Physiopathologie et épidémiologie des maladies respiratoires
Présentation
Les maladies respiratoires (asthme, broncho-pneumopathies chroniques obstructives -BPCO-, emphysème et fibrose pulmonaire), sont une cause majeure de morbidité et de mortalité en France et dans le monde. Ces maladies évoluent toutes, dans leurs formes sévères, vers l'insuffisance respiratoire, et l'arsenal thérapeutique actuellement disponible est largement insatisfaisant. L'insuffisance respiratoire liée à ces maladies résulterait d'un processus de remodelage tissulaire centré sur la bronche et/ou l'alvéole, dont les déterminants cellulaires et moléculaires seraient peu ou pas sensibles aux thérapeutiques conventionnelles. Ce remodelage est la conséquence d'une réparation tissulaire incomplète, ou anarchique en réponse à des agressions aigues ou chroniques. Le projet de l'Unité 700 est centré sur la recherche des facteurs environnementaux, personnels et biologiques responsables du remodelage bronchique et/ou alvéolaire conduisant à une insuffisance respiratoire sévère et irréversible dans les maladies bronchiques (asthme et BPCO), et alvéolaires (emphysème et fibroses pulmonaires). Les objectifs sont :
- d'identifier les facteurs de susceptibilité personnels et environnementaux impliqués dans la constitution d'une insuffisance respiratoire ;
- de définir les mécanismes qui contrôlent son initiation et sa progression ;
- de rechercher des marqueurs cellulaires et moléculaires caractérisant plus précisément ce remodelage et sa relation avec les anomalies de la fonction respiratoire ;
- de tester des nouvelles stratégies thérapeutiques préventives ou curatives visant à inhiber le remodelage pulmonaire et les anomalies fonctionnelles respiratoires qui l'accompagnent.
Equipes de recherche
Equipe 1 : Epidemiologie des allergies respiratoires et des bpco : etiologie, histoire naturelle et prise en charge
Equipe 2 : Mecanismes cellulaires et moleculaires du remodelage bronchique dans l'asthme severe et la bpco
Equipe 3 : Inflammation et fibrogenese pulmonaires.
Equipe 4 : Immunité Innée et défenses pulmonaires anti-infectieuses - voir aussi l'UFR Sciences du Vivant
[hal-03591438] Diagnostic contribution of EBUS in Interstitial Lung Desease (excluding Sarcoidosis)
Date: 28 Feb 2022 - 15:52
Desc: [...]
[hal-02191891] MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease
Date: 23 Jul 2019 - 17:57
Desc: BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7x10(-17)). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7x10(-35)) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3x10(-49)). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4x10(-5)), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5x10(-6)). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Societe Francaise de Rhumatologie and others.).
[hal-02348853] Occupational exposures and 20-year incidence of COPD: the European Community Respiratory Health Survey
Date: 23 Ene 2024 - 09:39
Desc: BACKGROUND: Occupational exposures have been associated with an increased risk of COPD. However, few studies have related objectively assessed occupational exposures to prospectively assessed incidence of COPD, using postbronchodilator lung function tests. Our objective was to examine the effect of occupational exposures on COPD incidence in the European Community Respiratory Health Survey. METHODS: General population samples aged 20-44 were randomly selected in 1991-1993 and followed up 20 years later (2010-2012). Spirometry was performed at baseline and at follow-up, with incident COPD defined using a lower limit of normal criterion for postbronchodilator FEV1/FVC. Only participants without COPD and without current asthma at baseline were included. Coded job histories during follow-up were linked to a Job-Exposure Matrix, generating occupational exposure estimates to 12 categories of agents. Their association with COPD incidence was examined in log-binomial models fitted in a Bayesian framework. FINDINGS: 3343 participants fulfilled the inclusion criteria; 89 of them had COPD at follow-up (1.4 cases/1000 person-years). Participants exposed to biological dust had a higher incidence of COPD compared with those unexposed (relative risk (RR) 1.6, 95% CI 1.1 to 2.3), as did those exposed to gases and fumes (RR 1.5, 95% CI 1.0 to 2.2) and pesticides (RR 2.2, 95% CI 1.1 to 3.8). The combined population attributable fraction for these exposures was 21.0%. INTERPRETATION: These results substantially strengthen the evidence base for occupational exposures as an important risk factor for COPD.
[hal-02052347] Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial
Date: 28 Feb 2019 - 14:08
Desc: [...]
[hal-02438688] Contribution of mutations in genes of the surfactant system to idiopathic interstitial pneumonia (IIP)
Date: 14 Ene 2020 - 12:21
Desc: <strong>Background:</strong> Children and adult IIP are heterogeneous and severe disorders. Whereas telomerase gene mutations are preferentially found in adult IIP, surfactant gene mutations are mainly reported in children. The study aimed to assess the contribution of surfactant gene mutations in a large pediatric and adult IIP cohort. <strong>Methods:</strong> Patients with IIP were prospectively included in the French network of rare lung diseases centres. All SFTPA1, SFTPA2, SFTPB, SFTPC, ABCA3, NKX2-1 exons and flanking intronic sequences were analyzed. The identified variations were assessed in silico. Only pathogenic or likely pathogenic mutations were taken into account. <strong>Results:</strong> 477 patients were included in 4 years (190 children; 287 adults). The mean age at diagnosis was 40 years (0-100) and the sex ratio was 1.47 M/F. The IIP was familial in 22% of cases. A personal or family history of lung cancer was found in 44 (15%) adults. A mutation was identified in a surfactant gene in 45 (9.4%) patients, including 22 (11.6%) children and 23 (8%) adults. Mutations were identified in all the studied genes in children and in adults, except for a SFTPB mutation identified in an adult. A mutation was found in 25% of the 44 adults with a history of IIP and lung cancer (SFTPA = 10, SFTPC = 1). <strong>Discussion and conclusion:</strong> Surfactant gene mutations encounter for an important part of IIP, thereby strongly suggesting that these molecular analyses should be part of the diagnosis process of IIP, regardless of the patient’s age, especially in case of family history of IIP and/or lung cancer. Such systematic approach should help guiding the most relevant genetic tests to be performed according to the disease phenotype. This is an ERS International Congress abstract. No full-text version is available.
Autres contacts
Université Paris Diderot - Paris 7
U.F.R. de Médecine Paris Diderot - Paris 7 (site Xavier Bichat)
16, rue Henri Huchard - B.P. 416
75870 PARIS CEDEX 18