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- MATERIALS AND METHODS
Cigarette smoking is clearly harmful in Crohn’s disease. More precisely, smoking is associated with a higher risk of developing the disease,1, 2 increased clinical activity,3, 4 lower quality of life,5 more frequent complications,6, 7 increased need for immunosuppressive drugs,8, 9 and faster recurrences after surgery.10–12
Many questions remain unanswered, however. Factors determining the importance of the harmful effect of smoking in one individual are poorly defined. Retrospective studies have suggested that women and patients with small bowel involvement are particularly susceptible.6, 8, 10 The putative additive role of other atherogenic or thrombogenic risk factors, such as obesity or dyslipidaemia has not been studied. The effect of smoking seems to be dose-dependent, but the respective effects of the daily tobacco consumption and the total life exposure are not easy to separate.7, 8, 11 Importantly, although the risk of post-surgical recurrence may be decreased in former smokers, compared to current smokers, there is no clear evidence that former smokers have a day-by-day disease course similar to that of non-smokers.8, 11
To address these questions, we conducted a prospective longitudinal study in a large population of patients followed in a single centre.
- Top of page
- MATERIALS AND METHODS
This prospective study confirms the harmful effect of current smoking in an unselected large cohort of patients with Crohn’s disease. The effects of smoking were more marked in patients who had no colonic lesions and in those whose disease was in remission, particularly if they were smoking more than 15 cigarettes per day. Neither obesity nor dyslipidaemia increased the deleterious effect of smoking. Alcohol intake had no effect. More importantly, this study clearly showed that patients who had stopped smoking were doing as well as non-smokers.
The effect of smoking may only be apparent in some particular subgroups of patients with Crohn’s disease, therefore care was taken in this study to include all consecutive patients seen during a long enrolment period of 1 year. As some patients with chronic active disease never reach clinical remission, we chose to include patients with a CDAI of up to 199, comprising those with low 1-week disease activity. We believe that these criteria minimized selection bias and allowed us to obtain an accurate estimate of the real effects of smoking. Although our recruitment may have missed some asymptomatic patients who, as they had done well for several years, escaped medical surveillance, we found a relatively low proportion (37%) of patients who developed a flare-up episode during the 12–18-month study period. This figure fits well with the data of a cohort of unselected Crohn’s patients from Denmark demonstrating the existence of a remarkably constant annual proportion of 30% of the patients with a moderate to high activity state.17
Year-by-year analyses of changes from active disease to remission and from remission to active disease have shown that about 70% of patients maintain their state of activity during the following year.17 In our study, the main risk factor for flare-up was indeed the recent activity of the disease at baseline. Although this factor tended to outweigh the others, the effect of smoking was still apparent. In this regard, it should be noted that previous disease activity was in part correlated with smoking status. In our statistical analysis, we calculated the relative risk of flare-up for current smokers after adjustment for recent disease activity, but not for current smoking during the year preceding inclusion. Thus the actual effect of smoking, even adjusted, may be slightly underestimated. Compared to non-smokers, current smokers were in a worse condition at inclusion, during the year of follow-up, and at the end of the study. One could argue that patients with severe disease are more prone to smoke, and that smoking may be a consequence rather than a cause of severe disease. However, this interpretation does not agree with the fact that the noxious effect of smoking was pre-eminent in patients whose disease was in remission. In addition, our previous retrospective study showed that the effect of smoking was protracted and discernible during the long-term evolution, even though the activity of Crohn’s disease in one individual may vary over time, exhibiting cycles of 3–7 years’ duration.8, 17 The reality of the effect of smoking was demonstrated further in the present study by the trend for a dose–effect relationship. This result confirms data from retrospective long-term studies, which are compatible with a dose-dependent effect of cigarette consumption.8, 11 Finally, the present study showed that the harmful effect of smoking was not significantly modified by gender, age, duration of Crohn’s disease, presence of small bowel and anoperineal lesions, and current therapy. Only patients who had active colonic lesions seemed less sensitive to the effect of smoking, but further studies are needed to confirm this result. Thus at the present time, every patient with Crohn’s disease who smokes should be advised to stop smoking.
The effect of associated vascular factors could be questioned as Wakefield et al. demonstrated the important pathogenic role of multifocal infarction in Crohn’s disease.18 We did not find an increased prevalence of dyslipidaemia nor obesity in our cohort of patients, and, when present, these abnormalities were not associated with an increased risk of flare-up. Similarly, we have shown in patients from this series the absence of effect of oral contraceptive use.15 In addition, very few patients were drinking alcohol and no association could be demonstrated between alcohol consumption and either a benign or a severe disease course.
Finally, the most important finding of this study was the fact that former smokers were doing as well as non-smokers. Although these patients were older and had a disease of longer duration than patients from the two other groups, there is no evidence that these differences may explain such findings. In the present study, age and duration of the disease had no effect on the flare-up rate and in the literature there are no data supporting the view that the activity of Crohn’s disease may decrease significantly with time.17 Moreover, former smokers tended to have a particularly benign clinical course, and very few patients required intensification of medical therapy or excisional surgery. These results should be presented to current smokers in order to convince them to quit.
In conclusion, the effect of smoking is clearly harmful in Crohn’s disease, in both the short and the long-term, particularly in heavy smokers. On the other hand, this effect is not long-lasting and stops after smoking cessation. Thus, every effort should be made to encourage patients to stop smoking. The inactive phase of the disease, including the post-operative period after curative resection, is the time when the resulting benefit will be greatest.19