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1. Improvement in severe asthma patients receiving biologics and factors associated with persistent insufficient control: a real-life national study

Author

Laurent Guilleminault, Claire Camus, Chantal Raherison-Semjen, Audrey Capdepon, Arnaud Bourdin, Philippe Bonniaud, Stéphanie Fry, Gilles Devouassoux, François-Xavier Blanc, Christophe Pison, Clairelyne Dupin, Naji Khayath, Joelle Courdeau, Judith Valcke-Brossollet, Cécilia Nocent-Ejnaini, Fabien Rolland, Carmen Lamandi, Alain Proust, Anaig Ozier, Laurent Portel, Wanda Gaspard, Pauline Roux-Claude, Antoine Beurnier, Stéphanie Martinez, Jean-Marc Dot, Florence Hennegrave, Guillaume Vignal, Etienne Auvray, Nicolas Paleiron, Nicolas Just, Jean Miltgen, Maud Russier, Cécile Olivier, Camille Taillé, and Alain Didier

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Background: Biological therapies have revolutionized the treatment of severe asthma with type 2 inflammation. Although such treatments are very effective in reducing exacerbation and the dose of oral steroids, little is known about the persistence of symptoms in severe asthma patients treated with biologics. Purpose: We aim to describe asthma control and healthcare consumption of severe asthma patients treated with biologics. Design: The Second Souffle study is a real-life prospective observational study endorsed by the Clinical Research Initiative in Severe Asthma: a Lever for Innovation & Science Network. Methods: Adults with a confirmed diagnosis of severe asthma for at least 12 months’ duration were enrolled in the study. A self-administered questionnaire including the Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ) and a compliance evaluation test was given to the patients. Healthcare consumption within 12 months prior to enrolment was documented. In patients receiving biologics, doctors indicated whether the patients were biologic responders or non-responders. Results: The characteristics of 431 patients with severe asthma were analysed. Among them, 409 patients (94.9%) presented asthma with type 2 inflammation (T2 high) profile, and 297 (72.6%) patients with a T2 high phenotype were treated with a biologic. Physicians estimated that 88.2% of patients receiving biologics were responders. However, asthma control was only achieved in 25.3% of those patients (ACQ > 0.75). A high proportion of patients (77.8%) identified as responders to biologics were not controlled according to the ACQ score. About 50% of patients continue to use oral corticosteroids either daily (25.2%) or more than three times a year for at least three consecutive days (25.6%). Gastro-oesophageal Reflux Disease (GERD) and Obstructive Sleep Apnoea syndrome (OSA) were identified as independent factors associated with uncontrolled asthma. Conclusion: Although a high proportion of severe asthma patients respond to biologics, only 25.3% have controlled asthma. GERD and OSA are independent factors of uncontrolled asthma.

Published
2023
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2. IL-22 Defect During Streptococcus pneumoniae Infection Triggers Exacerbation of Chronic Obstructive Pulmonary Disease

Author

Muriel Pichavant, Riti Sharan, Olivier Le Rouzic, Cécile Olivier, Florence Hennegrave, Gaëlle Rémy, Magdiel Pérez-Cruz, Bachirou Koné, Pierre Gosset, Nicolas Just, and Philippe Gosset

Subjects
Chronic obstructive pulmonary disease, Innate immunity, Bacterial infection, IL-22, Medicine, Medicine (General), R5-920
Abstract

Progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae. Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations. S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS) and to stimulate peripheral blood mononuclear cells (PBMC) from non-smokers, smokers and COPD patients. The immune response and the cytokine production were evaluated. Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells. This defect was related to a reduced production of IL-1β and IL-23 by antigen presenting cells. Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration. In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1β and IL-23 secretion. This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation. Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation.

