Smoking In Ulcerative Colitis Research Articles

Symptomatic Effects of Smoking in Ulcertive Colitis: A Clinical Dilemma

Inflammatory bowel disease (IBD) is a digestive tract disorder manifesting mainly in two forms, namely Crohn’s disease (inflammation of digestive tract) and ulcerative colitits (inflammation of large intestine lining) .Genetic and environmental factors could potentially predispose towards IBD. From a smoking perspective, ulcerative colitis is frequently observed in ex-smokers of non-smokers whereas Crohn’s disease is frequently observed among smokers. Smoking was reported to have distinct effects in these two types of disorders, nevertheless elicitation of humoral and cellular immunity was observed to be common in both the types of IBDs. Smoking has been implicated in disease amelioration in case of UC. However, smoking has been associated with several adverse effects including cardiovascular disease and carcinogenesis which outweigh the beneficial aspects. The present review collates information on the role of smoking in UC based on latest research outcomes and elucidates the effect of nicotine (an active constituent in smoking) and associated mechanism of action in IBD condition. Genetic and environmental factors are the cause of disorders like inflammatory bowel diseases (IBD). Ulcerative colitis (UC) is a type of IBD which is mostly seen in non-smokers or former smokers. In UC protective effect of smoking is seen due to nicotine presence. While in Crohn’s disease (CD) smoking show opposite effects hence, it is complex to know relationship between IBD’s. Humoral and cellular immunity changes are indulged in the relationship of both the IBD’s. Therapeutically, nicotine is used for many diseases like ulcerative colitis, Alzheimer's disease, Parkinson's disease, Tourette's syndrome, sleep apnea, and attention deficit disorder. In case of active UC nicotine is effective while in most cases this nicotine becomes harmful and causes side effects like nausea, headache, dermatitis etc. Smoking is linked to most hazardous effects like atherosclerosis, pulmonary hypertension, cardiovascular diseases, carcinogenic disorders which make patients to quit smoking. This sudden ceasing of smoking may potentially elevate symptoms. Correlating with the previous data here we will compare effect of smoking based on genetic susceptibility, twins, gender, and smokers and non- smokers. Data is highly contradictory while the involved mechanism in both the cases is still unknown. In this paper we have mainly focused on smoking role in Ulcerative colitis (UC) depending on many studies done in recent years and also the effect and mechanism of nicotine action on our body.

Protective effect of cigarette smoke on the course of dextran sulfate sodium-induced colitis is accompanied by lymphocyte subpopulation changes in the blood and colon

BackgroundCigarette smoke (CS) exerts protective effect against ulcerative colitis. The mechanism of this phenomenon remains unknown. One of the possible explanation by which CS exerts its anti-inflammatory action is modulation of immune system. Therefore, the aim of the study was to evaluate the effect of CS on the course of inflammation and subpopulations of lymphocytes in the blood and colon in mice with dextran sulfate sodium (DSS)-induced colitis.MethodsC57BL6/cmdb mice were exposed to CS for 4 weeks. Colitis was induced with 3.5% DSS given for 10 days. Severity of colitis was determined by disease activity index (DAI), body weight changes, and macro- and microscopic characteristics of inflammation. Peripheral subpopulations of lymphocytes were assessed by flow cytometry (blood) or immunohistochemistry (colonic tissue).ResultsMice treated with 3.5% DSS developed severe colitis with significantly decreased body weight, increased DAI, and macroscopic and histological features of colonic inflammation. These findings were diminished after concomitant exposure to CS. Mice exposed to DSS alone demonstrated significantly decreased percentage of total CD4+ cells (73.1 vs. 52%, p = 0.0007), accompanied by increase of CD8+ cells (18.4 vs. 39.5%, p = 0.0001). Concomitant CS exposure reversed inappropriate CD4+/CD8+ ratio both in the blood and colon and significantly increased B cell presence in the colon.ConclusionsOur study has demonstrated that CS exposure decreases severity of DSS-induced colitis. This phenomenon was accompanied by changes in CD4/CD8 ratio and B cell level in the peripheral blood and colon. These mechanisms may be responsible for protective effect of smoking in ulcerative colitis.

