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E-CIGARETTES AND HEAT-NOT-BURN TOBACCO INCREASE POSTOPERATIVE RECURRENCE OF CROHN’S DISEASE: A MULTICENTER EUROPEAN STUDY

Tommaso Lorenzo Parigi 1, Olga Maria Nardone 2, Maria Lisa 3, Luca Massimino 3, Roberto Gabbiadini 4, Tommaso Innocenti 5, Lorenzo Bertani 6, Angelo Del Gaudio 7, Pablo Florez Diez 8, Luisa Bertin 9, Brigida Barberio 10, Marianne Hupé 11, Loris Riccardo Lopetuso 12, Mariangela Allocca 13, Ferdinando D'Amico 13, Federica Furfaro 13, Alessandra Zilli 13, Gionata Fiorino 14, Federica Ungaro 13, Fabiana Castiglione 2, Edoardo Vincenzo Savarino 9, Gabriele Dragoni 5, Franco Scaldaferri 12, Alessandro Armuzzi 4, Laurent Peyrin-Biroulet 15, Vipul Jairath 16, Theresa Torres Pizarro 17, Silvio Danese 1

Affiliations

1 Vita-Salute San Raffaele University - IRCCS San Raffaele Hospital, Milan, Italy

2 University of Naples Federico II, Naples, Italy

3 Università Vita-Salute San Raffaele, Milan, Italy

4 IRCCS Humanitas Research Hospital, Milan, Italy

5 University of Florence - Careggi University Hospital, Florence, Italy

6 University of Pisa, Pontedera, Italy

7 Policlinico Gemelli, Rome, Italy

8 Hospital Universitario Central de Asturias, Oviedo, Spain

9 University of Padova, Padova, Italy

10 Azienda Ospedaliera Di Padova, Padova, Italy

11 CHU Grenoble Alpes, Grenoble, France

12 Fondazione Policlinico Universitario "A. Gemelli" IRCCS - Università Cattolica di Roma, Rome, Italy

13 IRCCS San Raffaele Hospital, Milan, Italy

14 ASL San Camillo Forlanini, Rome, Italy

15 Nancy University Hospital, Vandoeuvre-les-Nancy, France

16 Western University, London, Canada

17 Case Western Reserve University School of Medicine, Cleveland, United States

Summary

AI Generated

E-cigarettes and heat-not-burn tobacco are associated with significantly increased endoscopic recurrence rates after ileocolic resection in Crohn's disease patients, comparable to conventional cigarette smoking.

In 1157 Crohn's disease patients who underwent ileocolic resection, endoscopic recurrence rates at 6-12 months were 70% for e-cigarette users, 69% for heat-not-burn tobacco users, and 68% for conventional cigarette smokers, compared to 39% for non-smokers (all p<0.01).
The association between all smoking types and increased recurrence persisted in patients receiving pharmacological prophylaxis and after adjusting for confounders including sex, disease location and behavior, disease duration, type of anastomosis, and previous resections.
E-cigarette use was associated with a 3-fold increased risk of endoscopic recurrence (OR 3.06, 95% CI 1.08-9.57), heat-not-burn tobacco with a 4.5-fold risk (OR 4.47, 95% CI 2.00-10.77), and conventional cigarettes with a 4.7-fold risk (OR 4.66, 95% CI 3.07-7.20) compared to non-smoking.
Patients who smoked conventional cigarettes or used heat-not-burn tobacco had significantly shorter disease duration at time of surgery (7.2 and 5.2 years vs. 9.0 years for non-smokers), suggesting a more aggressive disease course, while e-cigarette users showed no significant difference.
This multicenter retrospective study provides evidence relevant to gastroenterologists counseling Crohn's disease patients about alternative tobacco products in the postoperative setting.

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Abstract

Introduction

Tobacco smoke is an established risk factor for Crohn’s disease (CD) postoperative recurrence (POR), however, the effect of e-cigarettes and heat-not-burn tobacco (HNBT) remains unknown. We aimed to evaluate the impact of e-cigarettes and HNBT on postoperative recurrence in CD patients.

Aims & Methods

We retrospectively included consecutive CD patients who underwent ileocolic resection and endoscopic evaluation between 6 and 12 months after surgery across 9 centers in Italy, Spain, and France. Based on smoking habits between surgery and endoscopy, patients were categorized as non-smokers, cigarette smokers, HNBT users, or e-cigarette users. To avoid confounding, the use of HNBT and e-cigarettes was confirmed by phone call, and patients smoking multiple products were excluded.
The primary outcome was endoscopic recurrence (Rutgeerts score ≥2) within the first year. Secondary analyses were conducted on the population receiving prophylactic treatment, using the modified Rutgeerts score (≥i2b), the mean Rutgeerts score, transmural disease activity, fecal calprotectin, time from diagnosis to surgery, and multivariable regression analysis.