Published
2015
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3. Diagnosis and management of idiopathic pulmonary fibrosis: French practical guidelines

Author

Bruno Crestani, Dominique Valeyre, Benoit Wallaert, Jacques Cadranel, Jean-Charles Dalphin, Philippe Delaval, Dominique Israel-Biet, Romain Kessler, Martine Reynaud-Gaubert, Bernard Aguilaniu, Benoit Bouquillon, Philippe Carré, Claire Danel, Jean-Baptiste Faivre, Gilbert Ferretti, Nicolas Just, Serge Kouzan, François Lebargy, Sylvain Marchand-Adam, Bruno Philippe, Grégoire Prévot, Bruno Stach, Françoise Thivolet-Béjui, and Jean-François Cordier

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic interstitial pneumonia in adults. The management of rare diseases in France has been organised by a national plan for rare diseases, which endorsed a network of expert centres for rare diseases throughout France. This article is an overview of the executive summary of the French guidelines for the management of IPF, an initiative that emanated from the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. This review aims at providing pulmonologists with a document that: 1) combines the current available evidence; 2) reviews practical modalities of diagnosis and management of IPF; and 3) is adapted to everyday medical practice. The French practical guidelines result from the combined efforts of a coordination committee, a writing committee and a multidisciplinary review panel, following recommendations from the Haute Autorité de Santé. All recommendations included in this article received at least 90% agreement by the reviewing panel. Herein, we summarise the main conclusions and practical recommendations of the French guidelines.

Published
2014
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4. French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis – 2021 update. Full-length version

Author

Vincent Cottin, Philippe Bonniaud, Jacques Cadranel, Bruno Crestani, Stéphane Jouneau, Sylvain Marchand-Adam, Hilario Nunes, Lidwine Wémeau-Stervinou, Emmanuel Bergot, Elodie Blanchard, Raphaël Borie, Arnaud Bourdin, Cécile Chenivesse, Annick Clément, Emmanuel Gomez, Anne Gondouin, Sandrine Hirschi, François Lebargy, Charles-Hugo Marquette, David Montani, Grégoire Prévot, Sébastien Quetant, Martine Reynaud-Gaubert, Mathieu Salaun, Olivier Sanchez, Bruno Trumbic, Karim Berkani, Pierre-Yves Brillet, Marion Campana, Lara Chalabreysse, Gérard Chatté, Didier Debieuvre, Gilbert Ferretti, Jean-Michel Fourrier, Nicolas Just, Marianne Kambouchner, Bertrand Legrand, Frédéric Le Guillou, Jean-Pierre Lhuillier, Anas Mehdaoui, Jean-Marc Naccache, Catherine Paganon, Martine Rémy-Jardin, Salim Si-Mohamed, Philippe Terrioux, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre national de référence des maladies pulmonaires rares [Lyon] (CRMPM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Pneumologie Soins Intensifs, Appareillage Respiratoire [CHU de Dijon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Avicenne [AP-HP], Institut Coeur Poumon [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pessac, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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), 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), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Pasteur [Nice] (CHU), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Marseille, Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Centre Hospitalier Régional d'Orléans (CHRO), Hospices Civils de Lyon (HCL), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Eure-Seine - Hôpital d'Evreux - Vernon (Evreux), Groupe Hospitalier Paris Saint-Joseph (hpsj), Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie (Hôpital Louis Pradel), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pulmonary and Respiratory Medicine, Biopsy, Biopsie, [SDV]Life Sciences [q-bio], Fibrose pulmonaire, Pneumopathie interstitielle commune, Interstitial lung disease, Common interstitial lung disease, Pneumopathie interstitielle diffuse, Pulmonary fibrosis
Abstract

National audience; BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients’ association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

Published
2022
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5. High frequency of Specific Polysaccharide Antibody Deficiency (SPAD) in adults with unexplained, recurrent and/or severe infections with encapsulated bacteria

Author

Sarah, Stabler, Catherine, Lamblin, Sacha, Gaillard, Nicolas, Just, Mirela, Mihailescu, Nathalie, Viget, Thierno Sy, Ndiaye, Arnaud Dzeing, Ella, Guillaume, Brunin, Pierre, Weyrich, Anne, Prevotat, Cécile, Chenivesse, Olivier, Le Rouzic, Geoffrey, Mortuaire, Fanny, Vuotto, Karine, Faure, Amélie, Leurs, Frédéric, Wallet, Caroline, Loiez, Marie, Titecat, Rémi R, Le Guern, Eric, Hachulla, Sébastien, Sanges, Etienne N, Nicolas, Louis, Terriou, David, Launay, Benjamin, Lopez, Mathilde, Bahuaud, Frédéric, Batteux, Sylvain, Dubucquoi, Cyrielle, Gesquière-Lasselin, Myriam, Labalette, and Guillaume, Lefèvre

