Description: Objectives To explore whether work schedules and physically demanding work were associated with markers of ovarian reserve and response. Methods This analysis included women (n=473 and n=313 for ovarian reserve and ovarian response analysis, respectively) enrolled in a prospective cohort study of couples presenting to an academic fertility centre (2004–2015). Information on occupational factors was collected on a take-home questionnaire, and reproductive outcomes were abstracted from electronic medical records. Generalised linear models and generalised linear mixed models were used to evaluate the associations. Results Women who reported lifting or moving heavy objects at work had 1.0 fewer total oocytes (p=0.08), 1.4 fewer mature oocytes (p=0.007) and 0.7 fewer antral follicles (p=0.06) compared with women who reported never lifting or moving heavy objects at work. The inverse association between heavy lifting and oocyte yield was stronger in women 〉37 years and with a Body Mass Index ≥25 kg/m 2 . Women who worked evening/night/rotating shifts had 2.3 (p〈0.001) fewer mature oocytes, on average, compared with women who worked day-only shifts. None of the occupational exposures were associated with day 3 follicle-stimulating hormone or peak oestradiol levels. Conclusions Women working non-daytime shifts and those with physically demanding jobs had fewer mature oocytes retrieved after controlled ovarian hyperstimulation. Our results provide insight into possible mechanisms linking these occupational exposures with decreased fecundity.

Description: Objective The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds. Methods The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Logistic regression and reverse-scale Cox regression models were used to estimate the associations between SDQ scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Results Increased prenatal cis -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3-phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans -DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03). Conclusions The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age.

Description: Objectives The use of genetically engineered enzymes in the synthesis of flavourings, fragrances and other applications has increased tremendously. There is, however, a paucity of data on sensitisation and/or allergy to the finished products. We aimed to review the use of genetically modified enzymes and the enormous challenges in human biomonitoring studies with suitable assays of specific IgE to a variety of modified enzyme proteins in occupational settings and measure specific IgE to modified enzymes in exposed workers. Methods Specific IgE antibodies against workplace-specific individual enzymes were measured by the specific fluorescence enzyme-labelled immunoassay in 813 exposed workers seen in cross-sectional surveys. Results Twenty-three per cent of all exposed workers showed type I sensitisation with IgE antibodies directed against respective workplace-specific enzymes. The highest sensitisation frequencies observed were for workers exposed enzymes derived from α-amylase (44%), followed by stainzyme (41%), pancreatinin (35%), savinase (31%), papain (31%), ovozyme (28%), phytase (16%), trypsin (15%) and lipase (4%). The highest individual antibody levels (up to 110 kU/L) were detected in workers exposed to phytase, xylanase and glucanase. In a subgroup comprising 134 workers, detailed clinical diagnostics confirmed work-related symptoms. There was a strong correlation (r=0.75, p〈0.0001) between the symptoms and antibody levels. Workers with work-related respiratory symptoms showed a higher prevalence for the presence of specific IgE antibodies against workplace-specific enzymes than asymptomatic exposed workers (likelihood ratio 2.32, sensitivity 0.92, specificity 0.6). Conclusions Our data confirm the previous findings showing that genetically engineered enzymes are potent allergens eliciting immediate-type sensitisation. Owing to lack of commercial diagnostic tests, few of those exposed receive regular surveillance including biomonitoring with relevant specific IgE assays.

Description: Objectives Casale Monferrato (north west Italy) is an area with an exceptionally high incidence of mesothelioma caused by asbestos contamination at work and in the general environment from the asbestos-cement Eternit plant that was operational until 1986. The purpose of this study was to quantify the association between pleural malignant mesothelioma (PMM) and asbestos cumulative exposure using individual assessment of environmental and domestic exposure, as well as of occupational exposure. Methods This population-based case-control study included cases of PMM diagnosed between January 2001 and June 2006 among residents in the Casale Monferrato Local Health Authority. Population controls were randomly sampled, matched by age and sex to cases. Cumulative exposure was estimated to account for the lifelong exposure history. Analyses were conducted using unconditional logistic regression models adjusting for gender, age at diagnosis and type of interview (direct or proxy respondents). Results 200 PMM cases of 223 eligible cases (89.7%) and 348 (63%) of 552 eligible controls accepted to be interviewed. ORs increased with cumulative exposure index (p〈0.0001) from 4.4 (CI 95% 1.7 to 11.3) (〈1 f/mL-years) to 62.1 (CI 95% 22.2 to 173.2) (≥10 f/mL-years). Among subjects never occupationally exposed, corresponding ORs were 3.8 (CI 95% 1.3 to 11.1) and 23.3 (CI 95% 2.9 to 186.9) (reference: background level of asbestos exposure). ORs of about 2, statistically significant, were observed for domestic exposure and for living in houses near buildings with large asbestos cement parts. Conclusions Risk of PMM increased with cumulative asbestos exposure and also in analyses limited to subjects non-occupationally exposed. Our results also provide indication of risk associated with common sources of environmental exposure and are highly relevant for the evaluation of residual risk after the cessation of asbestos industrial use.

