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Resume But de l’etude L’exposition aux produits de nettoyage est frequente, tant dans le cadre professionnel que domestique. L’objectif de cet article est de faire un etat de la question sur la relation entre l’asthme et les expositions aux produits de nettoyage. Methodes Une revue de la litterature a ete effectuee. Apres une breve presentation des produits de nettoyage ayant potentiellement un effet sur la sante respiratoire, les resultats d’etudes de cas, d’etudes de surveillance et d’etudes epidemiologiques sont synthetises. Resultats Les produits de nettoyage et de desinfection sont composes de nombreux agents chimiques, pouvant etre classes en irritants ou en sensibilisants. Les etudes de surveillance ont mis en avant la place importante de l’exposition aux produits de nettoyage dans l’asthme professionnel ou l’asthme exacerbe par le travail, en particulier dans le secteur de la sante. Dans des etudes epidemiologiques principalement transversales et dans une etude longitudinale prospective, des associations avec l’asthme ont ete mises en evidence pour les professions de sante ou de menage, ou l’exposition aux produits de nettoyage. Des associations avec l’asthme ont le plus souvent ete observees pour l’utilisation d’ammoniac, d’eau de javel et de produits sous forme de spray, lorsque ces informations etaient disponibles. Peu d’etudes ont evalue le role des produits de nettoyage sur des phenotypes d’asthme specifiques. Des associations avec l’asthme non IgE-dependant et l’asthme IgE-dependant ont ete observees. Des travaux methodologiques seraient necessaires pour ameliorer les estimations des expositions aux produits de nettoyage. Les estimations des expositions aux produits de nettoyage specifiques sont le plus souvent basees sur la declaration des sujets, ce qui peut engendrer des biais de declaration differentiels. Discussion et conclusion Il est maintenant etabli que l’exposition aux produits de nettoyage est liee a la fois a l’apparition de l’asthme et a des exacerbations d’asthmes preexistants. Il reste cependant de nombreuses questions sur les produits specifiques impliques et leurs mecanismes d’action. Des methodes d’estimation des expositions plus objectives et applicables a de grandes populations, comme les matrices tâche-exposition, pourraient etre developpees. Des mesures quantitatives seraient utiles pour ameliorer l’estimation des expositions.

Occupational exposure to disinfectants is associated with work-related asthma, especially in healthcare workers. However, little is known about the specific products involved. To evaluate disinfectant exposures, we designed job-exposure (JEM) and job-task-exposure (JTEM) matrices, which are thought to be less prone to differential misclassification bias than self-reported exposure. We then compared the three assessment methods: self-reported exposure, JEM and JTEM.Disinfectant use was assessed by an occupational questionnaire in 9073 US female registered nurses without asthma, aged 49-68 years, drawn from the Nurses' Health Study II. A JEM was created based on self-reported frequency of use (1-3, 4-7 days/week) of 7 disinfectants and sprays in 8 nursing jobs. We then created a JTEM combining jobs and disinfection tasks to further reduce misclassification. Exposure was evaluated in 3 classes (low, medium, high) using product-specific cut-offs (eg,30%, 30-49.9%, ≥50%, respectively, for alcohol); the cut-offs were defined from the distribution of self-reported exposure per job/task.The most frequently reported disinfectants were alcohol (weekly use: 39%), bleach (22%) and sprays (20%). More nurses were classified as highly exposed by JTEM (alcohol 41%, sprays 41%, bleach 34%) than by JEM (21%, 30%, 26%, respectively). Agreement between JEM and JTEM was fair-to-moderate (κ 0.3-0.5) for most disinfectants. JEM and JTEM exposure estimates were heterogeneous in most nursing jobs, except in emergency room and education/administration.The JTEM may provide more accurate estimates than the JEM, especially for nursing jobs with heterogeneous tasks. Use of the JTEM is likely to reduce exposure misclassification.

