Smoking and Crohn's disease: active modification of an independent risk factor (education alone is not enough).

INTRODUCTION: Smoking can induce the onset of Crohn's disease in genetically susceptible patients and may accelerate progression and disease severity. There is a paucity of information as to patient knowledge of the impact of smoking on disease progression. The aim of this study was to assess patient awareness, initiate smoking cessation therapy and monitor the effectiveness of an active smoking cessation programme in patients with Crohn's disease. METHODS: All patients with a diagnosis of Crohn's disease over a ten year period were identified from a prospectively managed database. Details of smoking history and patient knowledge of the link between Crohn's disease and smoking were collected through a telephone questionnaire. Current smokers who wished to quit were enrolled in a smoking cessation programme and followed prospectively for 12 months. RESULTS: 340 patients were identified with 281 eligible for inclusion. 181 patients agreed to a telephone survey (64.4% patient uptake). Smokers had an increased incidence of surgical intervention (OR 2.2; CI 1.02, 4.78 P=0.043). Awareness of the link between smoking and Crohn's disease was highest in the current smoking cohort and lowest in the non-smoking cohort (CS:NS; 79.5%:43% p<0.001). 29% of patients with a smoking history had previously been offered smoking cessation therapy. 77% of current smokers opted for smoking cessation therapy. At 6 months 53% of these patients remained smoke free and 37% at 12 months. CONCLUSION: In patients with Crohn's disease, information alone is ineffective at achieving smoking cessation. Good cessation rates are achievable if information is supported by active smoking cessation therapy.

The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival.

The expression of pathogen recognition receptors in human FOXP3+ T regulatory cells is established, yet the function of these receptors is currently obscure. In the process of studying the function of both peripheral and lamina propria FOXP3+ lymphocytes in patients with the human inflammatory bowel disease Crohn's disease, we observed a clear deficiency in the quantity of FOXP3+ lymphocytes in patients with disease-associated polymorphisms in the pathogen recognition receptor gene NOD2. Subsequently, we determined that the NOD2 ligand, muramyl dipeptide (MDP), activates NF-kappaB in primary human FOXP3+ T cells. This activation is functionally relevant, as MDP-stimulated human FOXP3+ T cells are protected from death receptor Fas-mediated apoptosis. Importantly, apoptosis protection was not evident in MDP-stimulated FOXP3+ T cells isolated from a patient with the disease-associated polymorphism. Thus, we propose that one function of pathogen recognition receptors in human T regulatory cells is the protection against death receptor-mediated apoptosis in a Fas ligand-rich environment, such as that of the inflamed intestinal subepithelial space.