Yuriko Iwatsubo

Pleural mesothelioma and exposure to asbestos: evaluation from work histories and analysis of asbestos bodies in bronchoalveolar lavage fluid or lung tissue in 131 patients.

Exposure to asbestos was evaluated in 131 patients with pleural malignant mesothelioma in the Paris area between 1986 and 1992 using data from a detailed specific questionnaire and light microscopy analysis of the retention of asbestos bodies in bronchoalveolar lavage fluid or lung tissue. Probable or definite exposure to significant levels of asbestos dust was identified in only 48 (36.6%) subjects, and significant asbestos body counts (above 1 asbestos body/ml in bronchoalveolar lavage fluid or 1000 asbestos bodies/g of dry lung tissue) were found in only 45 (34.3%) subjects. Overall 50 subjects had experienced exposure to only low levels of asbestos or no exposure at all and showed no significant retention of asbestos bodies in the biological sample analysed. Previous studies have shown that light microscopy may be useful in the identification of subjects with previous exposure to asbestos. In this study, apart from cases with obvious exposure to asbestos, a large group of subjects seemed to have a history of exposure or lung retention of asbestos bodies suggestive of very low levels of cumulative exposure, similar to those described in the general population.

Lung retention of cerium in humans

A retrospective study was conducted to evaluate lung retention of particles containing cerium in subjects with and without previous occupational exposure to mineral dusts. Analytical transmission electron microscopy was performed on 459 samples of bronchoalveolar lavage (BAL) fluid and 75 samples of lung tissue. Study of the distribution of mineralogical species in human samples showed that particles containing cerium were encountered in less than 10% of subjects. The proportion of subjects with particles containing cerium in their biological samples was not different between controls and subjects with previous occupational exposure to fibrous or nonfibrous mineral dusts. This was considered as the background level of lung retention of cerium in the general population. By contrast, determination of the absolute concentration of particles containing cerium in BAL fluid and lung tissue samples showed that 1.2% (from BAL fluid) and 1.5% (from lung tissue) of subjects with previous exposure to mineral particles had high lung retention of particles containing cerium. This study is believed to be the first one in which lung retention of cerium was estimated in the general population.

Attributable risk in men in two French case-control studies on mesothelioma and asbestos.

Pleural mesothelioma is a primary tumor of the pleura that is mainly due to asbestos exposure. To study the relationship between mesothelioma and occupational asbestos exposure in France, two case–control studies (A and B) were conducted. A substantial difference in the attributable risk in the population (ARp) was observed among men: 44.5% (95% CI: [32.6–56.4]) in study A and 83.2% (95% CI: [76.8–89.6]) in study B. As different exposure assessment expert methods were used, the main objective of this work was to re-estimate the ARp men in two case–control studies according to a common standardized exposure assessment by using a Job Exposure Matrix (JEM) and to assess the role of subjects’ selection. The initial observed ARp difference was maintained: 36.3% (95% CI: [24.3–50.3]) in study A and 69.7% (95% CI: [51.7–83.2]) in study B. Further investigations highlighted the potential selection bias introduced in both studies, especially among controls. The ARp could be underestimated in study A and overestimated in study B. After weighting subjects according to distribution of socio-economic status in the general population for controls and according to distribution of socio-economic status of cases registered by the French National Mesothelioma Surveillance Program, re-estimated ARp values were 52.4% in study A and 70.2% in study B. These results provide additional information to describe the relationship between pleural mesothelioma and occupational asbestos exposure, but also confirm the importance of subjects’ recruitment in case control studies, particularly control selection.

High incidence of renal tumours in vitamins A and E synthesis workers: A new cause of occupational cancer?

Stéphane RICHARD*, Marie-Noëlle CARRETTE, Christophe BÉROUD, Sophie FERLICOT, Ellen IMBERNON, Yuriko IWATSUBO, Hubert EGLOFF, Dominique SORDET and Jean-Michel SALÉ Génétique Oncologique EPHE and Service d’Urologie, UPRES 1602, CHU, Le Kremlin-Bicêtre, France Service de Médecine du Travail, Adisséo, Commentry, France Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Montpellier, France Laboratoire d’Anatomie Pathologique, CHU, Le Kremlin-Bicêtre, France Département Santé Travail, Institut de Veille Sanitaire, Saint-Maurice, France Laboratoire d’Anatomie Pathologique, Montluçon, France Service de Radiologie, Policlinique St. François-St. Antoine, Montluçon, France Service d’Urologie, Policlinique St. François-St. Antoine, Montluçon, France

French registry of workers handling engineered nanomaterials as an instrument of integrated system for surveillance and research

