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Physiopathologie et épidémiologie des maladies respiratoires

Tutelles >

Université Paris Diderot

UFR de rattachement >

UFR Médecine

Label unité >

UMRS

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INSERM

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-02377907] A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency

Date: 24 11 月 2019 - 17:22

Desc: PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles.METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included.RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04).CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode.

[hal-02348853] Occupational exposures and 20-year incidence of COPD: the European Community Respiratory Health Survey

Date: 5 11 月 2019 - 14:37

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.

[inserm-01814823] Association between air pollution and rhinitis incidence in two European cohorts

Date: 13 6 月 2018 - 16:29

Desc: BACKGROUND: The association between air pollution and rhinitis is not well established. AIM: The aim of this longitudinal analysis was to study the association between modeled air pollution at the subjects' home addresses and self-reported incidence of rhinitis. METHODS: We used data from 1533 adults from two multicentre cohorts' studies (EGEA and ECRHS). Rhinitis incidence was defined as reporting rhinitis at the second follow-up (2011 to 2013) but not at the first follow-up (2000 to 2007). Annual exposure to NO2, PM10 and PM2.5 at the participants' home addresses was estimated using land-use regression models developed by the ESCAPE project for the 2009-2010 period. Incidence rate ratios (IRR) were computed using Poisson regression. Pooled analysis, analyses by city and meta-regression testing for heterogeneity were carried out. RESULTS: No association between long-term air pollution exposure and incidence of rhinitis was found (adjusted IRR (aIRR) for an increase of 10 μg·m-3 of NO2: 1.00 [0.91-1.09], for an increase of 5 μg·m-3 of PM2.5: 0.88 [0.73-1.04]). Similar results were found in the two-pollutant model (aIRR for an increase of 10 μg·m-3 of NO2: 1.01 [0.87-1.17], for an increase of 5 μg·m-3 of PM2.5: 0.87 [0.68-1.08]). Results differed depending on the city, but no regional pattern emerged for any of the pollutants. CONCLUSIONS: This study did not find any consistent evidence of an association between long-term air pollution and incident rhinitis.

[hal-02893484] Second-hand smoke exposure in adulthood and lower respiratory health during 20 year follow up in the European Community Respiratory Health Survey

Date: 11 6 月 2021 - 11:33

Desc: Early life exposure to tobacco smoke has been extensively studied but the role of second-hand smoke (SHS) for new-onset respiratory symptoms and lung function decline in adulthood has not been widely investigated in longitudinal studies. Our aim is to investigate the associations of exposure to SHS in adults with respiratory symptoms, respiratory conditions and lung function over 20 years. Methods: We used information from 3011 adults from 26 centres in 12 countries who participated in the European Community Respiratory Health Surveys I-III and were never or former smokers at all three surveys. Associations of SHS exposure with respiratory health (asthma symptom score, asthma, chronic bronchitis, COPD) were analysed using generalised linear mixed-effects models adjusted for confounding factors (including sex, age, smoking status, socioeconomic status and allergic sensitisation). Linear mixed-effects models with additional adjustment for height were used to assess the relationships between SHS exposure and lung function levels and decline. Results: Reported exposure to SHS decreased in all 26 study centres over time. The prevalence of SHS exposure was 38.7% at baseline (1990-1994) and 7.1% after the 20-year follow-up (2008-2011). On average 2.4% of the study participants were not exposed at the first, but were exposed at the third examination. An increase in SHS exposure over time was associated with doctor-diagnosed asthma (odds ratio (OR): 2.7; 95% confidence interval (95%-CI): 1.2-5.9), chronic bronchitis (OR: 4.8; 95%-CI: 1.6-15.0), asthma symptom score (count ratio (CR): 1.9; 95%-CI: 1.2-2.9) and dyspnoea (OR: 2.7; 95%-CI: 1.1-6.7) compared to never exposed to SHS. Associations between increase in SHS exposure and incidence of COPD (OR: 2.0; 95%-CI: 0.6-6.0) or lung function (β: - 49 ml; 95%-CI: -132, 35 for FEV1 and β: - 62 ml; 95%-CI: -165, 40 for FVC) were not apparent. Conclusion: Exposure to second-hand smoke may lead to respiratory symptoms, but this is not accompanied by lung function changes.

[inserm-03156736] The Role of Socioeconomic Status in the Association of Lung Function and Air Pollution—A Pooled Analysis of Three Adult ESCAPE Cohorts

Date: 2 Mar 2021 - 16:25

Desc: Ambient air pollution is a leading environmental risk factor and its broad spectrum of adverse health effects includes a decrease in lung function. Socioeconomic status (SES) is known to be associated with both air pollution exposure and respiratory function. This study assesses the role of SES either as confounder or effect modifier of the association between ambient air pollution and lung function. Cross-sectional data from three European multicenter adult cohorts were pooled to assess factors associated with lung function, including annual means of home outdoor NO2. Pre-bronchodilator lung function was measured according to the ATS-criteria. Multiple mixed linear models with random intercepts for study areas were used. Three different factors (education, occupation and neighborhood unemployment rate) were considered to represent SES. NO2 exposure was negatively associated with lung function. Occupation and neighborhood unemployment rates were not associated with lung function. However, the inclusion of the SES-variable education improved the models and the air pollution-lung function associations got slightly stronger. NO2 associations with lung function were not substantially modified by SES-variables. In this multicenter European study we could show that SES plays a role as a confounder in the association of ambient NO2 exposure with lung function.