Observational Study Open Access
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2020; 26(29): 4343-4355
Published online Aug 7, 2020. doi: 10.3748/wjg.v26.i29.4343
Patients' perspectives on smoking and inflammatory bowel disease: An online survey in collaboration with European Federation of Crohn's and Ulcerative Colitis Associations
Catherine Le Berre, Laura Loy, Sanna Lönnfors, Luisa Avedano, Daniele Piovani
Catherine Le Berre, Institut des Maladies de l'Appareil Digestif, Nantes University Hospital, Nantes 44000, France
Laura Loy, IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Rozzano, Milan 20089, Italy
Sanna Lönnfors, Luisa Avedano, European Federation of Crohn's and Ulcerative Colitis Associations, Brussels B-1000, Belgium
Daniele Piovani, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele MI, Milan 20090, Italy
Daniele Piovani, Humanitas Clinical and Research Center - IRCCS, Milan, Rozzano 20089, Italy​
ORCID number: Catherine Le Berre (0000-0002-1124-2019); Laura Loy (0000-0002-5536-6152); Sanna Lönnfors (0000-0002-9229-7141); Luisa Avedano (0000-0001-6197-9126); Daniele Piovani (0000-0002-1414-6639).
Author contributions: Le Berre C and Loy L was the conception and design of the study, interpretation of data, and drafting the article; Lönnfors S and Avedano L was the acquisition of data, making critical revisions related to important intellectual content of the manuscript; Piovani D was the analysis and interpretation of data, drafting the article; All authors read and approved the final version of the article to be published.
Supported by Philip Morris Products SA and coordinated by Linkt Health Ltd.
Institutional review board statement: An institutional review board statement is not necessary for this study as this is a survey.
Informed consent statement: This was an online survey. Before answering the questions, patients were informed of the objectives of the study and gave their consent online.
Conflict-of-interest statement: The authors declare no conflicts of interest relevant to this work.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement checklist of items, and the manuscript was prepared and revised according to the STROBE Statement checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Catherine Le Berre, MD, Doctor, Institut des Maladies de l'Appareil Digestif, Nantes University Hospital, 1 place Alexis Ricordeau, Nantes 44000, France. catherine@leberre.org
Received: April 29, 2020
Peer-review started: April 29, 2020
First decision: May 13, 2020
Revised: May 25, 2020
Accepted: July 22, 2020
Article in press: July 22, 2020
Published online: August 7, 2020

Abstract
BACKGROUND

Smoking has detrimental effects on Crohn’s disease (CD) activity while data on ulcerative colitis (UC) are conflicting. Little is known about the use and impact of alternative smoking products in inflammatory bowel diseases (IBD).

AIM

To understand the patients’ perceptions of the impact of smoking on their IBD and to assess differences between CD and UC patients.

METHODS

The questionnaire was developed by Philip Morris Products SA in cooperation with European Federation of Crohn's and Ulcerative Colitis Associations. The final survey questionnaire consisted of 41 questions divided in 8 categories: (1) Subject screener; (2) Smoking history; (3) Background information; (4) IBD disease background; (5) Current disease status; (6) Current therapeutics and medications; and (7) Current nicotine/cigarettes use and awareness of the impacts of smoking on IBD. The questionnaire was submitted online from 4th November 2019 to 11th March 2020 through the European Federation of Crohn's and Ulcerative Colitis Associations website to IBD patients who were current smokers or had a history of smoking.

RESULTS

In total 1050 IBD patients speaking nine languages participated to the survey. Among them, 807 (76.9%) patients declared to have ever smoked or consumed an alternative smoking product, with a higher proportion of current cigarette smokers among CD patients (CD: 63.1% vs UC: 54.1%, P = 0.012). About two-thirds of the participants declared to have ever stopped cigarette smoking and restarted (67.0%), with a significantly higher proportion among UC patients compared to CD patients (73.1% vs 62.0%, P = 0.001). We also found significant differences between CD and UC patients in the awareness of the health consequences of smoking in their disease and in the perceived impact of smoking on disease activity, for both cigarettes and alternative smoking products.

CONCLUSION

This survey found significant differences between CD and UC patients in both awareness and perception of the impact of smoking on their disease. Further efforts should be done to encourage smoking cessation for all IBD patients, including UC patients.

Key Words: Inflammatory bowel disease, Ulcerative colitis, Crohn's disease, Cigarettes, Alternative smoking products, Tobacco, Nicotine, Marijuana

Core tip: We performed a European-wide online survey to understand the patients’ perceptions on how smoking has impacted their inflammatory bowel diseases (IBD). In total 1050 IBD patients [427 with Crohn’s disease (CD), 355 with ulcerative colitis (UC)] participated to the survey, with a higher proportion of cigarette smokers among CD patients. About two-thirds of the participants declared to have ever stopped cigarette smoking and restarted, with a higher proportion among UC compared to CD patients (73.1% vs 62.0%, P = 0.001). There were also differences between CD and UC patients in the awareness of the health consequences of smoking and in the perceived impact of smoking on disease activity.



INTRODUCTION

Environmental factors are probably primarily responsible for the growing incidence of inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), around the globe over the last decades[1-3]. Accumulating evidence supports an association between IBD and several environmental factors, including smoking, diet, drugs, geographical and social status, stress, microbial agents, intestinal permeability and appendectomy[4,5]. Among these factors, smoking is the one for which the most solid evidence is currently available[5]. Smoking increases the risk of CD and worsens its clinical course[6,7], especially after digestive surgery[8], but has a protective effect in UC[6,9]. Thus, smoking habits are much more frequent in CD patients than in UC patients, except in Jewish patients in Israel in whom the stronger genetic tendency in CD may contribute to this discrepancy[10].

