The asbestos-asbestosis exposure-response relationship: a cohort study of the general working population.

OBJECTIVES: The association between asbestos exposure and asbestosis in high-exposed industrial cohorts is well-known, but there is a lack of knowledge about the exposure-response relationship for asbestosis in a general working population setting. We examined the exposure-response relationship between occupational asbestos exposure and asbestosis in asbestos-exposed workers of the Danish general working population. METHODS: We followed all asbestos-exposed workers from 1979 to 2015 and identified incident cases of asbestosis using the Danish National Patient Register. Individual asbestos exposure was estimated with a quantitative job exposure matrix (SYN-JEM) from 1976 onwards and back-extrapolated to age 16 for those exposed in 1976. Exposure-response relations for cumulative exposure and other exposure metrics were analyzed using a discrete time hazard model and adjusted for potential confounders. RESULTS: The range of cumulative exposure in the population was 0.001 to 18 fibers per milliliter-year (f/ml-year). We found increasing incidence rate ratios (IRR) of asbestosis with increasing cumulative asbestos exposure with a fully adjusted IRR per 1 f/ml-years of 1.18 [95% confidence interval (CI) 1.15- -1.22]. The IRR was 1.94 (95% CI 1.53-2.47) in the highest compared to the lowest exposure tertile. We similarly observed increasing risk with increasing cumulative exposure in the inception population. CONCLUSIONS: This study found exposure-response relations between cumulative asbestos exposure and incident asbestosis in the Danish general working population with mainly low-level exposed occupations, but there is some uncertainty regarding the exposure levels.

Respirable crystalline silica and lung cancer in community-based studies: impact of job-exposure matrix specifications on exposure-response relationships.

OBJECTIVES: The quantitative job-exposure matrix SYN-JEM consists of various dimensions: job-specific estimates, region-specific estimates, and prior expert ratings of jobs by the semi-quantitative DOM-JEM. We analyzed the effect of different JEM dimensions on the exposure-response relationships between occupational silica exposure and lung cancer risk to investigate how these variations influence estimates of exposure by a quantitative JEM and associated health endpoints. METHODS: Using SYN-JEM, and alternative SYN-JEM specifications with varying dimensions included, cumulative silica exposure estimates were assigned to 16 901 lung cancer cases and 20 965 controls pooled from 14 international community-based case-control studies. Exposure-response relationships based on SYN-JEM and alternative SYN-JEM specifications were analyzed using regression analyses (by quartiles and log-transformed continuous silica exposure) and generalized additive models (GAM), adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. RESULTS: SYN-JEM and alternative specifications generated overall elevated and similar lung cancer odds ratios ranging from 1.13 (1st quartile) to 1.50 (4th quartile). In the categorical and log-linear analyses SYN-JEM with all dimensions included yielded the best model fit, and exclusion of job-specific estimates from SYN-JEM yielded the poorest model fit. Additionally, GAM showed the poorest model fit when excluding job-specific estimates. CONCLUSION: The established exposure-response relationship between occupational silica exposure and lung cancer was marginally influenced by varying the dimensions of SYN-JEM. Optimized modelling of exposure-response relationships will be obtained when incorporating all relevant dimensions, namely prior rating, job, time, and region. Quantitative job-specific estimates appeared to be the most prominent dimension for this general population JEM.

Cumulative occupational exposure to gases and fumes is associated with impairment in lung function and disease-related quality of life in a German COPD patient cohort.

