224 Physical Activity and Risk of Crohn's Disease and Ulcerative Colitis

Abstract

Background: Ulcerative colitis (UC) and Crohn's disease (CD) are chronic inflammatory disorders in which an intestinal barrier normally maintained by adaptive and innate immunity is disrupted. Physical activity enhances the innate immune response, decreases chronic inflammation, andmodulates autophagy, a cellular process known to play a role in pathogenesis of CD. We therefore sought to examine the association between physical activity and risk of UC and CD in two large prospective cohorts. Methods: We conducted a prospective cohort study of US women enrolled in the Nurses' Health Study (NHS) I and II since 1976 and 1989, respectively. A validated physical activity assessment was administered every four years starting in 1984 in NHS and 1989 in NHS II with greater than 90% follow-up. Diagnoses of CD and UC reported through 2007 in NHSII and 2008 in NHSI were confirmed through review of medical records by two gastroenterologists. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, smoking, bodymass index (BMI), history of appendectomy, and use of oral contraceptives, postmenopausal hormones, or non-steroidal anti-inflammatory drugs. We evaluated effect modification by age, smoking, and BMI using cross-classified categories with physical activity. Results: Among a total of 198,248 women, we documented 268 incident cases of CD and 331 cases of UC over 24 years of follow-up encompassing a total of 3,733,120 person years. Increasing levels of physical activity were associated with progressively lower incidence of CD (p for linear trend = 0.04). Compared to women in the lowest quintile of physical activity (most sedentary), the multivariate-adjusted HRs of CD were 0.73 (95% CI, 0.50-1.07) for those in quintile 2; 1.01 (95% CI, 0.72-1.43) for quintile 3; 0.70 (95% CI, 0.48-1.03) for quintile 4; and 0.64 (95% CI, 0.43-0.95) for quintile 5 (most active). Cumulative vigorous physical activity, defined as jogging, running, biking, swimming, tennis, aerobics, and other vigorous exercises, was also inversely associated with risk of CD (Ptrend = 0.03). Compared to women in the lowest quintile of cumulative vigorous physical activity, the multivariate-adjusted HR of CD among women in the highest quintile was 0.65 (95% CI, 0.44-0.98). In contrast, measures of either overall or vigorous physical activity were not associated with risk of UC (Ptrend = 0.44 and 0.27, respectively). Age, smoking, and BMI did not significantly modify associations between physical activity and risk of UC and CD (all Pinteraction. 0.35). Conclusions: In two large prospective cohorts of US women, physical activity was associated with a lower risk of incident CD but not UC. Future studies focusing on potential mechanisms, which mediate this association are needed.