602 research outputs found

    An international prospective general population-based study of respiratory work disability

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    Background: Previous cross-sectional studies have shown that job change due to breathing problems at the workplace (respiratory work disability) is common among adults of working age. That research indicated that occupational exposure to gases, dust and fumes was associated with job change due to breathing problems, although causal inferences have been tempered by the cross-sectional nature of previously available data. There is a need for general population-based prospective studies to assess the incidence of respiratory work disability and to delineate better the roles of potential predictors of respiratory work disability.Methods: A prospective general population cohort study was performed in 25 centres in 11 European countries and one centre in the USA. A longitudinal analysis was undertaken of the European Community Respiratory Health Survey including all participants employed at any point since the baseline survey, 6659 subjects randomly sampled and 779 subjects comprising all subjects reporting physician-diagnosed asthma. The main outcome measure was new-onset respiratory work disability, defined as a reported job change during follow-up attributed to breathing problems. Exposure to dusts (biological or mineral), gases or fumes during follow-up was recorded using a job-exposure matrix. Cox proportional hazard regression modelling was used to analyse such exposure as a predictor of time until job change due to breathing problems.Results: The incidence rate of respiratory work disability was 1.2/1000 person-years of observation in the random sample (95% CI 1.0 to 1.5) and 5.7/1000 person-years in the asthma cohort (95% CI 4.1 to 7.8). In the random population sample, as well as in the asthma cohort, high occupational exposure to biological dust, mineral dust or gases or fumes predicted increased risk of respiratory work disability. In the random sample, sex was not associated with increased risk of work disability while, in the asthma cohort, female sex was associated with an increased disability risk (hazard ratio 2.8, 95% CI 1.3 to 5.9).Conclusions: Respiratory work disability is common overall. It is associated with workplace exposures that could be controlled through preventive measures

    Leptin, acylcarnitine metabolites and development of adiposity in the Rhea mother-child cohort in Crete, Greece.

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    OBJECTIVE: This study aims to investigate relations of serum leptin at age 4 with development of adiposity and linear growth during 3 years of follow-up among 75 Greek children and to identify serum metabolites associated with leptin at age 4 and to characterize their associations with adiposity gain and linear growth. METHODS: Linear regression models that accounted for maternal age, education and gestational weight gain and child's age and sex were used to examine associations of leptin and leptin-associated metabolites measured at age 4 with indicators of adiposity and linear growth at age 7. RESULTS: Each 1-unit increment in natural log-(ln)-transformed leptin corresponded with 0.33 (95% CI: 0.10, 0.55) units greater body mass index-for-age z-score gain during follow-up. Likewise, higher levels of the leptin-associated metabolites methylmalonyl-carnitine and glutaconyl-carnitine corresponded with 0.14 (95% CI: 0.01, 0.27) and 0.07 (95% CI: -0.01, 0.16) units higher body mass index-for-age z-score gain, respectively. These relationships did not differ by sex or baseline weight status and were independent of linear growth. CONCLUSIONS: These findings suggest that leptin, methylmalonyl-carnitine and possibly glutaconyl-carnitine are associated with weight gain during early childhood. Future studies are warranted to confirm these findings in other populations

    Genome-wide interaction study of early-life smoking exposure on time-to-asthma onset in childhood

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    BACKGROUND: Asthma, a heterogeneous disease with variable age of onset, results from the interplay between genetic and environmental factors. Early-life tobacco smoke (ELTS) exposure is a major asthma risk factor. Only a few genetic loci have been reported to interact with ELTS exposure in asthma. OBJECTIVE: Our aim was to identify new loci interacting with ELTS exposure on time-to-asthma onset (TAO) in childhood. METHODS: We conducted genome-wide interaction analyses of ELTS exposure on time-to-asthma onset in childhood in five European-ancestry studies (totaling 8,273 subjects) using Cox proportional-hazard model. The results of all five genome-wide analyses were meta-analyzed. RESULTS: The 13q21 locus showed genome-wide significant interaction with ELTS exposure (P=4.3x10-8 for rs7334050 within KLHL1 with consistent results across the five studies). Suggestive interactions (P<5x10-6 ) were found at three other loci: 20p12 (rs13037508 within MACROD2; P=4.9x10-7 ), 14q22 (rs7493885 near NIN; P=2.9x10-6 ) and 2p22 (rs232542 near CYP1B1; P=4.1x10-6 ). Functional annotations and the literature showed that the lead SNPs at these four loci influence DNA methylation in the blood and are located nearby CpG sites reported to be associated with exposure to tobacco smoke components, which strongly support our findings. CONCLUSION AND CLINICAL RELEVANCE: We identified novel candidate genes interacting with ELTS exposure on time-to-asthma onset in childhood. These genes have plausible biological relevance related to tobacco smoke exposure. Further epigenetic and functional studies are needed to confirm these findings and to shed light on the underlying mechanisms. This article is protected by copyright. All rights reserved

    Exposure to Agent Orange and occurrence of soft-tissue sarcomas or non-Hodgkin lymphomas: an ongoing study in Vietnam.