OBJECTIVES: The impact of occupational exposures on lung function impairments and quality of life (QoL) in patients with chronic obstructive pulmonary disease (COPD) was analysed and compared with that of smoking. METHODS: Data from 1283 men and 759 women (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4 or former grade 0, without alpha-1-antitrypsin deficiency) of the COPD and Systemic Consequences Comorbidities Network cohort were analysed. Cumulative exposure to gases/fumes, biological dust, mineral dust or the combination vapours/gases/dusts/fumes was assessed using the ALOHA job exposure matrix. The effect of both occupational and smoking exposure on lung function and disease-specific QoL (St George's Respiratory Questionnaire) was analysed using linear regression analysis adjusting for age, body mass index, diabetes, hypertension and coronary artery disease, stratified by sex. RESULTS: In men, exposure to gases/fumes showed the strongest effects among occupational exposures, being significantly associated with all lung function parameters and QoL; the effects were partially stronger than of smoking. Smoking had a larger effect than occupational exposure on lung diffusing capacity (transfer factor for carbon monoxide) but not on air trapping (residual volume/total lung capacity). In women, occupational exposures were not significantly associated with QoL or lung function, while the relationships between lung function parameters and smoking were comparable to men. CONCLUSIONS: In patients with COPD, cumulative occupational exposure, particularly to gases/fumes, showed effects on airway obstruction, air trapping, gas uptake capacity and disease-related QoL, some of which were larger than those of smoking. These findings suggest that lung air trapping and QoL should be considered as outcomes of occupational exposure to gases and fumes in patients with COPD. TRIAL REGISTRATION NUMBER: NCT01245933.

Self-reported and urinary biomarker-based measures of exposure to glyphosate and mancozeb and sleep problems among smallholder farmers in Uganda.

OBJECTIVE: We aim to showcase the impact of applying eight different self-reported and urinary biomarker-based exposure measures for glyphosate and mancozeb on the association with sleep problems in a study among 253 smallholder farmers in Uganda. METHODS: The questionnaire-based exposure measures included: (1) the number of application days of any pesticide in the last 7 days (never, 1-2; >2 days) and six glyphosate and mancozeb-specific measures: (2) application status over the last 12 months (yes/no), (3) recent application status (never, last 7 days and last 12 months), (4) the number of application days last 12 months, (5) average exposure-intensity scores (EIS) and (6) EIS-weighted number of application days in last 12 months. Based on 384 repeated urinary biomarker concentrations of ethylene thiourea (ETU) and glyphosate from 84 farmers, we also estimated (7) average biomarker concentrations for all 253 farmers. Also in the 84 farmers the measured pre-work and post-work biomarker concentrations were used (8). Multivariable logistic regression models were used to assess the association between the exposure measures and selected Medical Outcomes Study Sleep Scale (MOS-SS) indices (6-item, sleep inadequacy and snoring). RESULTS: We observed positive associations between (1) any pesticide application in the last 7 days with all three MOS-SS indices. Glyphosate application in the last 7 days (3) and mancozeb application in the last 12 months (3) were associated with the 6-item sleep problem index. The estimated average urinary glyphosate concentrations showed an exposure-response association with the 6-item sleep problem index and sleep inadequacy in the same direction as based on self-reported glyphosate application in the last 7 days. In the analysis with the subset of 84 farmers, both measured and modelled post-work urinary glyphosate concentration showed an association with snoring. CONCLUSIONS: Self-reported, estimated average biomarker concentrations and measured urinary biomarker exposure measures of glyphosate and mancozeb showed similar exposure-response associations with sleep outcomes.

Impact of occupational pesticide exposure assessment method on risk estimates for prostate cancer, non-Hodgkin's lymphoma and Parkinson's disease: results of three meta-analyses.

Assessment of occupational pesticide exposure in epidemiological studies of chronic diseases is challenging. Biomonitoring of current pesticide levels might not correlate with past exposure relevant to disease aetiology, and indirect methods often rely on workers' imperfect recall of exposures, or job titles. We investigated how the applied exposure assessment method influenced risk estimates for some chronic diseases. In three meta-analyses the influence of exposure assessment method type on the summary risk ratio (sRR) of prostate cancer (PC) (25 articles), non-Hodgkin's lymphoma (NHL) (29 articles) and Parkinson's disease (PD) (32 articles) was investigated. Exposure assessment method types analysed were: group-level assessments (eg, job titles), self-reported exposures, expert-level assessments (eg, job-exposure matrices) and biomonitoring (eg, blood, urine). Additionally, sRRs were estimated by study design, publication year period and geographic location where the study was conducted. Exposure assessment method types were not associated with statistically significant different sRRs across any of the health outcomes. Heterogeneity in results varied from high in cancer studies to moderate and low in PD studies. Overall, case-control designs showed significantly higher sRR estimates than prospective cohort designs. Later NHL publications showed significantly higher sRR estimates than earlier. For PC, studies from North America showed significantly higher sRR estimates than studies from Europe. We conclude that exposure assessment method applied in studies of occupational exposure to pesticides appears not to have a significant effect on risk estimates for PC, NHL and PD. In systematic reviews of chronic health effects of occupational exposure to pesticides, epidemiological study design, publication year and geographic location, should primarily be considered.

