An adverse role of frequent domestic use of cleaning agents, especially in spray form, on asthma has been reported. However, sparse studies have investigated respiratory health effects of chronic domestic exposure to irritant cleaning agents. This study aims to investigate associations between weekly use of irritant domestic cleaning products and current allergic and non-allergic asthma in a large cohort of elderly women. We used data from the Asthma-E3N nested case-control study on asthma (n = 19,404 women, response rate: 91%, 2011), in which participants completed standardized questionnaires on asthma and on the use of domestic cleaning products including irritants (bleach, ammonia, solvents and acids). Allergic multimorbidity in asthma was assessed from allergic-related medications recorded in drug refunds database. The association between use of irritants and current asthma was estimated by logistic regression (current vs. never asthma) and multinomial logistic regression (never asthma, non-allergic asthma, allergic asthma) adjusted on age, smoking status and body mass index (BMI). In the 12,758 women included in the analysis (mean age: 70 years, current smokers: 4%, BMI ≥ 25 kg/m²: 32%, low education: 11%, current asthma: 23%), 47% reported weekly use of at least one irritant cleaning product at home. Weekly use of irritant products was associated with a higher risk of current asthma (adjusted Odds-Ratio: 1.17, 1.07-1.27). A statistically significant dose-response association was reported (p trend < 0.0001), with both the number of irritant products used weekly (1 irritant: 1.12, 1.02-1.23; 2 irritants: 1.21, 1.05-1.39; 3 irritants or more: 2.08, 1.57-2.75) and the frequency of use (1-3 days/week: 1.12, 1.02-1.23; 4-7 days/week: 1.41,1.22-1.64). A dose-response association was observed with the frequency of products used (p trend < 0.05), for both non-allergic (4-7 days/week: 1.27, 1.02-1.57) and allergic asthma (1.52, 1.27-1.82). In conclusion, weekly use of common cleaning irritants was associated with an increased risk of current asthma, whatever the allergic status.

Background: The exposure of house occupants to indoor air pollutants has increased in recent decades. Among microbiological contaminants, bacterial and fungal aerosols remain poorly studied and the debate on the impact of these aerosols on respiratory health is still open. This study aimed to assess the diversity of indoor microbial communities in relationship with the health of occupants. Methods: Measurements were taken from dwellings of 2 cohorts in Brittany (France), one with children without any pathology and the other with children and adults with asthma. Thirty dust samples were analyzed by next generation sequencing with a 16S and 18S targeted metagenomics approach. Analysis of sequencing data was performed using qiime 2, and univariate and multivariate statistical analysis using R software and phyloseq package. Results: A total of 2,637 prokaryotic (589 at genus level) and 2,153 eukaryotic taxa were identified (856 fungal taxa (39%) and 573 metazoa (26%)). The four main bacterial phyla were identified: Proteobacteria (53%), Firmicutes (27%), Actinobacteria (11%), Bacteroidetes (8%). Among Fungi, only 136 taxa were identified at genus level. Three main fungal phyla were identified: Ascomycota (84%), Basidiomycota (12%) and Mucoromycota (3%). No bacterial nor fungal phyla were significantly associated with asthma versus control group. A significant over representation in control group versus asthma was observed for Christensenellaceae family (p-value = 0.0015, adj. p-value = 0.033). Besides, a trend for over representation in control group was observed with Dermabacteraceae family (p-value = 0.0002, adj. p-value = 0.815). Conclusions: Our findings provide evidence that dust samples harbor a high diversity of human-associated bacteria and fungi. Molecular methods such as next generation sequencing are reliable tools for identifying and tracking the bacterial and fungal diversity in dust samples, a less easy strategy for the detection of eukaryotes at least using18S metagenomics approach. This study showed that the detection of some bacteria might be associated to indoor air of asthmatic patients. Regarding fungi, a higher number of samples and sequencing with more depth could allow reaching significant signatures.

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.

10061 Background: Platinum chemotherapy (CT) and cranial radiotherapy (RT) are risk factors of ototoxicity. Effects of RT dose at inner ear and of other CT were investigated. Methods: Of 7670 5-year childhood cancer survivors from the FCCSS treated before 20 years of age in 1942-2000 for solid cancer or lymphoma, 5243 with ototoxicity long-term follow-up data were included. Severe ototoxicity, defined as the need of hearing aids or Brock grade 3-4 hearing loss, was identified from self-administrated questionnaires, clinical visits and cohort linkage with the French Hospital Database and health insurance information system (SNIIRAM). The mean RT dose at inner ear was estimated using home-made software. Multivariable Cox models adjusted for gender, age at diagnosis, time period and social deprivation index was used to identify risk factors for severe ototoxicity. Results: After a mean follow-up of 30 years, 199 cases of severe ototoxicity were identified. Cumulative incidences at 30 and 50 years of age (30,50y-CumInc) were, 2.8% (95%CI = 2.4-3.3) and 5.5% (4.6-6.5), respectively. Mean RT dose at inner ear (Hazard Ratio HR = 1.6 (95%CI = 1.0-2.5), 4.5 (2.7-7.2), 5.7 (3.0-10.8) and 14.0 (9.2-21.2) for 0- < 5, 5- < 30, 30- < 40 and ≥40 Gy), as well as cisplatin (HR = 2.8, 95%CI = 1.9-4.0), melphalan (HR = 3.3, 95%CI = 1.9-5.7) and busulfan exposure (HR = 2.6, 95%CI = 1.6-4.4) were significantly associated with severe ototoxicity. Concerning melphalan (n = 199/5243 exposed), almost all cases were identified in neuroblostma patients (NBL), who also received cisplatin 200mg/m²/cycle (26/92 NBL, 30y-CumInc = 36.4% (95%CI = 25.9-48.4), vs. 3/107 non-NBL, 30y-CumInc = 1.6% (0.4-5.6)). Concerning busulfan (n = 131/5243 exposed), all cases were identified in NBL (n = 16/63, all treated with melphalan and cisplatin) and brain tumors (n = 13/28, all with RT at inner ear ≥5Gy). The 30y-CumInc in patients with RT at inner ear ≥5Gy was 7.4% (95%CI = 5.7-9.6) and 39.8% (22.5-60.0) respectively with and without busulfan. Conclusions: RT at inner ear has significant deleterious impact on audition, with cumulative incidence still worsening > 30years after RT, and with likely potentiation by busulfan. The deleterious effect of melphalan was related to previous treatment with cisplatin, either by interaction between these drugs, or by the high cisplatin dose by cycle used in NBL.

L’utilisation de produits de nettoyage est un facteur de risque d’asthme professionnel établi, mais leur rôle dans l’asthme lors d’un usage à domicile doit être approfondi. L’objectif général de cette thèse est double avec 1) un objectif étiologique qui vise à approfondir les connaissances actuelles sur les relations entre l’exposition domestique aux produits d’entretien et l’asthme chez de jeunes mères (cohorte couple-enfant Sepages ; n=484) et des femmes âgées (asthma-E3N, étude cas-témoin nichée au sein de L'Etude Epidémiologique auprès des femmes de la Mutuelle Générale et de l'Education Nationale; n=21 300) ; 2) un objectif méthodologique qui vise à évaluer deux méthodes novatrices d’estimation de l’exposition aux produits ménagers.Les associations entre la fréquence et le nombre hebdomadaire de produits (irritants, sprays, parfumés) utilisés et l’asthme actuel ou le score de symptômes d’asthme ont été évaluées par des modèles de régression. Une nouvelle méthode d’évaluation de l’usage de produits ménagers - une application smartphone (App-CB) permettant de scanner les codes-barres des produits, associées ensuite à une base de données de leurs ingrédients, et de renseigner leurs usages - a été comparée à un questionnaire. L’application rend aussi possible une première étude étiologique du Ménag’score® (A : pas de risque connu, à E risque le plus élevé ; INC), un score d’évaluation des risques des produits ménagers à partir de leur liste exhaustive d’ingrédients.L’usage hebdomadaire de produits d’entretien irritants était associé à un risque augmenté d’asthme actuel, quel que soit le statut allergique, dès l’utilisation d’un irritant (OR [IC 95%] =1,20 [1,10-1,30]), et croissant avec la fréquence (4-7j/semaine : OR=1,46 [1,26-1,69]) et le nombre de produits utilisés (≥3 irritants/semaine OR=2,20 [1,67-2,89]), chez les femmes âgées de la cohorte Asthma-E3N. Dans la cohorte Sepages, les accords observés entre les deux estimateurs des expositions disponibles (App-CB ; questionnaire ; n=101) étaient faibles à modérés pour les catégories de produit comparables : javel, sprays et produits parfumés (Κappas: 0,25 ; 0,35 ; 0,11 ; respectivement). Lors d’un usage hebdomadaire, le nombre de produits scannés (1,15 [1,00-1,32]), de produits parfumés (1,16 [1,02-1,32]) et un Ménag’score® élevé (≥1 produit D ou E : 3,13 [1,32-7,43]) étaient significativement associés à un risque plus élevé de présenter au moins un symptôme d’asthme.Les résultats suggèrent que l’utilisation hebdomadaire de produits d’entretien à domicile est associée à un risque plus élevé d’asthme. Au-delà des professionnels, des mesures de prévention lors de l’usage de produits ménagers doivent être prise à destination de l’ensemble de la population, notamment les femmes. Ce travail de thèse suggère aussi, grâce à une première étude étiologique, que le Ménag’score®, pourrait être un outil simple et intuitif de prévention en santé publique. Si cette association entre un Ménag’Score® élevé et une moins bonne santé respiratoire est confirmée dans d’autres études épidémiologiques, son affichage systématique sur les produits ménagers permettrait d’informer les consommateurs de leur toxicité et ainsi réduire à moyen terme le risque sanitaire pour la population.