Despite the lack of data on the human health potential risks related to the engineered nanomaterials (ENM) exposure, ENM handling spreads in industry. The French government officially charged the InVS to develop an epidemiological surveillance of workers occupationally exposed to ENM. An initial surveillance plan was proposed on the basis of literature review and discussions with national and international ENM and occupational safety and health (OSH) experts. In site investigations and technical visits were then carried out to build an adequate surveillance system and to assess its feasibility. The current plan consists of a multi-step methodology where exposure registry construction is paramount. Workers potentially exposed to carbon nanotubes (CNT) or nanometric titanium dioxide (TiO 2 ) will be identified using a 3-level approach: 1-identification and selection of companies concerned with ENM exposure (based on compulsory declaration and questionnaires), 2-in site exposure assessment and identification of the jobs/tasks with ENM exposure (based on job-expose matrix, further supplemented with measurements), and 3-identification of workers concerned. Data of interest will be collected by questionnaire. Companies and workers inclusion questionnaires are designed and currently under validation. This registration is at the moment planned for three years but could be extended and include other ENM. A prospective cohort study will be established from this registry, to pursue surveillance objectives and serve as an infrastructure for performing epidemiological and panel studies with specific research objectives.

An extensive epidemiological investigation of a kidney cancer cluster in a chemical plant: what have we learned?

Objectives In 2003, a cluster of renal cell carcinoma (RCC) cases was reported among men working at a French chemical plant using a proprietary process to produce vitamin A. The 10 index cases yielded a standardised incidence ratio of 13.1 for 1994–2002. Nine of these 10 cases were diagnosed by a plant-specific abdominal ultrasonography screening programme that targeted exposure to an intermediate chemical, 4-chloro-1,1-dimethoxy-3-methyl-2-butene, commonly named ‘chloracetal C5’, suspected as the cause by some experts. Epidemiological investigations sought to examine the relations between occupational exposures and RCC. Methods A retrospective cohort mortality study and a nested case–control study were conducted. The cohort study included all workers who had been employed at the plant for at least 6 months between 1960 and 2003. The case–control study included an extensive search within the region for other kidney cancer cases among the cohort members. Industrial hygienists assessed occupational exposure. Results From 1968 to 2006, no significant excess mortality was observed for all causes of death or for all cancers. We found excess mortality for kidney cancer only among women. The nested case–control study showed a dose–response relation for cumulative exposure to chloracetal C5: the OR rose from 2.5 in the low-exposure category to 10.5 in the high-exposure group. Adjustment for screening attenuated this relation. Conclusions The results of the case–control study were consistent with the positive results of in vivo genotoxic tests and suggest that chloracetal C5 can have a causal role in RCC.

Prediction model of asthma using antiasthma drug claims for epidemiological surveillance of asthma in self-employed workers in France

Objectives To develop a prediction model of asthma based on antiasthma drug claims among affiliates to the health insurance for self-employed workers in France. Methods A random sample of the affiliates, stratified on their drug claims for antiasthma medications, was selected in three regions in France. Drug claims data for the 3 previous years was used. Ten categories of antiasthma medications, demographic variables and medical examination were introduced in multivariate logistic regression. The performance of the prediction model was examined against current asthma defined by a self-administered questionnaire. Asthma estimated by the prediction model was used to study prevalence and odds-ratios according to economic activities. Results Among the 2753 respondents with antiasthma drug claims, 520 had current asthma. Variables retained in the model were short or long acting bronchodilator, inhaled glucocorticosteroid, long-acting inhaled bronchodilator combined with inhaled glucocorticosteroid, leukotriene modifiers, one antihistamine (ketotifen) and medical examinations by a chest physician. The area under the ROC curve was excellent (0.90). The optimal cut-off yielded a sensitivity of 80% and a specificity of 86%. Prevalence of current asthma estimated by the prediction model was 3.4%. Significantly elevated odds-ratios were observed in the production of food products and beverages (OR=2.2 (95% CI 1.7 to 2.7)) and in the manufacture of machinery and equipment (OR=2.0 (95% CI 1.0 to 4.0)). Conclusions Prediction models of asthma using antiasthma drug claims can be a useful tool for asthma surveillance in the working population. The next step is an external validation which will be carried out on workers of the agriculture industry.