Impact of Education on COPD Severity and All-Cause Mortality in Lifetime Never-Smokers and Longtime Ex-Smokers: Results of the COSYCONET Cohort.

Background: Beyond smoking, several risk factors for the development of chronic obstructive pulmonary disease (COPD) have been described, among which socioeconomic status including education is of particular interest. We studied the contribution of education to lung function and symptoms relative to smoking in a group of never-smokers with COPD compared to a group of long-time ex-smokers with COPD. Methods: We used baseline data of the COSYCONET cohort, including patients of GOLD grades 1-4 who were either never-smokers (n=150, age 68.5y, 53.3% female) or ex-smokers (≥10 packyears) for at least 10 years (n=616, 68.3y, 29.9% female). Socioeconomic status was analyzed using education level and mortality was assessed over a follow-up period of 4.5 years. Analyses were performed using ANOVA and regression models. Results: Spirometric lung function did not differ between groups, whereas CO diffusing capacity and indicators of lung hyperinflation/air-trapping showed better values in the never-smoker group. In both groups, spirometric lung function depended on the education level, with better values for higher education. Quality of life and 6-MWD were significantly different in never-smokers as well as patients with higher education. Asthma, alpha-1-antitrypsin deficiency, and bronchiectasis were more often reported in never-smokers, and asthma was more often reported in patients with higher education. Higher education was also associated with reduced mortality (hazard ratio 0.46; 95% CI 0.22-0.98). Conclusion: Overall, in the COSYCONET COPD cohort, differences in functional status between never-smokers and long-time ex-smokers were not large. Compared to that, the dependence on education level was more prominent, with higher education associated with better outcomes, including mortality. These data indicate that non-smoking COPD patients' socioeconomic factors are relevant and should be taken into account by clinicians.

Improving Exposure Assessment Methodologies for Epidemiological Studies on Pesticides: Study Protocol.

BACKGROUND: Exposure to certain pesticides has been associated with several chronic diseases. However, to determine the role of pesticides in the causation of such diseases, an assessment of historical exposures is required. Exposure measurement data are rarely available; therefore, assessment of historical exposures is frequently based on surrogate self-reported information, which has inherent limitations. Understanding the performance of the applied surrogate measures in the exposure assessment of pesticides is therefore important to allow proper evaluation of the risks. OBJECTIVE: The Improving Exposure Assessment Methodologies for Epidemiological Studies on Pesticides (IMPRESS) project aims to assess the reliability and external validity of the surrogate measures used to assign exposure within individuals or groups of individuals, which are frequently based on self-reported data on exposure determinants. IMPRESS will also evaluate the size of recall bias on the misclassification of exposure to pesticides; this in turn will affect epidemiological estimates of the effect of pesticides on human health. METHODS: The IMPRESS project will recruit existing cohort participants from previous and ongoing research studies primarily of epidemiological origin from Malaysia, Uganda, and the United Kingdom. Consenting participants of each cohort will be reinterviewed using an amended version of the original questionnaire addressing pesticide use characteristics administered to that cohort. The format and relevant questions will be retained but some extraneous questions from the original (eg, relating to health) will be excluded for ethical and practical reasons. The reliability of pesticide exposure recall over different time periods (<2 years, 6-12 years, and >15 years) will then be evaluated. Where the original cohort study is still ongoing, participants will also be asked if they wish to take part in a new exposure biomonitoring survey, which involves them providing urine samples for pesticide metabolite analysis and completing questionnaire information regarding their work activities at the time of sampling. The participant's level of exposure to pesticides will be determined by analyzing the collected urine samples for selected pesticide metabolites. The biomonitoring measurement results will be used to assess the performance of algorithm-based exposure assessment methods used in epidemiological studies to estimate individual exposures during application and re-entry work. RESULTS: The project was funded in September 2017. Enrollment and sample collection was completed for Malaysia in 2019 and is on-going for Uganda and the United Kingdom. Sample and data analysis will proceed in 2020 and the first results are expected to be submitted for publication in 2021. CONCLUSIONS: The study will evaluate the consistency of questionnaire data and accuracy of current algorithms in assessing pesticide exposures. It will indicate where amendments can be made to better capture exposure data for future epidemiology studies and thus improve the reliability of exposure-disease associations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/16448.

