Background/Purpose Exposure to silica is a well-defined inhalation exposure, and is known to be associated with moderately increased rheumatoid arthritis (RA) risk, with the effect confined to anti-citrullinated protein/peptide antibody (ACPA) positive RA. The interaction between silica exposure and current smoking, but not past smoking, in the etiology of ACPA-positive RA has also been described. Whereas the overall association of current smoking status, silica, and their interaction in RA could be regarded as established, considerably less is known about how much smoking is needed to bring about this synergistic effect, that is, the influence from cumulative dose (pack-years) among current smokers and the influence from cessation duration among past smokers. This study is to explore the interaction between silica exposure and smoking dose on one hand, as well as duration of smoking cessation on the other, with regard to the risk of developing RA defined by the presence/absence of ACPA.

Methods We analyzed 927 incident male RA cases (fulfill 1987 ACR criteria) and 1403 randomly selected male controls, aged 18-70, from the Swedish EIRA study, a population based case-control study. Information on silica exposure and cigarette smoking were collected through self-reported questionnaires at the inclusion. Men with a history of having occupations as rock drilling and stone crushing were defined as silica exposed. Additive interaction (attributable proportion due to interaction (AP) and 95% confidence interval (95%CI)) between silica exposure, pack-years of smoking, and duration of smoking cessation (years after quit smoking) were calculated. ACPA status among cases was determined.

Results A high risk of developing ACPA-positive RA was observed among silica-exposed current smokers (OR=8.03 (95%CI: 4.47-14.03)), and a statistically significant additive interaction was present (AP=0.41 (95%CI: 0.04-0.77)). The magnitude of the estimated silica-smoking interaction increased as the pack-year of smoking increased, with the highest AP observed for smoking ≥ 29 pack-years (AP=0.62 (95%CI: 0.29-0.94)). Although a relevant high risk of developing ACPA-positive RA was also observed for silica-exposed ex-smokers in general, no significant interaction was revealed (OR=4.09 (95%CI: 2.46-6.82); AP=0.07 (95%CI: -0.45-0.60)). Through further analysis, we found those ex-smokers who quit smoking no more than 10 years ago had a similarly high silica-smoking AP as current smokers (AP=0.46 (95%CI: -0.02-0.95), p=0.06). No significant interaction was observed after 10 years after smoking cessation. No statistically significant results were found for ACPA-negative RA.

Conclusion Silica exposure and smoking interact significantly in a dose dependent manner regarding risk of developing ACPA-positive RA among men. It might take up to 10 years after smoking cessation for the diminishment of the smoking-silica interaction effect, and even longer for the main effect of smoking to return to the baseline. Since silica dust is hard to get rid of once in the lung, it is yet another reason to advise silica exposed  persons not to start smoking, smoke less, and to quit smoking as early as possible.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/amount-of-smoking-duration-of-smoking-cessation-and-their-interaction-with-silica-exposure-in-the-risk-of-rheumatoid-arthritis-results-from-the-swedish-epidemiological-investigation-of-rheumatoid-a/