Frans van der Heide

Effects of active and passive smoking on disease course of Crohn's disease and ulcerative colitis

Background: Smoking is a remarkable risk factor for inflammatory bowel disease (IBD), aggravating Crohns disease (CD) while having beneficial effects on ulcerative colitis (UC). We studied the effects of active and passive smoking in Dutch IBD patients. Methods: A questionnaire focusing on cigarette smoke exposure was sent to 820 IBD patients. Returned questionnaires were incorporated into a retrospective chart review, containing details about disease behavior and received therapy. Results: In all, 675 IBD patients (380 [56%] CD and 295 [44%] UC) responded. At diagnosis there were 52% smokers in CD, 41% in the general population, and 28% in UC. The number of present smokers in CD is lower than in the general population (26% versus 35%). No detrimental effects of active smoking on CD were observed, but passive smokers needed immunosuppressants and infliximab more frequently than nonpassive smokers. Active smoking had beneficial effects on UC, indicated by reduced rates of colectomy, primary sclerosing cholangitis, and backwash‐ileitis in active smokers compared to never smokers, and higher daily cigarette dose correlated with less extensive colitis and a lower need for therapy. Furthermore, smoking cessation after diagnosis was detrimental for UC patients, indicated by increased needs for steroids and hospitalizations for patients that stopped smoking after compared to before the diagnosis. Conclusions: Active smoking is a risk factor for CD, but does not affect the outcome; passive smoking is detrimental for the outcome of CD patients. In UC, active smoking shows dose‐dependent beneficial effects. Our data suggest that passive smoking is a novel risk factor for CD. (Inflamm Bowel Dis 2009)

Smoking Behavior in Liver Transplant Recipients

Long‐term morbidity and survival after orthotopic liver transplantation (OLT) are to a large degree determined by cardiovascular disease and cancer. Tobacco use is a well‐known risk factor for both. The aim of this study was to examine smoking behavior before and after OLT and to define groups at risk for resuming tobacco use after OLT. In addition, we looked for a relation between smoking and morbidity after OLT. All 401 adult patients with a follow‐up of at least 2 years after OLT were included. Data were collected from the charts. A questionnaire about smoking habits at 4 time points before and after OLT was sent to all 326 patients alive, and 301 (92%) patients responded. Both before and after OLT, 53% of patients never used tobacco, and around 17% were active smokers. Of the active smokers during the evaluation for OLT, almost one‐third succeeded in cessation, often during the waiting time for OLT. Twelve percent of former smokers restarted smoking, mainly after OLT. Tobacco use was the highest in patients with alcoholic liver disease (52% were active smokers before OLT, and 44% were after OLT) and the lowest in patients with primary sclerosing cholangitis (1.4% were active smokers before OLT). At 10 years, the cumulative rate of malignancies was 12.7% in active smokers versus 2.1% in nonsmokers (P = 0.019). No effect on skin cancer or cardiovascular disease was found. In conclusion, smoking is a serious problem after OLT and increases the risk for malignancy. Prevention programs should focus not only on active smokers but also on former smokers. Liver Transpl 15: 648–655, 2009.

Differences in Genetic Background Between Active Smokers, Passive Smokers, and Non-Smokers With Crohn's Disease

OBJECTIVES:Smoking behavior and genetic variations are important factors for the development of Crohns disease (CD), but studies investigating the interaction between smoking and genetic background are scarce. We studied allelic associations of 19 confirmed variants located in 14 CD-associated genes or loci, in CD patients stratified for active smoking at diagnosis and passive smoking in childhood.METHODS:Genotyping data of 19 CD-associated single-nucleotide polymorphisms (SNPs) were available for 310 CD patients and 976 controls. Data on active smoking at diagnosis and passive smoking in childhood were obtained through a written questionnaire and a review of medical charts.RESULTS:The loci associated in smoking, but not in non-smoking, CD patients were 5p13.1 (rs17234657), DLG5 (rs2165047), NKX2-3 (rs10883365), and NOD2 (R702W). The loci associated in non-smoking, but not in smoking, CD patients were IL23R (rs7517847), 5p13.1 (rs9292777), IRGM (rs13361189 and rs4958847), IL12B (rs6887695), and CCNY (rs3936503). PTPN2 (rs2542151) was only associated in the smoking CD cohort (P=0.041), and not in the entire cohort (P=0.23) or in the non-smoking CD cohort (P=0.80). In passively smoking CD patients, associations with 13 SNPs in 9 loci were found, including PTPN2. In non-passive smoking CD patients, only associations with NOD2 (1007fsinsC and G908R) were found.CONCLUSIONS:The difference in associated genes between smoking and non-smoking CD patients implies a complex gene–environment interaction. Therefore, genetic studies of CD should be stratified for smoking behavior, as otherwise moderately associated genes such as PTPN2 can be missed.

