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1. 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

2. Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway

Author

Martin A. Weber, Louise Devisme, Przemyslaw Szafranski, Fernando Scaglia, Megan K. Dishop, Eric Bieth, Claire Beneteau, Bruce Bennetts, Chantal Missirian, David Mowat, Sébastien Küry, Mark H. Lipson, Jennifer N. Dines, Justyna A. Karolak, James R. Lupski, Iben Bache, Amanda S. Freed, Véronique Secq, Bertrand Isidor, Gwenaelle André, Linda Pons, Anne Chun Hui Tsai, Qian Liu, Maria Orsaria, Claudia Gonzaga-Jauregui, Francesco Vetrini, Wendy K. Chung, Nicolas Joram, Jelena Martinovic, Marie Vincent, Cornelius F. Boerkoel, Arie van Haeringen, Tina M. Bartell, Gail H. Deutsch, Olivier Pichon, John A. Phillips, Marie Denis-Musquer, Zeynep Tümer, Tomasz Gambin, Nicolas Chassaing, Thomas Besnard, Edwina J. Popek, Arnaud Molin, Andrew J. Gifford, Zeynep Coban Akdemir, Benjamin Cogné, Kathleen A. Leppig, Galen M. Schauer, Catherine Mercer, Catherine Ward-Melver, Chester W. Brown, Jean Michel Liet, Dominique Carles, Madeleine Joubert, Lara Chalabreysse, Cédric Le Caignec, Damien Sanlaville, Tiphaine Bihouée, Heather C Mefford, Jean P. Pfotenhauer, Pawel Stankiewicz, Massimiliano Don, Anna F. Lee, Jérémie Mortreux, Katrina M. Dipple, Florence Petit, Katie Golden-Grant, Stéphane Bézieau, Shalini N. Jhangiani, Dorothy K. Grange, Laurent Pasquier, Daryl A. Scott, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biomolécules et biotechnologies végétales (BBV EA 2106), Université de Tours, Division of Genetic Medicine [Seattle], University of Washington [Seattle], Laboratoire de dynamique des systèmes neuroendocriniens, Institut National de la Santé et de la Recherche Médicale (INSERM), Copenhagen University Hospitals, Clinical genetic clinic, Copenhagen University Hospital, Service de Pathologie, Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Femme-Enfant-Adolescent, Service de foetopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Normandie Université (NU)-Normandie Université (NU), Service d'anatomie pathologique, CHU Bordeaux [Bordeaux], Université Bordeaux Segalen - Bordeaux 2, Service de Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle de Pathologie, Centre de Biologie Pathologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique clinique [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM), service hospitalier d'anatomie et cytologie pathologique humaine, APHM, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire de génétique chromosomique [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence des anomalies du développement [Lyon], Hospices Civils de Lyon (HCL), Service de Génétique, Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Groupe Hospitalier Est, University of Missouri [Columbia], University of Missouri System, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Baylor College of Medicine (BCM), Baylor University, Poznan University of Medical Sciences [Poland] (PUMS), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Seattle Children’s Hospital, Institute of Mother and Child, Baylor College of Medecine, Kaiser Permanente, Phoenix Children's Hospital, Sydney Children's hospital, The University of Sydney, Prince of Wales Hospital, University of British Columbia (UBC), Akron Children's Hospital, University of Copenhagen = Københavns Universitet (UCPH), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Lille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Sant’Antonio General Hospital, Università degli Studi di Udine - University of Udine [Italie], Université de Lyon, The University of Tennessee Health Science Center [Memphis] (UTHSC), University of Colorado [Colorado Springs] (UCCS), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Regeneron Pharmaceuticals [Tarrytown], University of Missouri [Columbia] (Mizzou), University Hospital Southampton NHS Foundation Trust, Universiteit Leiden, University of Copenhagen = Københavns Universitet (KU), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Leiden University

Subjects
0301 basic medicine, Lung Diseases, Male, Pathology, Organogenesis, 030105 genetics & heredity, Fibroblast growth factor, T-box transcription factor 4, Infant, Newborn, Diseases, Lung, Genetics (clinical), lacrimoauriculodentodigital (LAAD) syndrome, respiratory system, Hypoplasia, 3. Good health, Pedigree, medicine.anatomical_structure, lung hypoplasia, Paternal Inheritance, Female, Maternal Inheritance, Signal Transduction, medicine.medical_specialty, DNA Copy Number Variations, 17q23.1q23.2 recurrent deletion, neonatal lung disease, Gestational Age, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 5p12 deletion, Genetics, medicine, Humans, Lung hypoplasia, Receptor, Fibroblast Growth Factor, Type 2, Enhancer, [SDV.GEN]Life Sciences [q-bio]/Genetics, FGF10, Infant, Newborn, medicine.disease, 030104 developmental biology, Gene Expression Regulation, Dysplasia, aplasia of lacrimal and salivary glands, T-Box Domain Proteins, Fibroblast Growth Factor 10
Abstract