Results

In total, 1157 patients were included, of which 860 (75%) were non-smokers, 220 (19%) conventional cigarette smokers, 37 (3%) HNBT users, and 33 (3%) e-cigarette users. Groups were homogeneous for most clinical and demographic variables, including a history of intestinal surgery for CD, use of biologics in the 12 months before surgery, and prescription of POR prophylaxis, but not age. HNBT users were younger than other groups.
Recurrence rates were significantly higher in all smoking groups compared to non-smokers: 70%, 69%, and 68% for e-cigarette, HNBT, and cigarette users, respectively, vs. 39% for non-smokers; all p<0.01. The association persisted in patients receiving pharmacological prophylaxis, with 75%, 69%, 70%, and 40% recurrence for the same groups, and all comparisons remaining significant (all p<0.005).
Using the modified Rutgeerts score cutoff of i2b to define POR overall rates decreased, with 57% recurrence for e-cigarette and HNBT users, 54% for conventional cigarette smokers, and 29% for non-smokers. However, the relative proportions remained consistent, and the differences between groups did not change.
When analyzing the Rutgeerts score as a continuous variable, traditional cigarette smoking, HNBT use, and e-cigarette use remained associated with significantly greater endoscopic disease activity compared to non-smokers (2.02, 2.09, and 1.7,4 respectively, vs. 1.12; all p<0.05). Interestingly, the mean Rutgeerts score among e-cigarette users was numerically lower than that of conventional tobacco cigarettes and HNBT, although the difference was not statistically significant (1.74 vs. 2.02 and 2.09, respectively, both p>0.05). When restricting the analysis to patients receiving prophylactic biologics, differences persisted (p<0.05).
The average fecal calprotectin levels and imaging assessments confirmed the trends observed in endoscopy. The mean calprotectin levels at the time of endoscopy were 221 μ/g, 206 μ/g and 174 μ/g for tobacco, HNBT, and e-cigarettes, respectively, vs. 124 μ/g in non-smokers. Rates of transmural remission were 35%, 48%, 56%, and 61% for the same groups, respectively. Nevertheless, in calprotectin and radiologic analyses, only the differences between conventional smokers and non-smokers reached statistical significance (p<0.05), possibly due to the limited availability of these data and the wide variability of calprotectin levels.
After accounting for potential confounders such as sex, location and behavior of disease at diagnosis, disease duration, type of anastomosis, and previous intestinal resections, all smoking groups remained significantly associated with an increased risk of endoscopic recurrence compared to nonsmokers, e-cigarette (OR 3.06, 95% CI 1.08-9.57, p=0.041), and HNBT (OR 4.47, 95% CI 2.00-10.77, p<0.001), and conventional tobacco (OR 4.66, 95% CI 3.07-7.20, p<0.001).
Finally, we compared disease duration at the time of surgery. Compared to those who never smoked, patients who smoked traditional cigarettes and used HNBT had a significantly shorter disease duration at the time of intervention (7.2 and 5.2 years vs 9.0; p=0.029 and p=0.046, respectively), suggestive of a more aggressive disease course. Instead, the difference with e-cigarettes was not significant (7.5 years vs 9.0, p=0.76).

Conclusion

E-cigarettes and heat-not-burn tobacco are associated with increased endoscopic recurrence of CD compared to non-smoking.

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

The environment and GI disease (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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A MULTICENTER RETROSPECTIVE STUDY OF INFLUENTIAL FACTORS ON STENOSIS AFTER MODERATE RESECTION OF CIRCUMFERENCE IN ESOPHAGEAL ENDOSCOPIC SUBMUCOSAL DISSECTION

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A MULTICENTER RETROSPECTIVE STUDY OF INFLUENTIAL FACTORS ON STENOSIS AFTER MODERATE RESECTION OF CIRCUMFERENCE IN ESOPHAGEAL ENDOSCOPIC SUBMUCOSAL DISSECTION

Akira Dobashi 1, Tsugumi Habu 2, Osamu Goto 3, Toshiyuki Yoshio 4, Waku Hatta 5, Noboru Kawata 6, Atsushi Goto 7, Unknown Unknown 8, Yugo Iwaya 9, Tetsuya Tatsuta 10, Takuto Hikichi 11, Jun Nakamura 11, Shinjiro Yamaguchi 12, Takashi Ohta 12, Yohei Furumoto 13, Tsutomu Nishida 14, Masashi Yamamoto 14, Mikitaka Iguchi 15, Tatsuo Yachida 16, Hiroko Nebiki 17, Tomoaki Yamasaki 17, Toshiaki Narasaka 18, Eriko Koizumi 2, Yosuke Tsuji 19, Kazuki Sumiyama 1, Mitsuhiro Fujishiro 19

Affiliations

1 The Jikei University School of Medicine, Tokyo, Japan

2 Nippon Medical School Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan

3 Nippon Medical School, Tokyo, Japan

4 Cancer Institute Hospital, Japanese Foundation for Cancer Reserch, Tokyo, Japan

5 Tohoku University, Graduate School of Medicine, Sendai, Japan

6 Shizuoka Cancer Center, Shizuoka, Japan

7 Yamaguchi University Graduate School of Medicine, Ube, Japan

8 Tonan Hospital, Hokkaido, Japan

9 Shinshu University School of Medicine, Matsumoto, Japan

10 Hirosaki University Hospital, Aomori, Japan

11 Fukushima Medical University Hospital, Fukushima, Japan

12 Kansai Rosai Hospital, Hyogo, Japan

13 Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan

14 Toyonaka Municipal Hospital, Toyonaka, Japan

15 Wakayama Medical University, Wakayama, Japan

16 Faculty of Medicine, Kagawa University, Kagawa, Japan

17 Osaka City General Hospital, Osaka, Japan

18 University of Tsukuba, Tsukuba, Japan

19 The University of Tokyo, Tokyo, Japan