In CD, the odds of flare of disease activity, flare after surgery, need for first and second surgery among ex-smokers diminish upon smoking cessation and become comparable to non-smokers[11]. In UC, nicotine has been tested as a therapeutic agent in the form of chewing gum, transdermal patches, and nicotine-based enemas[12-17], with conflicting results and variable efficacy in the induction of remission when compared to placebo and conventional treatments[18-20]. However, it is clear that the protective effect of cigarette smoking in UC is temporary, since the relative risk of developing the disease increases after smoking cessation compared with patients who have never smoked[21].

Until now, there has been little patient-centered research aiming at assessing the perceived impact of smoking or nicotine use on IBD symptoms by patients who are current adult smokers and/or nicotine-containing products users. Few studies demonstrated that a high proportion of patients with IBD are unaware of the effects of tobacco on their disease, but these limited available data are solely based on small-scale studies[22-26]. Yet, making patients aware of the impact of nicotine use on the course of their IBD is essential to expect smoking cessation and improve the management of their disease.

Thus, the objectives of this European-wide online survey developed in collaboration with European Federation of Crohn’s and Ulcerative Colitis Association (EFCCA) were to understand the patients’ perceptions on the impact of smoking on their IBD and to assess differences of these perceptions between CD and UC patients. The results of this study will be shared with the IBD community through EFCCA in order to facilitate the management of smoking cessation among patients.

MATERIALS AND METHODS
Questionnaire development

The questionnaire was developed by Philip Morris Products SA in cooperation with EFCCA and reviewed prior to use by health informaticians. Le Berre C and Loy L also participated in the design of the questionnaire. The final survey questionnaire consisted of 41 questions divided in 8 categories: (1) Subject screener; (2) Smoking history; (3) Background information; (4) IBD disease background; (5) current disease status; (6) current therapeutics and medications; and (7) Current nicotine/cigarettes use and awareness of the impacts of smoking on IBD (Supplemental document).

In most questions, participants were allowed to tick one applicable option. In some questions, such as those concerning the type of alternative smoking products that were used, several options could be chosen. In others, such as questions concerning the duration of use of nicotine products, therapy change due to smoking habits or use of alternative smoking products, or the perceived impact of nicotine use on disease activity, participants were given multiple categorical options.

The survey was made available in English, French, German, Spanish, Portuguese, Italian, Greek, Finnish and Slovenian. Translations were made by translators that EFCCA has previously worked with. They were proofread by native speakers from EFCCA's member associations and revised, if necessary. Philip Morris International did final checks and revisions on the translations in order to have a double validation before the survey was launched.

Questionnaire administration

The questionnaire was submitted through EFCCA to IBD patients who were current smokers or had a history of smoking. Patients were not pre-screened and were eligible for inclusion if they were aged over 18 years and had a confirmed diagnosis of IBD, including CD or UC. Patients gave their consent and were not paid for participating.

The online survey was open from 4th November 2019 to 11th March 2020 on the EFCCA website. National associations were encouraged to promote the survey online by providing their members with an online link on their website. Information on this survey was also displayed in posters and flyers at the clinic of each participating investigator. The survey was closed after having enrolled more than 1000 participants, whatever their characteristics in terms of gender or nationality.

As this was a non-interventional survey, ethics committee approval was not required. Data was collected anonymously online, and participation was entirely optional. Since it was an anonymous survey, there was no data or user tracking. EFCCA strictly follows the General Data Protection Regulation and does not own the data that was transferred in a secured way to the biostatistician.

Statistical analysis

Descriptive statistics included means with standard deviations and medians with interquartile ranges (IQR) for continuous variables, and frequency analyses (percentages) for categorical variables. The association between categorical variables was investigated with the Fisher’s exact test. Stata 15.0 software was used for all the analyses (Stata Corp, College Station, TX, United States). P values less than 0.05 were considered statistically significant. All statistical tests were two-sided.

RESULTS

This survey enrolled 1180 IBD patients speaking nine different languages. However, 130 patients only selected their language and did not answer the first question (i.e., if they have ever smoked or consumed an alternative smoking product). This group of patients was excluded, and we considered 1050 patients as participants. The most represented countries were Italy (20.3%), Finland (13.9%) and Portugal (13.9%). Among them, 807 (76.9%) patients declared to have ever smoked or consumed an alternative smoking product and proceeded to complete the rest of the questionnaire.

Baseline characteristics and treatmen

Participants were mainly females (65.4%) with a median age of 40 (IQR: 32-51) years old. Most patients were diagnosed with CD (53.5%) with a disease duration of 11 (IQR: 5-20) years. Patients diagnosed with UC (44.5%) had a shorter median disease duration (4 years; IQR: 1-8). About one quarter of the participants perceived their disease as severe (26.2%) and 28.8% had undergone surgery. The most common type of surgery was ileocaecal resection (11.8%). The most common drug treatment regimens were oral aminosalicylates (39.8%), anti-TNF agents (28.2%) and immunomodulators (26.7%). Baseline characteristics reported by the patients are detailed in (Table 1 and Supplemental Table 1) compares these baseline characteristics by type of IBD diagnosis.