0457 Consequences of asthma on occupational and socio-economic characteristics in the sip study

Objective To study the employment and financial characteristics among asthmatics. Methods This study was based on the data from the prospective French national representative SIP (Santé et Itinéraire Professionnel) survey. In 2006, 13 648 individuals aged between 20 to 74 years living in metropolitan France were interviewed. In 2010, 11 221 of those who had participated in 2006 accepted to be re-interviewed. The 2006 questionnaire collected occupational and medical histories. Asthma cases were identified by the statement of the subjects at different moments of their medical and occupational histories. The 2010 questionnaire collected the duration of unemployment and that of sickness absences between 2006 and 2010 and the annual income in 2010. The analyses considered the individuals who had completed occupational history. Asthmatic subjects identified in 2006 were compared to the subjects without asthma for employment and financial outcomes between 2006 and 2010. Results A total of 426 asthmatic subjects were identified in 2006. Due to lost to follow-up, analyses were conducted with 362 asthmatics (138 men and 224 women) and 10 858 non asthmatics. Between 2006 and 2010, the female asthmatics experienced more frequently a period of unemployment and that of sickness absences compared to non asthmatics. They presented lower annual income in 2010. Among males, no significant association was observed. Conclusions These results suggest that asthmatic women experience rather negative work life events and lower income than non asthmatics. In contrast, no such results were observed in men. These results must be confirmed in future prospective cohort studies.

O48-2 Exposure assessment to engineered nanomaterials within the french epinano program: inter-method reliability study

Inter-method reliability is a measure of the ability of two different methods which evaluate the same underlying exposure to yield similar results on the same subjects. In this study we compared an observational “EpiNano-method” developed for assessing exposure to nano-objects and their agglomerates and aggregates (NOAA) in workplaces within the framework of the French epidemiological surveillance program EpiNano with a more accurate but more expensive and time-consuming “Reference-method”. Methods EpiNano-method consists in an onsite visit of facilities and an observation of workstations where NOAA are present using a standardised tool, the Onsite technical logbook. Reference-method involved an onsite visit, interviews with operators and supervisors, analysis of the available exposure measurements data, a debriefing meeting and an expert’s report to validate results through consensus. Seven workstations which synthesise and functionalize carbon nanotubes were assessed by Reference-method and by EpiNano-method implemented by three evaluators. All statistics were calculated based on pairwise comparisons of the evaluator’s respective results with the results from the Reference-method by using mainly Spearman correlation coefficients (ρ) and weighted Fleiss kappa (kF). Results The prediction of exposure to NOAA using EpiNano-method exhibited substantial agreement with that of the reference method ((kF = 0.70, sensitivity = 0.88, specificity = 0.92). The best reliability of quantitative exposure scores was found for the EpiNano-method results of Evaluator#1, when comparing with the Reference-method (ρ = 0.75). The correlation was positive but of moderate strength (ρ = 0.57) for Evaluator#2 and negative for Evaluator#3. When comparing the semi-quantitative exposure potential variable almost perfect correlation was found; all but one workstation were classified in the first category corresponding to “Negligible to low” exposure potential. Conclusion This study allowed a first validation of the EpiNano-method. However, it should be confirmed by further comparison with more robust quantitative exposure measurement data, available for a larger workstation number, with more contrasting exposure conditions and various types of NOAA.

0155 Use of a prediction model of asthma with antiasthma drug claims for epidemiological surveillance of asthma in self-employed workers in France

Objectives To estimate prevalence and risk of current asthma among affiliates to the health insurance for self-employed workers according to economic activities. Method We defined current asthma using a prediction model developed in a study conducted in 2006 among workers aged between 18 to 65, affiliated to the Régime Social des Indépendants (RSI) in three French regions. The model used as predictors antiasthma drug claims data and the prescriber’s medical speciality. In 2013, we obtained from the RSI, economic sectors and drug claims data of all French affiliates on whom we applied our prediction model. We used logistic regression to estimate asthma risk of each economic sector versus all the others. Results The population comprised 967391 workers. In men, the asthma prevalence was 5.6%. Elevated odds-ratios were observed in the production of food products (OR=1.70 [95% CI 1.63–1.78]), recycling (OR=1.44 [95% CI 1.23–1.70]), health and social work (OR=1.34 [95% CI 1.16–1.54]) and land transport (OR=1.08 [95% CI 1.03–1.13]). In women, the asthma prevalence was 7%. High odds-ratios were observed in education (OR=1.27 [95% CI 1.08–1.50]), manufacture of medical and precision instruments (OR=1.25 [95% CI 0.99–1.58]), land transport (OR=1.11 [95% CI 0.98–1.25]) and hotel/restaurants (OR=1.10 [95% CI 1.05–1.15]). Conclusions Prevalence estimated by the model was close to that observed among self-employed workers within a national survey conducted in 2003. Elevated risks were observed in several industries known to be at risk but also in those not expected. Prediction model approach will allow asthma surveillance in workers without interview with health insurance organisation data when occupational data are available.