Occupational factors and risk of rheumatoid arthritis : studies on silica, physical workload and cold work environment

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that could lead to joint destruction and disabilities. Around 30-70 million people worldwide are affected by RA. Both genetic and environmental factors are involved in the etiology of RA. However, researches aiming at understanding the environmental factors leading to RA are relatively few.

Aims: The main aim of this thesis is to investigate occupational risk factors for RA. The sub- aims are: 1.) To investigate the interaction between the dose of cigarette smoking and silica exposure regarding risk of anti-citrullinated protein antibody (ACPA) positive RA among male subjects. 2.) To investigate the association between different types of physical workload and risk of RA. 3.) To investigate the association between different types of physical workload and development of antibodies against collagen type II (anti-CII) in RA. 4.) To investigate the association between working in cold environment and risk of RA.

Materials and Methods: This thesis was based on the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) Study, which is a population-based case-control study involving more than 3000 incident RA cases and more than 5000 controls recruited between 1996 and 2014. Information on exposures (i.e. cigarette smoking, silica, physical workload and cold work environment) was obtained through self-reported questionnaire. RA cases were ascertained based on the ACR 1987 or 2010 criteria. The associations between exposures and outcome (risk of developing RA) were estimated using logistic regression by calculating the odds ratios (OR) and 95% confidence intervals (CI). Presence of additive interaction between risk factors was evaluated by calculating the attributable proportion due to interaction (AP).

Results: As the dose of smoking increased, the magnitude of interaction between silica and smoking also increased, with the highest AP value (AP=0.7; 95%CI: 0.4-0.9) observed at 28 pack-years of smoking. The interaction between silica and smoking among those who quitted smoking for ≤10 years was estimated to have an AP of 0.5 (95%CI: 0.1-0.9). The associations between different types of physical workload and risk of developing RA ranged from 1.3(95%CI: 1.1-1.4) to 1.8(95%CI: 1.6-2.0). The ORs between physical workloads and risk of developing anti-CII positive RA was comparable with the corresponding ORs observed between physical workloads and risk of developing anti-CII negative RA. Those who reported they had worked in cold environment had a 50% higher risk of developing RA than those who did not (OR=1.5 (95%CI:1.4-1.7)).

Conclusions: The interaction between smoking and silica depends on the cumulative dose of smoking and the effect of interaction could remain even after nearly 10 years of smoking cessation. Both exposure to physical workload and exposure to cold work environment were found to be associated with an increased risk of developing RA. These factors are new potential risk factors for RA and need confirmation. The findings may provide new clues for unraveling the etiology of RA and contribute to the endeavor of making RA a preventable and curable disease.

List of scientific papers

I. Zeng P, Chen Z, Klareskog L, Alfredsson L, Bengtsson C, Jiang X. Amount of smoking, duration of smoking cessation and their interaction with silica exposure in the risk of rheumatoid arthritis among males: results from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study. Annals of the Rheumatic Diseases. 15 September 2017.
https://doi.org/10.1136/annrheumdis-2017-212145

II. Zeng P, Klareskog L, Alfredsson L, Bengtsson C. Physical workload is associated with increased risk of rheumatoid arthritis: results from a Swedish population-based case–control study. RMD Open. 2017;3:e000324.
https://doi.org/10.1136/rmdopen-2016-000324

III. Zeng P, Alfredsson L, Klareskog L, Mullazehi M, Saevarsdottir S, Bengtsson C, Rönnelid J. Occupational physical workload and development of anti-collagen type II antibodies in rheumatoid arthritis. [Manuscript]

IV. Zeng P, Bengtsson C, Klareskog L, Alfredsson L. Working in cold environment and risk of developing rheumatoid arthritis: results from the Swedish EIRA case–control study. RMD Open. 2017;3:e000488.
https://doi.org/10.1136/rmdopen-2017-000488