Table 1 Baseline characteristics reported by the participants (n = 1050).
Questionnaire itemsmean ± SD; median (IQR) or n(%)
Demographic characteristics
Age (n = 796)41.9 ± 12.4; 40.0 (32.0–51.0)
Gender
Female522/798 (65.4)
Male276/798 (34.6)
Language
Italian213 (20.3)
Finnish146 (13.9)
Portuguese146 (13.9)
Slovenian128 (12.2)
Spanish120 (11.4)
Greek102 (9.7)
English83 (7.9)
German57 (5.4)
French55 (5.3)
IBD characteristics and treatments
Diagnosis
Crohn’s disease427/798 (53.5)
Ulcerative colitis355/798 (44.5)
No gastrointestinal condition5/798 (0.6)
Other gastrointestinal condition11/798 (1.4)
Crohn’s disease duration (yr)13.6 ± 10.6; 11 (5–20)
Ulcerative colitis duration (yr)7.52 ± 9.12; 4 (1–8)
Self-perceived disease activity
Inactive155/770 (20.1)
Mildly active261/770 (33.9)
Moderately active251/770 (32.6)
Severely active76/770 (9.9)
Not sure27/770 (3.5)
Self-perceived disease severity since diagnosis
Mild173/768 (22.5)
Moderate360/768 (46.9)
Severe201/768 (26.2)
Not sure34/768 (4.4)
Intestinal surgery230/798 (28.8)
Type of surgery
Partial colectomy41/798 (5.1)
Full colectomy29/798 (3.6)
Small-bowel resection48/798 (6.0)
Ileocaecal resection94/798 (11.8)
Other79/798 (9.9)
Current IBD-related medications
Antibiotics41/798 (5.1)
Oral aminosalicylate318/798 (39.8)
Topical aminosalicylate91/798 (11.4)
Topical steroid47/798 (5.9)
Systemic steroid78/798 (9.8)
Budesonide28/798 (3.5)
Immunomodulator213/798 (26.7)
Anti-TNF225/798 (28.2)
Combination of anti-TNF and immunomodulator69/798 (8.6)
Anti-integrin51/798 (6.4)
Tofacitinib6/798 (0.8)
Ustekinumab28/798 (3.5)
None76/798 (9.5)
Other135/798 (16.9)
Duration of current medical therapy (yr)
< 1240/765 (31.4)
1-5262/765 (34.2)
> 5263/765 (34.4)
Concomitant non-IBD drug treatment
Yes282/767 (63.2)
No485/767 (36.8)
Smoking habits and use of alternative smoking products

Among patients declaring themselves as having ever smoked cigarettes or having ever used an alternative smoking product, more than half were current cigarette smokers (59.0%). This proportion was significantly higher in CD than in UC patients (63.1% vs 54.1%, P = 0.012) (Table 2). Most ever smokers smoked cigarettes for more than 10 years (63.4%) and declared to have consumed on average more than 10 cigarettes per day (50.6%). The extent of cigarette smoking was significantly higher in CD than in UC patients (P < 0.001). The most commonly used products were cigarettes (91.6%), followed by e-cigarettes (19.2%) and marijuana (17.0%). There were no significant differences in the use of any nicotine-containing product between CD and UC patients.

Table 2 Smoking habits and use of alternative smoking products based on type of diagnosis.
Questionnaire itemsCrohn’s diseaseUlcerative colitisP value1
Smoking habits and use of an alternative smoking product
Current cigarettes smoker
Yes268/425 (63.1)187/346 (54.1)0.012
No157/425 (36.9)159/346 (45.9)
Duration of cigarette smoking (yr)
< 122/410 (5.4)26/317 (8.2)0.13
1-546/410 (11.2)47/317 (14.8)
6-1069/410 (16.8)56/317 (17.7)
> 10273/410 (66.6)188/317 (59.3)
Extent of cigarette smoking (cigarettes per day)
< 112/425 (2.8)22/341 (6.5)< 0.001
1-551/425 (12.0)67/341 (19.6)
6-10120/425 (28.3)106/341 (31.1)
11-20179/425 (42.1)113/341 (33.1)
> 2063/425 (14.8)33/341 (9.7)
Current use of an alternative smoking product
Yes343/427 (80.3)282/355 (79.4)0.79
No84/427 (19.7)73/355 (20.6)
Type of smoking/nicotine product ever used
Cigarettes409/427 (95.8)330/355 (93.0)0.11
E-cigarettes84/427 (19.7)71/355 (20.0)0.93
Heat not burn tobacco product19/427 (4.5)25/355 (7.0)0.12
Nicotine gum37/427 (8.7)36/355 (10.1)0.54
Nicotine patches21/427 (4.9)23/355 (6.5)0.35
Chewing tobacco/snus/snuff10/427 (2.3)15/355 (4.2)0.16
Cigars44/427 (10.3)31/355 (8.7)0.47
Pipes13/427 (3.0)8/355 (2.3)0.66
Marijuana81/427 (19.0)56/355 (15.8)0.26
Any other combustion/smoking product11/427 (2.6)5/355 (1.4)0.31
None of the above2/427 (0.5)7/355 (2.0)0.09
Ever stopped cigarette smoking and restarted
Yes264/426 (62.0)253/346 (73.1)0.001
No162/426 (38.0)93/346 (26.9)
Ever user of an alternative smoking product
Yes215/427 (50.4)196/354 (55.4)0.17
No212/427 (49.6)158/354 (44.6)
Current use of an alternative smoking product
Yes84/427 (19.7)73/355 (20.6)0.79
No343/427 (80.3)282/355 (79.4)
Duration of use of alternative smoking products
< 144/76 (55.3)46/81 (56.7)0.33
1-523/76 (30.3)16/81 (19.8)
6-1010/76 (13.1)16/81 (19.8)
> 101/76 (1.3)3/81 (3.7)
Started cigarette smoking
Before IBD diagnosis392/426 (92.0)290/343 (84.6)0.001
After IBD diagnosis34/426 (8.0)53/343 (15.4)
Stopped cigarette smoking
Before IBD diagnosis85/250 (34.0)146/247 (59.1)< 0.001
After IBD diagnosis165/250 (66.0)101/247 (40.9)
Restarted cigarette smoking
Before IBD diagnosis89/260 (34.2)66/243 (27.2)0.10
After IBD diagnosis171/260 (65.8)177/243 (72.8)
Started using an alternative smoking product
Before IBD diagnosis85/210 (40.5)85/185 (46.0)0.31
After IBD diagnosis125/210 (59.5)100/185 (54.0)
Switched from cigarette smoking to using an alternative smoking product
Before IBD diagnosis77/207 (37.2)81/184 (44.0)0.18
After IBD diagnosis130/207 (62.8)103/184 (56.0)

