS), used as the reference method, was compared with the OGTT, intravenous glucose tolerance test (IGTT), homeostasis model assessment index of insulin resistance (HOMA-IR), homeostasis model assessment index of β-cell function (HOMA-%B) and glycated haemoglobin AResults:Twenty-nine patients (median age: 13.1 years) were recruited. According to CGMS, 11 had DM, 12 IGT and six NGT, whereas OGTT identified three patients with DM and five with IGT. While 13 of 27 had insulin deficiency according to IGTT, there was 19 of 28 according to HOMA-%B. According to HOMA-IR, 12 of 28 had insulin resistance. HOMA-%B was the most sensitive method for CFRD screening [sensitivity 91% (95% CI), specificity 47% (95% CI) and negative predictive value 89% (95% CI)].Conclusions:OGTT showed the weak capacity to diagnose DM in CF and should no longer be considered as the reference method for CFRD screening in patients with CF. In our study, HOMA-%B showed promising metrics for CFRD screening. Finally, CGMS revealed that pathological glucose excursions were frequent even early in life.
Published: 2017

40. A simplified, semi-quantitative structural lung disease computed tomography outcome during quiet breathing in infants with cystic fibrosis

Author: Magali Saguintaah, R Gauthier, Philippe Reix, Ikram Taleb Arrada, Nicolas Molinari, Laure Couderc, Cécile Duboibaudry, Stefan Matecki, Muriel Le Bourgeois, Raphaël Chiron, Yann Cabon, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Amiens-Picardie, CHRU de Brest - Département de Pédiatrie (CHU BREST Pédiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 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 d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie générale [CHU 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), Hospices Civils de Lyon (HCL), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rouen] (CIC Rouen), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Charles Nicolle [Rouen], and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen
Subjects: Pulmonary and Respiratory Medicine, Lung Diseases, Male, medicine.medical_specialty, Concordance, Sedation, Chest tomography, Air trapping, Cystic fibrosis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Stage (cooking), Lung, ComputingMilieux_MISCELLANEOUS, Bronchiectasis, business.industry, Respiration, Reproducibility of Results, Infant, medicine.disease, 3. Good health, Surgery, medicine.anatomical_structure, Early Diagnosis, 030228 respiratory system, Lung disease, Research Design, Pediatrics, Perinatology and Child Health, Female, Radiology, medicine.symptom, business, Tomography, X-Ray Computed, Scoring
Abstract: International audience; Chest tomography (CT) using the controlled ventilation technique (CTCV) is a sensitive method to detect features of lung cystic fibrosis (CF) disease in infants with CF. However, this technique needs sedation and is not easily applied for the clinician who may need, in the follow-up, to evaluate more precisely lung disease in infants with CF. Thus, our study aims to evaluate if CT assessment of lung disease, without the need of sedation, during quiet breathing, using a semi-quantitative scoring system, is reproducible and may discriminate infants with CF from control infants at an early stage of the lung disease. 39 infants with CF underwent a first CT at 10.3 [9.4, 11.4] weeks of age. Among them, 33 underwent a second CT at 56.1 [53.1, 59.6] weeks of age. CF scoring images of the different scanner variables, i.e. bronchial wall thickening, bronchiectasis, mucus plugging and air trapping were compared to CT scoring obtained in 2 different groups of control infants of similar age without lung disease. Among all the constituents of the scoring, air trapping is the only parameter discriminating infants with CF from control infants at both ages in our study (p≤0.01). Moreover, air trapping explains 90% of the total score variability with r2=0.89 with a good concordance after re-scoring in blind, 6months apart, by the same operator for both infant populations: ICC=0.98 [0.97, 0.99]. In this study, we propose that CT during quiet breathing could be a useful clinical tool to evaluate the early presence of gas trapping in infants with CF.
Published: 2017