Description: Introduction The oxidative potential (OP) of particulate matter (PM) has been proposed as a health-relevant metric, but currently few epidemiological studies investigated associations of OP with health. Our main aim was to assess associations of long-term exposure to OP with respiratory health in children. Our second aim was to evaluate whether OP is more consistently associated with respiratory health than PM mass, PM composition or nitrogen dioxide (NO 2 ). Methods For 3701 participants of a prospective birth cohort, annual average concentrations of OP (assessed by spin resonance (OP ESR ) and dithiothreitol assay (OP DTT )), PM with an aerodynamic diameter of less than 2.5 µm (PM 2.5 ) mass, NO 2 , and PM 2.5 constituents at the home addresses at birth and at all follow-up addresses were estimated by land-use regression. Repeated questionnaire reports of asthma and hay fever until age 14 years, and measurements of allergic sensitisation, lung function and fractional exhaled nitric oxide at age 12 years were linked with air pollution concentrations. Results Asthma incidence, prevalence of asthma symptoms and rhinitis were positively associated with OP DTT (adjusted OR (95% CI) per IQR increase in exposure 1.10 (1.01 to 1.20), 1.08 (1.02 to 1.16), 1.15 (1.05 to 1.26), respectively). These associations persisted after adjustment for most co-pollutants. Forced expiratory volume in 1s and forced vital capacity were negatively associated with OP DTT . These associations were sensitive to adjustment for NO 2 . Respiratory health was not significantly associated with PM 2.5 mass and OP ESR . Conclusions Respiratory health was more strongly associated with OP DTT than with PM 2.5 mass; OP DTT associations with lung function, but not symptoms, were sensitive to adjustment for NO 2 .

Description: Objectives To describe the health burden among Fire Department of the City of New York (FDNY) emergency medical service (EMS) workers and examine its association with work at the World Trade Center (WTC) disaster site. Methods In this observational cohort study, we used FDNY physician diagnoses to estimate the cumulative incidence of physical health conditions including rhinosinusitis, gastroesophageal reflux disease (GERD), obstructive airways disease (OAD) and cancer among EMS workers and demographically similar firefighters who were active on 11 September 2001 (9/11). Validated screening instruments were used to estimate the prevalence of probable post-traumatic stress disorder (PTSD), probable depression and probable harmful alcohol use. We also analysed the association between health conditions and WTC-exposure. Results Among 2281 EMS workers, the 12-year post-9/11 cumulative incidence (11 September 2001 to 31 December 2013) of rhinosinusitis was 10.6%; GERD 12.1%; OAD 11.8%; cancer 3.1%. The prevalence of probable PTSD up to 12 years after exposure was 7%; probable depression 16.7%; and probable harmful alcohol use 3%. Compared with unexposed, EMS workers who arrived earliest at the site had higher adjusted relative risks (aRR) for most conditions, including rhinosinusitis (aRR=3.7; 95% CI 2.2 to 6.0); GERD (aRR=3.8; 95% CI 2.4 to 6.1); OAD (aRR=2.4: 95% CI 1.7 to 3.6); probable PTSD (aRR=7.0; 95% CI 3.6 to 13.5); and, probable depression (aRR=2.3; 95% CI 1.6 to 3.1). Conclusions In this 12-year study, we documented a high burden of health conditions associated with WTC-exposure among FDNY EMS workers. These findings underscore the importance of continued monitoring and treatment of this workforce.

Description: Objectives Several respirable hazards, including smoking and indoor air pollution from biomass, were suggested to increase the risk of tuberculosis. Few studies have been conducted on ambient air pollution and tuberculosis. We investigated the association between exposure to ambient air pollution and incidence of active tuberculosis. Methods We conducted a cohort study using 106 678 participants of a community-based screening service in Taiwan, 2005–2012. We estimated individual exposure to air pollution using data from the nearest air quality monitoring station and the road intensity within a 500 m buffer zone. The incidence of tuberculosis was ascertained from the national tuberculosis registry. Results After a median follow-up of 6.7 years, 418 cases of tuberculosis occurred. Exposure to fine particulate matter (PM 2.5 ) was associated with increased risk of active tuberculosis (adjusted HR: 1.39/10 μg/m 3 (95% CI 0.95 to 2.03)). In addition, traffic-related air pollution including nitrogen dioxide (adjusted HR: 1.33/10 ppb; 95% CI 1.04 to 1.70), nitrogen oxides (adjusted HR: 1.21/10 ppb; 95% CI 1.04 to 1.41) and carbon monoxide (adjusted HR: 1.89/ppm; 95% CI 0.78 to 4.58) was associated with tuberculosis risk. There was a non-significant trend between the length of major roads in the neighbourhood and culture-confirmed tuberculosis (adjusted HR: 1.04/km; 95% CI 0.995 to 1.09). Conclusions Our study revealed a possible link between ambient air pollution and risk of active tuberculosis. Since people from developing countries continue to be exposed to high levels of ambient air pollution and to experience high rates of tuberculosis, the impact of worsening air pollution on global tuberculosis control warrants further investigation.