The vast majority of patients declared to be aware of the adverse health consequences of smoking (97.0%) and started cigarette smoking before IBD diagnosis (88.7%). This proportion was significantly higher in CD than in UC patients (92.0% vs 84.6%, P = 0.001). About two-thirds of the participants declared to have ever stopped cigarette smoking and restarted (67.0%), with a significantly higher proportion among UC patients compared to CD patients (73.1% vs 62.0%, P = 0.001). Most UC patients stopped cigarette smoking before diagnosis (59.1%), while this was true for only about one-third of CD patients (34.0%).

Among patients declaring to have ever smoked cigarettes or used an alternative smoking product, 20.0% were current users of an alternative smoking product. Differently from cigarette smokers, most users of these products declared a duration of use of less than one year (56.1%). Most users of alternative smoking products started using them (57.0%) or switched from cigarettes to these products after IBD diagnosis (59.6%).

Impact of cigarette smoking or use of alternative smoking products on IBD

Most cigarette smoking patients perceived that smoking significantly or moderately worsened disease activity (60.9%), while a lower proportion of patients using alternative smoking products had the same impression (15.3%). A much lower proportion of patients believed their habit had no impact on disease activity among cigarette smokers (8.3%) than among users of alternative smoking products (66.4%).

Most patients did not have any therapy change due to smoking habits or use of alternative smoking products (66.7% after starting smoking, 79.2% after restarting smoking, 75.2% after stopping smoking, 90.1% after switching to alternative smoking products and 89.7% after starting to use an alternative smoking product).

The perception of the impact of cigarette smoking significantly differed between CD and UC patients (P < 0.001) (Table 3). More than three-quarters (79.2%) of CD patients perceived that smoking significantly or moderately worsened disease activity versus 34.0% of UC patients. Similarly, the perceived impact of using alternative smoking products on disease activity significantly differed between CD and UC patients (P = 0.004), even though the magnitude of the effect was less strong (Table 3).

Table 3 Perceived effect of smoking on inflammatory bowel diseases based on type of diagnosis.
Questionnaire itemsCrohn’s diseaseUlcerative colitisP value1
Perceived impact of cigarette smoking on disease activity
Significantly worsened12/279 (4.3)2/191 (1.0)< 0.001
Moderately worsened209/279 (74.9)63/191 (33.0)
No impact27/279 (9.7)12/191 (6.3)
Moderately improved25/279 (9.0)58/191 (30.4)
Significantly improved6/279 (2.2)56/191 (29.3)
Perceived impact of using alternative smoking products on disease activity
Significantly worsened4/211 (1.9)12/187 (6.4)0.004
Moderately worsened31/211 (14.7)14/187 (7.5)
No impact146/211 (69.2)118/187 (63.1)
Moderately improved23/211 (10.9)28/187 (15.0)
Significantly improved7/211 (3.3)15/187 (8.0)
Discussion with own physician about the effect of smoking on IBD

Among patients having ever smoked cigarettes, 31.7% did not receive any information from their physician on the effect of smoking on disease activity, while 45.4% of them received the information that smoking is detrimental to disease activity. These proportions were significantly different in CD than in UC patients (not discussed: 21.6% vs 44.6%; detrimental: 69.4% vs 14.6%; P < 0.001) (Table 4).

Table 4 Extent of discussing with own physician the effect of smoking on inflammatory bowel diseases based on type of diagnosis.
Questionnaire itemsCrohn’s diseaseUlcerative colitisP value1
Cigarette smoking
Not discussed89/412 (21.6)143/321 (44.6)< 0.001
Detrimental286/412 (69.4)47/321 (14.6)
Possibly beneficial37/412 (9.0)131/321 (40.8)
Use of alternative smoking products
Not discussed43/83 (51.8)45/72 (62.5)< 0.001
Detrimental31/83 (37.4)8/72 (11.1)
Possibly beneficial9/83 (10.8)19/72 (26.4)

Among patients having ever used alternative smoking products, 56.8% did not discuss the effect of these products on disease activity, and 25.2% of them received the information that using them is detrimental to disease activity. These proportions were significantly different in CD than in UC patients (not discussed: 51.8% vs 62.5%; detrimental: 37.4% vs 11.1%; P < 0.001) (Table 4).

DISCUSSION

Our first objective was to assess patients’ perceptions about the impact of smoking on their disease, and next to assess differences of these perceptions between CD and UC patients, with the aim to understand how different smoker profiles perceived the impact of smoking on their IBD.