HSPA6 is an ulcerative colitis susceptibility factor that is induced by cigarette smoke and protects intestinal epithelial cells by stabilizing anti-apoptotic Bcl-XL

BackgroundCigarette smoking ameliorates ulcerative colitis (UC) and aggravates Crohn's disease (CD). Cigarette smoke suppresses inflammation-induced apoptosis in intestinal epithelial cells (DLD-1), which may explain its protective effect in UC. Here, we performed transcriptome profiling of cigarette smoke extract (CSE)-exposed DLD-1 and Jurkat cells (T-lymphocytes) and related this to UC susceptibility genes with protective functions in the intestinal epithelium. MethodsCSE-regulated genes in DLD-1 and Jurkat cells were identified by Illumina microarrays and compared to genes in UC susceptibility loci. Colon biopsies were analyzed by immunohistochemistry for cell-specific expression of HSPA6. CSE-induced gene expression was analyzed by Q-PCR, Western blotting and immunofluorescence microscopy. Protein (HSPA6/Bcl-XL) interactions were analyzed by immunoprecipitation. ResultsCSE changed the expression of 536 and 2560 genes in DLD-1 and Jurkat cells, respectively. The “response to unfolded protein” was one of the most significantly affected gene sets with prominent induction (20.3-fold) of heat shock protein A6 (HSPA6). Six CSE-induced genes in DLD-1 cells were located in UC-susceptibility loci, including HSPA6 (rs1801274). HSPA6 is highly expressed in the human colonic epithelium. CSE caused a dose-dependent strong (>100-fold at 30% CSE for 6h), but transient induction of HSPA6 mRNA and protein in DLD-1 cells. HSPA6 co-immune precipitated with anti-apoptotic Bcl-XL, protein levels of which were increased while mRNA levels were unchanged. ConclusionsHSPA6 is a cigarette smoke-induced UC-susceptibility gene. The HSPA6 risk locus is associated with decreased HSPA6 expression. HSPA6 provides epithelial protection by stabilizing anti-apoptotic Bcl-XL, thereby contributing to the beneficial effect of cigarette smoking in UC.

Nicotine-induced cellular stresses and autophagy in human cancer colon cells: A supportive effect on cell homeostasis via up-regulation of Cox-2 and PGE2 production

Nicotine, one of the active components in cigarette smoke, has been described to contribute to the protective effect of smoking in ulcerative colitis (UC) patients. Furthermore, the nicotinic acetylcholine receptor α7 subunit (α7nAChR) expressed on immune cells, is an essential regulator of inflammation. As intestinal epithelial cells also express α7nAChR, we investigated how nicotine could participate in the homeostasis of intestinal epithelial cells. First, using the human adenocarcinoma cell line HT-29, we revealed that nicotine, which triggers an influx of extracellular Ca2+ following α7nAChR stimulation, induces mitochondrial reactive oxygen species (ROS) production associated with a disruption of the mitochondrial membrane potential and endoplasmic reticulum stress. This results in caspase-3 activation, which in turn induces apoptosis. Additionally, we have shown that nicotine induces a PI3-K dependent up-regulation of cyclooxygenase-2 (Cox-2) expression and prostaglandin E2 (PGE2) production. In this context, we suggest that this key mediator participates in the cytoprotective effects of nicotine against apoptosis by stimulating autophagy in colon cancer cells. Our results provide new insight into one potential mechanism by which nicotine could protect from UC and suggest an anti-inflammatory role for the cholinergic pathway at the epithelial cell level.

Smoking prevalence and its influence on disease course and surgery in Crohn's disease and ulcerative colitis.

Smoking demonstrates divergent effects in Crohn's disease (CD) and ulcerative colitis (UC). Smoking frequency is greater in CD and deleterious to its disease course. Conversely, UC is primarily a disease of nonsmokers and ex-smokers, with reports of disease amelioration in active smoking. To determine the prevalence of smoking and its effects on disease progression and surgery in a well-characterised cohort of inflammatory bowel diseases (IBD) patients. Patients with smoking data of the Sydney IBD Cohort were included. Demographic, phenotypic, medical, surgical and hospitalisation data were analysed and reported on the basis of patient smoking status. 1203 IBD patients were identified comprising 626 CD and 557 UC with 6725 and 6672 patient-years of follow-up, respectively. CD patients were more likely to smoke than UC patients (19.2% vs. 10.2%, P<0.001). A history of smoking in CD was associated with an increased proportional surgery rate (45.8% vs. 37.8%, P=0.045), requirement for IBD-related hospitalisation (P=0.009) and incidence of peripheral arthritis (29.8% vs. 22.0%, P=0.027). Current smokers with UC demonstrated reduced corticosteroid utilisation (24.1% vs. 37.5%, P=0.045), yet no reduction in the rates of colectomy (3.4% vs. 6.6%, P=0.34) or hospital admission (P=0.25) relative to nonsmokers. Ex-smokers with UC required proportionately greater immunosuppressive (36.2% vs. 26.3%, P=0.041) and corticosteroid (43.7% vs. 34.5%, P=0.078) therapies compared with current and never smokers. This study confirms the detrimental effects of smoking in CD, yet failed to demonstrate substantial benefit from smoking in UC. These data should encourage all patients with IBD to quit smoking.