Effects of active and passive smoking on Crohn's disease and ulcerative colitis in a cohort from a regional hospital.

Objective Smoking is detrimental for Crohns disease (CD), but beneficial for ulcerative colitis (UC). Earlier, we studied the effects of active and passive smoking in CD and UC patients from a university hospital. This study was conducted to assess the same effects in patients from aregional hospital. Methods A questionnaire focusing on cigarette smoke exposure was sent to 382 patients. Returned questionnaires (84%: 128 CD and 192 UC patients) were incorporated into a retrospective chart review about disease behaviour and received therapy. Results At diagnosis there were 52% (95% confidence interval: 43–60%) smokers among CD patients, 40% in a control population and 25% (95% confidence interval: 18–31%) among UC patients. There were less former (19 vs. 31%, P=0.013) and never smokers at diagnosis (30 vs. 44%, P=0.009) in CD than in UC. No detrimental effects of active or passive smoking on the course of CD were observed. UC patients who continued smoking after diagnosis needed less often two or more hospitalizations than never smokers (5 vs. 25%, P=0.036). Otherwise no clear beneficial effects of active smoking on UC were observed. Passively smoking UC patients experienced more often extraintestinal manifestations (25 vs. 7%, P=0.029) than nonpassive smokers. Conclusion Also in a regional hospital inflammatory bowel disease population smoking is a risk factor to develop CD and protects against developing UC. We found no detrimental effects of smoking on the disease course of CD and no clear beneficial effects on the course of UC.

Active and passive smoking behaviour and cessation plans of patients with Crohn's disease and ulcerative colitis

BACKGROUND Smoking is a remarkable risk factor in inflammatory bowel disease (IBD), with negative effects on Crohns disease (CD) and positive effects on ulcerative colitis (UC). This makes different changes in smoking behaviour after diagnosis between CD and UC likely. Changes in active smoking, cessation plans and passive smoking were studied in IBD patients. METHODS 820 IBD patients were sent a questionnaire on active and passive smoking, and cessation plans. A total of 675 (82%) patients (380 CD and 295 UC) responded. RESULTS More ever smoking UC patients stopped smoking before diagnosis than CD patients (63% vs 22%; p<0.001), resulting in 30% former smokers at diagnosis in UC and 13% in CD (p<0.001). The smoking cessation rates at and after diagnosis are equal between CD and UC. Half of the CD patients stopped smoking after diagnosis leading to less present smokers in CD than in a control population (26% (95% confidence interval: 21.1%-29.9%) vs 33%). For both CD (22% vs 35%; p=0.044) and UC (24% vs 53%; p=0.024) continuing smokers after diagnosis were less often higher educated than quitters. Cessation plans (89%), passive smoking in childhood and present passive smoking were not different between CD and UC patients. CONCLUSION There are no differences in changes in smoking behaviour at and after diagnosis between CD and UC patients, suggesting a lack of knowledge in these patients about the link between their disease and smoking behaviour. However, CD patients seem less refractory to smoking cessation than the general population. Therefore it is worthwhile putting energy in helping CD patients stop smoking.

Thiopurines Are Associated with a Reduction in Surgical Re-resections in Patients with Crohn's Disease: A Long-term Follow-up Study in a Regional and Academic Cohort

Background:Combination therapy of thiopurines and anti–tumor necrosis factor alpha (TNF-&agr;) antibodies is the most effective medical treatment of Crohns disease (CD). Data on thiopurines and anti-TNF-&agr; antibodies in preventing surgical recurrence (need for re-resection) of CD are scarce. Therefore, we analyzed which factors were involved in surgical recurrence of CD in a large cohort of patients with CD operated in a regional and a university hospital. Methods:This is a retrospective cohort study of 567 patients who underwent surgery for CD. Clinical data and risk factors for surgical recurrence were analyzed, focusing on medical therapy and hospital type. Results:Overall, 237 (41.8%) patients developed a surgical recurrence, after a median of 70 (2–482) months. Before surgical recurrence, 235 patients (41.4%) and 116 patients (20.5%) used thiopurines and anti-TNF-&agr; antibodies, respectively. Multivariate analysis identified 3 independent risk factors associated with surgical recurrence of CD. A higher risk was seen in patients with colonic disease compared with patients with ileal disease (hazard ratio, 1.56; 95% confidence interval, 1.10–2.21; P = 0.012) and in patients using multiple types of medication (hazard ratio, 1.38; 95% confidence interval, 1.25–1.54; P < 0.001). However, a lower risk was seen in patients using thiopurines (hazard ratio, 0.51; 95% confidence interval, 0.34–0.77; P = 0.001). Conclusions:Thiopurines are effective in preventing surgical recurrence of CD. The role of anti-TNF-&agr; antibodies seems promising as well. Combination therapy of thiopurines and anti-TNF-&agr; antibodies for prevention of surgical recurrence of CD should be studied in a randomized trial.