What is the link between the use of tobacco and IBD?

This is the authors' abstract. We don't add key points for this paper.

The link between tobacco use and inflammatory bowel disease (IBD) was first made in 1982 when a British case-control study by Harris noticed that a low proportion of ulcerative colitis (UC) patients were smokers. Some time later it was observed that most Crohn's disease (CD) patients smoked. Since then, it has been shown that current smoking also has a major impact on the course of both diseases. The reasons why smoking has an opposite effect in 2 conditions that share many similarities remain obscure. Current smoking protects against UC. The risk of developing UC is decreased in current smokers compared with lifetime nonsmokers (odds ratio [OR] 0.41 [0.34–0.48]).1 The effect of smoking is only suspenspory, as the relative risk of UC is not decreased in former smokers. Moreover, in smokers when compared to nonsmokers, UC runs a more benign disease course: Flare-up and hospitalization rates, the need for oral steroids, and, more important, the colectomy rate are lower in smokers.2 Conversely, stopping smoking increases the risk of developing UC when compared to never smokers (OR 1.64 [1.36–1.98])1 and increases disease activity: Smokers with UC who quit experience more relapses, hospital admissions, and the need for oral steroids and immunosuppressants.3 On the contrary, smoking increases the risk of developing CD (OR 2.0 [1.65–2.47] in current smokers when compared to life-time nonsmokers1). Smoking might determine disease location, with most studies reporting a higher prevalence of ileal disease and a lower prevalence of colonic involvement in smokers.4 Compared to nonsmoking, current smoking is associated with more frequent flares, increased need for steroids and immunosuppressants, and a lower quality of life.5 The deleterious effect of smoking in CD is particularly manifest in patients who have been operated on. In such patients, macroscopic lesions on the ileal site of the anastomosis were observed 1 year after surgery in 70% of smokers, versus 35% of nonsmokers.6 The cumulative rates of clinical and surgical recurrence, respectively, were found consistently more elevated in smokers than in nonsmokers.7 Of note, the negative effects of smoking are dose-dependent, maximum in heavy smokers, and more marked in women than in men, and for ileal disease versus colitis. Conversely, smoking cessation improves the course of CD. From 1 year after the quit date, exsmokers have disease activity and therapeutic requirements similar to never smokers.8 The mechanism of the effect of smoking on IBD is poorly understood. Tobacco smoke contains hundreds of substances, including nicotine and carbon monoxide, and acts on different targets: mucus layer, cytokine production, macrophage function, and microvasculature, probably in different directions in each individual. The result sum of these contradictory effects may be modulated by gender, genetic background, disease location and activity, cigarette dose, and nicotine concentration. Nicotine may be beneficial by increasing mucin synthesis, decreasing IL-8 expression, and reducing TNFα production through its action on the nicotinic acetylcholine receptor. In CD, increased carbon monoxide concentration may amplify the impairment in vasodilation capacity in the chronically inflamed microvessel, resulting in ischemia, and perpetuating ulceration and fibrosis. A defect in bacterial clearance or macrophage deficiency may also have a detrimental role. From a therapeutic point of view, transdermal nicotine was shown to achieve remission in moderate attacks of UC, but was ineffective as maintenance treatment. Side effects (nausea, headache, dermatitis) were frequent and tended to overcome the clinical benefit. Thus, the place of nicotine in the therapeutic armamentarium of UC is questionable.9 In fact, achieving smoking cessation remains an important objective for both IBDs. Taking into account the reduced risk for lung cancer and cardiovascular disease in nonsmokers with UC, the gastroenterologist should not discourage patients with UC from stopping smoking but strengthen medical treatment during the year following smoking cessation. In CD, patients should be informed of the adverse association between smoking and their disease and an individually based smoking cessation strategy should be defined. Nicotine substitution during the first 6–12 weeks of abstinence is required in heavy smokers and in smokers with high levels of dependency. Serotoninergic agents increase the probability of successful smoking cessation and are used routinely during the first months of abstinence. Bupropion, a psychotropic inhibitor of dobutamine and noradrenaline recapture, significantly increases the smoking cessation rate in smokers motivated to stop smoking,10 and may have a beneficial effect on CD activity. In summary, smoking modifies the risk of developing IBD, increasing the risk of CD and decreasing that of UC. In an individual genetically at risk for IBD, smoking may be the main factor determining the phenotype of the disease, either UC or CD. In addition, smoking changes considerably the course of the disease, improving UC and worsening CD, while smoking cessation is followed rapidly by reversal of the effect. Even though the effect of smoking appears opposite in the two IBDs, smoking should be discouraged in both. In UC the increased risks of neoplasia and vascular disease in smokers largely overcome the benefits. In CD, smoking is harmful and persuading patients to stop smoking is probably the most cost-effective strategy for controlling disease activity.