Opposing Effects of Smoking in Ulcerative Colitis and Crohnʼs Disease May Be Explained by Differential Effects on Dendritic Cells

The mechanisms underlying the differential effects of cigarette smoking in patients with Crohn's disease (CD) and ulcerative colitis (UC) remain unknown. Smoking has been demonstrated to be protective in UC, whereas in CD it has been shown to be associated with a more severe course, more frequent relapses, and postoperative recurrence. Dendritic cells (DC) play a critical role in T-cell activation and differentiation. Thus, we examined the effects of in vitro exposure to cigarette smoke extract (CSE) on phenotype/function of DC obtained from patients with UC and CD. Sixty-eight subjects were recruited including 30 patients with CD, 19 patients with UC, and 19 healthy controls. Peripheral blood monocytes were differentiated to DC in presence of IL-4 and granulocyte-macrophage colony-stimulating factor. The influence of CSE on Mo-DC subsets, cytokine expression, and ability to drive T cell proliferation and polarization were examined. CSE affected DC phenotypes including increases in class-2 major histocompatibility complex and costimulatory molecules and decreases in CXCL10 and CCL3 levels in UC compared with CD samples. Furthermore, CSE also altered DC function resulting in increasing T cell proliferation and Th1 polarization in CD, whereas it increased Foxp3+ T cells and decreased the Th1 subset in UC samples. CSE modulates DC phenotype and function in patients with UC leading to increased prevalence of Foxp3+ CD4 T cells, whereas in patients with CD it skews toward Th1 subsets. Differential DC responses to CSE between CD and UC may contribute to the differential effects associated with cigarette smoking status.

Is Current Smoking Still an Important Environmental Factor in Inflammatory Bowel Diseases? Results from a Population-based Incident Cohort

Previous studies suggest that smoking is an important environmental factor in inflammatory bowel diseases (IBDs), with dichotomous effects in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to analyze the relationship between smoking and IBD risk in a population-based database from Veszprem Province, which included incident cases diagnosed between January 1, 1977, and December 31, 2008. Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 years; CD: 506, age at diagnosis: 31.5 years). Both inpatient and outpatient records were collected and comprehensively reviewed. Overall, smoking frequency in the adult general population was 36.1%. Of patients with CD, 47.2% were current smokers at diagnosis. Smoking was more frequent in male patients (P = 0.002) and was associated with an increased risk of CD (odds ratio, 1.96; 95% confidence interval, 1.63-2.37; P < 0.001). In contrast, current smoking was protective against UC (odds ratio, 0.33; 95% confidence interval, 0.27-0.41). The effect of smoking was linked to gender (in CD, more deleterious in male patients) and age at diagnosis and was most prominent in young adults, with a difference already being seen in 18- to 19-year-olds. In CD, a change in disease behavior (P = 0.02), location from ileal or colonic to ileocolonic (P = 0.003), arthritis/arthropathy (P = 0.002), need for steroids (P = 0.06), or AZA (P = 0.038) was more common in current smokers. Smoking in UC was associated with more extensive disease (P = 0.01) and a tendency for decreased need for colectomy (P = 0.06). Current smoking was associated with the risk of IBD. This effect was linked to gender and age at diagnosis and was most prominent in young adults. No association was observed in pediatric or elderly patients. The deleterious and protective effects of smoking on the course in CD and UC were partially confirmed.

Appendectomy, tonsillectomy, and risk of inflammatory bowel disease: a case control study in Iran

There is some controversy about the prevalence of appendectomy and tonsillectomy among patients with Crohn's disease and a lower rate of appendectomy among patients with ulcerative colitis (UC). The objective of this study was to elucidate the role of appendectomy and tonsillectomy in Iranian patients with inflammatory bowel disease (IBD). Three hundred and eighty-two consecutive cases of UC and 46 cases of CD were included. Age and sex-matched controls were randomly selected. A total of 382 controls for UC and 184 controls for CD were enrolled. A standard record concerning smoking habit, history of appendectomy and tonsillectomy, OCP, and NSAID use was completed. Logistic regression analysis was used to evaluate potential confounding variables. Twelve patients (3.1%) with UC reported a previous history of appendectomy compared with 30 controls (7.9%) (OR=0.38, 95%CI=0.19-0.76, P<0.004). Appendectomy was reported by five patients (10.9%) with CD compared with four controls (2.2%) (OR=5.49, 95%CI=1.41-21.34, P<0.02). The logistic regression analysis showed that appendectomy is a risk factor in CD but has a modest protective effect for development of UC. No association with tonsillectomy was found for either disease. A statistically significant protective effect for smoking in UC was found (OR=0.2, 95%CI=0.13-0.32, P<0.0001). We have found an inverse association between OCP and NSAID use with UC, but not CD (P<0.0001 and P<0.001, respectively). Appendectomy is protective in UC, but a risk factor in CD among Iranian population. Tonsillectomy was not associated with either UC or CD disease. UC, but not CD, is a disease of non-smokers. The inverse association between ulcerative colitis and OCP or NSAID in the Iranian population is noted.