Most patients were aware of the adverse health consequences of smoking and started cigarette smoking before IBD diagnosis. However, CD and UC patients showed different awareness about the impact of smoking cigarettes on their disease activity. Indeed, most CD patients were aware of a detrimental effect of smoking, and a large proportion of UC patients was aware of possible beneficial impact of smoking on their disease activity. Interestingly, most UC patients did not discuss this topic with their own physician. This is in line with previous studies conducted on this issue[25,26]. Both Wahed et al[25] and Ducharme-Bénard et al[26] reported informed rates of 52% and 57.7% in patients with CD, whilst this was the case in only 21% and 13% of patients with UC Saadoune et al[27] Reported about two-thirds of smoking CD patients were aware of the harmful effects on the course of disease, whereas all UC patients were aware of its protective role[27]. The detrimental effects of smoking on CD are well-established in the literature. On the contrary, health professionals might be reticent to explain the apparent and less-proven benefit of smoking to UC patients, by fear of discouraging them to stop[28-30].

We also can presume that a different perception of smoking on IBD activity between CD and UC patients could influence the need to be informed about risks and benefits of smoking habits. In our cohort, the large majority of CD patients perceived their disease activity significantly or moderately worsened by cigarette smoking, while 59.7% of UC patients perceived a positive effect of cigarette smoking on their disease activity. Patients’ perceptions in our cohort thus confirm previous results in literature on this topic[11,18-21]. It was not surprising to find different smoking profiles between CD an UC patients based on timing of IBD diagnosis. Most CD patients stopped cigarette smoking after IBD diagnosis, whereas most UC patients stopped cigarettes before IBD diagnosis. Among participants declaring to have ever stopped cigarette smoking and restarted, we expected to find a large majority of UC patients restarting smoking after IBD diagnosis. Quite surprisingly, the same result was observed in the CD group of patients while smoking is known to worsen the course of CD. In a study conducted by the Nancy group, similar results were reported, with about one-third of IBD patients who had already stopped smoking to prevent flares with a significant difference between CD and UC patients[27], whereas we did not observe any significant difference among CD and UC patients restarting smoking to prevent flares.

Evidence from literature underlines the importance of informing patients with CD about the negative influence of smoking on their disease, as this will directly influence their intent to quit smoking and positively impact clinical outcomes if they succeed[26,31,32]. Education on smoking is probably insufficiently considered for the management of our patients, particularly in CD. Hilsden et al[33] suggested that patients with CD are not more refractory to smoking cessation compared to the general population of active smokers and factors unrelated to CD may be more important in their decision to smoke than CD-related factors[33].

Furthermore, recent data from the Epi-IBD cohort also highlights the economic impact of smoking on IBD, especially in CD, where smoking cessation has medical and economic benefits[34].

To our knowledge, the present study represents the most complete survey evaluating the consumption of any type of nicotine-containing products in IBD patients. The available literature previously addressed the topic of smoking habits focusing on cigarettes, which are the most commonly used nicotine-containing products[7,9,11,20]. Our survey represents a further effort to fill the gap about former or present use in IBD patients also considering alternative smoking products, like e-cigarettes.

Despite the absence of any significant differences in the use of any nicotine-containing product between CD and UC patients, the two groups had a different perception about the impact of using alternative smoking products on their disease activity, with a trend in favor of worsening in CD patients and a trend in favor of improvement in UC patients; however, in both groups most patients perceived no change in their disease activity. Additionally, a higher proportion of CD patients discussed with their physician about a detrimental effect of these products, while a higher proportion of UC patients never discussed about this subject.

Despite the study design did not allow to stratify our data for the specific type of nicotine-alternative products used, it is interesting to appreciate a growing interest regarding the consumption of electronic cigarettes and its possible impact in IBD populations. A recently published study conducted in United Kingdom showed the proportion of e-cigarette users among IBD patients was marginally lower than in the general population, with no significant difference between CD and UC patients. However, due to the small number of cases, the authors failed to demonstrate a significant different rate of disease-related complications in e-cigarettes users (higher in UC, lower in CD) compared with cigarette users[35].

Regarding e-cigarettes, that deliver nicotine via aerosol formed through the heating of a mixture of liquid usually made up of nicotine, propylene glycol or glycerol (glycerine) and flavouring chemicals, their use among European population has been growing steadily since they entered the European market in 2006[36]. The impact of e-cigarettes remains unknown. The lack of evidence about safety requires to remain vigilant over potential adverse effects; however, current available research also suggests the potential benefits of e-cigarettes as a harm reduction model for those who use combustible cigarettes, and e-cigarettes may have an important role to play in preventing death and disability from tobacco use[37,38]. Those devices may theoretically have less impact on the course of IBD because of lower nicotine concentrations, but the latter vary considerably. Despite that, the safety of e-cigarettes in diseases such as IBD remains unknown. Thus, further research is warranted to assess whether e-cigarettes could be an effective smoking cessation tool, and to evaluate both short- and long-term health effects of e-cigarettes.

In this large, European, multicenter survey of over 1000 IBD patients, we assessed the level of knowledge of patients with IBD regarding the impact of any type of nicotine-containing products in both CD and UC. We found significant differences between CD and UC patients in both awareness and perception of the impact of smoking on their disease. Furthermore, despite most CD patients were aware of a detrimental effect of smoking, and a large part of UC patients was aware of possible beneficial impact of smoking in their disease, further efforts should be done to encourage smoking cessation for all IBD patients, including UC patients, because of the well-established beneficial effects of smoking cessation on general health. In light of the increasing use of alternative nicotine-containing products, like e-cigarettes, further studies are mandatory to explore the safety and impact of these products in patients with IBD.

