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Background and Aims: Cigarette smoking worsens prognosis of Crohn's disease [CD]. We conducted a systematic review and meta-analysis to examine the association between smoking and induction of clinical response or remission with anti-tumour necrosis factor [TNF] therapy., Methods: MEDLINE, EMBASE, PubMed, and Cochrane CENTRAL [June 2019] were searched for studies reporting the effect of smoking on short-term clinical response and remission to anti-TNF therapy [≤16 weeks following the first treatment] in patients with CD. Risk ratios [RR] with 95% confidence intervals [CI] were calculated using random-effects models., Results: Eighteen observational studies and three randomised controlled trials [RCT] were included. Current smokers and non-smokers [never or former] had similar rates of clinical response [observational studies RR: 0.96; 95% CI: 0.88, 1.05; RCTs RR: 1.09; 95% CI: 0.84, 1.41]. When restricted to studies clearly defining the smoking exposure, smokers treated with anti-TNF were less likely to achieve clinical response than non-smokers [smokers defined as having ≥5 cigarettes/day for ≥6 months RR: 0.63; 95% CI: 0.48, 0.83; lifetime never smokers vs ever smokers excluding former smokers RR: 0.81; 95% CI: 0.71, 0.93]. Current smokers were also less likely to achieve clinical remission in observational studies [RR: 0.75; 95% CI: 0.57, 0.98], though this association was not seen in RCTs [RR: 1.04; 95% CI: 0.89, 1.21]., Conclusions: Smoking is significantly associated with a reduction in the ability of infliximab or adalimumab to induce short-term clinical response and remission when pooling studies where smoking status was clearly defined. When patients with CD are treated with highly effective therapy, including anti-TNF agents, concurrent smoking cessation may improve clinical outcomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: NOD2 and smoking are risk factors for Crohn's disease. We meta-analyzed NOD2-smoking interactions in Crohn's disease (Phase 1), then explored the effect of age at diagnosis on NOD2-smoking interactions (Phase 2)., Methods: Phase 1: MEDLINE and EMBASE were searched for studies (n=18) providing data on NOD2 and smoking in Crohn's disease. NOD2-smoking interactions were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) calculated using random effects models. Phase 2: A case-only study compared the proportion of smokers and carriers of the 1007fs variant across ages at diagnosis (≤16, 17-40, >40years)., Findings: Phase 1: Having ever smoked was less common among carriers of the 1007fs variant of NOD2 (OR 0.74, 95%CI:0.66-0.83). There was no interaction between smoking and the G908R (OR 0.96, 95%CI:0.82-1.13) or the R702W variant (OR 0.89, 95%CI:0.76-1.05). Phase 2: The proportion of patients (n=627) carrying the 1007fs variant decreased with age at diagnosis (≤16years: 15%; 17-40: 12%; >40: 3%; p=0.003). Smoking was more common in older patients (≤16years: 4%; 17-40: 48%; >40: 71%; p<0.001)., Interpretation: The negative NOD2-smoking interaction in Crohn's disease is specific to the 1007fs variant. However, opposing rates of this variant and smoking across age at diagnosis may explain this negative interaction., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Studies examining the association between smoking and the need for surgery in patients with Crohn's disease and ulcerative colitis have reached inconsistent conclusions. These studies often do not differentiate between patients undergoing early surgery and patients having surgery later in their disease course. Our study examined the association between smoking status and time to first bowel resection in patients with Crohn's disease and ulcerative colitis., Methods: We searched MEDLINE and EMBASE for studies (n = 12) reporting on the association between smoking status (current, former, and never) and surgery in IBD, and incorporated disease duration in the analysis. Hazard ratios (HR) with 95% confidence intervals (CI) were pooled across studies using random effects models., Results: Current smokers with Crohn's disease were at increased risk of intestinal resection compared to never smokers (HR 1.27, 95% CI 1.08 to 1.49); however, there was no difference in the need for surgery when comparing former and never smokers (HR 1.11, 95% CI 0.95 to 1.30). In patients with ulcerative colitis, there was no difference in the need for colectomy when comparing current smokers to never smokers (HR 0.98, 95% CI 0.67 to 1.44). Former smokers with ulcerative colitis were at increased risk of colectomy (HR 1.38, 95% CI 1.04 to 1.83) compared to never smokers., Conclusions: Current smokers with Crohn's disease are at increased risk of surgery, while former smokers with ulcerative colitis have increased risk of colectomy.

Importance: Cigarette smoking increases the risk of surgery in Crohn's disease. However, the effect of smoking on the need for surgery for diverticulitis is unknown., Objective: We evaluated whether smoking was a risk factor for surgery among patients admitted to hospital with acute diverticulitis., Design: We conducted a population-based comparative cohort study of patients admitted to hospital for diverticulitis who were treated with medical versus surgical management., Setting & Participants: We used the population-based Discharge Abstract Database to identify 176 adults admitted emergently with a diagnosis of diverticulitis between 2009 and 2010 in Calgary., Intervention & Main Outcome: We performed a medical chart review to confirm the diagnosis of diverticulitis and to extract clinical data. The primary outcome was a partial colectomy during hospitalization. Logistic regression evaluated the association between smoking and surgery after adjusting for potential confounders, including age, sex, comorbidity, and disease severity., Results: A partial colectomy was performed on 35.6% of patients with diverticulitis and 1.3% died. Among diverticulitis patients, 26.8% were current smokers, 31.5% were ex-smokers, and 41.6% never smoked. Compared to non-smokers, current smokers (adjusted odds ratio [OR] 9.02; 95% confidence interval [CI]: 2.47-32.97) and former smokers (adjusted OR 5.41; 95% CI: 1.54-18.96) had increased odds of surgery., Conclusion and Relevance: Smoking is associated with the need for surgical management of diverticulitis.

Purpose: Growing evidence suggests asthma and Crohn's disease commonly cooccur. However, the impact of asthma on the prognosis of Crohn's disease is unknown. The aim of our study was to assess the effect of asthma on the need for intestinal resection in patients with Crohn's disease while adjusting for smoking status, imputed from a smaller, secondary data set. Patients and methods: Using health administrative data from a universally funded healthcare plan in Alberta, Canada, we conducted a cohort study to assess the effect of asthma on the need for surgery in patients with Crohn's disease diagnosed between 2002 and 2008 (N=2,113). Validated algorithms were used to identify incident cases of Crohn's disease, cooccurring asthma, and intestinal resection. The association between asthma and intestinal resection was estimated using multivariable Cox proportional hazards regression. Smoking status was imputed using a novel method using martingale residuals, derived from a data set of 485 patients enrolled in the Alberta Inflammatory Bowel Disease Consortium (2007 to 2014) who completed environmental questionnaires. All analyses were adjusted for age, sex, rural/urban status, and mean neighborhood income quintile. Results: Asthma did not increase the risk of surgery in the health administrative data when not adjusting for smoking status (HR 1.03, 95% CI 0.81 to 1.29). The association remained nonsignificant after imputing smoking status in the health administrative data (HR 1.03, 95% CI 0.81 to 1.29). Conclusion: Although asthma is associated with an increased risk of Crohn's disease, co-occurring asthma is not associated with the risk of surgery in these patients. This null association persisted after adjusting for smoking status. This study described a novel method to adjust for confounding (smoking status) in time-to-event analyses, even when the confounding variable is unmeasured in health administrative data. [ABSTRACT FROM AUTHOR]