Etat de la question L’asthme touche 300 millions de personnes dans le monde et la pollution atmospherique est l’un des facteurs environnementaux associes a son apparition. Parmi les mecanismes biologiques qui pourraient expliquer cette association, le stress oxydant est fortement suggere. Les 8-isoprostanes (8-iso) sont des marqueurs de dommages tissulaires lies au stress oxydant, pouvant etre doses dans le condensat de l’air expire (CAE). L’objectif de cette etude est double : – confirmer l’association entre la pollution atmospherique et l’asthme actuel ; – etudier l’association entre la pollution atmospherique et les 8-iso et l’association entre les 8-iso et l’asthme actuel, chez l’adulte dans l’etude EGEA. Methodes Les analyses ont concerne 663 participants adultes vus au premier suivi de l’etude epidemiologique des facteurs genetiques et environnementaux de l’asthme (EGEA, http://egeaintranet.vjf.inserm.fr/ ), etude cas-temoin, familiale et multicentrique. La pollution atmospherique (NO 2 , NOx, PM 10 , PM 2,5 et trafic routier) a ete estimee dans le cadre du programme FP7 ESCAPE ( http://www.escapeproject.eu/ ). Les 8-iso ont ete mesures dans le CAE, fluide proche du poumon et recueilli de maniere non invasive. Des modeles lineaires generalises avec prise en compte de la dependance familiale et des modeles mixtes sur la ville ont ete utilises. Resultats L’âge moyen des participants etait de 41,9 ans, 49 % etaient des hommes et 36,2 % avaient un asthme actuel. Les niveaux de pollution etaient disponibles a Paris, Lyon, Grenoble et Marseille et etaient plus eleves a Paris ( p 8-iso ) et des 25 e et 75 e percentiles de 3,25 pg/mL (1,43;7,76). A Paris, la MG 8-iso etait 7 fois plus elevee que dans les trois autres villes ( p n = 368), la MG 8-iso etait de 2,69 pg/mL (1,12;6,78) et elle etait plus elevee chez la femme ( p 95 % ] = 1,10 [1,00;1,19]). Seules les PM 2,5 etaient associees positivement et significativement aux 8-iso (β [IC95 %] = 0,29 [0,06;0,51] ; p = 0,01). Enfin, les 8-iso etaient associes positivement a l’asthme actuel qu’ils soient exprimes en continu (OR [IC95 %] = 1,50 [1,06;2,12]) ou en classes, definies selon la mediane (OR [IC95 %] = 1,57 [1,03;2,40]). Conclusions Cette etude montre pour la premiere fois chez l’adulte une association entre la pollution atmospherique et la [8-iso]. Elle souligne l’interet du CAE en epidemiologie respiratoire, et l’utilite des 8-iso comme marqueurs potentiels de dommages lies a la pollution dans l’asthme.

The aim of the present study was to determine dietary patterns and investigate their association with asthma incidence, current asthma and frequent asthma exacerbations. Dietary habits and asthma data were collected from the large E3N study (of French females, mostly teachers). Of the 54,672 females followed-up in 2003, 2,634 reported ever-adulthood asthma, 1,063 reported current asthma, 206 reported frequent asthma attacks (one or more a week), and 628 reported asthma onset between 1993 and 2003. Using principal component analysis, three dietary patterns were identified: the "prudent" pattern (fruits and vegetables); the "Western" pattern (pizza/salty pies, dessert and cured meats); and the "nuts and wine" pattern. Pattern scores were categorised into tertiles, and the incidence and prevalence of asthma was compared between tertiles. After adjustment for confounders, no association of dietary patterns was observed with asthma incidence, ever-asthma or current asthma. The Western pattern was associated with an increased risk of reporting frequent asthma attacks (highest versus lowest tertile odds ratio (OR) 1.79, 95% confidence interval (CI) 1.11-3.73). Increasing scores of the nuts and wine pattern were associated with a decreased risk of reporting frequent asthma attacks (highest versus lowest tertile OR 0.65, 95% CI 0.31-0.96). The results of the present study suggest that overall diet could be involved in frequent asthma exacerbations, one aspect of asthma severity.

Resume Introduction L’etude EGEA (Etude epidemiologique des facteurs Genetiques et Environnementaux de l’Asthme, l’atopie et l’hyperreactivite bronchique), une etude cas-temoins et familiale regroupant 2 048 individus, a ete initiee afin de rechercher les facteurs environnementaux et genetiques de l’asthme. Nous presentons les resultats portant sur les aspects phenotypiques et environnementaux de l’asthme severe et de l’allergie obtenus depuis 2002 dans l’etude EGEA. Methodes et Resultats Les resultats etayent le role de facteurs hormonaux dans la severite de l’asthme et certains marqueurs allergiques associes a l’asthme. Un indice de masse corporelle eleve etait associe a la severite de l’asthme chez les femmes ayant eu des regles precoces. Des associations sont apparues entre des marqueurs d’allergie (eosinophiles, IgE, atopie) et des evenements hormono-dependants chez les femmes (asthme premenstruel, menopause et contraceptifs oraux). Chez les asthmatiques, l’exposition professionnelle aux nuisances asthmogenes, le tabagisme actif et passif etaient associes a un score clinique de severite plus eleve. L’etude a mis en evidence le role protecteur de la vie a la campagne et de l’exposition aux animaux domestiques dans la petite enfance vis-a-vis de l’allergie chez l’adulte, etayant ainsi l’hypothese hygieniste. Conclusions De nouvelles hypotheses seront prochainement testees grâce a la seconde phase de l’etude actuellement en cours.

