Early-life exposure to tobacco, inflammation, and risk of rheumatic diseases: a prospective cohort study

Abstract Background Tobacco smoke exposure was associated with inflammation and adverse health outcomes. However, the impact of early-life tobacco exposure on rheumatic diseases, including rheumatoid arthritis, osteoarthritis, gout, and spondyloarthritis, and the potential modifying role of inflammation are unclear. Methods A prospective analysis of over 200 000 participants without rheumatic diseases at baseline in the UK Biobank was conducted. Cox proportional hazards regression models were employed to assess the associations between early-life tobacco exposure with rheumatic diseases. Furthermore, we evaluated whether inflammation status modified these associations. Results Among participants, 77,825 (29.0%) experienced in utero tobacco exposure, and 14,216 (5.4%) initiated smoking during childhood. In utero tobacco exposure was associated with increased rheumatic disease incidence, with hazard ratios of 1.18 (1.08, 1.28) for rheumatoid arthritis, 1.10 (1.08, 1.13) for osteoarthritis, 1.12 (1.05, 1.19) for gout, and 1.24 (1.13, 1.35) for spondyloarthritis. Earlier smoking initiation significantly increased the incidence of rheumatic diseases (P < .001), with remarkable trends (Ptrend < .001). Combined associations and interactions were observed between in utero tobacco exposure, smoking initiation age, and inflammation. Participants with high inflammation, in utero tobacco exposure, and earlier smoking initiation had the highest rheumatic disease risk. Conclusions In utero tobacco exposure and earlier smoking initiation were associated with an increased risk of rheumatic diseases, especially in those with high inflammation status.