International audience; Primary defects in lung branching morphogenesis, resulting in neonatal lethal pulmonary hypoplasias, are incompletely understood. To elucidate the pathogenetics of human lung development, we studied a unique collection of samples obtained from deceased individuals with clinically and histopathologically diagnosed interstitial neonatal lung disorders: acinar dysplasia (n = 14), congenital alveolar dysplasia (n = 2), and other lethal lung hypoplasias (n = 10). We identified rare heterozygous copy-number variant deletions or single-nucleotide variants (SNVs) involving TBX4 (n = 8 and n = 2, respectively) or FGF10 (n = 2 and n = 2, respectively) in 16/26 (61%) individuals. In addition to TBX4, the overlapping similar to 2 Mb recurrent and nonrecurrent deletions at 17q23.1q23.2 identified in seven individuals with lung hypoplasia also remove a lung-specific enhancer region. Individuals with coding variants involving either TBX4 or FGF10 also harbored at least one non-coding SNV in the predicted lung-specific enhancer region, which was absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies. The occurrence of rare coding variants involving TBX4 or FGF10 with the putative hypomorphic non-coding SNVs implies a complex compound inheritance of these pulmonary hypoplasias. Moreover, they support the importance of TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in human lung organogenesis and help to explain the histopathological continuum observed in these rare lethal developmental disorders of the lung.

Published
2019

3. Consecutive Food and Respiratory Allergies Amplify Systemic and Gut but Not Lung Outcomes in Mice

Author

Phillippe Aubert, Tiphaine Bihouée, Pascal Gourbeyre, Grégory Bouchaud, Sandra Denery-Papini, David Lair, Marie-Aude Cheminant, Antoine Magnan, Michel Neunlist, Marie Bodinier, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies de l'Appareil Digestif, Hôpital Hôtel-Dieu, Centre de Recherche en Nutrition Humaine, European Project: 267196,EC:FP7:PEOPLE,FP7-PEOPLE-2010-COFUND,AGREENSKILLS(2012), and Unité de recherche de l'institut du thorax (ITX-lab)

Subjects
Allergy, [SDV]Life Sciences [q-bio], Respiratory System, medicine.disease_cause, chemistry.chemical_compound, Mice, 0302 clinical medicine, Allergen, immune system diseases, wheat, house dust mite, Lung, Inbred BALB C, Cell proliferation, Triticum, Mice, Inbred BALB C, 0303 health sciences, biology, Pyroglyphidae, respiratory system, 3. Good health, medicine.anatomical_structure, gut, General Agricultural and Biological Sciences, Histamine, Food Hypersensitivity, Lymphoid Tissue, Immunoglobulins, 03 medical and health sciences, medicine, Respiratory Hypersensitivity, Animals, mouse, 030304 developmental biology, Asthma, House dust mite, Intestinal permeability, T-cells, General Chemistry, Allergens, asthma, medicine.disease, biology.organism_classification, allergy, immunity, cytokines, respiratory tract diseases, 030228 respiratory system, chemistry, Immunology, Cytokine secretion
Abstract

International audience; Epidemiological data suggest a link between food allergies and the subsequent development of asthma. Although this progression may result from the additional effects of exposure to multiple allergens, whether both allergies amplify each other's effects remains unknown. This study investigated whether oral exposure to food allergens influences the outcomes of subsequent respiratory exposure to an asthma-inducing allergen. Mice were sensitized and orally challenged with wheat (FA) and then exposed to house dust mite (HDM) extract (RA). Immunoglobulin (Ig), histamine, and cytokine levels were assayed by ELISA. Intestinal and lung physiology was assessed. Ig levels, histamine release, and cytokine secretion were higher after exposure to both allergens than after separate exposure to each. Intestinal permeability was higher, although airway hyper-responsiveness and lung inflammation remained unchanged. Exposure to food and respiratory allergens amplifies systemic and gut allergy-related immune responses without any additional effect on lung function and inflammation.

Published
2015

4. Food allergy enhances allergic asthma in mice

Author

Sophie Brouard, David Lair, Camille Rolland-Debord, Grégory Bouchaud, Julie Chesné, Antoine Magnan, Faouzi Braza, Guillaume Mahay, Philippe Aubert, Tiphaine Bihouée, Marie Bodinier, Michel Neunlist, Christine Sagan, Marie-Aude Cheminant, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Médecine Personnalisée des Maladies Chroniques [CHU Nantes] (DHU 2020), Direction de la Recherche Département Partenariats et Innovation ( DHU 2020)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Direction de la Recherche/Département Partenariats et Innovation [CHU Nantes] (DRDPI - Nantes), Département de pédiatrie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'anatomie et cytologie pathologiques [CHU Nantes], Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Service de pneumologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), 'Région Pays de la Loire' through the 'REAL2' research grant., Fonds de recherche en santé respiratoire., Fondation Recherche Médicale., Nantes Metropole and the Pays de la Loire Region., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), European Project: 624910, FP7/2007-2013, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Centre hospitalier universitaire de Nantes (CHU Nantes)-Direction de la Recherche Département Partenariats et Innovation ( DHU 2020)-Direction de la Recherche/Département Partenariats et Innovation [CHU Nantes] (DRDPI - Nantes), Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, The People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme - FP7/2007-2013 - 624910 - INCOMING, ANR: ANR-10IBHU-005, and Magnan, Antoine

