Scientific Abstract

Proposal No. IBD-0216R
Principal Investigator:  Gilaad G. Kaplan, M.D., M.P.H.
Applicant Organization:  University of Calgary (Alberta, Canada)
Project Title:  The effect of air pollution on the development of Crohn's disease and ulcerative colitis in England and Wales
Period of Award:  September 1, 2007 – December 31, 2009

Crohn’s disease and ulcerative colitis are chronic inflammatory conditions of the gut that are believed to occur in genetically predisposed individuals exposed to unknown environmental triggers. Epidemiologic studies of the inflammatory bowel diseases (IBD) have shown that IBD first emerged in the last century in industrialized nations. The annual incidence rates of ulcerative colitis, followed by Crohn’s disease, have also increased as developing nations became industrialized. A possible explanation of these epidemiologic trends in IBD is that air pollution increased the risk of developing Crohn’s disease and ulcerative colitis. Air pollution is produced as a consequence of industrialization. In urban centers air pollutants from motor vehicle exhaust, such nitrogen dioxide, have been shown to increase the risk of developing adverse health effects including asthma, cardiovascular disease, malignancy, and all-cause mortality. In part, these adverse effects arise through the exacerbation of an inflammatory response by air pollutants. The systemic inflammatory responses stimulated by the exposure to air pollutants are consistent with the pro-inflammatory profile associated in the pathogenesis of IBD. Thus, a plausible epidemiologic and biologic link between air pollution exposure and the development of IBD exists. We propose to evaluate whether exposure to higher levels of air pollutants, such as nitrogen dioxide from motor vehicle exhaust, are associated with an increased risk of developing Crohn’s disease and/or ulcerative colitis.

We plan to conduct a cohort study with a nested case-control component. A cohort of individuals registered in the Health Improvement Network (THIN) database in the United Kingdom (UK) will be followed between July 1, 2006 and July 1, 2007 for a new diagnosis of Crohn’s disease or ulcerative colitis. All incident cases of Crohn’s disease and ulcerative colitis will be compared to randomly selected controls that are matched by attained age and gender. Conditional logistic regression analysis will be used to assess whether cases are more likely to live in areas that are exposed to higher annual mean air pollutant concentrations for nitrogen dioxide, nitrogen oxides, sulfur dioxide, and particulate matter after adjusting for these air pollutants, as well as other potential confounders (e.g., smoking). Effect modification will be assessed to determine if age, gender, and smoking interacts with the relationship between air pollution exposure and the development of Crohn’s disease or ulcerative colitis.

This will be the first study to explore the association between the exposure to air pollutants and the development of Crohn’s disease and ulcerative colitis. The implications of this finding could be enormous, as it could provide evidence to support additional basic science, clinical, and epidemiological research to confirm and explore this relationship. Air pollution is potentially a modifiable risk factor. A positive association could lead to policies that reduce emissions, which may prevent the occurrence of IBD in some individuals.