Abstract

Primary immunodeficiencies (PIDs) in adults are mainly revealed by recurrent and/or severe bacterial infections. The objective of this study was to evaluate a systematic research strategy of PIDs in adults with unexplained bacterial infections, with a special focus on specific polysaccharide antibody deficiency (SPAD).In this prospective multicenter study, inclusion criteria were recurrent benign upper and lower respiratory tract infections (RTIs) for at least two years (group 1), at least one upper or lower RTI requiring hospitalization (group 2), and/or at least one invasive infection documented with encapsulated bacteria (group 3). Main exclusion criteria were all local and general conditions that could explain infections. If no PID diagnosis was made, response to polysaccharide antigens was assessed using a pneumococcal polysaccharide vaccine.From March 2015 to March 2020, 118 patients were included (37 males, median age of 41 years): 73, 17, and 28 in groups 1, 2, and 3, respectively. Forty-seven PIDs were diagnosed, giving an estimated frequency of 39.8% (95% IC [30.4; 48.8]). SPAD was the most frequent diagnosis by far (n = 37/47, 78.7%), and was made in 23, 5, and 9 patients from groups 1 to 3, respectively. All SPAD patients received conjugate vaccines, and according to their infectious history, were on surveillance or treated with preventive antibiotics (n = 6) and/or with immunoglobulins replacement therapy (n = 10), the latter being dramatically efficient in all cases.Considering its high prevalence among adults with unexplained recurrent and/or severe bacterial infections, SPAD should be screened in those patients.

Published
2022

6. IL-22 Defect During Streptococcus pneumoniae Infection Triggers Exacerbation of Chronic Obstructive Pulmonary Disease

Author

Cecile Olivier, Olivier Le Rouzic, Riti Sharan, Philippe Gosset, Magdiel Pérez-Cruz, Florence Hennegrave, Gaëlle Rémy, Pierre Gosset, Muriel Pichavant, Nicolas Just, and Bachirou Koné

Subjects
Male, Exacerbation, Neutrophils, medicine.medical_treatment, lcsh:Medicine, CS, cigarette smoke, medicine.disease_cause, Interleukin 22, Mice, Pulmonary Disease, Chronic Obstructive, DC, dendritic cells, IL-22, Lung, Innate immunity, lcsh:R5-920, COPD, Chronic obstructive pulmonary disease, APC, antigen presenting cells, Smoking, Interleukin-17, General Medicine, Bacterial Infections, Middle Aged, NKT, natural killer T cells, Pneumococcal infections, Cytokine, PBMC, peripheral blood mononuclear cells, Disease Progression, Cytokines, Female, medicine.symptom, lcsh:Medicine (General), Research Article, Adult, Antigen-Presenting Cells, Inflammation, Infections, General Biochemistry, Genetics and Molecular Biology, NK, natural killer cells, Pneumococcal Infections, Immune system, Streptococcus pneumoniae, medicine, Animals, Humans, Lung Diseases, Obstructive, AM, alveolar macrophages, Aged, BAL, broncho-alveolar lavage, business.industry, Interleukins, lcsh:R, Interleukin-8, Sputum, medicine.disease, CFU, colony forming unit, respiratory tract diseases, Disease Models, Animal, COPD, chronic obstructive pulmonary disease, Immunology, Chronic Disease, Commentary, Sp, Streptococcus pneumoniae, Th17 Cells, Bacterial infection, business
Abstract

Progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae. Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations. S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS) and to stimulate peripheral blood mononuclear cells (PBMC) from non-smokers, smokers and COPD patients. The immune response and the cytokine production were evaluated. Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells. This defect was related to a reduced production of IL-1β and IL-23 by antigen presenting cells. Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration. In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1β and IL-23 secretion. This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation. Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation.•Increased bacterial susceptibility during COPD is related to a defect in Th17 cytokines.•Cigarette smoke alters the production of immunoregulatory cytokines by lung APC.•Immunotherapy restoring the defective IL-22 response could represent an ideal therapy to prevent exacerbation in COPD patients.The progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations mostly due to bacterial infections. It is not well understood why COPD patients are more susceptible to infections. In our experimental model of COPD as well as in COPD patients, we identified a defect in the IL-17/IL-22 response to