Resume Introduction et methode L’etude francaise EGEA (etude epidemiologique des facteurs genetiques et environnementaux de l’asthme, l’hyperactivite bronchique et l’atopie) combine une etude cas-temoins et une etude familiale de cas (n = 2120) avec trois enquetes sur 20 ans. Cet article de synthese presente les travaux realises depuis 2007 (42 articles) sur la caracterisation phenotypique et l’etude de facteurs environnementaux et genetiques de l’asthme et des phenotypes associes. Resultats Les resultats epidemiologiques et genetiques confirment le caractere heterogene de l’asthme. L’âge de debut, le statut allergique et le niveau d’activite de la maladie jouent un role preponderant dans l’identification des differents phenotypes et des facteurs genetiques sous-jacents. Le role nefaste du tabagisme, des expositions a la pollution atmospherique, aux asthmogenes professionnels et aux produits de nettoyage sur la prevalence et/ou l’activite de l’asthme est etaye. La prise en compte d’interactions gene–environnement a permis d’identifier de nouveaux facteurs genetiques de susceptibilite et de preciser leur mode d’action. Conclusion L’etude EGEA participe aux avancees de la recherche en pneumologie au niveau international. Les nouvelles donnees phenotypiques, environnementales et biologiques permettront de caracteriser l’evolution a long terme de l’asthme et les facteurs associes a cette evolution.

Occupational exposure to disinfectants is associated with work-related asthma, especially in healthcare workers. However, little is known about the specific products involved. In epidemiologic studies, assessment of exposure by job-exposure matrices (JEM) is less prone to differential misclassification bias than self-report. We designed JEM and job-task-exposure matrices (JTEM) to better evaluate disinfectant exposures using data from the Nurses9 Health Study II, a prospective study of U.S. female registered nurses. Disinfectant use was assessed by an occupational questionnaire in a random sample of 8,580 nurses (49-68 years) without asthma. A JEM was created based on the frequency (1-3, >4 days/week) of reported use of 8 disinfectants in 8 nursing jobs. Nurses reported weekly disinfection tasks to clean instruments (21%) and surfaces (54%). A JTEM combining job types and disinfection tasks was created to further reduce misclassification. Exposure was evaluated in 3 classes: no, medium, high. Alcohol (weekly use: 39%), bleach (22%) and sprays (19%) were the most frequently used; more nurses were classified exposed (medium/high) by JEM (84% for alcohol, bleach and sprays) and JTEM (75%, 64%, 59%, respectively). Agreement between JEM and JTEM were fair (kappa: 0.2 to 0.4). For Emergency Room and administration nursing jobs, JEM and JTEM estimates were similar; more variations were observed for other jobs. The JTEM may provide more accurate estimates than the JEM especially for nursing jobs with heterogeneous tasks, which will reduce exposure misclassification. These methods and others based on exposure intensity/frequency will be applied to study associations with asthma. Grant: R01 OH-10359.

The EGEA study (epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), which combines a case-control and a family-based study of asthma case (n=2120 subjects) with three surveys over 20 years, aims to identify environmental and genetic factors associated with asthma and asthma-related phenotypes. We summarize the results of the phenotypic characterization and the investigation of environmental and genetic factors of asthma and asthma-related phenotypes obtained since 2007 in the EGEA study (42 articles).Both epidemiological and genetic results confirm the heterogeneity of asthma. These results strengthen the role of the age of disease onset, the allergic status and the level of disease activity in the identification of the different phenotypes of asthma. The deleterious role of active smoking, exposure to air pollution, occupational asthmogenic agents and cleaning products on the prevalence and/or activity of asthma has been confirmed. Accounting for gene-environment interactions allowed the identification of new genetic factors underlying asthma and asthma-related traits and better understanding of their mode of action.The EGEA study is contributing to the advances in respiratory research at the international level. The new phenotypic, environmental and biological data available in EGEA study will help characterizing the long-term evolution of asthma and the factors associated to this evolution.