Interventions to Reduce Exposures in the Workplace: A Systematic Review of Intervention Studies Over Six Decades, 1960-2019.

Background: Reducing occupational ill-health from chemical and biological agents is realized primarily through the mitigation and elimination of hazardous exposures. Despite evidence of declining exposure in European and North-American workplaces, comprehensive studies of the effectiveness of workplace interventions for reducing hazardous exposure and associated work-related ill-health seem rare. We reviewed occupational intervention studies targeting exposure to chemical and biological agents, and determined trends in frequency and quality of such studies. Methods: We searched Embase, Medline, and Web of Science for peer-reviewed original articles on occupational intervention studies published 1960-2019, aimed at reducing workers' exposure to dusts, gases, fumes, or liquids of chemical, biological, or mineral nature, or workers' risks for associated health outcomes. The frequency of articles, intervention types, intervention endpoints, and study quality of published intervention studies between 1960 and 2019 and according to 10-year intervals were analyzed. Results: Of 3,663 retrieved articles, 146 intervention studies were identified and reviewed, of which 63 concerned control measures, 43 behavioral change, 28 use of personal protective equipment, and 12 workplace policies. Intervention endpoints were occupational exposures (73%), health outcomes (22%), and a combination of both (5%). Of reviewed studies, 38% involved a control group, 16% randomized the intervention, 86% were planned interventions, and 86% compared exposure or health outcomes pre and post intervention. Over time the number of intervention studies identified in this search increased from none during 1960-1969 to ~60 during 2000-2009 and 2010-2019, respectively. The study quality improved over time, with no studies during 1960-1989 that complied with the highest quality criteria. During 2000-2009 and 2010-2019 16 and 12% of studies, respectively, were judged to be of highest quality. Conclusion: Despite an improvement over the last six decades in the frequency and quality of intervention studies targeting exposure to chemicals and biological agents, the absolute number of intervention studies remains low, particularly when considering only high quality studies. Occupational exposure to chemical and biological agents is still causing excessive disease in workforces worldwide. To reduce occupational ill-health caused by these exposures, it is important to expand the evidence on (cost-)effectiveness and transferability of interventions to reduce exposure and health effects.

Systematic review of methods used to assess exposure to pesticides in occupational epidemiology studies, 1993-2017.

OBJECTIVE: Numerous exposure assessment methods (EAM) exist for investigating health effects of occupational exposure to pesticides. Direct (eg, biomonitoring) and indirect methods (eg, self-reported exposures) are however associated with degrees of exposure misclassification. We systematically reviewed EAM in studies of occupational pesticide exposure. METHODS: We searched for articles reporting observational epidemiological studies in MEDLINE and Embase published 1993 to 2017. The relative frequency of EAM was analysed according to EAM type (direct and indirect methods), health outcome, study design, study location (country) and specificity of assessment. Temporal trends in EAM were analysed. RESULTS: In 1298 included articles 1521 EAM occurrences were documented. Indirect EAM (78.3%), primarily self-reported exposures (39.3%) and job titles assessments (9.5%), were mainly applied in case-control studies (95.0%), in high-income countries (85.0%) and in studies of doctor-diagnosed health outcomes (>85%). Direct EAM (20.8%), primarily biomonitoring of blood (15.6%) or urine (4.7%), were predominantly applied in cross-sectional studies (29.8%), in lower middle-income countries (40.9%) and in studies of neurological (50.0%) outcomes. Between 1993 to 2017 no distinct time trends regarding the ratio indirect to direct methods was seen. Within the category of indirect methods use of self-reported exposures and job exposure matrices increased while assessments by job titles and registers decreased. The use of algorithms showed no trend. The specificity of pesticide assessment increased since studies assessing exposure by using job title as a proxy declined. Assessments of type of pesticide increased. CONCLUSION: Over the last 25 years, the ratio (5:1) of indirect to direct EAM applied in articles on occupational pesticide epidemiology stayed relatively constant; changes were mainly attributable to increasing use of self-reported exposures and job exposure matrices. This review, combined with studies assessing EAM validity, will inform on magnitudes of exposure misclassification and help improve the quality of studies on occupational pesticides exposure.