ARTICLE HIGHLIGHTS
Research background

Environmental factors are probably primarily responsible for the growing incidence of inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), around the globe over the last decades. Among these factors, smoking is the one for which the most solid evidence is currently available. Smoking increases the risk of CD and worsens its clinical course but has a protective effect in UC.

Research motivation

Until now, there has been little patient-centered research aiming at assessing the perceived impact of smoking or nicotine use on IBD symptoms by patients who are current adult smokers and/or nicotine-containing products users. Few studies demonstrated that a high proportion of patients with IBD are unaware of the effects of tobacco on their disease, but these limited available data are solely based on small-scale studies. Yet, making patients aware of the impact of nicotine use on the course of their IBD is essential to expect smoking cessation and improve the management of their disease.

Research objectives

To understand the patients’ perceptions on the impact of smoking on their IBD and to assess differences of these perceptions between CD and UC patients.

Research methods

This was a European-wide online survey developed by Philip Morris Products SA in collaboration with European Federation of Crohn’s and Ulcerative Colitis Association. The final survey questionnaire consisted of 41 questions divided in 8 categories: (1) Subject screener; (2) Smoking history; (3) Background information; (4) IBD disease background; (5) Current disease status; (6) Current therapeutics and medications; and (7) Current nicotine/cigarettes use, and awareness of the impacts of smoking on IBD. The survey was made available in English, French, German, Spanish, Portuguese, Italian, Greek, Finnish and Slovenian. The online survey was open from 4th November 2019 to 11th March 2020 on the European Federation of Crohn’s and Ulcerative Colitis Association website.

Research results

This survey enrolled 1050 IBD patients speaking nine different languages. Among them, 807 declared to have ever smoked or consumed an alternative smoking product. More than half were current cigarette smokers (59.0%). This proportion was significantly higher in CD than in UC patients. There were no significant differences in the use of any nicotine-containing product between CD and UC patients. The perception of the impact of cigarette smoking significantly differed between CD and UC patients. Similarly, the perceived impact of using alternative smoking products on disease activity significantly differed between CD and UC patients. Among patients having ever smoked cigarettes, 31.7% did not receive any information from their physician on the effect of smoking on disease activity, while 45.4% of them received the information that smoking is detrimental to disease activity. These proportions were significantly different in CD and in UC patients.

Research conclusions

We found significant differences between CD and UC patients in both awareness and perception of the impact of smoking on their disease. Further efforts should be done to encourage smoking cessation for all IBD patients, including UC patients, because of the well-established beneficial effects of smoking cessation on general health.

Research perspectives

In light of the increasing use of alternative nicotine-containing products, like e-cigarettes, further studies are mandatory to explore the safety and impact of these products in patients with IBD.

ACKNOWLEDGEMENTS

The authors thank Laurent Peyrin-Biroulet and Silvio Danese for their assistance in the conception of the study.

Footnotes

Manuscript source: Unsolicited manuscript

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: France

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): 0

Grade C (Good): C, C, C

Grade D (Fair): D

Grade E (Poor): 0

P-Reviewer: Lee MG, M'Koma A, Odes S, Triantafyllou K S-Editor: Zhang L L-Editor: A E-Editor: Ma YJ

