Description: Objectives The healthy worker effect usually leads to underestimation of the association between occupational exposure and asthma. The role of irritants in work-related asthma is disputed. We estimated the effect of occupational exposure on asthma expression in a longitudinal study, using marginal structural modelling to control for the healthy worker effect. Methods Analyses included 1284 participants (17–79 years, 48% men) from the follow-up (2003–2007) of the French Epidemiological study on the Genetics and Environment of Asthma (case-control study). Age at asthma onset, periods with/without attacks over lifetime and occupational history were recorded retrospectively. Exposures to known asthmagens, irritants or low level of chemicals/allergens were evaluated through a job-exposure matrix. The job history was reconstructed into 5-year intervals. Results Thirty-one per cent of subjects had ever been exposed to occupational asthmagens. Among the 38% of subjects who had asthma (ever), presence of attacks was reported in 52% of all time periods. Using standard analyses, no association was observed between exposure to known asthmagens (OR (95% CI): 0.99 (0.72 to 1.36)) or to irritants/low level of chemicals/allergens (0.82 (0.56 to 1.20)) and asthma attacks. Using a marginal structural model, all associations increased with suggestive evidence for known asthmagens (1.26 (0.90 to 1.76)), and reaching statistical significance for irritants/low level of chemicals/allergens (1.56 (1.02 to 2.40)). Conclusions The healthy worker effect has an important impact in risk assessment in work-related asthma studies. Marginal structural models are useful to eliminate imbalances in exposure due to disease-driven selection. Results support the role of irritants in work-related asthma.

Description: Objectives We assessed the evidence relating preterm delivery (PTD), low birth weight, small for gestational age (SGA), pre-eclampsia and gestational hypertension to five occupational exposures (working hours, shift work, lifting, standing and physical workload). We conducted a systematic search in Medline and Embase (1966 to 2011), updating a previous search with a further 6 years of observations. Methods As before, combinations of keywords and medical subject headings were used. Each relevant paper was assessed for completeness of reporting and potential for important bias or confounding, and its effect estimates abstracted. Where similar definitions of exposure and outcome existed we calculated pooled estimates of relative risk (RR) in meta-analysis. Results Analysis was based on 86 reports (32 cohort investigations, 57 with usable data on PTD, 54 on birth weight and 11 on pre-eclampsia/gestational hypertension); 33 reports were new to this review. For PTD, findings across a substantial evidence base were generally consistent, effectively ruling out large effects (eg, RR〉1.2). Larger and higher quality studies were less positive, while meta-estimates of risk were smaller than in previous analyses and best estimates pointed to modest or null effects (RR 1.04 to 1.18). For SGA, the position was similar but meta-estimates were even closer to the null (eight of nine RRs≤1.07). For pre-eclampsia/gestational hypertension the evidence base remains insufficient. Conclusions The balance of evidence is against large effects for the associations investigated. As the evidence base has grown, estimates of risk in relation to these outcomes have become smaller.

Description: Objectives Occupational exposure to chlorinated aliphatic solvents has been associated with an increased cancer risk, including brain cancer. However, many of these solvents remain in active, large-volume use. We evaluated glioma risk from non-farm occupational exposure (ever/never and estimated cumulative exposure) to any of the six chlorinated solvents—carbon tetrachloride, chloroform, methylene chloride, trichloroethylene, tetrachloroethylene or 1,1,1-trichloroethane—among 798 cases and 1175 population-based controls, aged 18–80 years and non-metropolitan residents of Iowa, Michigan, Minnesota and Wisconsin. Methods Solvent use was estimated based on occupation, industry and era, using a bibliographic database of published exposure levels and exposure determinants. Unconditional logistic regression was used to calculate ORs adjusted for frequency matching variables age group and sex, and age and education. Additional analyses were limited to 904 participants who donated blood specimens (excluding controls reporting a previous diagnosis of cancer) genotyped for glutathione- S -transferases GSTP1, GSTM3 and GSTT1 . Individuals with functional GST genes might convert chlorinated solvents crossing the blood–brain barrier into cytotoxic metabolites. Results Both estimated cumulative exposure (ppm-years) and ever exposure to chlorinated solvents were associated with decreased glioma risk and were statistically significant overall and for women. In analyses comparing participants with a high probability of exposure with the unexposed, no associations were statistically significant. Solvent-exposed participants with functional GST genes were not at increased risk of glioma. Conclusions We observed no associations of glioma risk and chlorinated solvent exposure. Large pooled studies are needed to explore the interaction of genetic pathways and environmental and occupational exposures in glioma aetiology.

Description: Background There is limited information regarding the occupational exposures of subjects with a diagnosis of work-exacerbated asthma (WEA). Objectives To: (1) identify potential specific occupational, chemical, biological and physical agents associated with incident cases of WEA and (2) compare these agents with occupational exposures of occupational asthma (OA) and non-work-related asthma (NWRA) cases. Methods Subjects were workers with work-related asthma (WRA) or NWRA referred between 2005 and 2008 to two Quebec clinics specialised in the field of WRA. Specific inhalation challenges were performed to differentiate OA from WEA. Work exposures were assessed using a detailed occupational questionnaire. Exposures to 41 chemical and biological agents were coded in a semiquantitative way according to a combination of indices for concentration in workplace air, frequency and confidence of exposure by an occupational hygienist expert in occupational exposure coding. This expert was blind to the medical status of WEA, OA or NWRA. Five physical agents were coded on a yes/no scale. Results 153 subjects were enrolled (53 WEA, 67 OA and 33 NWRA). WEA cases were significantly more exposed to ammonia, engine exhaust fumes, silica, mineral fibres, aerosol propellants and solvents, and significantly less exposed to animal derived dust and enzymes than were OA cases. Exposure to physical conditions did not differ between WEA and OA. Conclusions Exposures associated with WEA differ from those associated with OA in this study. A proportion of subjects with WEA may suffer from low-dose irritant asthma, which remains a hypothesis to be tested.

Description: Objective Cleaning products may cause work-related asthma, but information regarding the specific exposures involved is scarce. We aimed to determine the associations between asthma and occupational exposure to cleaning agents in hospital workers. Methods Analyses were conducted in 179 (136 women) hospital workers and a reference population of 545 subjects (18–79 years) from the French case-control and familial Epidemiological study on the Genetics and Environment of Asthma (2003–2007). Exposures to cleaning agents were estimated using three methods: self-report, expert assessment and an asthma-specific job-exposure matrix (JEM). Associations between cleaning products and current asthma were evaluated by logistic regressions, stratified by sex and adjusted for age and smoking status. Results According to expert assessment, 55% of male and 81% of female hospital workers were exposed to cleaning/disinfecting tasks weekly (p〈0.001). No association was observed between cleaning/disinfecting tasks and current asthma in men or in women whatever the assessment method used. In women, exposure to decalcifiers (expert assessment) was associated with current asthma (OR (95% CI):2.38 (1.06 to 5.33)). In hospital workers classified as exposed according to both the expert assessment and the JEM, additional associations were observed for exposure to ammonia (3.05 (1.19 to 7.82)) and to sprays with moderate/high intensity (2.87 (1.02 to 8.11)). Conclusions Female hospital workers are often exposed to numerous cleaning products, some of which were markedly associated with current asthma. Low numbers prevented a meaningful analysis in men. Objective and more accurate estimates of occupational exposure to cleaning products are needed to better understand the adverse effects of cleaning products.