Effects of current cigarette smoking on clinical course of Crohn's disease and ulcerative colitis.

Cigarette smoking worsens Crohn's disease (CD) but ameliorates ulcerative colitis (UC). In Israel, where there is no epidemiological association of smoking with CD, we examined the effects of current smoking on the course of CD and UC. Patients at nine public hospitals completed a questionnaire detailing their smoking history, disease course and treatments; subjects altering their smoking habit after the onset of disease were excluded. Sixty-four smokers and 144 nonsmokers had CD, and 34 smokers and 158 nonsmokers had UC. No differences were found between CD smokers and nonsmokers for hospitalizations, operations, and requirement for corticosteroid and immunosuppressive treatment. By contrast, UC smokers had less extensive disease than nonsmokers (P < 0.02) and fewer hospitalizations (P = 0.01) and operations (P = 0.025). Our results agree with a minority of studies showing no adverse effect of smoking on the course of CD, and confirm the protective effect of smoking in UC.

Lifestyle Issues in Inflammatory Bowel Disease – Smoking

During the pa t decade, smoking habit has been identified as a major exogenous factor in inflammatory bowel disease (IBD). It is associated not only with the development of the disease but al o with the clinical course in established disease. IBD combines absolute opposites as smoking is associated with Crohn’s disease and nonsmoking or former smoking with ulcerative colitis. The first reports of a negative association between smoking and ulcerative colitis were based on independent, clinical observations; from those studies a positive association was found between smoking and Crohn’s disease. Epidemiological studies that followed consistently showed that smokers have a reduced risk of ulcerative colitis and an increased risk of Crohn’s disease and that exsmokers have an increased risk of ulcerative colitis. In ulcerative colitis, but not in Crohn’s disease, a dose-response pattern has been demonstrated. Changes in clinical course, in disease severity and extension, and in recurrence rate indicate substantial clinical effects of smoking with a protective effect of smoking in ulcerative colitis and an aggravating effect in Crohn’s disease. There are also indications of smoking’s effects on changes in IBD epidemiology and sex distribution. The biological explanation to the finding is unknown. Smoking may aggravate Crohn’s disease by vascular effects. Theories on the protective effect in ulcerative colitis include effects on immune and inflammatory response, on mucus and on intestinal permeability. Possibly, beneficial effects in ulcerative colitis are exerted by nicotine but further studies are needed. Due to overall negative effects of smoking, IBD patients should not smoke. It seems, however, reasonable to give individual advice in patients with ulcerative colitis who have experienced a beneficial effect of ·making considering both current health status and life situation.

Smoking and Inflammatory Bowel Disease: Comparison with Systemic Lupus Erythematosus: A Case-Control Study

Smoking is rare in patients with ulcerative colitis (UC). Onsets are common after stopping smoking. Several observations suggest possible immunologic mechanisms in UC. As smoking has an immunosuppressive effect, a possible role of smoking in UC could be immunosuppression. In this study an analogous hypothesis was investigated by studying smoking habits in patients with systemic lupus erythematosus (SLE), an inflammatory multisystemic disease of unknown etiology, characterized by disturbances in cellular and humoral immunity. At onset, 23 of 56 patients were smokers and 2 probable smokers. Few were ex-smokers. The patients were matched for age, sex, and geographic vicinity, and multiple relative risks were calculated. No correlation could be found between smoking/ex-smoking and SLE either at diagnosis or at interview, and no resemblance in habit to patients with UC was found. The present study provides no evidence that the immunosuppressive effect of smoking is sufficient to influence the clinical course of SLE and therefore by analogy does not support an immunosuppressive explanation of the possible protective effect of smoking in UC.

Does Smoking Tighten the Gut?

There is a low prevalence of smoking in ulcerative colitis. The disease often starts or relapses after stopping smoking. Increased intestinal permeability for harmful substances has been proposed as one causal factor in ulcerative colitis. We therefore wanted to study the relationship between smoking and intestinal permeability in healthy subjects. In 25 smoking and 25 non-smoking healthy persons urine recoveries of two different oral probes, 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) and low-molecular-weight polymers of polyethylene glycol (PEG 400), were measured. The smokers had significantly lower 24-h urine recoveries of 51Cr-EDTA than the non-smokers (median, 1.6; range, 0.8-4.2, versus 2.1; range, 1.1-5.8; 2 p less than 0.001). In contrast, 6-h urine recoveries of PEG 400 were not significantly different in smokers and non-smokers. Thus, smoking appears to tighten the gut either by effects on the paracellular junctions in the intestinal epithelium or by decreasing the permeability in the distal small bowel and the colon.