41. Lung clearance index: Evidence for use in clinical trials in cystic fibrosis

Author: Stefan Zielen, Judy Bradley, Cesare Braggion, Katherine O'Neill, H.G.M. Arets, K. De Boeck, Keith G. Brownlee, Diana Bilton, Katie J Bayfield, S. Lever, M. Le Bourgeois, J. A. Innes, Daniela Savi, Isabelle Sermet, Philippe Reix, Jane C. Davies, Lisa Kent, and Anders Lindblad
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Cystic Fibrosis, Lung Clearance Index, Severity of Illness Index, Cystic fibrosis, clinimetric properties, lung clearance index, multiple breath washout, outcome measures, surrogate endpoints, Outcome Assessment, Health Care, Clinical endpoint, Humans, Medicine, In patient, Pediatrics, Perinatology, and Child Health, Intensive care medicine, Randomized Controlled Trials as Topic, business.industry, Surrogate endpoint, Outcome measures, Reproducibility of Results, medicine.disease, Respiratory Function Tests, Clinical trial, Breath Tests, Lung disease, Pediatrics, Perinatology and Child Health, Physical therapy, Feasibility Studies, business, Biomarkers
Abstract: The ECFS-CTN Standardisation Committee has undertaken this review of lung clearance index as part of the group's work on evaluation of clinical endpoints with regard to their use in multicentre clinical trials in CF. The aims were 1) to review the literature on reliability, validity and responsiveness of LCI in patients with CF, 2) to gain consensus of the group on feasibility of LCI and 3) to gain consensus on answers to key questions regarding the promotion of LCI to surrogate endpoint status. It was concluded that LCI has an attractive feasibility and clinimetric properties profile and is particularly indicated for multicentre trials in young children with CF and patients with early or mild CF lung disease. This is the first article to collate the literature in this manner and support the use of LCI in clinical trials in CF. © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V.
Published: 2014

42. P273 Human papilloma virus vaccination among female patients attending the Auvergne-Rhône Alpes paediatric cystic fibrosis centres

Author: Philippe Reix, M. Perceval, C. Rousset-Jablonski, Isabelle Pin, Isabelle Durieu, C. Llerena, Quitterie Reynaud, S. Touzet, and A. Labbé
Subjects: Pulmonary and Respiratory Medicine, Human papilloma virus, Vaccination, Pediatrics, medicine.medical_specialty, business.industry, Pediatrics, Perinatology and Child Health, Female patient, Medicine, business, medicine.disease, Cystic fibrosis
Published: 2018

43. P034 Are patients with cystic fibrosis in clinical trials sensitive to the placebo effect? A metanalysis

Author: V. Veuillet, Behrouz Kassai-Koupai, François Gueyffier, Michel Cucherat, Philippe Reix, Julie Coton, Perrine Janiaud, and Ha-Hai Le
Subjects: Pulmonary and Respiratory Medicine, Clinical trial, medicine.medical_specialty, business.industry, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, business, Placebo, medicine.disease, Gastroenterology, Cystic fibrosis
Published: 2018

44. Infections broncho-pulmonaires à Staphylococcus aureus

Author: Christian Chidiac, Philippe Reix, Tristan Ferry, N. Chebib, Y. Gillet, Florent Valour, and Frédéric Laurent
Subjects: Pulmonary and Respiratory Medicine, Gynecology, 0303 health sciences, medicine.medical_specialty, 030306 microbiology, business.industry, Bronchopneumonia, Hospital-acquired pneumonia, medicine.disease, Staphylococcal infections, medicine.disease_cause, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Staphylococcus aureus, Medicine, 030212 general & internal medicine, business
Abstract: Resume Staphylococcus aureus represente 2 a 5 % des etiologies des pneumopathies communautaires. Ces infections surviennent principalement chez des patients âges avec comorbidite, dans un contexte post-grippal. S. aureus est egalement responsable de pneumonie necrosante, heureusement rare, touchant des adolescents ou adultes jeunes, egalement dans un contexte post-grippal. Les pneumonies necrosantes sont associees a la production d’une toxine particuliere, la leucocidine de Panton-Valentine, impliquee dans la necrose pulmonaire, la survenue d’hemoptysies, d’une leucopenie, et d’une mortalite elevee. En Europe, ces souches restent majoritairement sensibles a la penicilline M, qui doit etre utilisee en intraveineuse a forte dose en association avec un antibiotique « anti-toxinique » tel que la clindamycine, et a des immunoglobulines intraveineuses polyvalentes dans les formes graves. Par ailleurs, S. aureus est l’un des pathogenes implique le plus precocement dans les infections respiratoires des patients porteurs de mucoviscidose, ou la resistance a la meticilline joue un role pronostique important. En revanche, l’implication de S. aureus dans les exacerbations de BPCO semble rare. Enfin, S. aureus represente 20 a 30 % des causes de pneumopathies nosocomiales, notamment acquises sous ventilation mecanique. La resistance a la meticilline est alors frequente, peut jouer un role pronostique, et necessite l’utilisation de glycopeptides ou de linezolide. La place des nouveaux anti-staphylococciques tels que les cephalosporines de nouvelle generation ou encore la tigecycline reste a definir.
Published: 2013

45. Extracoronary echocardiographic findings as predictors of coronary artery lesions in the initial phase of Kawasaki disease