References
1.  Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, Panaccione R, Ghosh S, Wu JCY, Chan FKL, Sung JJY, Kaplan GG. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2018;390:2769-2778.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1450]  [Cited by in F6Publishing: 627]  [Article Influence: 362.5]  [Reference Citation Analysis (0)]
2.  Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn's disease. Lancet. 2017;389:1741-1755.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 615]  [Cited by in F6Publishing: 246]  [Article Influence: 123.0]  [Reference Citation Analysis (0)]
3.  Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet. 2017;389:1756-1770.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 830]  [Cited by in F6Publishing: 324]  [Article Influence: 166.0]  [Reference Citation Analysis (0)]
4.  Danese S, Sans M, Fiocchi C. Inflammatory bowel disease: the role of environmental factors. Autoimmun Rev. 2004;3:394-400.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 244]  [Cited by in F6Publishing: 209]  [Article Influence: 14.4]  [Reference Citation Analysis (0)]
5.  Piovani D, Danese S, Peyrin-Biroulet L, Nikolopoulos GK, Lytras T, Bonovas S. Environmental Risk Factors for Inflammatory Bowel Diseases: An Umbrella Review of Meta-analyses. Gastroenterology. 2019;157:647-659.e4.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 103]  [Cited by in F6Publishing: 85]  [Article Influence: 51.5]  [Reference Citation Analysis (0)]
6.  Mahid SS, Minor KS, Soto RE, Hornung CA, Galandiuk S. Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clin Proc. 2006;81:1462-1471.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 410]  [Cited by in F6Publishing: 357]  [Article Influence: 27.3]  [Reference Citation Analysis (0)]
7.  Lunney PC, Kariyawasam VC, Wang RR, Middleton KL, Huang T, Selinger CP, Andrews JM, Katelaris PH, Leong RW. Smoking prevalence and its influence on disease course and surgery in Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther. 2015;42:61-70.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 58]  [Cited by in F6Publishing: 47]  [Article Influence: 9.7]  [Reference Citation Analysis (0)]
8.  Reese GE, Nanidis T, Borysiewicz C, Yamamoto T, Orchard T, Tekkis PP. The effect of smoking after surgery for Crohn's disease: a meta-analysis of observational studies. Int J Colorectal Dis. 2008;23:1213-1221.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 164]  [Cited by in F6Publishing: 148]  [Article Influence: 12.6]  [Reference Citation Analysis (0)]
9.  Bastida G, Beltrán B. Ulcerative colitis in smokers, non-smokers and ex-smokers. World J Gastroenterol. 2011;17:2740-2747.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 63]  [Cited by in F6Publishing: 52]  [Article Influence: 6.3]  [Reference Citation Analysis (0)]
10.  Reif S, Lavy A, Keter D, Fich A, Eliakim R, Halak A, Broide E, Niv Y, Ron Y, Patz J, Odes S, Villa Y, Gilat T. Lack of association between smoking and Crohn's disease but the usual association with ulcerative colitis in Jewish patients in Israel: a multicenter study. Am J Gastroenterol. 2000;95:474-478.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 46]  [Cited by in F6Publishing: 45]  [Article Influence: 2.2]  [Reference Citation Analysis (0)]
11.  To N, Gracie DJ, Ford AC. Systematic review with meta-analysis: the adverse effects of tobacco smoking on the natural history of Crohn's disease. Aliment Pharmacol Ther. 2016;43:549-561.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 88]  [Cited by in F6Publishing: 69]  [Article Influence: 17.6]  [Reference Citation Analysis (0)]
12.  Lashner BA, Hanauer SB, Silverstein MD. Testing nicotine gum for ulcerative colitis patients. Experience with single-patient trials. Dig Dis Sci. 1990;35:827-832.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 70]  [Cited by in F6Publishing: 16]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
13.  Pullan RD, Rhodes J, Ganesh S, Mani V, Morris JS, Williams GT, Newcombe RG, Russell MA, Feyerabend C, Thomas GA. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994;330:811-815.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 336]  [Cited by in F6Publishing: 90]  [Article Influence: 12.4]  [Reference Citation Analysis (0)]
14.  Thomas GA, Rhodes J, Ragunath K, Mani V, Williams GT, Newcombe RG, Russell MA, Feyerabend C. Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis. Eur J Gastroenterol Hepatol. 1996;8:769-776.  [PubMed]  [DOI]  [Cited in This Article: ]
15.  Sandborn WJ, Tremaine WJ, Leighton JA, Lawson GM, Zins BJ, Compton RF, Mays DC, Lipsky JJ, Batts KP, Offord KP, Hurt RD, Green J. Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study. Aliment Pharmacol Ther. 1997;11:663-671.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 48]  [Cited by in F6Publishing: 41]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
16.  Guslandi M, Frego R, Viale E, Testoni PA. Distal ulcerative colitis refractory to rectal mesalamine: role of transdermal nicotine versus oral mesalamine. Can J Gastroenterol. 2002;16:293-296.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 27]  [Cited by in F6Publishing: 21]  [Article Influence: 1.4]  [Reference Citation Analysis (0)]
17.  Ingram JR, Thomas GA, Rhodes J, Green JT, Hawkes ND, Swift JL, Srivastava ED, Evans BK, Williams GT, Newcombe RG, Courtney E, Pillai S. A randomized trial of nicotine enemas for active ulcerative colitis. Clin Gastroenterol Hepatol. 2005;3:1107-1114.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 48]  [Cited by in F6Publishing: 15]  [Article Influence: 3.2]  [Reference Citation Analysis (0)]
18.  McGrath J, McDonald JW, Macdonald JK. Transdermal nicotine for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2004;CD004722.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 46]  [Cited by in F6Publishing: 34]  [Article Influence: 2.7]  [Reference Citation Analysis (0)]
19.  Nikfar S, Ehteshami-Ashar S, Rahimi R, Abdollahi M. Systematic review and meta-analysis of the efficacy and tolerability of nicotine preparations in active ulcerative colitis. Clin Ther. 2010;32:2304-2315.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 29]  [Cited by in F6Publishing: 27]  [Article Influence: 2.9]  [Reference Citation Analysis (0)]
20.  Lunney PC, Leong RW. Review article: Ulcerative colitis, smoking and nicotine therapy. Aliment Pharmacol Ther. 2012;36:997-1008.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 86]  [Cited by in F6Publishing: 68]  [Article Influence: 9.6]  [Reference Citation Analysis (0)]