Published
2015
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7. Diagnosis and management of idiopathic pulmonary fibrosis: French practical guidelines

Author

Jean-François Cordier, Philippe Carré, Romain Kessler, Nicolas Just, Bernard Aguilaniu, Serge Kouzan, François Lebargy, Philippe Delaval, Jacques Cadranel, Benoit Wallaert, Sylvain Marchand-Adam, Bruno Crestani, Dominique Valeyre, Jean-Baptiste Faivre, B. Philippe, Jean-Charles Dalphin, B. Bouquillon, Grégoire Prévot, Françoise Thivolet-Béjui, Martine Reynaud-Gaubert, B. Stach, Dominique Israel-Biet, Gilbert Ferretti, Vincent Cottin, Claire Danel, Department of Pneumology [Lyon], Hospices Civils de Lyon (HCL), Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Service de Pneumologie et Immuno-Allergologie [CHU LIlle], Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Pontchaillou [Rennes], 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), CHU Strasbourg, CHU Marseille, Clinique du Mail, Opened Mind Health and Associates, Polyclinique Montréal, Partenaires INRAE, Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Cancérologie-Radiothérapie Hôpital Albert MICHALLON (CHU de Grenoble), Université Joseph Fourier - Grenoble 1 (UJF), Centre Hospitalier Victor Provo, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier René Dubos [Pontoise], Hopital Larrey, Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie A, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Bichat, Département Hospitalo-universtaire FIRE (Fibrosis, Inflammation and Remodeling), LabEx Inflamex, Service de Pneumologie A, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de compétence des maladies pulmonaires rares, Service des maladies respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Avicenne-Jean Verdier-René Muret, Interactions cellulaires tumorales et leur environnement et réponse aux agents anti-cancéreux, Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Pneumologie, Paris, Nouvel Hôpital Civil Strasbourg, Service de chirurgie thoracique, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital nord, HYLAB : Physiologie de l'exercice et interprétation clinique, Department of Physical Education, McGill University = Université McGill [Montréal, Canada], Service d'Anatomie et cytologie pathologique, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Département de radiologie, CHU Grenoble-Hôpital Michallon, Unité d'Aide Méthodologique, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Registre Multicentrique à Vocation Nationale des Mésothéliomes Pleuraux (MESONAT), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hospices Civils de Lyon ( HCL ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Bichat, AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Centre de compétence des maladies pulmonaires rares, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Avicenne-Jean Verdier-René Muret, Service de Pneumologie et Immuno-Allergologie, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service de pneumologie et réanimation [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Intergroupe Francophone de Cancérologie Thoracique [Paris] ( IFCT ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital nord, McGill University-Université de Montréal, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre national référent cancers rares - mésothéliomes malins pleuraux et tumeurs péritonéales rares ( MESOPATH ), CHU Caen-Hôpital côte de nacre, Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Diagnostic Imaging, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pediatrics, Consensus, MEDLINE, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Pulmonary Medicine, medicine, Humans, 030212 general & internal medicine, Idiopathic interstitial pneumonia, Competence (human resources), Pulmonologists, lcsh:RC705-779, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Evidence-Based Medicine, Modalities, Executive summary, business.industry, lcsh:Diseases of the respiratory system, Evidence-based medicine, medicine.disease, Idiopathic Pulmonary Fibrosis, 3. Good health, Treatment Outcome, 030228 respiratory system, Family medicine, France, business
Abstract

Initiative that emanated from the French National Reference Centre and the Network of Competence Centres for Rare Lung Diseases; International audience; Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic interstitial pneumonia in adults. The management of rare diseases in France has been organised by a national plan for rare diseases, which endorsed a network of expert centres for rare diseases throughout France. This article is an overview of the executive summary of the French guidelines for the management of IPF, an initiative that emanated from the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. This review aims at providing pulmonologists with a document that: 1) combines the current available evidence; 2) reviews practical modalities of diagnosis and management of IPF; and 3) is adapted to everyday medical practice. The French practical guidelines result from the combined efforts of a coordination committee, a writing committee and a multidisciplinary review panel, following recommendations from the Haute Autorité de Santé. All recommendations included in this article received at least 90% agreement by the reviewing panel. Herein, we summarise the main conclusions and practical recommendations of the French guidelines.