Author: Sylvie Di Filippo, Corinne Ducreux, Daniel Floret, André Bozio, Philippe Reix, Rolando Cimaz, Magali Veyrier, and Jean-Christophe Lega
Subjects: Male, medicine.medical_specialty, Adolescent, Coronary Artery Disease, Disease, Mucocutaneous Lymph Node Syndrome, Pericardial effusion, Predictive Value of Tests, Internal medicine, medicine, Humans, Child, Retrospective Studies, Mitral regurgitation, business.industry, Immunoglobulins, Intravenous, Infant, Retrospective cohort study, medicine.disease, Coronary Vessels, humanities, medicine.anatomical_structure, Echocardiography, Child, Preschool, Predictive value of tests, Multivariate Analysis, Pediatrics, Perinatology and Child Health, Cardiology, Female, Kawasaki disease, Abnormality, business, Artery
Abstract: Objective To describe the significance of pericardial effusion (PE), mitral regurgitation (MR) and impaired systolic function in predicting coronary artery lesions (CAL) at diagnosis and follow-up in Kawasaki disease (KD). Design Echocardiographic records on admission, at 1–3 weeks of illness, and at 6–8 weeks of illness were retrospectively retrieved in children with acute KD treated by intravenous immunoglobulins. Setting, patients The study included 194 consecutive children (113 male; median age 2.1 years) in a paediatric cardiology tertiary care centre, from 1988 to 2007. Results Overall, children with CAL (64/194) were more likely to have PE (OR=3.00, CI 1.34 to 6.72) and MR (OR=2.51, CI 1.22 to 5.16) at diagnosis; PE was the sole echocardiographic abnormality associated with CAL in multivariable analysis. These abnormalities were predictive of the presence of CAL at the first echocardiography in the acute phase of the disease only. MR, systolic dysfunction and PE were not associated with persistence of CAL in the convalescent phase. Male gender, CAL size and resistance to immunoglobulin treatment were independent factors predictive of the persistence of CAL. Conclusions Children with MR or PE should undergo careful assessment of coronary status at diagnosis. However, PE or MR at diagnosis is not predictive of persistent CAL at follow-up.
Published: 2012

46. Severe Pulmonary Fibrosis as the First Manifestation of Interferonopathy (TMEM173 Mutation)

Author: Christelle Ménard, Martine Reynaud-Gaubert, Cécile Picard, Nadia Jeremiah, Bruno Crestani, Philippe Reix, Frédéric Rieux-Laucat, Alexandre Belot, Jean-Christophe Dubus, Françoise Thivolet-Béjui, Véronique Secq, Caroline Kannengiesser, Guillaume Thouvenin, Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Etablissement Français du Sang, Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Service de Pneumologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratory of Excellence GR-Ex ' The red cell : from genesis to death ', PRES Sorbonne Paris Cité, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes ( URMITE ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Service de Pneumologie et Centre de Compétence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Physiopathologie et Epidémiologie des Maladies Respiratoires, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Genetic Medicine, University of Manchester [Manchester]-Faculty of Human and Medical Sciences, Service de néphrologie, rhumatologie et dermatologie pédiatriques, Hospices Civils de Lyon ( HCL ) -Hôpital Mère Enfant, Centre International de Recherche en Infectiologie ( CIRI ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre national référent cancers rares - mésothéliomes malins pleuraux et tumeurs péritonéales rares ( MESOPATH ), CHU Caen-Hôpital côte de nacre, Centre de Recherche en Cancérologie de Marseille ( CRCM ), Aix Marseille Université ( AMU ) -Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), APHP Service de Génétique, Hôpital Bichat, Hôpital Nord [CHU - APHM], Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Bichat, Departement de Genetique, Hôpital de la Timone [CHU - APHM] (TIMONE), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, 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), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), RespiRare - Centre pédiatrique de pneumologie et de référence pour les maladies pulmonaires rares [AP-HP Hôpital Armand-Trousseau], AP-HP Hôpital Armand-Trousseau [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Pathology, medicine.medical_treatment, Pulmonary Fibrosis, Primary Graft Dysfunction, Disease, Critical Care and Intensive Care Medicine, Gastroenterology, Severity of Illness Index, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Fatal Outcome, Fibrosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Pulmonary fibrosis, medicine, Lung transplantation, Humans, Child, 030203 arthritis & rheumatology, Inflammation, business.industry, Interstitial lung disease, Infant, Membrane Proteins, medicine.disease, 3. Good health, Transplantation, Chilblains, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030104 developmental biology, Mutation, Female, Cardiology and Cardiovascular Medicine, business, Vasculitis, Tomography, X-Ray Computed
Abstract: International audience; We report three cases of pulmonary disease suggesting fibrosis in two familial and one sporadic case. Pulmonary symptoms were associated with various clinical features of systemic inflammation and vasculitis involving the skin, and appeared at different ages. A strong interferon signature was found in all three cases. Disease was not responsive to corticosteroids, and lung transplantation was considered for all three subjects at an early age. One of them underwent double-lung transplantation, but she immediately experienced a primary graft dysfunction and died soon after. Recognized causes of familial interstitial lung disease were all excluded. All three subjects had a mutation in the previously described autoinflammatory disease called SAVI (stimulator of interferon genes [STING]-associated vasculopathy with onset in infancy). These cases emphasize the need to consider this possibility in children and young adults with lung fibrosis after common causes have been ruled out.
Published: 2016