21.  Calkins BM. A meta-analysis of the role of smoking in inflammatory bowel disease. Dig Dis Sci. 1989;34:1841-1854.  [PubMed]  [DOI]  [Cited in This Article: ]
22.  Shields PL, Low-Beer TS. Patients' awareness of adverse relation between Crohn's disease and their smoking: questionnaire survey. BMJ. 1996;313:265-266.  [PubMed]  [DOI]  [Cited in This Article: ]
23.  Ryan WR, Ley C, Allan RN, Keighley MR. Patients with Crohn's disease are unaware of the risks that smoking has on their disease. J Gastrointest Surg. 2003;7:706-711.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 7]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
24.  van der Heide F, Dijkstra A, Albersnagel FA, Kleibeuker JH, Dijkstra G. Active and passive smoking behaviour and cessation plans of patients with Crohn's disease and ulcerative colitis. J Crohns Colitis. 2010;4:125-131.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 16]  [Article Influence: 1.4]  [Reference Citation Analysis (0)]
25.  Wahed M, Goodhand JR, West O, McDermott A, Hajek P, Rampton DS. Tobacco dependence and awareness of health risks of smoking in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2011;23:90-94.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 12]  [Cited by in F6Publishing: 1]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
26.  Ducharme-Bénard S, Côté-Daigneault J, Lemoyne M, Orlicka K, Lahaie R, Weber A, Bouin M. Patients With Inflammatory Bowel Disease Are Unaware of the Impact of Smoking on Their Disease. J Clin Gastroenterol. 2016;50:490-497.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 2]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
27.  Saadoune N, Peyrin-Biroulet L, Baumann C, Bigard MA, Wirth N, Martinet Y, Peyrin-Biroulet C. Beliefs and behaviour about smoking among inflammatory bowel disease patients. Eur J Gastroenterol Hepatol. 2015;27:797-803.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 3]  [Article Influence: 1.6]  [Reference Citation Analysis (0)]
28.  Jess T, Loftus EV, Harmsen WS, Zinsmeister AR, Tremaine WJ, Melton LJ, Munkholm P, Sandborn WJ. Survival and cause specific mortality in patients with inflammatory bowel disease: a long term outcome study in Olmsted County, Minnesota, 1940-2004. Gut. 2006;55:1248-1254.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 154]  [Cited by in F6Publishing: 127]  [Article Influence: 10.3]  [Reference Citation Analysis (0)]
29.  Winther KV, Jess T, Langholz E, Munkholm P, Binder V. Survival and cause-specific mortality in ulcerative colitis: follow-up of a population-based cohort in Copenhagen County. Gastroenterology. 2003;125:1576-1582.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 136]  [Cited by in F6Publishing: 122]  [Article Influence: 8.0]  [Reference Citation Analysis (0)]
30.  Masala G, Bagnoli S, Ceroti M, Saieva C, Trallori G, Zanna I, D'Albasio G, Palli D. Divergent patterns of total and cancer mortality in ulcerative colitis and Crohn's disease patients: the Florence IBD study 1978-2001. Gut. 2004;53:1309-1313.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 52]  [Cited by in F6Publishing: 48]  [Article Influence: 3.1]  [Reference Citation Analysis (0)]
31.  Cosnes J, Carbonnel F, Beaugerie L, Le Quintrec Y, Gendre JP. Effects of cigarette smoking on the long-term course of Crohn's disease. Gastroenterology. 1996;110:424-431.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 273]  [Cited by in F6Publishing: 252]  [Article Influence: 10.9]  [Reference Citation Analysis (0)]
32.  Nunes T, Etchevers MJ, Merino O, Gallego S, Garcí, a-Sá, nchez V, Marí, n-Jimé, nez I, Menché, n L, Barreiro-de Acosta M, Bastida G, Garcí, a S, Gento E, Ginard D, Martí, E, Gomolló, n F, Arroyo M, Monfort D, Garcí, a-Planella E, Gonzalez B, Loras C, Agustí, C, Figueroa C, Sans M, TABACROHN Study Group of GETECCU. High smoking cessation rate in Crohn's disease patients after physician advice--the TABACROHN Study. J Crohns Colitis. 2013;7:202-207.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 34]  [Cited by in F6Publishing: 28]  [Article Influence: 3.8]  [Reference Citation Analysis (0)]
33.  Hilsden RJ, Hodgins D, Czechowsky D, Verhoef MJ, Sutherland LR. Attitudes toward smoking and smoking behaviors of patients with Crohn's disease. Am J Gastroenterol. 2001;96:1849-1853.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 17]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
34.  Burisch J, Vardi H, Schwartz D, Friger M, Kiudelis G, Kupčinskas J, Fumery M, Gower-Rousseau C, Lakatos L, Lakatos PL, D'Incà R, Sartini A, Valpiani D, Giannotta M, Arebi N, Duricova D, Bortlik M, Chetcuti Zammit S, Ellul P, Pedersen N, Kjeldsen J, Midjord JMM, Nielsen KR, Winther Andersen K, Andersen V, Katsanos KH, Christodoulou DK, Domislovic V, Krznaric Z, Sebastian S, Oksanen P, Collin P, Barros L, Magro F, Salupere R, Kievit HAL, Goldis A, Kaimakliotis IP, Dahlerup JF, Eriksson C, Halfvarson J, Fernandez A, Hernandez V, Turcan S, Belousova E, Langholz E, Munkholm P, Odes S; Epi-IBD group. Health-care costs of inflammatory bowel disease in a pan-European, community-based, inception cohort during 5 years of follow-up: a population-based study. Lancet Gastroenterol Hepatol. 2020;5:454-464.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 26]  [Cited by in F6Publishing: 10]  [Article Influence: 26.0]  [Reference Citation Analysis (0)]
35.  Chong C, Rahman A, Loonat K, Sagar RC, Selinger CP. Current smoking habits in British IBD patients in the age of e-cigarettes. BMJ Open Gastroenterol. 2019;6:e000309.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 5]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
36.  Attitudes of Europeans Towards Tobacco. Belgium: European Commission; 2017.  Available from: http://ec.europa.eu/COMMFrontOffice/PublicOpinion.  [PubMed]  [DOI]  [Cited in This Article: ]
37.  Cooke A, Fergeson J, Bulkhi A, Casale TB. The Electronic Cigarette: The Good, the Bad, and the Ugly. J Allergy Clin Immunol Pract. 2015;3:498-505.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 37]  [Cited by in F6Publishing: 29]  [Article Influence: 7.4]  [Reference Citation Analysis (0)]
38.  Fadus MC, Smith TT, Squeglia LM. The rise of e-cigarettes, pod mod devices, and JUUL among youth: Factors influencing use, health implications, and downstream effects. Drug Alcohol Depend. 2019;201:85-93.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 77]  [Cited by in F6Publishing: 50]  [Article Influence: 38.5]  [Reference Citation Analysis (0)]