Faecal calprotectin: factors affecting levels and its potential role as a surrogate marker for risk of development of Crohn's Disease.

BACKGROUND: Faecal calprotectin (FC) is one of the most widely used non-invasive tests for the diagnosis and assessment of Crohn's disease (CD) activity. Despite this, factors other than disease activity which affect levels have not been extensively reviewed. This is of importance when using FC in the diagnostic setting but also may be of utility in studying the aetiology of disease. OBJECTIVES: Our review outlines environmental risk factors that affect FC levels influencing diagnostic accuracy and how these may be associated with risk of developing CD. FC as a surrogate marker could be used to validate risk factors established in case control studies where prospective studies are not feasible. Proof of this concept is provided by our identification of obesity as being associated with elevated FC, our subsequent confirmation of obesity as risk factor for CD and the subsequent verification in prospective studies, as well as associations of lack of physical activity and dietary fibre intake with elevated FC levels and their subsequent confirmation as risk factors in prospective studies. CONCLUSION: We believe that FC is likely to prove a useful surrogate marker for risk of developing CD. This review has given a theoretical basis for considering the epidemiological determinants of CD which to date has been missing

Infliximab induction regimens in steroid refractory acute severe colitis: a multi-centre retrospective cohort study with propensity score analysis

Background:Accelerated induction regimens of infliximab have been proposed to improve response rates in patients with steroid refractory acute severe colitis. Aims:We aimed to determine differences in outcome for acute severe ulcerative colitis between accelerated and standard-dose infliximab.Methods:We collected data on hospitalised patients receiving differing regimens of rescue therapy for steroid refractory Acute Severe Ulcerative Colitis. Our primary outcome was 30-day colectomy rate. Secondary outcomes were colectomy within index admission, 90 days and 12 months. We used propensity score analysis with optimal calliper matching using a priori defined high-risk covariates to reduce potential provider selection bias.Results:We included 131 patients receiving infliximab rescue therapy; 102 patients received standard induction and 29 received accelerated induction. In the unmatched cohort, there was no difference by type of induction in 30-day colectomy rates (18% vs. 20%, p=0.45), colectomy during index admission (13% vs. 20%, p = 0.26) or overall colectomy (20% vs. 24%, p= 0.38). In the propensity score-matched cohort of 52 patients, 30-day colectomy (57% vs. 27%, p = 0.048) and index admission colectomy (53% vs. 23%,p =0.045) rates were higher in those receiving standard induction compared to accelerated induction but there was no difference in overall colectomy rates between the 2 groups (57% vs. 31%, p =0.09). There was no significant difference in length of stay or in complication and infection rates.Conclusion:In a propensity score matched cohort, steroid refractory Acute Severe Ulcerative Colitis patients, short-term, but not long-term, colectomy rates appear to be lower in those receiving accelerated induction regimen

The role of diet in the aetiopathogenesis of inflammatory bowel disease

Crohn’s disease and ulcerative colitis, collectively known as IBD, are chronic inflammatory disorders of the gastrointestinal tract. Although the aetiopathogenesis of IBD is largely unknown, it is widely thought that diet has a crucial role in the development and progression of IBD. Indeed, epidemiological and genetic association studies have identified a number of promising dietary and genetic risk factors for IBD. These preliminary studies have led to major interest in investigating the complex interaction between diet, host genetics, the gut microbiota and immune function in the pathogenesis of IBD. In this Review, we discuss the recent epidemiological, gene–environment interaction, microbiome and animal studies that have explored the relationship between diet and the risk of IBD. In addition, we highlight the limitations of these prior studies, in part by explaining their contradictory findings, and review future directions

The effect of cigarette smoke exposure on the development of inflammation in lungs, gut and joints of TNFΔARE mice

The inflammatory cytokine TNF-alpha is a central mediator in many immune-mediated diseases, such as Crohn's disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNF Delta ARE mice; in which a systemic TNF-alpha overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNF Delta ARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNF Delta ARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNF Delta ARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNF Delta ARE mice. The lung responses towards CS in TNF Delta ARE mice however depend on the duration of CS exposure

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability