Narrative review of occupational exposures and noncommunicable diseases.

OBJECTIVE: Within the scope of the Exposome Project for Health and Occupational Research on applying the exposome concept to working life health, we aimed to provide a broad overview of the status of knowledge on occupational exposures and associated health effects across multiple noncommunicable diseases (NCDs) to help inform research priorities. METHODS: We conducted a narrative review of occupational risk factors that can be considered to have "consistent evidence for an association," or where there is "limited/inadequate evidence for an association" for 6 NCD groups: nonmalignant respiratory diseases; neurodegenerative diseases; cardiovascular/metabolic diseases; mental disorders; musculoskeletal diseases; and cancer. The assessment was done in expert sessions, primarily based on systematic reviews, supplemented with narrative reviews, reports, and original studies. Subsequently, knowledge gaps were identified, e.g. based on missing information on exposure-response relationships, gender differences, critical time-windows, interactions, and inadequate study quality. RESULTS: We identified over 200 occupational exposures with consistent or limited/inadequate evidence for associations with one or more of 60+ NCDs. Various exposures were identified as possible risk factors for multiple outcomes. Examples are diesel engine exhaust and cadmium, with consistent evidence for lung cancer, but limited/inadequate evidence for other cancer sites, respiratory, neurodegenerative, and cardiovascular diseases. Other examples are physically heavy work, shift work, and decision latitude/job control. For associations with limited/inadequate evidence, new studies are needed to confirm the association. For risk factors with consistent evidence, improvements in study design, exposure assessment, and case definition could lead to a better understanding of the association and help inform health-based threshold levels. CONCLUSIONS: By providing an overview of knowledge gaps in the associations between occupational exposures and their health effects, our narrative review will help setting priorities in occupational health research. Future epidemiological studies should prioritize to include large sample sizes, assess exposures prior to disease onset, and quantify exposures. Potential sources of biases and confounding need to be identified and accounted for in both original studies and systematic reviews.

A Cohort Study on Cancer Incidence among Women Exposed to Environmental Asbestos in Childhood with a Focus on Female Cancers, including Breast Cancer.

OBJECTIVES: To examine the risk of cancer in former school children exposed to environmental asbestos in childhood with a focus on female cancers, including breast cancer. METHODS: We retrieved a cohort of females (n = 6024) attending four schools located in the neighborhood of a large asbestos cement plant in Denmark. A reference cohort was frequency-matched 1:9 (n = 54,200) in sex and five-year age intervals. Using Danish registries, we linked information on historical employments, relatives' employments, cancer, and vital status. We calculated standardized incidence rates (SIRs) for all and specific cancers, comparing these rates with the reference cohort. Hazard ratios were calculated for selected cancers adjusted for occupational and familial asbestos exposure. RESULTS: For cancer of the corpus uteri (SIR 1.29, 95% CI 1.01-1.66) and malignant mesothelioma (SIR 7.26, 95% CI 3.26-16.15), we observed significantly increased incidences. Occupationally, asbestos exposure had a significantly increased hazard ratio for cancer in the cervix, however, a significantly lower risk of ovarian cancer. The overall cancer incidence was similar to that of the reference cohort (SIR 1.02, 95% CI 0.96-1.07). The risk of cancer of the lung was increased for those exposed to occupational asbestos, those with family members occupationally exposed to asbestos and for tobacco smokers. CONCLUSIONS: In our study, environmental asbestos exposure in childhood is associated with an increased risk of cancer of the corpus uteri and malignant mesothelioma in women.

Cancer Incidence and Risk of Multiple Cancers after Environmental Asbestos Exposure in Childhood-A Long-Term Register-Based Cohort Study.

OBJECTIVES: To examine the asbestos-associated cancer incidence and the risk of multiple cancers in former school children exposed to environmental asbestos in childhood. METHODS: A cohort of 12,111 former school children, born 1940-1970, was established using 7th grade school records from four schools located at a distance of 100-750 m in the prevailing wind direction from a large asbestos-cement plant that operated from 1928 to 1984 in Aalborg, Denmark. Using the unique Danish personal identification number, we linked information on employments, relatives' employments, date of cancer diagnosis, and type of cancer and vital status to data on cohortees extracted from the Supplementary Pension Fund Register (employment history), the Danish Cancer Registry, and the Danish Civil Registration System. We calculated standardized incidence rates (SIRs) for asbestos-associated cancers, all cancers, and multiple cancers using rates for a gender and five-year frequency-matched reference cohort. RESULTS: The overall incidence of cancer was modestly increased for the school cohort (SIR 1.07, 95% confidence interval (CI) 1.02-1.12) compared with the reference cohort. This excess was driven primarily by a significantly increased SIR for malignant mesothelioma (SIR 8.77, 95% CI 6.38-12.05). Former school children who had combined childhood environmental and subsequent occupational exposure to asbestos had a significantly increased risk of lung cancer. Within this group, those with additional household exposure by a relative had a significantly increased SIR for cancer of the pharynx (SIR 4.24, 95% CI 1.59-11.29). We found no significant difference in the number of subjects diagnosed with multiple cancers between the two cohorts. CONCLUSIONS: Our study confirms the strong association between environmental asbestos exposure and malignant mesothelioma and suggests that environmental asbestos exposure in childhood may increase the overall cancer risk later in life.