Description: Background Asthma prevalence and acute exacerbations have been associated with endotoxin exposure. However, there are limited data on relations between acute asthma outcomes in children and personal exposure to endotoxin or whether this relation is modified by personal air pollution exposures. Methods We made repeated measurements of the fractional concentration of exhaled NO (F e NO ), forced expiratory volume in 1 s (FEV 1 ) and personal endotoxin exposures in patients with persistent asthma aged 9–18 years, each of whom was followed for 10 consecutive days in Riverside and Whittier, California. Endotoxin was measured in PM 2.5 , and simultaneously we measured personal exposure to air pollutants: NO 2 and PM 2.5 mass, elemental carbon and organic carbon. Endotoxin exposure–response relations and interactions between endotoxin and air pollutants were analysed with mixed models controlling for personal temperature, humidity and the 10-day period. Results Neither percent-predicted FEV 1 nor F e NO was associated with personal endotoxin overall; however, endotoxin was associated with FEV 1 among patients with average percent-predicted FEV 1 〈80%. When NO 2 was above its median, F e NO increased by 2.2% (95% CI –0.8% to 5.2%) for an interquartile increase in personal endotoxin, whereas F e NO was lower by –1.8% (95% CI –4% to 0.5%) when NO 2 was≤its median. However, this is out of 12 interaction tests between personal endotoxin and a binary air pollutant for each outcome (FEV 1 and F e NO ), and there were no interactions with any continuous-scaled pollutant. Conclusions Personal endotoxin exposure was not associated with acute daily changes in F e NO or FEV 1 in a cohort panel of schoolchildren with asthma, except for decreased FEV 1 among patients with more severe asthma (percent-predicted FEV 1 〈80%). There was limited evidence of effect modification of endotoxin by personal exposure to air pollution.

Description: Introduction Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160 000 tons/year. The National Register of Mesotheliomas (ReNaM, "Registro Nazionale dei Mesoteliomi" in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure. Methods The Operating Regional Center (COR) actively researches cases and defines asbestos exposure on the basis of national guidelines. Diagnostic, demographic and exposure characteristics of non-occupationally exposed cases are analysed and described with respect to occupationally exposed cases. Results Standardised incidence rates for pleural mesothelioma in 2008 were 3.84 (per 100 000) for men and 1.45 for women, respectively. Among the 15 845 mesothelioma cases registered between 1993 and 2008, exposure to asbestos fibres was investigated for 12 065 individuals (76.1%), identifying 530 (4.4%) with familial exposure (they lived with an occupationally exposed cohabitant), 514 (4.3%) with environmental exposure to asbestos (they lived near sources of asbestos pollution and were never occupationally exposed) and 188 (1.6%) exposed through hobby-related or other leisure activities. Clusters of cases due to environmental exposure are mainly related to the presence of asbestos-cement industry plants (Casale Monferrato, Broni, Bari), to shipbuilding and repair activities (Monfalcone, Trieste, La Spezia, Genova) and soil contamination (Biancavilla in Sicily). Conclusions Asbestos pollution outside the workplace contributes significantly to the burden of asbestos-related diseases, suggesting the need to prevent exposures and to discuss how to deal with compensation rights for malignant mesothelioma cases induced by non-occupational exposure to asbestos.

Description: Background In several studies, exposure to fine particulate matter (PM) has been associated with inflammation, with inconsistent results. We used repeated measurements to examine the association of long-term fine and ultrafine particle exposure with several blood markers of inflammation and coagulation. Methods We used baseline (2000–2003) and follow-up (2006–2008) data from the Heinz Nixdorf Recall Study, a German population-based prospective cohort of 4814 participants. A chemistry transport model was applied to model daily surface concentrations of PM air pollutants (PM 10 , PM 2.5 ) and particle number on a grid of 1 km 2 . Applying mixed regression models, we analysed associations of long-term (mean of 365 days prior to blood draw) particle exposure at each participant's residence with the level of high-sensitivity C reactive protein (hs-CRP), fibrinogen, platelet and white cell count (WCC), adjusting for short-term PM exposure (moving averages of 1–7 days), personal characteristics, season, ambient temperature (1–5 days), ozone and time trend. Results We analysed 6488 observations: 3275 participants with baseline data and 3213 with follow-up data. An increase of 2.4 µg/m 3 in long-term PM 2.5 was associated with an adjusted increase of 5.4% (95% CI 0.6% to 10.5%) in hs-CRP and of 2.3% (95% CI 1.4% to 3.3%) in the platelet count. Fibrinogen and WCC were not associated with long-term particle exposure. Conclusions In this population-based cohort, we found associations of long-term exposure to PM with markers of inflammation (hs-CRP) and coagulation (platelets). This finding supports the hypothesis that inflammatory processes might contribute to chronic effects of air pollution on cardiovascular disease.