47. High incidence of non-tuberculous mycobacteria-positive cultures among adolescent with cystic fibrosis

Author: Raphaele Nove-Josserand, Zoe Cavalli, Philippe Reix, Isabelle Durieu, Quitterie Reynaud, Michèle Pérouse de Montclos, Stéphane Durupt, M. Perceval, Gerard Lina, and Romain Bricca
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Multivariate analysis, Adolescent, Cystic Fibrosis, Itraconazole, Mycobacterium Infections, Nontuberculous, Mycobacterium abscessus, Cystic fibrosis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Longitudinal Studies, Respiratory Tract Infections, Univariate analysis, biology, business.industry, Incidence (epidemiology), Incidence, Case-control study, Nontuberculous Mycobacteria, bacterial infections and mycoses, medicine.disease, biology.organism_classification, Respiratory Function Tests, 030228 respiratory system, Case-Control Studies, Pediatrics, Perinatology and Child Health, Immunology, Female, France, Allergic bronchopulmonary aspergillosis, business, medicine.drug
Abstract: Background We evaluated the prevalence of non-tuberculous mycobacteria (NTM)-positive cultures among our cystic fibrosis (CF) center patients, reviewed risk factors for NTM positivity, and determined its impact on lung function evolution. Methods From 2009 to 2014, CF adults and children attending the CF center of Lyon (France) and having at least one positive NTM isolate were included. Each case was matched by age and gender with two CF patients with no NTM isolate (controls). Results 48 CF patients with NTM-positive isolates were matched to 96 controls. The age group for whom incident NTM was higher was young adolescents aged 13 to 17. A significant association for NTM positivity was found with Staphylococcus aureus in multivariate analysis and with allergic bronchopulmonary aspergillosis, corticosteroid and itraconazole in univariate analysis. Mean annual FEV1 decline was faster for NTM-positive patients compared to controls. Conclusion These data highlight the high incidence of NTM-positive cultures among young adolescents with CF.
Published: 2016

48. Moderate intake of docosahexaenoic acid raises plasma and platelet vitamin E levels in cystic fibrosis patients

Author: Stéphane Mazur, Michel Lagarde, Romain Colas, Véronique Delaup, Philippe Reix, Evelyne Véricel, Isabelle Durieu, Gabriel Bellon, Catherine Calzada, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 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), Université Nice Sophia Antipolis - Faculté de Chirurgie Dentaire (UNS UFR Odontologie), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Service de Pneumologie Pédiatrique, Hospices Civils de Lyon (HCL)-Hôpital Debrousse, Inserm, Association 'Vaincre la mucoviscidose', Vericel, Evelyne, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)
Subjects: Adult, Blood Platelets, Male, 0301 basic medicine, medicine.medical_specialty, Antioxidant, Adolescent, Cystic Fibrosis, Docosahexaenoic Acids, genetic structures, medicine.medical_treatment, Clinical Biochemistry, Placebo, medicine.disease_cause, Cystic fibrosis, antioxidant status, Drug Administration Schedule, platelet lipid, Lipid peroxidation, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Double-Blind Method, Internal medicine, medicine, Humans, Vitamin E, oxidative stress, Child, plasma, Cross-Over Studies, business.industry, food and beverages, Cell Biology, docosahexaenoic acid, medicine.disease, 3. Good health, Thromboxane B2, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, Endocrinology, chemistry, Docosahexaenoic acid, lipids (amino acids, peptides, and proteins), Lipid Peroxidation, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Oxidative stress
Abstract: International audience; Patients with cystic fibrosis have increased oxidative stress and impaired antioxidant systems. Moderate intake of docosahexaenoic acid (DHA) may favor the lowering of oxidative stress. In this randomized, double-blind, cross-over study, DHA or placebo capsules, were given daily to 10 patients, 5 mg/kg for 2 weeks then 10 mg/kg DHA for the next 2 weeks (or placebo). After 9 weeks of wash-out, patients took placebo or DHA capsules. Biomarkers of lipid peroxidation and vitamin E were measured at baseline, and after 2 and 4 weeks of treatment in each phase. The proportions of DHA increased both in plasma and platelet lipids after DHA supplementations. The lipid peroxidation markers did not significantly decrease, in spite of a trend, after the first and/or the second dose of DHA but plasma and platelet vitamin E amounts increased significantly after DHA supplementation. Our findings reinforce the antioxidant potential of moderate DHA intake in subjects displaying increased oxidative stress.
Published: 2016