The role of smoking as potential risk factor, selection factor ("healthy smoker" effect) and modifying factor (severity) of asthma was studied in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). The analysis involved 200 adult asthmatic cases recruited in chest clinics, 265 nonasthmatic controls and 586 relatives of asthmatics (147 with asthma). Asthma in childhood was not associated with a reduced take-up of smoking (odds ratio (OR)=1.06 in males and 0.98 in females), but smoker asthmatic cases quit more often than controls (OR = 2.20 (95% confidence interval (95% CI) 1.11-4.34) in males and 2.76 (1.19-6.42) in females). Adult onset asthma was unrelated to ever smoking (OR 1.07 in males and 1.02 in females). In asthmatic cases, active smoking was associated with asthma severity. Current smokers, compared to never and exsmokers, had more asthma symptoms, more frequent (> or =1 attack x day(-1)) asthma attacks (OR 2.39 (95% CI 1.06-5.36)) and higher asthma severity scores. No clear pattern regarding the relationships of smoking habits with asthma was observed in first degree relatives. It is concluded that active smoking is not a risk factor for asthma in adulthood, but that smoking increases asthma severity.

Introduction Un risque eleve d’asthme a ete observe chez les infirmieres et pourrait etre lie a l’exposition aux desinfectants. Nous avons etudie l’influence de l’asthme sur le type et les changements de metier chez les infirmieres chez 98 048 femmes participant a la Nurses’ Health Study II, une etude prospective americaine d’infirmieres suivies depuis 1989 (âge : 24-44 ans). Methodes Les informations sur les types de metier, l’asthme et la date de diagnostic etaient recueillies par questionnaires a l’inclusion en 1989 puis tous les 2 ans entre 1993 en 2011. Les associations entre l’asthme diagnostique avant l’inclusion et le type de metier et les changements de metiers entre 1989 et 2011, ont ete evaluees (regressions logistiques et modeles de Cox, ajustes sur l’âge et l’ethnicite). Resultats A l’inclusion, 44 % des femmes exercaient des metiers impliquant une exposition potentiellement elevee aux desinfectants (notamment bloc operatoire et urgences), et 12 % exercaient des metiers avec une probabilite faible d’exposition (formation/administration). Les femmes avec un asthme diagnostique avant l’inclusion ( n = 5311) etaient moins souvent employees en bloc operatoire ( odds ratio : 0,73 [IC 95 %, 0,63–0,86]) et aux urgences ou autres service exposes (0,89 [0,82–0,97]) qu’en formation/administration. Pendant le suivi, les femmes avec de l’asthme changeaient plus souvent de metier pour des metiers avec une faible probabilite d’exposition aux desinfectants ( hazard ratio : 1,13 [1,07–1,18]), en particulier celles avec un asthme plus severe (hazard ratio pour l’asthme leger persistant : 1,13, modere persistant : 1,26 ; severe persistant : 1,50, en comparaison avec l’asthme intermittent, p tendance : 0,004). Conclusion L’asthme etait associe au type de metier a l’inclusion et aux changements de metier chez les infirmieres. Cela pourrait en partie refleter l’evitement de tâches impliquant l’usage de desinfectants. Financements : R01 OH-10359 ; FRM SPE20130326585 ; FRSR.

OBJECTIVES--The aim of this analysis of the French Cooperative PAARC (Pollution Atmosphérique et Affections Respiratoires Chroniques) survey, was to test whether occupational exposures to dusts, gases, or chemical fumes or to specific hazards, estimated by job exposure matrices, were related to a decrease in forced expiratory volume in one second (FEV1). METHODS--The most recent occupation was recorded in adults, aged 25-59, from non-manual worker households. Analysis was restricted to 10,046 subjects whose occupation was encountered at least 10 times in the study and who performed good FEV1 tracings. From occupational title, exposures to dusts, gases, and chemical fumes, and to specific hazards were classified in three categories (no, low, and high) with a British, a French, and an Italian job exposure matrix. Specific hazards were analysed for the British and French job exposure matrices for the same 42 specific dusts, gases, and chemical fumes. To limit spurious associations, a selection of seven hazard groups and 12 specific hazards was set before the start of the analysis. Based on the consistency of the relations according to sex and the British and French job exposure matrices, associations of age, height, city, and smoking adjusted FEV1 score with occupational exposures were classified as very likely, possible, or unlikely. RESULTS--For the three job exposure matrices and both sexes clear exposure-response relations between the level of exposure to dusts, gases, and chemical fumes, and a decrease in FEV1 were found. Associations with FEV1 were classified as very likely for known hazards such as organic dusts and textile dusts, and not previously recognised hazards such as polycyclic aromatic hydrocarbons (PAHs) and detergents, and as possible for solvents, waxes and polishes, and diesel fumes. Associations found for PAHs and solvents were confirmed by the Italian job exposure matrix. Associations remained significant in women, but not in men, after adjustment for educational level. CONCLUSIONS--Hypotheses have been generated for exposure to detergents, PAHs, and solvents, but they need to be interpreted with caution before replication. Significant associations found for known risk factors with a decrease in FEV1 are arguments for the validity of the matrices. Despite the expected limitations of job exposure matrices, these results encourage further work to improve exposure assessment by job exposure matrices.

