Occupational exposure to particles in relation to chronic obstructive pulmonary disease and cardiovascular disease

Sammanfattning: Objective The working life is expanding with increased retirement ages as the population is aging, in Sweden but in also other parts of the world. However, workers with poor health might not cope with working in higher ages. Two of the world’s most common causes of death, chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs) are partly due to exposures from work. Exposure to particles increase the risk of incident COPD and CVD. However, more research is needed on the effect of occupational exposure of particles of different origin, and to which extent they contribute to COPD and different types of CVD, including dose-response relationships. The overall aim of this thesis was to investigate occupational particle exposure in relation to COPD and CVD, investigate effects of different particle types, dose-response relationships, and potential differences in effects in men and women. Methods This thesis comprises four studies, two epidemiological studies, one on COPD and one on CVD resulting in two papers, and two field studies on CVD. Study I is a populationbased longitudinal study in which we investigated the smoking-adjusted risk of COPD associated with occupational exposure to 13 particles/groups (inorganic, organic, combustion particles, and welding fumes). We formed a cohort of subjects born in 1965 or earlier who responded to the Stockholm Public Health Survey in 2002, 2006, or 2010 with follow-up surveys in 2007, 2010, and 2014, in total 43,641 subjects. Participants were identified as COPD cases if they had been diagnosed with COPD by a physician during 1990-2014 or were prescribed anticholinergic medication specific for COPD. A job exposure matrix (JEM) was used to estimate occupational particle exposure. Study II and III investigated the association between particle exposure and markers of CVD. They are based on measurements of respirable silica, respirable dust, and dust of PM 0.1-10, and on biological sampling of included participants within construction industry. Study II, based on 65 participants, investigated if occupational particle exposure is affecting common biomarkers for CVD, both cross-sectionally at work and longitudinally before and after vacation. In study III, based on 46 participants, our aim was to study short-term effects on pulse rate and blood pressure associated with rapid varying particle levels at work, but also intermittent noise. Study IV analyzed the association between occupational exposure to 41 different particles and chemicals and first MI adjusted for joint exposures of lack of decision authority, physical workload, noise, and other particles/chemicals. It is based on the Swedish National Cohort on Work and Health (SNOW) and includes all persons who were born between 1930 and 1990 and working in Sweden (6,437,660 subjects), in this study working at any time between 1985-2013. Occupational history was retrieved from the 1980, 1985, and 1990 National censuses and the Occupational register within the Statistic Sweden’s Longitudinal Integrated Database for Health Insurance and Labour Market Studies (LISA). Cases of first MI were identified from the National Patient Register and the National Cause of Death Register. Other registries and cohorts were matched to add additional information of education, smoking, and body mass index (BMI). Four different JEMs were used to estimate the different occupational exposures. Results After adjusting for smoking, men occupationally exposed to any type of inorganic, organic, high levels to any combustion particles, and high levels of welding fumes had increased risk of incident COPD. Specifically, respirable crystalline silica (RCS), gypsum and insulation, diesel exhaust, and high levels of welding fumes were associated with COPD and showed dose-response relationships. There was also a tendency of dose-response relationship among men exposed to particles of asphalt/bitumen. For women there was an increased risk of COPD among those highly exposed to various organic particles from animal, flour, leather, plastic, soil, soot, and textile. The population attributable fractions in all ages were 10 % for men and 3 % for women (study I). The two field studies showed changed levels of markers of CVD. Low to moderate occupational exposure to all types of the particles included (median levels: respirable silica 0.015 mg/m3, respirable dust 0.259 mg/m3, particulate matter (PM) 0.1-10 0.473 mg/m3) was associated with higher homocysteine levels, lower high-density lipoprotein-levels, and higher resting pulse rate. Also, long-term (years) occupational exposure to particles was associated with changes in low-density lipoprotein and homocysteine levels (study II). Furthermore, PM 0.1-10 in levels above 0.480 mg/m3 was significantly associated with elevated pulse rate within the same minute. A significant positive association with pulse rate was also found for noise exposure, and there was an additive effect on pulse rate if simultaneously exposed to particles and noise (study III). With regard to first MI, for the whole population of all ages, significant increased risks were observed with cumulative exposure of particles adjusted for joint occupational exposures for the combustion compounds diesel and gasoline engine exhaust, polycyclic aromatic hydrocarbons (PAH) including benzo(a)pyrene (BAP), and sulfur dioxide (SO2), the gases carbon monoxide (CO) and volatile sulfur compounds, and the metals cadmium (Cd), chromium (Cr), iron (Fe) and lead (Pb), as well as for oil mist, benzene, gasoline, pulp or paper dust, and respirable dust. Near significant associations were seen for welding fumes and quartz dust. There were some differences between sexes. Recent exposure was also significantly associated with MI in the whole study population for diesel engine exhaust, PAH including BAP, SO2, CO, volatile sulfur compounds, Cd, Fe, formaldehyde, welding fumes, asbestos, and flour dust, for most exposures with dose-response relationships (study IV). Conclusions There are several particle types which are associated with COPD and first MI, respectively. Additionally, some particle types show effect on these two outcomes in two or more of the included studies, i.e., diesel engine exhaust, welding fumes, and respirable particles/silica which all are associated with both COPD and MI, even in levels below the OELs for respirable silica, and respirable inorganic particles. Results from the field studies also indicate changes in markers of CVD if occupationally exposed to respirable particles and particles of PM 0.1-10. Preventing poor health by improving work environment, for example by reducing occupational exposure to particles, will increase the likelihood of people remaining longer at work, and would most likely prevent incident COPD and CVD.