Published
2014
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8. Oxidative stress-mediated iNKT-cell activation is involved in COPD pathogenesis

Author

O. Le Rouzic, G. Kervoaze, Didier Cataldo, E. Vilain, Philippe Gosset, Nicolas Just, François Trottein, Gaëlle Rémy, Isabelle Tillie-Leblond, Sandrine Bekaert, and Muriel Pichavant

Subjects
Immunology, Antigen-Presenting Cells, Inflammation, Biology, Lymphocyte Activation, medicine.disease_cause, Article, Antioxidants, Pathogenesis, Mice, Pulmonary Disease, Chronic Obstructive, Benzene Derivatives, medicine, Animals, Humans, Immunology and Allergy, Lymphocyte Count, Lung, Mice, Knockout, COPD, Interleukin, Dendritic Cells, Natural killer T cell, medicine.disease, respiratory tract diseases, Disease Models, Animal, Oxidative Stress, medicine.anatomical_structure, Natural Killer T-Cells, Tobacco Smoke Pollution, medicine.symptom, Cell activation, Oxidative stress
Abstract

Chronic obstructive pulmonary disease (COPD) is a major clinical challenge mostly due to cigarette smoke (CS) exposure. Invariant natural killer T (iNKT) cells are potent immunoregulatory cells that have a crucial role in inflammation. In the current study, we investigate the role of iNKT cells in COPD pathogenesis. The frequency of activated NKT cells was found to be increased in peripheral blood of COPD patients relative to controls. In mice chronically exposed to CS, activated iNKT cells accumulated in the lungs and strongly contributed to the pathogenesis. The detrimental role of iNKT cells was confirmed in an acute model of oxidative stress, an effect that depended on interleukin (IL)-17. CS extracts directly activated mouse and human dendritic cells (DC) and airway epithelial cells (AECs) to trigger interferonγ and/or IL-17 production by iNKT cells, an effect ablated by the anti-oxidant N-acetylcystein. In mice, this treatment abrogates iNKT-cell accumulation in the lung and abolished the development of COPD. Together, activation of iNKT cells by oxidative stress in DC and AECs participates in the development of experimental COPD, a finding that might be exploited at a therapeutic level.

Published
2014
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9. B-Cell and T-Cell Phenotypes in CVID Patients Correlate with the Clinical Phenotype of the Disease

Author

Gaël, Mouillot, Maryvonnick, Carmagnat, Laurence, Gérard, Jean-Luc, Garnier, Claire, Fieschi, Nicolas, Vince, Lionel, Karlin, Jean-François, Viallard, Roland, Jaussaud, Julien, Boileau, Jean, Donadieu, Martine, Gardembas, Nicolas, Schleinitz, Felipe, Suarez, Eric, Hachulla, Karen, Delavigne, Martine, Morisset, Serge, Jacquot, Nicolas, Just, Lionel, Galicier, Dominique, Charron, Patrice, Debré, Eric, Oksenhendler, Claire, Rabian, and L, Gérard

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Protein-Losing Enteropathies, T-Lymphocytes, T cell, Immunology, Cell Separation, Infections, Immunophenotyping, Lymphopenia, Humans, Immunology and Allergy, Medicine, fas Receptor, B cell, Aged, B-Lymphocytes, biology, business.industry, Common variable immunodeficiency, Autoimmune Cytopenia, Protein losing enteropathy, Middle Aged, Flow Cytometry, medicine.disease, Immunoglobulin Class Switching, Lymphocyte Subsets, Common Variable Immunodeficiency, medicine.anatomical_structure, Immunoglobulin class switching, CD4 Antigens, Disease Progression, biology.protein, Female, France, Antibody, business, Immunologic Memory
Abstract

Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by recurrent infections and defective immunoglobulin production.The DEFI French national prospective study investigated peripheral T-cell and B-cell compartments in 313 CVID patients grouped according to their clinical phenotype, using flow cytometry.In patients developing infection only (IO), the main B-cell or T-cell abnormalities were a defect in switched memory B cells and a decrease in naive CD4(+) T cells associated with an increase in CD4(+)CD95(+) cells. These abnormalities were more pronounced in patients developing lymphoproliferation (LP), autoimmune cytopenia (AC), or chronic enteropathy (CE). Moreover, LP and AC patients presented an increase in CD21(low) B cells and CD4(+)HLA-DR(+) T cells and a decrease in regulatory T cells.In these large series of CVID patients, the major abnormalities of the B-cell and T-cell compartments, although a hallmark of CVID, were only observed in half of the IO patients and were more frequent and severe in patients with additional lymphoproliferative, autoimmune, and digestive complications.