Epidemiological research is mostly based on observational studies. Whether such studies can provide evidence of causation remains discussed. Several causal analysis methods have been developed in epidemiology. This paper aims at presenting an overview of these methods: graphical models, path analysis and its extensions, and models based on the counterfactual approach, with a special emphasis on marginal structural models. Graphical approaches have been developed to allow synthetic representations of supposed causal relationships in a given problem. They serve as qualitative support in the study of causal relationships. The sufficient-component cause model has been developed to deal with the issue of multicausality raised by the emergence of chronic multifactorial diseases. Directed acyclic graphs are mostly used as a visual tool to identify possible confounding sources in a study. Structural equations models, the main extension of path analysis, combine a system of equations and a path diagram, representing a set of possible causal relationships. They allow quantifying direct and indirect effects in a general model in which several relationships can be tested simultaneously. Dynamic path analysis further takes into account the role of time. The counterfactual approach defines causality by comparing the observed event and the counterfactual event (the event that would have been observed if, contrary to the fact, the subject had received a different exposure than the one he actually received). This theoretical approach has shown limits of traditional methods to address some causality questions. In particular, in longitudinal studies, when there is time-varying confounding, classical methods (regressions) may be biased. Marginal structural models have been developed to address this issue. In conclusion, "causal models", though they were developed partly independently, are based on equivalent logical foundations. A crucial step in the application of these models is the formulation of causal hypotheses, which will be a basis for all methodological choices. Beyond this step, statistical analysis tools recently developed offer new possibilities to delineate complex relationships, in particular in life course epidemiology.

International audience; OBJECTIVES: The aim of the study was to determine whether self-reported occupational exposure to cleaning/disinfecting agents in hospital workers is accurate, in comparison to expert assessment, taken to be the gold standard. METHODS: In the Epidemiological Study of the Genetics and Environment of Asthma (EGEA), participants were interviewed on occupation with a specific questionnaire for hospital workers regarding tasks and cleaning/disinfecting agents. Two estimates of exposure were available: self-report and expert assessment. The expert assessment involved a standardised procedure to estimate intensity, frequency and probability of exposure for each job. The present analysis focused on eight exposures: formaldehyde, glutaraldehyde, bleach/chlorine, alcohol, quaternary ammonium components, ammonia, sprays and latex gloves. Agreement and differences between self-reported and expert estimates were studied by kappa and phi coefficients and McNemar tests, respectively. RESULTS: In the survey of 1571 adults, 176 ever hospital workers (327 occupations) with both self-reported and expert exposure assessments were studied. An underestimation of self-reported exposure was observed especially for formaldehyde (26.5% vs 32.7%, p=0.01), ammonia (7.4% vs 18.8%, p

The aims were to assess longitudinally 1) the role of asthma as a potential selection factor for smoking initiation and 2) the role of smoking as a potential risk factor for asthma incidence in relatives of asthmatics. The analyses were conducted in the EGEA study, a 12−year follow−up of asthmatic cases, their first degree relatives and controls (n=1848). The first question was addressed in 511 non smoker children at inclusion (258 asthmatics, 253 non asthmatics). The second question was addressed in 496 adult relatives of cases, non asthmatic at inclusion. Survival analyses (Cox model) were conducted with adjustment on confounders (age, sex, ETS, father educational level, centre for question 1, and sex, age, educational level, atopy, rhinitis for question 2) and stratification for age. Children with asthma at inclusion started smoking as often as non asthmatic children (45.4% vs 48.6% respectively, RR[IC 95%] = 1.0 [0.7;1.3]). Among adult relatives of cases, 37 had incident asthma at follow−up (7.5%). Both smoking at inclusion (non smoker n=242, ex−smoker n=124, smoker n=130) and a time dependant smoking variable were used (never (n=341), beginner (n=22), persistent (n=74), former (n=55)). Smoking at inclusion did not affect asthma incidence (RR for smokers and ex−smokers compared to non smokers were 1.8 [0.8;3.9] and 0.7 [0.3;2.1] respectively). However, compared to never smokers, the risk for asthma incidence was increased in beginner and persistent smokers (RR=3.2 [1.0;10.1] and 2.5 [1.0;5.9]). Asthmatics started smoking as often as non asthmatics. This analysis indicates that smoking may be a risk factor for asthma incidence in first degree relatives of asthmatics, a potentially more sensitive population.

