Background/Purpose: Environmental factors play an important role in the development of rheumatoid arthritis (RA), and airway exposures to environmental agents are postulated to be of special importance. We examined whether long-term exposures to ambient air pollution were associated with risk of RA in the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) Study and in the US Nurses' Health Study (NHS).
Method: We studied 1,330 incident RA cases and 2,235 controls from EIRA and 91,203 members of the NHS, among whom 762 had developed RA. Exposures to particulate matter (PM10, PM2.5) and gaseous pollutants (SO2, NO2, and NOx, in EIRA only) were predicted for all residential addresses. We examined the association of an interquartile range increase in each air pollutant with the risk of RA, and risks of seropositive (rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA)) RA phenotypes, using multivariable logistic regression for EIRA and Cox proportional hazards models for NHS. Models in EIRA were adjusted for age, gender, smoking status, and educational attainment. Models in NHS were adjusted for age, race, reproductive factors, hormone use, physical activity, body mass index, smoking status and pack-years, and individual and area level measures of socioeconomic status. As the relevant etiological time period of exposure is unknown, we examined pollution in various years before RA onset.
Result: In both studies there was no evidence for an increased risk of RA with PM10 or PM2.5 in any exposure window or with any pollutant in the year of onset, and in some cases modest inverse associations were observed. In EIRA, elevated risks with increases in SO2, NO2, and NOx in the 10th and 20th years prior to RA symptom onset were observed, particularly in models restricted to RF+ and ACPA+ phenotypes. For each interquartile range increase (2 µg/m3 for SO2, 7 µg/m3 for NO2, and 8 µg/m3 for NOx) in exposure in the 10th year prior to onset, the fully-adjusted odds ratios for ACPA+ RA (95% confidence intervals (CI)) were 1.07 (1.01-1.13), 1.11 (1.01-1.21) and 1.07 (1.00-1.14) for SO2, NO2, and NOx respectively. Results were strongest in individuals with less than a university education (Figure 1). In the NHS, only exposures to SO2 were associated with modest increases in total RA risk (fully adjusted hazard ratio (95%CI) for an interquartile range (16 µg/m3) increase in SO2 10 years prior to onset 1.05 (0.92-1.19)).
Conclusion: In EIRA, we observed elevations in the odds of developing RA and seropositive RA in individuals with higher levels of gaseous air pollution exposures, particularly SO2. These risks were strongest in those with less than a university education. In NHS, we observed modest elevations only with increasing exposures to SO2. To the best of our knowledge, this is the first study to examine the effects of air pollution on risk of RA.
Disclosure: J. E. Hart, None; H. Källberg, None; F. Laden, None; K. H. Costenbader, None; M. Holmqvist, None; L. Klareskog, None; L. Alfredsson, None; E. W. Karlson, None.