Published
2010
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10. Direct regulatory immune activity of lactic acid bacteria on Der p 1–pulsed dendritic cells from allergic patients

Author

Hamida Hammad, Joël Pestel, Céline Ratajczak, André-Bernard Tonnel, Nicolas Just, Pierre Pochard, Anne-Sophie Charbonnier-Hatzfeld, and Pulmonary Medicine

Subjects
T-Lymphocytes, medicine.medical_treatment, Immunology, Biology, Lymphocyte Activation, Arthropod Proteins, Flow cytometry, Immune system, Antigen, medicine, Animals, Humans, Immunology and Allergy, Antigens, Dermatophagoides, Lactic Acid, Antigen-presenting cell, House dust mite, Toll-like receptor, medicine.diagnostic_test, Cell Differentiation, Dendritic Cells, Dendritic cell, Flow Cytometry, biology.organism_classification, Interleukin-12, Interleukin-10, Cysteine Endopeptidases, Cytokine, Lactobacillus plantarum
Abstract

Background Lactic acid bacteria (LAB) are suggested to play a regulatory role in the development of allergic reactions. However, their potential effects on dendritic cells (DCs) directing the immune polarization remain unclear. Objective The immunologic effect of Lactobacillus plantarum NCIMB 8826 (LAB1) on monocyte-derived dendritic cells (MD-DCs) from patients allergic to house dust mite was evaluated. Methods MD-DCs were stimulated for 24 hours with the related allergen Der p 1 in the presence or absence of LAB1. Cell-surface markers were assessed by means of FACS analysis, and the key polarizing cytokines IL-12 and IL-10 were quantified. The subsequent regulatory effect of pulsed MD-DCs on naive or memory T cells was evaluated by determining the T-cell cytokine profile. Results LAB1 induced the maturation of MD-DCs, even if pulsed with Der p 1. Interestingly, after incubation with LAB1 and Der p 1, MD-DCs produced higher amounts of IL-12 than Der p 1–pulsed DCs. Indeed, the T H 2 cytokine (IL-4 and IL-5) production observed when naive or memory autologous T cells were cocultured with Der p 1–pulsed MD-DCs was highly reduced in the presence of LAB1. Finally, in contrast to naive or memory T cells exposed once to Der p 1–pulsed DCs, T cells stimulated by MD-DCs pulsed with Der p 1 and LAB1 failed to produce T H 2 cytokines in response to a new stimulation with Der p 1–pulsed DCs. Conclusion Thus in the presence of LAB1, MD-DCs from allergic patients tend to reorientate the T-cell response toward a beneficial T H 1 profile.

Published
2005
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11. Implication des cellules dendritiques en pathologie respiratoire allergique

Author

André-Bernard Tonnel, Nicolas Just, Joël Pestel, Isabelle Tillie-Leblond, Hamida Hammad, C. Rataczak, François Lebargy, and Gaëtan Deslée

Subjects
Pulmonary and Respiratory Medicine, business.industry, Medicine, business, Molecular biology
Abstract