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    Agent Orange was the most common herbicide used in the Second Indochina War in the course of military operations in the former South Vietnam. Agent Orange is contaminated by the carcinogen 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) in mean concentrations of 2 mg/kg. After much dispute of a causal association between exposure to herbicides containing TCDD and occurrence of soft-tissue sarcoma and non-Hodgkin lymphoma, two simultaneous case-control studies were set up in Vietnam to examine possible relationships. Subject recruitment is ongoing, with target numbers of 150 cases of soft-tissue sarcoma and 150 cases of non-Hodgkin lymphoma and diagnoses at the Cancer Center at Ho Chi Minh City, Vietnam. Two hospital controls are matched to each case. As in other studies of cancer in persons occupationally or otherwise exposed to herbicides and their contaminants, evaluation of past exposure of the recruited subjects is among the most complicated issues. Because accurate records are usually unavailable, surrogate measures of likely exposure are often calculated. As a first approach in our studies we used the Stellman and Stellman exposure index. The index is based on matching subjects' history of residence and the information on times and locations of Agent Orange spraying recorded on HERBS tape by the U.S. Army and taking into account the distance from the spraying as well as environmental and biologic half-life of TCDD. The exposure index is calculated in two centers, New York and Hanoi, with slightly different assumptions. In addition, samples of body tissues from the subjects (20 ml blood, 2 g adipose tissue, and tumor sections in paraffin blocks) are taken and stored. Their future analysis will provide additional source of exposure assessment. Strengths and weaknesses of both exposure measures are discussed in this paper

    The polyAT, intronic IVS11-6 and Lys939Gln XPC polymorphisms are not associated with transitional cell carcinoma of the bladder

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    Chemical carcinogens from cigarette smoking and occupational exposure are risk factors for bladder transitional cell carcinoma (TCC). The Xeroderma Pigmentosum Group C (XPC) gene is essential for repair of bulky adducts from carcinogens. The Xeroderma Pigmentosum Group C gene polymorphisms may alter DNA repair capacity (DRC), thus giving rise to genetic predisposition to bladder cancer. Recent studies have demonstrated linkage disequilibrium between three polymorphisms in the XPC gene (polyAT, IVS11-6 and Lys939Gln) and these have been shown to influence the DRC, as well as to be associated with bladder cancer risk. We analysed all three XPC polymorphisms in 547 bladder TCC patients and 579 cancer-free controls to investigate the association between these polymorphisms and bladder cancer susceptibility, and we also attempted to assess gene–environmental interactions. We confirmed strong linkage disequilibrium among the polymorphisms (Lewontin's D′>0.99). Using logistic regression adjusting for smoking, occupational and family history, neither the heterozygote nor the homozygote variants of these polymorphisms were associated with increased bladder cancer risk (adjusted odds ratio [95% confidence interval] for heterozygote 0.82 [0.63–1.07], 0.82 [0.63–1.08] and 0.83 [0.63–1.08] for PolyAT, IVS11-6 and Lys939Gln, respectively and homozygote variant, 0.98 [0.68–1.42], 0.99 [0.69–1.43] and 1.01 [0.70–1.46]). Moreover, we did not find any significant interaction between these XPC polymorphisms and environmental exposure to cigarette smoking and occupational carcinogens

    Respiratory symptoms and occupation: a cross-sectional study of the general population

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    BACKGROUND: This study focused on respiratory symptoms due to occupational exposures in a contemporary general population cohort. Subjects were from the Dutch Monitoring Project on Risk Factors for Chronic Diseases (MORGEN). The composition of this population enabled estimation of respiratory risks due to occupation from the recent past for both men and women. METHODS: The study subjects (aged 20–59) were all inhabitants of Doetinchem, a small industrial town, and came from a survey of a random sample of 1104 persons conducted in 1993. A total of 274 cases with respiratory symptoms (subdivided in asthma and bronchitis symptoms) and 274 controls without symptoms were matched for age and sex. Relations between industry and occupation and respiratory symptoms were explored and adjusted for smoking habits and social economic status. RESULTS: Employment in the 'construction' (OR = 3.38; 95%CI 1.02 – 11.27), 'metal' (OR = 3.17; 95%CI 0. 98 – 10.28), 'rubber, plastics and synthetics' (OR = 6.52; 95%CI 1.26 – 53.80), and 'printing' industry (OR = 3.96; 95%CI 0.85 – 18.48) were positively associated with chronic bronchitis symptoms. In addition, the 'metal' industry was found to be weakly associated with asthma symptoms (OR = 2.59; 95%CI 0.87 – 7.69). Duration of employment within these industries was also positively associated with respiratory symptoms. CONCLUSION: Respiratory symptoms in the general population are traceable to employment in particular industries even in a contemporary cohort with relatively young individuals

