Airborne Occupational Exposures and Risk of Developing Rheumatoid Arthritis: A Job‐Exposure Matrix Approach in a Swedish Population‐Based Case–Control Study

Background: Rheumatoid Arthritis (RA) is an autoimmune, inflammatory disease with multifaceted aetiology. Cigarette smoke is the strongest environmental risk factor of RA, and research suggests that airborne exposures may trigger RA among genetically susceptible individuals. The aim of this thesis was to investigate the influence of airborne, occupational exposures on the risk of developing RA. The purpose of Study I was to explore whether there was any association between occupation and risk of developing RA. The airborne occupational exposures later studied were textile dust (Study II), asbestos and crystalline silica dust (Study III) and five types of organic dusts (Study IV). Methods: All four PhD projects are case-control studies. Study I is based on the Swedish Eipidemiological Investigation of Rheumatoid Arthritis (EIRA) study. In Study I we identified newly diagnosed RA cases from the age of 18 in the southern and central parts of Sweden from May 1996 until September 2014. 1-2 controls per case were randomly selected from the population register, matched on age, sex and residential area. Data on occupational titles and environmental risk factors were collected through an extensive questionnaire. Study II is based on the Malaysian EIRA (MyEIRA) study. We identified newly diagnosed female RA cases from 18 to 70 years of age from Peninsular Malaysia between August 2005 and December 2009. One control per case was selected and matched on age and residential area. Data on occupational titles and environmental risk factors were collected through an interview, based on an extensive questionnaire. In Study III and IV the study base comprised of men and women in Sweden from 1996 until 2013. RA patients were selected based on the information from EIRA, the national patient register, the Swedish Rheumatology Quality Register (SRQ) and the Swedish Prescribed Drug Register. Apart fom the EIRA controls, ten additional controls per case were randomly selected from the total population register. For Study III and IV the occupational titles were retrieved from the national Population and Housing censuses (1960-1990) and from Statistics Sweden’s LISA-register (2001-2010). We assessed the occupational exposure to the inorganic dusts asbestos, silica and five organic dusts by applying job-exposure matrices (JEMs) to the occupations of the participants. In all four studies, we calculated odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) by means of logistic regression analysis to assess the association between the main exposure and risk of RA. Results: Among men the production-related occupations bricklayers and concrete workers, electrical and electronics workers and material handling operators were associated with an increased risk of RA compared to workers within the professional, administrative and technical sectors after adjustment for potential confounding from cigarette pack-years, alcohol use, education and body mass index (BMI). Among women, we observed an increased risk of RA among assistant nurses and attendants. Men working with crystalline silica or asbestos had an increased risk of developing RA compared to unexposed workers. This finding may partly explain the increased risk among men working in production related occupations. The highest risk estimates for both asbestos and crystalline silica were observed among male workers with the longest duration of exposure, and for seropositive RA there was a significant dose-response trend for both agents. We could not detect an increased risk among women from asbestos or crystalline silica exposure. But fewer women than men had been working in occupations where they had been exposed to inorganic dusts and they also tended to have been exposed for a shorter period of time and to lower intensities. For the organic dusts wood, animal, paper, textile and flour, the risk estimates were more similar for men and women. Among these five types of dust, animal dust showed the most solid association with an increased risk of RA. The OR also increased with duration of exposure to animal dust. We observed an increased risk of RA among women from exposure to textile dust in Malaysia. There was also an interaction between textile dust exposure and HLA-DRB1 shared epitope (SE) alleles, predominantly for the risk of developing AntiCitrullinated Protein/Peptide Antibody (ACPA) + RA. Also in the Swedish population there were signs of an association between textile dust and seropositive RA. Conclusions: This thesis demonstrates that your occupation may be associated with an increased risk of developing both seropositive and seronegative RA, where exposures to inorganic but also organic dusts play a role. Duration of exposure to organic and inorganic dusts is associated mainly with seropositive RA. These findings support the notion that the lung plays an important role in the pathogenesis of RA. The results can contribute to preventive measures at workplaces where workers are associated with an increased risk. This doctoral thesis highlights the importance to study inorganic and organic airborne exposures in countries with high or long-term exposure.