Smoking and inflammatory bowel disease: trends in familial and sporadic cohorts.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) result from genetic and environmental factors. Never smoking and formerly smoking increase the risk of UC, whereas smoking exacerbates the course of CD. We sought to define the age-dependent effects of smoking on the development of UC and CD in familial and sporadic cohorts. METHODS: University of Chicago patients diagnosed with UC or CD between 1990 and 2002 were surveyed about their tobacco use relative to their diagnosis. Smoking trends were used to estimate age-dependent odds ratios and the attributable risks of smoking in the IBD cohort compared to in the general population. RESULTS: One thousands and thirteen patients were included in the study: 245 with sporadic UC; 216 with sporadic CD; 249 with familial UC; and 303 with familial CD. Being an ex-smoker conferred an increased risk for UC in the 25-44 age group in both the sporadic and familial cohorts, but not in the 45-64 age group in the familial UC cohort. Furthermore, there was no difference in tobacco use between patients with sporadic CD and the general population, although there was a significant increase in smoking in younger patients with familial CD. CONCLUSIONS: Ex-smokers make up an increasing percentage of older patients diagnosed with UC, accounting for more than 35% of the attributable risk of late onset (>45 years) UC and a large component of the second peak in diagnosis. Current smokers account for a large percentage of patients diagnosed at a younger age with familial CD but not with sporadic CD. Families with IBD should be counseled that early tobacco use significantly increases the risk of developing CD or, if an ex-smoker, UC at a young age.

Novel therapies in the treatment of ulcerative colitis.

Ulcerative colitis is a chronic inflammatory disease of the colon of unknown cause. Its course is one of relapse and remission and requires therapy for both the induction and maintenance of remission. Progress in the fields of genetics and immunology affords important advances in our understanding of the inflammatory process. Traditional therapy for ulcerative colitis with nonspecific anti-inflammatories remains our gold standard. This review examines the most recent compounds in development for the treatment of ulcerative colitis, including data from early clinical trials and the potential clinical impact of future entities.

Phenotype-stratified genetic linkage study demonstrates that IBD2 is an extensive ulcerative colitis locus.

OBJECTIVES: The complete elucidation of genetic variants that contribute to inflammatory bowel disease (IBD) will likely include variants that increase risk to both Crohn's disease and ulcerative colitis as well as variants that increase risk for particular phenotypic subsets. The purpose of this study was to assess phenotypic subsets that contribute to the major IBD susceptibility loci. METHODS: This linkage study encompassed 904 affected relative pairs, representing the largest combined phenotyped cohort to date, and allowing for meaningful subset analyses. Genetic linkage data were stratified by disease location and age at diagnosis. RESULTS: We establish that some loci, notably the IBD3 and chromosome 3q linkage regions demonstrate contributions from both small intestine and colon cohorts, whereas others, notably the IBD1 (NOD2/CARD15) and IBD2 regions increase risk for small intestine or colon inflammation, respectively. The strongest linkage evidence in this study was for the subset of extensive ulcerative colitis in the region of IBD2 (lod 3.27; p < 0.001). Evidence for linkage in the region of NOD2/CARD15 (IBD1) was stronger for the subset of Crohn's patients with ileal disease (lod 2.56; p= 0.035) compared to the overall Crohn's group, consistent with previous findings that NOD2/CARD15 variants are associated with ileal disease. CONCLUSIONS: Analyses incorporating disease location in IBD increase the power and enhance the accuracy of genomic localization. Our data provide strong evidence that extensive ulcerative colitis represents a pathophysiologic subset of IBD.