    Sex ratio of the offspring of New Zealand phenoxy herbicide producers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

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    Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has inconsistently been associated with a decreased sex ratio of the offspring (number of male births divided by total births). We conducted a study among men and women who were employed in a New Zealand phenoxy herbicide production plant between 1969 and 1984, to study their offspring sex ratio in relation to their back-calculated TCDD serum concentrations determined in 2007/2008. A total of 127 men and 21 women reported that 355 children were conceived after starting employment at the plant. The association between their lipid-standardised TCDD serum concentrations back-calculated to the time of their offspring's birth and the probability of a male birth was estimated through logistic regression, adjusting for the age of the exposed parent at birth, current body mass index and smoking. The overall sex ratio was 0.55 (197 boys, 158 girls). For fathers with serum TCDD concentrations ≥20 pg/g lipid at time of birth, the sex ratio was 0.47 (OR 0.49; 95% CI 0.30 to 0.79). The probability of a male birth decreased with higher paternal serum TCDD at time of birth (&lt;4; 4-20; 20-100; ≥100 pg/g lipid), with ORs of 1.00 (reference); 1.00 (95% CI 0.50 to 2.02); 0.52 (95% CI 0.29 to 0.92); 0.45 (95% CI 0.23 to 0.89), p trend 0.007. For exposed mothers, the sex ratio was not reduced. This study indicates that paternal serum TCDD concentrations in excess of an estimated 20 pg/g lipid at time of conception are associated with a reduced sex ratio

    Asthma caused by occupational exposures is common – A systematic analysis of estimates of the population-attributable fraction

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    <p>Abstract</p> <p>Background</p> <p>The aim of this paper is to highlight emerging data on occupational attributable risk in asthma. Despite well documented outbreaks of disease and the recognition of numerous specific causal agents, occupational exposures previously had been relegated a fairly minor role relative to other causes of adult onset asthma. In recent years there has been a growing recognition of the potential importance of asthma induced by work-related exposures</p> <p>Methods</p> <p>We searched Pub Med from June 1999 through December 2007. We identified six longitudinal general population-based studies; three case-control studies and eight cross-sectional analyses from seven general population-based samples. For an integrated analysis we added ten estimates prior to 1999 included in a previous review.</p> <p>Results</p> <p>The longitudinal studies indicate that 16.3% of all adult-onset asthma is caused by occupational exposures. In an overall synthesis of all included studies the overall median PAR value was 17.6%.</p> <p>Conclusion</p> <p>Clinicians should consider the occupational history when evaluating patients in working age who have asthma. At a societal level, these findings underscore the need for further preventive action to reduce the occupational exposures to asthma-causing agents.</p

    Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers.

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    The authors studied noncancer mortality among phenoxyacid herbicide and chlorophenol production workers and sprayers included in an international study comprising 36 cohorts from 12 countries followed from 1939 to 1992. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin or higher chlorinated dioxins (TCDD/HCD) was discerned from job records and company questionnaires with validation by biologic and environmental measures. Standard mortality ratio analyses suggested a moderate healthy worker effect for all circulatory diseases, especially ischemic heart disease, among both those exposed and those not exposed to TCDD/HCD. In Poisson regression analyses, exposure to TCDD/HCD was not associated with increased mortality from cerebrovascular disease. However, an increased risk for circulatory disease, especially ischemic heart disease (rate ratio [RR] 1.67, 95% confidence interval [Cl] 1.23-2.26) and possibly diabetes (RR 2.25, 95% Cl 0.53-9.50), was present among TCDD/HCD-exposed workers. Risks tended to be higher 10 to 19 years after first exposure and for those exposed for a duration of 10 to 19 years. Mortality from suicide was comparable to that for the general population for all workers exposed to herbicides or chlorophenols and was associated with short latency and duration of exposure. More refined investigations of the ischemic heart disease and TCDD/HCD exposure association are warranted
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