Snap-fit assembly and upper limb functional limitations in automotive production workers: a nested case-control study.

OBJECTIVES: The use of snap-fits in car-part assembling has developed into an industrial standard. Cross-sectional evidence indicates, however, that this assembling process might adversely affect workers' upper limb function. The objective of this study was to analyze incident cases of upper limb functional limitations (ULFL) in relation to exposure to snap-fit assembly. METHODS: We performed a nested case-control study within a population of 5139 blue-collar automotive production workers. Cases with ULFL detected during follow-up were matched with controls based on employment duration and investigated on their exposure to snap-fit assembly. By conditional logistic regression, we modeled the risk for ULFL according to person-years of exposure to snap-fit assembly, adjusted for gender and baseline BMI. RESULTS: Overall, 64 ULFL cases were detected during a follow-up of 20610.8 person-years (3.1 cases per 1000 person-years). Cases, matched with an average of 4 controls, had significantly longer exposure duration to snap-fit assembly compared with controls (M = 1.15 person-years, SD = 1.68 person-years vs. M = 0.41 person-years, SD = 1.25 person-years). One person-year of exposure to snap-fit assembly was associated with an approximate 20% risk increase of developing ULFLs (OR 1.23, 95% CI 1.08-1.39). CONCLUSIONS: We confirm an association between accumulated exposure to snap-fits in car-part assembling and upper limb musculoskeletal disorders. Company physicians should thus be vigilant to symptoms of musculoskeletal disorders of the upper limbs in snap-fit assembly and support the development of threshold values for snap-fit insertion forces.

Mercury and neuromotor function among children in a rural town in Chile.

BACKGROUND: Mercury (Hg) exposure from artisanal gold mining has adverse effects on the neuromotor function in adults. However, few studies have examined this relationship in children. OBJECTIVES: To investigate the impact of Hg exposure on children's neuromotor function. METHODS: Cross-sectional data on Hg risk factors and demographics were collected from n = 288 children (response = 68.9%). Based on complete cases (CCs) (n = 130) and multiple imputations (n = 288), associations between fingernail Hg and four different neuromotor function components were calculated using multiple logistic regression adjusted for confounders. RESULTS: Of the children, 11.1, 14.9, 63.9, and 10.4% had pathologic pure motor skills, adaptive fine motor skills, adaptive gross motor skills, and static balance, respectively. No significant association between fingernail Hg and any neuromotor component was found. However, Hg burning in the household was significantly associated with children's pathologic pure motor skills (OR 3.07 95% CI 1.03-9.18). CONCLUSION: Elemental Hg exposure in the household might have adverse long-term effects on children's pure motor skills.

Asthma prevalence in Olympic summer athletes and the general population: An analysis of three European countries.

BACKGROUND: Some studies have shown a higher prevalence of asthma in elite athletes as compared to the general population. It is inconclusive to what extent certain sport categories are especially affected. The present study offered a unique opportunity to assess these differences in asthma prevalence in the general population and elite summer athletes from a wide range of sport disciplines across various geographical areas. METHODS: Cross-sectional data for 1568 general population participants from the European Community Respiratory Health Survey II and 546 elite athletes from the Global Allergy and Asthma European Network Olympic study from three European countries were analyzed. Using logistic regression, the asthma risks associated with athlete sport practice, endurance level and aquatic sport practice, respectively, were investigated. RESULTS: Athletes in the highest endurance category had increased risk of doctor-diagnosed asthma (OR 3.5; 95% CI 1.7-7.5), asthma symptoms (OR 3.0; CI 1.5-6.0) and asthma symptoms or medication use (OR 3.5; CI 1.8-6.7) compared to the general population. Aquatic athletes were at increased risk of doctor-diagnosed asthma (OR 2.0; CI 1.1-3.9), asthma symptoms (OR 2.6; CI 1.3-5.0) and asthma symptoms or medication use (OR 2.3; CI 1.2-4.4) when compared to individuals not involved in aquatic sports. Regarding the entire athlete population, no increase in asthma was found when compared to the general population. CONCLUSIONS: Practice of very high endurance and aquatic sports may be associated with increased asthma risks. Athlete participation as such showed no association with asthma risk.

