Smoking is associated with risk for developing inflammatory bowel disease including late onset ulcerative colitis: a prospective study.

OBJECTIVES: Life style factors have been associated with inflammatory bowel disease (IBD) but there is a lack of data on the exposure of life styles factors before the onset of IBD. Our aim was to study the association between lifestyle factors and the development of IBD in a prospective setting. MATERIALS AND METHODS: We performed a case control study of 72 patients who later developed ulcerative colitis (UC), 26 patients who developed Crohn's disease (CD) and 427 healthy controls from the Västerbotten intervention project matched for gender, age, year of health survey and area of residence. At recruitment, participants completed validated lifestyle questionnaires including data on alcohol intake. Information from this was used to assess the connection between lifestyle factors and later developing IBD. RESULTS: For CD and UC, the median age at diagnosis was 53 and 52 years and median time of survey was 4 and 6 years before diagnosis, respectively. Multivariate odds ratio (OR) showed an association between never smoking and not developing IBD, including both UC and CD, OR (95% CI) 0.341 (0.136-0.853) and 0.473 (0.259-0.864), respectively. Marital status, educational level, alcohol consumption, reported physical activity and use of moist smokeless tobacco (snus) did not differ between patients and controls. CONCLUSIONS: Smoking proves to be a risk factor for both CD and UC in this prospective case-control study. No association was seen for snus users, implying a non-nicotine pathogenic mechanism from combusted tobacco.

Preclinical Markers in Inflammatory Bowel Disease. A Nested Case-Control Study.

Background: Our objective was to determine if patients who later develop inflammatory bowel disease (IBD) show signs of increased inflammatory activity in plasma measured with high sensitivity C-reactive protein (CRP), calprotectin, and albumin before the clinical onset of IBD. Methods: We identified 96 subjects who later developed IBD (70 ulcerative colitis [UC] and 26 Crohn's disease [CD]). High sensitivity CRP, calprotectin, and albumin were analyzed in frozen plasma, donated from cases and sex-age matched controls 1-15 years before diagnosis. Results: We found that subjects who later developed UC had lower albumin levels, and subjects who later developed CD had higher CRP levels than controls. Multivariable conditional logistic regression with albumin, calprotectin, and CRP showed a lower risk for developing IBD and UC with higher albumin levels (odds ratio [OR] 0.79, confidence interval [CI] 0.69-0.90; respective OR 0.77, CI 0.66-0.91). Higher CRP levels were associated with an increased risk of developing CD (OR 1.314, CI 1.060-1.630). When adjusting for body mass index or smoking in the logistic regression model, similar results were found. Plasma calprotectin levels in the preclinical period among patients with IBD did not differ from controls. Conclusions: In this nested case-control study, subjects who later developed IBD had signs of low-grade systemic inflammation, indicated by significantly higher CRP plasma levels in CD and lower albumin plasma levels in UC, before the onset of clinical disease.

Patients developing inflammatory bowel disease have iron deficiency and lower plasma ferritin years before diagnosis: a nested case-control study.

BACKGROUND: Iron deficiency is common among inflammatory bowel disease (IBD) patients, generally reported without comparisons with controls. The aim of this study was to analyse if iron deficiency was more common among those later developing IBD compared to matched controls in a prospective setting. METHODS: We included 96 healthy subjects later developing IBD and 191 matched controls from the Northern Sweden Health and Disease Study. We analysed iron, ferritin, transferrin, and calculated transferrin saturation in plasma sampled at least 1 year prior to IBD diagnosis. Iron deficiency was defined as plasma ferritin <30 µg/L if C-reactive protein (CRP) was <3 mg/L. When CRP was >3 mg/L, iron deficiency could not be excluded if ferritin was <100 µg/L. RESULTS: Iron deficiency could not be excluded among more male cases vs controls (25.0% vs 2.2%; P < 0.001), whereas with no differences for women (39.6% vs 35.3%; P = 0.538). Ferritin was lower among male IBD cases (P = 0.001) and for ulcerative colitis (P = 0.016 for males and 0.017 for females), but not for Crohn's disease. Ferritin was associated with a lower risk for IBD and in the ulcerative colitis subgroup when using sex-based z-scores. Ferritin quartiles 2-4 had a 65% lower odds ratio for all IBD, ulcerative colitis, and Crohn's disease in multivariable analysis. CONCLUSIONS: Lower ferritin was associated with higher risk for developing IBD in a prospective setting. Iron deficiency was more common among healthy males years later developing IBD compared to matched controls, but not among women.

Elevated plasma cotinine is associated with an increased risk of developing IBD, especially among users of combusted tobacco.

OBJECTIVE: Smoking has previously been associated with inflammatory bowel disease (IBD), but no study has reported on cotinine, an objective, biochemical measure of tobacco use. We aimed at testing the hypothesis that cotinine levels among healthy subjects are associated with an increased risk of developing IBD in later life. DESIGN: We analysed plasma cotinine and evaluated corresponding lifestyle questionnaires that included tobacco habits in subjects (n = 96) who later developed late-onset IBD (70 ulcerative colitis (UC) and 26 Crohn's disease (CD)) and in sex and age-matched controls (n = 191). RESULTS: Patients who later developed IBD had significantly higher plasma cotinine levels compared to controls. In multivariable analysis, higher log-cotinine was associated with a higher risk of developing IBD (OR 1.34 (95% CI 1.01-1.63)). After stratifying for time to diagnosis, the association was only significant in subjects with shorter time (< 5.1 years) to diagnosis (OR 1.45 (1.09-1.92)). The findings were similar for UC- and CD-cases, but did not reach statistical significance in CD-cases. Although plasma cotinine concentrations were higher in snuff users compared to combusted tobacco users, no increase in the risk of IBD and lower risk of developing IBD among subjects with shorter time (< 5.1 years) to diagnosis was seen among snuff users. CONCLUSIONS: Cotinine, a biomarker of tobacco use, is associated with increased risk of developing late-onset IBD in general, and UC in particular. No increased risk among snuff users indicates that other components in combusted tobacco than nicotine may be involved in the pathogenesis of IBD among smokers.