Background: Cigarette smoking has been associated with rheumatoid arthritis (RA), but the importance of smoking intensity, duration, and time since quitting, and whether the risk is primarily for rheumatoid factor (RF) seropositive versus seronegative RA are still unclear.
Methods: We conducted a prospective analysis of smoking and the risk of RA among 103,818 women in the Nurses' Health Study. A total of 680 RA cases, diagnosed from 1976 and 2002, were confirmed using a questionnaire and medical record review. Sixty percent were RF positive. Cox proportional hazards models calculated the relative risks (RRs) of RA with smoking, adjusting for reproductive and lifestyle factors.
Results: The RR of RA was significantly elevated among current (RR 1.43 [95% confidence interval 1.16-1.75]) and past smokers (RR 1.47 [95% confidence interval 1.23-1.76]), compared with never smokers. The risk of RA was significantly elevated with 10 pack-years or more of smoking and increased linearly with increasing pack-years (P trend <.01). A greater number of daily cigarettes and longer duration of smoking were associated with increased risk. The effect of smoking was much stronger among RF-positive cases than among RF-negative cases. The risk remained elevated in past smokers until 20 years or more after cessation.
Conclusions: In this large cohort, past and current cigarette smoking were related to the development of RA, in particular seropositive RA. Both smoking intensity and duration were directly related to risk, with prolonged increased risk after cessation.