Shift work and hypertension: Prevalence and analysis of disease pathways in a German car manufacturing company.

BACKGROUND: Hypertension and cardiovascular disease (CVD) may share a similar pathophysiology. Despite shift workers' CVD excess risk, studies on shift work and hypertension are inconclusive. METHODS: Blood pressure and shift status for 25,343 autoworkers were obtained from medical check-ups and company registers. Cross-sectional associations modeling the total effect from shift work (day shifts, shift work without nights, rotating shift work with nights, and night shifts) on hypertension were assessed. By sequential adjustments, the influence of behavioral, psychosocial, and physiological factors on the total effect was examined, with subsequent mediation and moderation analyses. RESULTS: Adjusted for confounders, shift work without nights (vs. day shifts) was significantly associated with hypertension (OR 1.15, 95%CI 1.02-1.30). The total effect was mediated by BMI, physical inactivity, and sleep disorders. No moderation of the total effect by behaviors was found. CONCLUSION: The association between shift work and hypertension seems mainly attributable to behavioral mechanisms.

Working conditions and effort-reward imbalance of German physicians in Sweden respective Germany: a comparative study.

OBJECTIVE: Work stress among physicians is a growing concern in various countries and has led to migration. We compared the working conditions and the work stress between a migrated population of German physicians in Sweden and a population of physicians based in Germany. Additionally, specific risk factors for work stress were examined country wise. METHOD: Using a cross-sectional design, 85 German physicians employed in Sweden were surveyed on working conditions and effort-reward imbalance and compared with corresponding data on 561 physicians working in Germany. Multiple linear regression analyses were applied on both populations separately to model the associations between working conditions and effort-reward ratio (ERR), adjusted for a priori confounders. RESULTS: German physicians in Sweden had a significantly lower ERR than physicians in Germany: mean (M) = 0.47, standard deviation (SD) = 0.24 vs. M = 0.80, SD = 0.35. Physicians in Sweden worked on average 8 h less per week and reported higher work support and responsibility. Multivariate analyses showed in both populations a negative association between work support and the ERR (ß = -0.148, 95% CI -0.215 to (-0.081) for physicians in Sweden and ß = -0.174, 95% CI -0.240 to (-0.106) for physicians in Germany). Further significant associations with the ERR were found among physicians in Sweden for daily breaks (ß = -0.002, 95% CI -0.004 to (-0.001)) and among physicians in Germany for working hours per week (ß = 0.006, 95% CI 0.002-0.009). CONCLUSION: Our findings show substantial differences in work stress and working conditions in favor of migrated German physicians in Sweden. To confirm our results and to explain demonstrated differences in physicians' work stress, longitudinal studies are recommended.

Risk factors for mercury exposure of children in a rural mining town in northern Chile.

OBJECTIVE: Traditional gold mining is associated with mercury exposure. Especially vulnerable to its neurotoxic effects is the developing nervous system of a child. We aimed to investigate risk factors of mercury exposure among children in a rural mining town in Chile. METHODS: Using a validated questionnaire distributed to the parents of the children, a priori mercury risk factors, potential exposure pathways and demographics of the children were obtained. Mercury levels were measured through analyzing fingernail samples. Logistic regression modeling the effect of risk factors on mercury levels above the 75(th) percentile were made, adjusted for potential confounders. RESULTS: The 288 children had a mean age of 9.6 years (SD = 1.9). The mean mercury level in the study population was 0.13 µg/g (SD 0.11, median 0.10, range 0.001-0.86 µg/g). The strongest risk factor for children's odds of high mercury levels (>75(th) percentile, 0.165 µg/g) was to play inside a house where a family member worked with mercury (OR adjusted 3.49 95% CI 1.23-9.89). Additionally, children whose parents worked in industrial gold mining had higher odds of high mercury levels than children whose parents worked in industrial copper mining or outside mining activities. CONCLUSION: Mercury exposure through small-scale gold mining might affect children in their home environments. These results may further help to convince the local population of banning mercury burning inside the households.