Asbestos exposure and haematological malignancies: a Danish cohort study.

Environmental asbestos exposure and occupational asbestos exposure increase the risk of several types of cancer, but the role of such exposures for haematological malignancies remains controversial. We aimed to examine the risk of haematological malignancies: first, in subjects exposed early in life, independently of any occupational exposure occurring later; second, in subjects exposed occupationally. We established an environmentally exposed cohort from four schools located near the only former asbestos cement production plant in Denmark. We identified nearly all pupils in the seventh grade and created an age and sex-matched 1:9 reference cohort from the Danish Central Population Register. Participants were born 1940-1970 and followed up in national registers until the end of 2015. Occupational asbestos exposure was assessed for all participants using two different job exposure matrices. The school cohort included 12,111 participants (49.7% girls) and the reference cohort 108,987 participants. Eight subgroups of haematological malignancy were identified in the Danish Cancer Registry. These cases were analysed for combined overall haematological malignancy, a combined subgroup of lymphomas and a combined subgroup of leukaemias. The data were analysed using Cox regression (hazard ratios (HR)) including other cancers and death as competing risks. Haematological malignancy was identified in 1125 participants. The median follow-up was 49.3 years (0.1-63.4). Early environmental asbestos exposure was not associated with an increased risk of haematological malignancy. Long-term occupational asbestos exposure was associated with overall haematological malignancy (HR 1.69, 95% CI 1.04-2.73); in particular for the leukaemia subgroup (HR 2.14, 95% CI 1.19-3.84). This large follow-up study suggests that long-term occupational asbestos exposure is associated with increased leukaemia risk. However, further studies are needed to confirm these observations.

Heme oxygenase 1 polymorphism, occupational vapor, gas, dust, and fume exposure and chronic obstructive pulmonary disease in a Danish population-based study.

Objectives The number of dinucleotide repeats (GT) nmodulate expression of heme oxygenase 1 (HMOX1), a stress response gene. Multiple repeats might affect chronic obstructive pulmonary disease (COPD) susceptibility. We aimed to investigate the association of this polymorphism with COPD and its interaction with occupational exposures (vapor, gas, dust, or fumes). Methods This population-based cross-sectional study included 4703 Danes, aged 45-84 years. HMOX1 (GT) nwas genotyped and grouped as short: ≤26, medium: 27-32 and long: ≥33 alleles. COPD was defined by the lower limit of normal (2.5 thFEV 1/FVC and FEV 1centiles). Occupational exposure was defined as ever exposed to vapor, gas, dust, or fume in expert-selected jobs. Associations were analyzed by adjusted mixed logistic regression. Results The population included 6% with COPD, 48% who had smoked ≥10 pack-years, and 46% with occupational exposure. HMOX1 was genotyped in 4423 participants. The adjusted odds ratio (OR) for the association between HMOX1 long allele and COPD was 1.75 [95% confidence interval (CI) 1.18-2.60]. An interaction was evident between HMOX1 long allele and occupational exposure, OR 2.38 (95% CI 1.04-5.46), versus HMOX1 short/medium without exposure. Analyses were replicated in another cohort, aged 20-44 years, N=1168, including 3% with COPD, 25% who had smoked ≥10 pack-years and 20% with occupational exposure. No associations were seen between COPD and HMOX1 long allele here. Conclusions Long alleles in HMOX1 alone and in interaction with occupational exposure seem to be associated with COPD. Failure to replicate data may be due to premature age for COPD development and low occupational exposure prevalence. We propose this long allele may be a genetic contributor to the COPD pathogenesis.

Environmental asbestos exposure in childhood and risk of mesothelioma later in life: a long-term follow-up register-based cohort study.

OBJECTIVE: To examine the risk of malignant mesothelioma (MM) in former pupils who attended primary school near an asbestos cement plant. METHODS: A cohort of 12 111 former pupils, born 1940-1970, was established from individual historical records from four primary schools located at a distance of 100-750 m in the prevailing wind direction from an asbestos cement plant operating from 1928 to 1984 in Aalborg, Denmark. The school cohort and a comparison cohort consisting of 108 987 gender and 5-year frequency-matched subjects were followed up (2015) for MM in the Danish Cancer Registry. Using Cox regression, HRs were estimated for the incidence of MM. Adjustments for occupational and familial asbestos exposure were made with a job exposure matrix. An SIR analysis including latency periods testing the cancer incidence rate was performed with the comparison cohort as the reference rate. RESULTS: The median person-years of follow-up were 62.5 years in the school cohort and 62.2 years in the comparison cohort. There were 32 males and 6 females of the former pupils who developed MM during the follow-up: HRmale 7.01 (95% CI 4.24 to 11.57), HRfemale 7.43 (95% CI 2.50 to 22.13). Those who attended school 250 m north of the plant had the highest HR for MM, 10.65 (95% Cl 5.82 to 19.48). No significant trend between school distance and risk of MM was established (p=0.35). CONCLUSION: Our results suggest that boys and girls who attended schools and lived in the neighbourhood of an asbestos cement plant later in life have a significantly increased risk of MM.