Resume Introduction Les cellules dendritiques (cellules dentritiques) sont capables de presenter l’antigene aux lymphocytes T et d’orienter la reponse immune vers un profil Th1 ou Th2. Etat des connaissances Cette synthese expose une serie de travaux portant sur l’etude comparative des cellules dentritiques issues de patients allergiques aux acariens et de sujets sains, en conditions experimentales in vitro et in vivo . Ces travaux ont permis de montrer que les cellules dentritiques de patients allergiques aux acariens : i) capturent plus efficacement l’allergene d’acarien, ii) secretent apres stimulation avec l’allergene d’acarien un panel particulier de cytokines et de chimiokines, et expriment preferentiellement certaines molecules de co-stimulation favorisant un profil Th2, iii) induisent apres stimulation par l’allergene d’acarien une secretion de cytokines de type Th2 par les lymphocytes T, et iv) favorisent le developpement d’une reaction inflammatoire de type Th2 specifique de l’allergene dans un modele in vivo de souris humanisee. Perspectives La modulation fonctionnelle des cellules dentritiques pourrait constituer la base de nouveaux concepts therapeutiques en pathologie allergique respiratoire. Conclusions Ces resultats montrent l’existence de specificites phenotypiques et fonctionnelles des cellules dentritiques chez les patients allergiques aux acariens, et soulignent le role-cle des cellules dentritiques dans la physiopathologie de la reponse respiratoire allergene-dependante.

Published
2004
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12. Defects in the CD19 complex predispose to glomerulonephritis, as well as IgG1 subclass deficiency

Author

Nicolas Vince, Jean-Laurent Casanova, Mary Ellen Conley, Claire Fieschi, Nicolas Just, Maria Peralta, Marion Malphettes, Gael Mouillot, Eric Oksenhendler, Jean-Christophe Bories, David Boutboul, Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunité et Infection, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Pneumologie [Roubaix], Centre hospitalier de Roubaix, Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Immunology, St Jude Children's Research Hospital-The University of Tennessee Health Science Center [Memphis] (UTHSC), Différenciation des cellules B, hémopathies, lymphoïdes et déficit de l'immunité humorale, Université Paris Diderot - Paris 7 (UPD7), Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes (UN), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), and Vince, Nicolas

Subjects
Immunology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Immunoglobulin D, CD19, Subclass, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, business.industry, Glomerulonephritis, medicine.disease, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Mutation (genetic algorithm), biology.protein, IgG deficiency, business, 030215 immunology, Kidney disease
Abstract

International audience

Published
2011
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14. Capacité des immunostimulants à restaurer une réponse IL-17, IL-22, IFN-γ dans le cadre de la BPCO

Author

P. Gosset, Nicolas Just, F. Hennegrave, Muriel Pichavant, Jean-Claude Sirard, and O. Le Rouzic

Subjects
Pulmonary and Respiratory Medicine
Abstract

Introduction La bronchopneumopathie chronique obstructive (BPCO), dont le tabagisme est le principal facteur de risque, est un probleme majeur de sante publique pour lequel il n’existe que des traitements symptomatiques. La progression de la maladie fait intervenir des episodes d’exacerbations favorises par une susceptibilite de ces patients aux infections. Des travaux du laboratoire ont montre le role du defaut d’IL-17 et d’IL-22 dans la susceptibilite a l’infection par S. pneumoniae et H. influenzae . Notre objectif est d’evaluer la capacite d’immunostimulants agonistes de TLR (LPS, Flagelline et CpG) a moduler la reponse IL-17 et IL-22 mais aussi d’IFN-γ. Methodes Les taux d’IL-17, d’IL-22 et d’IFN-γ en reponse au LPS, a la Flagelline et au CpG ont ete mesures par Elisa dans les surnageants de cellules mononucleees (CMN) de : – sujets temoins non-fumeurs ; – sujets fumeurs ; – patients BPCO. Les cellules productrices de ces cytokines en reponse a ces immunostimulants ont ete identifiees par cytometrie en flux. L’impact de la fumee de cigarette (CSE) sur la reponse aux immunostimulants a ete evalue in vitro chez des sujets non-fumeurs. Le role des cellules presentatrices d’antigenes (APC) a egalement ete analyse apres exposition aux immunostimulants en presence ou non de CSE. Resultats Parmi les immunostimulants testes, seule la Flagelline induit une reponse IL-17 et IL-22 chez les patients BPCO. Cette reponse Th17 est observee principalement dans les cellules NK, NKT et Lineage − . Cette reponse est liee a une action directe sur les APC, puisque la Flagelline et le LPS augmentent la secretion des cytokines pro-Th17 par les monocytes et les cellules dendritiques de sujets temoins. L’exposition in vitro au CSE inhibe l’action de la Flagelline avec un effet direct sur les APC entrainant une diminution de production de cytokines pro-Th17. Conclusion Ce travail montre l’efficacite de la Flagelline a restaurer une reponse de cytokines Th17 par les cellules immunitaires innees chez les patients BPCO. Cependant, l’effet de ce ligand du TLR5 est contrecarre par l’exposition au CSE. L’utilisation de cet immunostimulant pourrait representer une nouvelle strategie therapeutique pour restaurer une immunite competente chez les patients BPCO.