EGEA (Epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), a case control and family study including 2048 individuals, was initiated to look for environmental and genetic risk factors for asthma. A synthesis of the results obtained since 2002 on phenotypic and environmental aspects of asthma severity and allergy are presented in this article.The results support a role for hormonal factors in asthma severity and in various allergic markers of asthma. A greater body mass index was related to a more severe asthma in women with early menarche. Associations between markers of allergy (eosinophils, IgE and atopy) and hormonal dependent events in women (premenstrual asthma, menopause and oral contraceptive use) have been found. In asthmatics, exposure to agents known to be associated with occupational asthma, active and passive smoking were associated with an increased clinical asthma severity score. The study underlines the protective role of country living and exposure to pets in early life on allergy markers in adulthood, supporting the hygiene hypothesis.New hypothesis will be tested in the near future from the second stage of this survey.

International audience; AIMS AND METHODS: Long term effects of air pollution on mortality were studied in 14,284 adults who resided in 24 areas from seven French cities when enrolled in the PAARC survey (air pollution and chronic respiratory diseases) in 1974. Daily measurements of sulphur dioxide, total suspended particles, black smoke, nitrogen dioxide, and nitric oxide were made in 24 areas for three years (1974-76). Cox proportional hazards models controlling for individual confounders (smoking, educational level, body mass index, occupational exposure) were applied, and frailty models used to take into account spatial correlation. Indicators of air pollution were the mean concentration. RESULTS: Models were run before and after exclusion of six area monitors influenced by local traffic (NO/NO2 >3 in ppb). After exclusion of these areas, analyses showed that adjusted risk ratios (95% CI) for TSP, BS, NO2, and NO for non-accidental mortality were 1.05 (1.02 to 1.08), 1.07 (1.03 to 1.10), 1.14 (1.03 to 1.25), and 1.11 (1.05 to 1.17) for 10 microg/m3 respectively. Consistent patterns for lung cancer and cardiopulmonary causes were observed. CONCLUSIONS: Urban air pollution assessed in the 1970s was associated with increased mortality over 25 years in France.

International audience; In the sample of 295 French EGEA families with at least one asthmatic subject, a genome screen was conducted to identify potential linkage regions specific either to allergic rhinitis (AR) or to asthma as well as those shared by the two diseases. Two binary rhinitis phenotypes based on (1) diagnosis (ARbin1) and (2) symptoms (ARbin2) and a categorical ordered trait (ARcat) were considered. Asthma phenotype was based on answers to a standardized questionnaire plus the presence of bronchial hyper-responsiveness. Linkage analyses were conducted using the maximum likelihood binomial (MLB) method. These analyses provided potential evidence for linkage to three regions in the whole sample: 1p31 for the phenotype defined by ARbin2 plus asthma (P=0.00016), 2q32 for ARbin2 (P=0.00016) and 3p24-p14 for ARcat (P=0.001). Two other regions were detected in the subset of 185 families with at most one asthmatic sib: 9p22 and 9q22-q34 for ARbin1 (P=0.001 and 0.0007, respectively). No region showed evidence for linkage to asthma without being also linked to AR. While 1p31 may contain a genetic determinant common to asthma and AR, 2q32, 3p24-p14, 9p22 and 9q22-q34 are more likely to harbor genetic factors specific to AR.