49. Is the raised volume rapid thoracic compression technique ready for use in clinical trials in infants with cystic fibrosis?

Author: Isabelle Sermet, Judy Bradley, Stefan Matecki, Lisa Kent, Stephanie D. Davis, Stefan Zielen, Kris De Boeck, Hubertus G.M. Arets, Philippe Reix, Cesare Braggion, Muriel Le Bourgeois, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Health and Rehabilitation Sciences Research Institute, University of Ulster, University of Ulster, Newtownabbey, University of Leuven Medical School, University Hospitals KULeuven, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), J.W. Goethe Universität, Institut für Geowissenschaften, Altenhöferallee 1, D-60438 Frankfurt am Main, Germany, Anna Meyer Children's Hospital Florence, University of Florence, University Medical Center [Utrecht], Belfast Health and Social Care Trust, Cystic Fibrosis Pediatric Centre, Indianapolis, Centre de recherche Croissance et signalisation (UMR_S 845), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Firenze = University of Florence (UniFI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and MORNET, Dominique
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Standardization, [SDV]Life Sciences [q-bio], Context (language use), Review, Pediatrics, Cystic fibrosis, Surrogate outcome, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Clinical trials, Outcome Assessment, Health Care, medicine, Journal Article, Humans, 030212 general & internal medicine, Raised volume rapid thoracic compression, Pediatrics, Perinatology, and Child Health, Societies, Medical, Clinical Trials as Topic, Surrogate endpoint, business.industry, Patient Acuity, Infant, medicine.disease, Perinatology, Respiratory Function Tests, 3. Good health, [SDV] Life Sciences [q-bio], Europe, and Child Health, Natural history, Clinical trial, 030228 respiratory system, Reference values, Pediatrics, Perinatology and Child Health, Physical therapy, business, Infant pulmonary function, Clinimetric properties
Abstract: The European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) has established a Standardization Committee to undertake a rigorous evaluation of promising outcome measures with regard to use in multicentre clinical trials in cystic fibrosis (CF). The aim of this article is to present a review of literature on clinimetric properties of the infant raised-volume rapid thoracic compression (RVRTC) technique in the context of CF, to summarise the consensus amongst the group on feasibility and answer key questions regarding the promotion of this technique to surrogate endpoint status. Methods A literature search (from 1985 onwards) identified 20 papers that met inclusion criteria of RVRTC use in infants with CF. Data were extracted and tabulated regarding repeatability, validity, correlation with other outcome measures, responsiveness and reference values. A working group discussed the tables and answered 4 key questions. Results Overall, RVRTC in particular forced expiratory volume in 0.5s, showed good clinimetric properties despite presence of individual variability. Few studies showed a relationship between RVRTC and inflammation and infection, and to date, data remains limited regarding the responsiveness of RVRTC after an intervention. Concerns were raised regarding feasibility in multi-centre studies and availability of reference values. Conclusion The ECFS-CTN Working Group considers that RVRTC cannot be used as a primary outcome in clinical trials in infants with CF before universal standardization of this measurement is achieved and implementation of inter-institutional networking is in place. We advise its use currently in phase I/II trials and as a secondary endpoint in phase III studies. We emphasise the need for (1) more short-term variability and longitudinal ‘natural history' studies, and (2) robust reference values for commercially available devices.
Published: 2016

50. EPS1.4 Real life acute changes in spirometric indices after lumacaftor/ivacaftor first administration in pediatric patients with cystic fibrosis

Author: A. Labaste, M.-C. Werck-Gallois, A. Toutain-Rigolet, Philippe Reix, Laurianne Coutier, S. Vrielynck, M. Perceval, Catherine Mainguy, and V. Jubin
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, business.industry, Lumacaftor, medicine.disease, Cystic fibrosis, Ivacaftor, chemistry.chemical_compound, chemistry, Pediatrics, Perinatology and Child Health, medicine, business, Intensive care medicine, medicine.drug
Published: 2017

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