Abstract and Introduction

Abstract

Background Smoking is the best-characterised environmental association of ulcerative colitis (UC). Smoking has been observed to exert protective effects on both the development and progression of UC.

Aims To examine the association between UC and smoking, possible pathogenic mechanisms and the potential of nicotine as a therapeutic agent in the treatment of UC.

Methods A literature search was conducted through MEDLINE, using the MeSH search terms 'ulcerative colitis' and 'smoking' or 'nicotine'. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles.

Results Ulcerative colitis is less prevalent in smokers. Current smokers with a prior diagnosis of UC are more likely to exhibit milder disease than ex-smokers and nonsmokers. There is conflicting evidence for smokers having reduced rates of hospitalisation, colectomy and need for oral corticosteroids and immunosuppressants to manage their disease. Multiple potential active mediators in smoke may be responsible for these clinical effects, including nicotine and carbon monoxide, but the precise mechanism remains unknown. Nicotine has demonstrated variable efficacy in the induction of remission in UC when compared to placebo and conventional medicines. Despite this, the high frequency of adverse events limits its clinical significance.

Conclusions Nicotine's application as a therapeutic treatment in ulcerative colitis is limited. Presently, it may be an option considered only in selected cases of acute ulcerative colitis refractory to conventional treatment options. This review also questions whether nicotine is the active component of smoking that modifies risk and inflammation in ulcerative colitis.

Introduction

Ulcerative Colitis (UC) is a chronic idiopathic inflammatory bowel disease (IBD) that differentiates itself by exhibition of a nontransmural, continuous and symmetrical pattern of inflammation limited to the colon with distal to proximal extension in disease progression. UC follows a chronic course, punctuated by clinical remissions and relapses. The induction and maintenance of remission is an important goal in the management of UC, as the disease poses substantial direct and indirect healthcare costs in addition to significant morbidity for the patient. Genetic, immunological and environmental factors all play a role in the development of UC, but curiously, UC features frequently in nonsmokers.

Cigarette smoking is the best characterised environmental association of UC.[1–4] Paradoxically, UC appears to be predominantly a disease of ex-smokers and nonsmokers.[2,4–24] First noted by Samuelsson in 1976[25] and confirmed by Harries, Baird and Rhodes in 1982,[26] it was observed that there was a distinct lack of current smokers in a cohort of UC patients, compared with that of a group of matched control subjects. Since then, numerous studies of the relationship between smoking and UC have confirmed this observation and demonstrated that smoking not only appears to protect against the development of UC, but in fact ameliorates the clinical course of the disease.[1–6,24] Subjectively, in a cohort of smokers with UC, over half-indicated smoking improved their disease and none felt smoking had a detrimental effect on their UC.[27] Similarly, in a group of ex-smokers with refractory UC, 14 out of 15 achieved prolonged clinical remission without steroids, following resumption of low-dose smoking.[28] Observations, such as these have further generated interest in the potential application of nicotine, a major constituent of cigarette smoke, as a treatment option for the induction of remission in UC.