Introduction Un risque eleve d’asthme a ete observe chez les infirmieres et pourrait etre lie a l’exposition aux desinfectants. Nous avons etudie l’influence de l’asthme sur le type et les changements de metier chez les infirmieres chez 114 778 femmes participant a la « Nurses’ Health Study II », une etude prospective americaine d’infirmieres suivies depuis 1989 (âge : 24–44 ans). Methodes Les informations sur les types de metier, l’asthme et la date de diagnostic etaient recueillies par questionnaires a l’inclusion en 1989 puis tous les deux ans entre 1993 en 2011. Les associations entre l’asthme diagnostique avant l’inclusion et le type de metier et les changements de metiers entre 1989 et 2011, ont ete evaluees (regressions logistiques et modeles de Cox, ajustes sur l’âge et l’ethnicite). Resultats A l’inclusion, 44 % des femmes exercaient des metiers impliquant une exposition potentiellement elevee aux desinfectants (notamment bloc operatoire et urgences), et 12 % exercaient des metiers avec une probabilite faible d’exposition (formation/administration). Les femmes avec un asthme diagnostique avant l’inclusion ( n = 5739 ; 5 %) etaient moins souvent employees en bloc operatoire ( odds ratio : 0,71–2 [IC95 %, 0,61–0,82]) et aux urgences ou autres service exposes (0,88 [0,81–0,96]) qu’en formation/administration. Pendant le suivi, les femmes avec de l’asthme changeaient plus souvent de metier pour des metiers avec une faible probabilite d’exposition aux desinfectants ( hazard ratio : 1,14 [1,09–1,20]). Conclusion L’asthme etait associe au type de metier a l’inclusion et aux changements de metier chez les infirmieres. Cela pourrait en partie refleter l’evitement de tâches impliquant l’usage de desinfectants.

OBJECTIVES—To compare the performance of population specific job exposure matrices (JEMs) and self reported occupational exposure with data on exposure and lung function from three European general populations. METHODS—Self reported occupational exposure (yes or no) and present occupation were recorded in the three general population surveys conducted in France, The Netherlands, and Norway. Analysis was performed on subjects, aged 25-64, who provided good forced expiratory volume in 1 second (FEV1) tracings and whose occupations were performed by at least two people, in the French (6217 men and 5571 women), the Dutch (men from urban (854) and rural (780) areas), and the Norwegian (395 men) surveys. Two population specific JEMs, based on the percentage of subjects who reported themselves exposed in each job, were constructed for each survey and each sex. The first matrix classified jobs into three categories of exposure according to the proportion of subjects who reported themselves exposed in each job (P10-50 JEM, low

Workplace and home exposures to cleaning products constitute an emerging health issue. The aim is to address the potential adverse role of exposure to cleaning agents on asthma in private homes and healthcare workers. Regarding healthcare workers, recent publications showed that they may be exposed to high level of cleaning products. As a cause of concern, they underestimated their exposures and appeared as a high risk group for asthma. Regarding home cleaning, two studies have published on this topic and suggested a deleterious role of the frequent use of cleaning sprays on asthma activity and incidence. One of them suggested a possible avoidance of spray use by women with asthma. More recently, in a nested case-control survey on asthma of French women from the ‘Etude Epidemiologique aupres des femmes de la MGEN’ (E3N study), we investigated the association between self-reported weekly use of cleaning products (evaluated as previously) and current asthma among 570 women (235 with current asthma and 335 without asthma; 68 years, 59% never smokers). A positive association was suggested between weekly use of at least one spray and current asthma (odds ratio [95% confidence interval] adjusted for age, diploma, body mass index and smoking status: 1.45 [0.94–2.24], p = 0.09), with a significant association in women without cleaning help (1.86 [1.04–3.33]). Avoidance of polluted places was significantly more frequent in women with current asthma who had at least two symptoms. Domestic exposure to cleaning sprays may represent an important public health issue especially in women and it may be important to limit their use. Female hospital workers are exposed to numerous cleaning products at high risk for asthma. Selection bias may be important for both domestic and workplace exposures. More work is needed to identify the underlying mechanism (allergic or non-allergic) and to have accurate estimates of cleaning agents.