Published
2015
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15. Chronic bronchial allergic inflammation increases alveolar liquid clearance by TNF-alpha -dependent mechanism

Author

André-Bernard Tonnel, Philippe Gosset, Rozenn Leberre, Isabelle Tillie-Leblond, Anne Janin, Nicolas Just, Benoit Guery, and Jean-Francois Pittet

Subjects
Pulmonary and Respiratory Medicine, Male, Allergy, Pathology, medicine.medical_specialty, Physiology, Ovalbumin, Inflammation, Allergic inflammation, Capillary Permeability, Interstitial space, Physiology (medical), Submucosa, Albumins, Rats, Inbred BN, medicine, Hypersensitivity, Animals, Humans, Bronchitis, Lung, Bronchus, Blood-Air Barrier, business.industry, Tumor Necrosis Factor-alpha, Cell Biology, respiratory system, Immunoglobulin E, medicine.disease, Body Fluids, Capillaries, Rats, Pulmonary Alveoli, medicine.anatomical_structure, Immunology, Chronic Disease, Cattle, Immunization, medicine.symptom, Pulmonary alveolus, business, Respiratory tract
Abstract

Bronchial inflammation in allergic asthma is associated with active exudation from the bronchial tree into the interstitial space of both mucosa and submucosa. The aim of this study was to evaluate epithelial and endothelial permeability as well as alveolar fluid movement in a model of chronic allergic inflammation in Brown-Norway rats sensitized and challenged with ovalbumin (OA). Control groups were challenged with saline solution (C), and rats were immunized by OA but not challenged (Se). Lung sections showed a marked inflammatory infiltrate associated with perivascular and peribronchiolar edema in OA. To measure alveolar liquid clearance, a 5% bovine albumin solution with 1 μCi of125I-labeled human albumin was instilled into the air spaces. Alveolar-capillary barrier permeability was evaluated by intravascular injection of 1 μCi of 131I-labeled albumin. Endothelial permeability was significantly increased in OA, from 0.08 ± 0.01 in the C group to 0.19 ± 0.03 in OA group ( P < 0.05). Final-to-initial protein ratio was also statistically higher in OA (1.6 ± 0.05) compared with C (1.38 ± 0.03, P = 0.01) and Se groups (1.42 ± 0.03, P = 0.04). Administration of anti-tumor necrosis factor-α antibodies within the instillate significantly decreased this ratio (1.32 ± 0.08, P = 0.003 vs. OA). To conclude, we demonstrated a tumor necrosis factor-α-dependent increase in alveolar fluid movement in a model of severe bronchial allergic inflammation associated with endothelial and epithelial leakage.

Published
2002

17. Severe Toxoplasmosis in Immunocompetent Hosts: Be Aware of Atypical Strains

Author

Nicolas Just, Daniel Ajzenberg, Nathalie Bautin, Vincent Sobanski, Laurence Delhaes, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre National de Référence (CNR) Toxoplasmose/Toxoplasma Biological Resource Center (BRC) (CNR Toxoplasmose-Toxoplasma BRC), CHU Limoges, Université de Limoges (UNILIM), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)

Subjects
Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, MESH: Pyrimethamine, 030231 tropical medicine, Treatment outcome, MEDLINE, MESH: Sweating, Critical Care and Intensive Care Medicine, 03 medical and health sciences, MESH: Weight Loss, 0302 clinical medicine, Weight loss, MESH: Severity of Illness Index, Severity of illness, MESH: Fever, medicine, MESH: Immunocompromised Host, MESH: Antiprotozoal Agents, ComputingMilieux_MISCELLANEOUS, MESH: Treatment Outcome, 0303 health sciences, MESH: Humans, MESH: Middle Aged, 030306 microbiology, business.industry, MESH: Toxoplasma, medicine.disease, Toxoplasmosis, MESH: Male, MESH: Dyspnea, MESH: Toxoplasmosis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business
Abstract

International audience

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