Occupational COPD among Danish never-smokers: a population-based study.

Occupational exposures have been shown to be risk factors for chronic obstructive pulmonary disease (COPD) among never-smokers. In a Danish population-based cohort, we analysed this association and the population attributable fraction. The study population (N=1575) was aged 45-84, COPD was defined by lung function measurements and the method of lower limit of normal (LLN), and occupational exposure was assessed by questionnaire and expert judgement. Furthermore, the estimates additionally were provided according to the Global Initiative for Chronic Obstructive Lung Diseases. More than a threefold increased risk (LLN OR=3.69 (95% CI 1.36 to 10.04) was found for occupational exposure to vapour, gas, dust and fumes (predominantly organic dust) in this never-smoking population, with a corresponding 48% (95% CI 30% to 65%) population attributable fraction among never-smokers.

Occupational Chronic Obstructive Pulmonary Disease in a Danish Population-Based Study.

The aim was to explore the impact of occupation on chronic obstructive pulmonary disease (COPD) in a cross-sectional population-based study among subjects aged 45 to 84 years. In a stratified sampling 89 general practitioners practices (GPP) in Denmark recruited 3106 males and 1636 females through the Danish Civil Registration System. COPD was defined by spirometry by the 2.5(th)-centile Lower Limit of Normal of FEV1 and FEV1/FVC. Information about smoking, occupational exposure and the respective occupations were obtained from questionnaires. Occupations followed the Danish adaptation of The International Standard Classification of Occupations, revision 1988 (DISCO-88). Exposure to vapour, gas, dust (organic and inorganic), and fume (VGDF) in each occupation (yes/no) was evaluated by two independent specialist in occupational medicine. Exposures were divided in no, low, medium, and high exposure as 0, < 5, 5-14, and ≥ 15 years in the job, respectively. Data was analysed by a mixed random effect logistic regression model. The age-standardised COPD study prevalence was 5.0%. Of 372 DISCO-88 codes 72 were identified with relevant exposure to VGDF. 46% of the participants reported at least one occupation with VGDF exposure. Adjusted for smoking, age, sex, and GPP a dose-dependent association of COPD was found among workers in jobs with high organic dust exposure, with OR 1.56 (95% CI 1.09-2.24). Restricted to agriculture the OR was 1.59 (95% CI: 1.08-2.33). No association was observed for workers in jobs with inorganic dust, fume/gas, or vapour exposures. In summary, occupational organic dust exposure was associated to the prevalence of COPD.

Occupational chronic obstructive pulmonary disease: a systematic literature review.

OBJECTIVE: Occupational-attributable chronic obstructive pulmonary disease (COPD) presents a substantial health challenge. Focusing on spirometric criteria for airflow obstruction, this review of occupational COPD includes both population-wide and industry-specific exposures. METHODS: We used PubMed and Embase to identify relevant original epidemiological peer-reviewed articles, supplemented with citations identified from references in key review articles. This yielded 4528 citations. Articles were excluded for lack of lung function measurement, insufficient occupational exposure classification, lack of either external or internal referents, non-accounting of age or smoking effect, or major analytic inadequacies preventing interpretation of findings. A structured data extraction sheet was used for the remaining 147 articles. Final inclusion was based on a positive qualitative Scottish Intercollegiate Guidelines Network (SIGN) score (≥2+) for study quality, yielding 25 population-wide and 34 industry/occupation-specific studies, 15 on inorganic and 19 on organic dust exposure, respectively. RESULTS: There was a consistent and predominantly significant association between occupational exposures and COPD in 22 of 25 population-based studies, 12 of 15 studies with an inorganic/mineral dust exposure, and 17 of 19 studies on organic exposure, even though the studies varied in design, populations, and the use of measures of exposure and outcome. A nearly uniform pattern of a dose-response relationship between various exposures and COPD was found, adding to the evidence that occupational exposures from vapors, gas, dust, and fumes are risk factors for COPD. CONCLUSION: There is strong and consistent evidence to support a causal association between multiple categories of occupational exposure and COPD, both within and across industry groups.

[Occupational exposure for dust and gases is an important risk factor for developing COPD]. / Erhvervseksposition for støv og dampe er en betydende risikofaktor for KOL.

Some patients with chronic obstructive pulmonary disease (COPD) are never-smokers, which suggests that there must be other important risk factors. This paper describes the evidence for an association between occupational exposure and COPD. In several studies a consistent and predominantly significant association between occupational exposures and COPD is found, even though the studies vary in design, enrolled populations and in measures of exposure and outcome. Strong evidence supports a causal association between multiple categories of occupational exposure and COPD, both within and across industry groups.