Objective This epidemiologic study was undertaken after a cluster of five cases of rare forms of cancer (bone sarcoma, non-Hodgkin's lymphoma) had been observed among biomedical research workers at the Pasteur Institute in Paris to ascertain whether their disease was connected with exposure during this research. Methods A mortality study included 3765 people who worked at the Pasteur Institute between 1971 and 1986 and were followed until the end of 1987. Within this cohort a nested case-referent study included 23 cases of cancer [non-Hodgkin's lymphoma (6), multiple myeloma (1), leukemia (3), pancreatic cancer (7), bone cancer (3), brain tumor (3)], and four referents per case, matched for gender and year of birth. Results Total mortality from cancer was less than expected, the standardized mortality ratio (SMR) being 72 for the men and 82 for the women. Among the women the proportion of pancreatic cancer cases was larger than expected [SMR 490, 95% confidence interval (95%CI) 158--1144], as was the number of brain cancer cases (SMR 239, 95% CI 48--696). Among the men, mortality from bone cancer was greater than expected (SMR 553, 95% CI 62--2006). In the nested case-referent study, more cases than referents had worked in the areas of molecular biology [odds ratio (OR) 7.1, 95% CI 1.5--33] and microbial genetics (OR 6.7, 95% CI 1.3--35). These cases especially included non-Hodgkin's lymphoma and bone cancer. Associated with this finding was the fact that more cases had used certain chemicals, including ethidium bromide, acrylamide, methylnitronitrosoguanidine and ethylmethanesulfonate, and radioactive compounds (essentially 32phosphorus). Conclusion As the products used are potent genotoxicants, the present findings suggest that work in biomedical research might well involve an increased risk of certain types of cancer; this conclusion should be balanced by the fact that two of the five index cases were included in the mortality study and four in the nested case-referent study.

The relationships between occupational risk factors in France and bladder cancer were assessed from a hospital-based case-control study conducted between 1984 and 1987 in five regions representing various industries, including mining, textile manufacture, metallurgy and the production of rubber and chemicals. The study concerned 765 cases (658 men and 107 women) and the same number of controls. Odds ratios (OR) adjusted for matching variables (age, place of residence and hospital), and tobacco smoking were estimated by unconditional logistic regression. A significantly increased risk of bladder cancer was observed among men employed in coal mining (OR = 2.42; 95% confidence interval (Cl) : 1.25-4.67) and the chemicals industry (OR = 2.36; 95% Cl : 1.23-4.53). Aircraft and ship's officers (OR = 11.8; 95% Cl : 1.46-95.7), managers (OR = 1.64; 95% Cl : 1.11-2.43) and street vendors (OR = 3.60; 95% Cl : 1.15-11.3) also had an increased risk. Among women, employment in the clothing industry was associated with a high OR (= 3.21; 95% Cl : 1.34-7.71). Assessment of individual exposures by a panel of industrial hygiene experts showed that significantly more cases than controls had been exposed to the following substances: chlorinated solvents (OR = 1.86; 95% Cl : 1.19-2.90), industrial oils and greases (OR = 1.44; 95% Cl : 1.10-1.89), welding fumes (OR = 1.40; 95% Cl : 0.98-2.01), coal dust (OR = 1.71; 95% Cl : 1.02-2.89) and metallic oxide dust (OR = 2.99; 95% Cl : 1.12-8.01).(ABSTRACT TRUNCATED AT 250 WORDS)

International audience; Household disinfectant and cleaning products (HDCPs) assessment is challenging in epidemiological research. We hypothesized that a newly-developed smartphone application was more objective than questionnaires in assessing HDCPs. Therefore, we aimed to compare both methods, in terms of exposure assessments and respiratory health effects estimates. The women of the SEPAGES birth cohort completed repeated validated questionnaires on HDCPs and respiratory health and used an application to report HDCPs and scan products barcodes, subsequently linked with an ingredients database. Agreements between the two methods were assessed by Kappa coefficients. Logistic regression models estimated associations of HDCP with asthma symptom score. The 101 participants (18 with asthma symptom score ≥1) scanned 617 different products (580 with available ingredients list). Slight to fair agreements for sprays, bleach and scented HDCP were observed (Kappa: 0.35, 0.25, 0.11, respectively). Strength of the associations between HDCP and asthma symptom score varied between both methods but all odds ratios (OR) were greater than one. The number of scanned products used weekly was significantly associated with the asthma symptom score (adjusted-OR [CI 95%]: 1.15 [1.00–1.32]). This study shows the importance of using novel tools in epidemiological research to objectively assess HDCP and therefore reduce exposure measurement errors.

International audience; Background: Asthma is an inflammatory heterogeneous disease. Asthma inflammatory phenotypes based on blood eosinophil and neutrophil counts have never been identified and characterized in population-based studies.Methods: Adults with current asthma and available blood eosinophil and neutrophil counts from the French population-based CONSTANCES cohort were included. Current asthma was defined by reports of asthma attacks, symptoms or treatments in the last 12 months. Inflammatory phenotypes were based on low (L) and high (H) blood (B) eosinophil (E) (LBE/HBE