Subjects
Allergy, Asthma, Th2 cytokines, Gut, House dust mite, Immunity, Mouse, Ovalbumin, Time Factors, allergie, souris, Immunoglobulin E, cytokine, Medicine, Intestinal Mucosa, allergie alimentaire, Chemokine CCL5, Lung, Sensitization, Mice, Inbred BALB C, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, digestive, oral, and skin physiology, respiratory system, 3. Good health, Intestines, medicine.anatomical_structure, Allergology, Female, Bronchial Hyperreactivity, acarien, dermatite atopique, Food Hypersensitivity, Pulmonary and Respiratory Medicine, Bronchoconstriction, Permeability, Allergologie, Arthropod Proteins, Th2 Cells, Food allergy, Animals, Antigens, Dermatophagoides, Pulmonary Eosinophilia, business.industry, Research, Pneumonia, medicine.disease, biology.organism_classification, asthme, respiratory tract diseases, Disease Models, Animal, Immunology, biology.protein, business, immunité, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; BACKGROUND: Atopic march refers to the typical transition from a food allergy in early childhood to allergic asthma in older children and adults. However the precise interplay of events involving gut, skin and pulmonary inflammation in this process is not completely understood.OBJECTIVES: To develop a mouse model of mixed food and respiratory allergy mimicking the atopic march and better understand the impact of food allergies on asthma.METHODS: Food allergy to ovalbumin (OVA) was induced through intra-peritoneal sensitization and intra-gastric challenge, and/or a respiratory allergy to house dust mite (HDM) was obtained through percutaneous sensitization and intra-nasal challenges with dermatophagoides farinae (Der f) extract. Digestive, respiratory and systemic parameters were analyzed.RESULTS: OVA-mediated gut allergy was associated with an increase in jejunum permeability, and a worsening of Der f-induced asthma with stronger airway hyperresponsiveness and pulmonary cell infiltration, notably eosinophils. There was overproduction of the pro-eosinophil chemokine RANTES in broncho-alveolar lavages associated with an enhanced Th2 cytokine secretion and increased total and Der f-specific IgE when the two allergies were present. Both AHR and lung inflammation increased after a second pulmonary challenge.CONCLUSION: Gut sensitization to OVA amplifies Der f-induced asthma in mice.

Published
2014

5. [Untitled]

Author

Maire-Aude Cheminant, Tiphaine Bihouée, Pascal Gourbeyre, Michel Neunlist, Sandra Denery, Marie Bodinier, Grégory Bouchaud, Philippe Aubert, Antoine Magnan, and David Lair

Subjects
Allergy, Immunology, Immunoglobulin E, medicine.disease_cause, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Allergen, Food allergy, Splenocyte, Immunology and Allergy, Medicine, Respiratory system, Molecular Biology, 030304 developmental biology, 0303 health sciences, Lung, biology, business.industry, Hematology, medicine.disease, 3. Good health, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, biology.protein, business, Histamine
Abstract

Aims Increasing clinical data suggest a link between food allergy and the later development of respiratory allergy. This progression may be triggered by exposures to different allergens but the mechanism implicated remains unknown. This study aimed to identify the impact of a first exposure to food allergen on the development of a new form of allergy caused by exposure to a novel allergen using a mouse model. Method In our model, mice were intraperitoneally sensitized to wheat proteins (modified gliadins) to induce a systemic response, then they were exposed orally to the same allergen and finally they were intranasally exposed to HDM (Dermatophagoides farinae extract) a respiratory allergen without adjuvant to assess an impact on lung mucosa. Results After food and respiratory allergen exposures, mice displayed stronger amount of blood markers: IgE specific and histamine. Moreover, splenocyte secretion of IL-4 and IL-17 were increased whereas weaker levels of IFN γ were observed In parallel Peyer patches lymphocytes secreted higher amount of IL-4 with a decreased in IFN γ , IL-10 and TGF- β productions. These mice exhibited intestine damages, higher paracellular flux and modification of transcellular permeability. In contrast, airway hyper-responsiveness, inflammatory cells and cytokines in lung remained unchanged compared to the respiratory allergy model. Conclusion We show that dual exposure induces a raise in specific IgE and local Th2 and Th17 cytokines secretion before triggering phase. During the latter, gut morphology and functions were affected but not lung in dual exposed mice compared to single one underlying the organospecific impact. Altogether, our data make a step further in the elucidation of the mechanisms linking allergy history to immunological and clinical status potentially linked to atopic March development.

Published
2014

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