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Open Access

Peer-reviewed

Research Article

Global smoking trends in inflammatory bowel disease: A systematic review of inception cohorts

  • Tom Thomas ,

    Contributed equally to this work with: Tom Thomas, Joht Singh Chandan

    Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Validation, Visualization, Writing – original draft, Writing – review & editing

    tom.thomas@nhs.net

    Affiliations Translational Gastroenterology Unit, University of Oxford, Oxford, United Kingdom, Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom

    ⨯
  • Joht Singh Chandan ,

    Contributed equally to this work with: Tom Thomas, Joht Singh Chandan

    Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Validation, Visualization, Writing – review & editing

    Affiliation Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom

    ⨯
  • Venice Sze Wai Li,

    Roles Formal analysis, Methodology, Visualization, Writing – review & editing

    Affiliation Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, Chinese University of Hong Kong, Hong Kong, China

    ⨯
  • Cheuk Yin Lai,

    Roles Methodology, Visualization, Writing – review & editing

    Affiliation Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, Chinese University of Hong Kong, Hong Kong, China

    ⨯
  • Whitney Tang,

    Roles Data curation, Writing – review & editing

    Affiliation Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, Chinese University of Hong Kong, Hong Kong, China

    ⨯
  • Neeraj Bhala,

    Roles Methodology, Supervision, Writing – review & editing

    Affiliations Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom

    ⨯
  • Gilaad G. Kaplan ,

    Roles Conceptualization, Data curation, Supervision, Validation, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliation Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada

    ⨯
  • Siew C. Ng ,

    Roles Conceptualization, Methodology, Supervision, Validation, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliation Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, Chinese University of Hong Kong, Hong Kong, China

    ⨯
  • Subrata Ghosh

    Roles Conceptualization, Formal analysis, Resources, Supervision, Validation, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliations University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom, NIHR Biomedical Research Centre Birmingham, Institute of Translational Medicine, University of Birmingham, Birmingham, United Kingdom

    ⨯

Abstract

Background and aims

The effect of smoking on the risk of developing inflammatory bowel diseases (IBD) may be heterogeneous across ethnicity and geography. Although trends in smoking for the general population are well described, it is unknown whether these can be extrapolated to the IBD cohort. Smoking prevalence trends specific to the global IBD cohort over time have not been previously reported. This is a systematic review of smoking prevalence specific to the IBD cohort across geography.

Methods

A systematic literature search was conducted on Medline and Embase from January 1st 1946 to April 5th 2018 to identify population-based studies assessing the prevalence of smoking at diagnosis in inception cohorts of Crohn’s disease(CD) or ulcerative colitis(UC). Studies that did not report smoking data from time of diagnosis or the year of IBD diagnosis were excluded. Prevalence of smoking in IBD was stratified by geography and across time.

Results

We identified 56 studies that were eligible for inclusion. Smoking prevalence data at diagnosis of CD and UC was collected from twenty and twenty-five countries respectively. Never-smokers in the newly diagnosed CD population in the West has increased over the last two decades, especially in the United Kingdom and Sweden; +26.6% and +11.2% respectively. Never-smokers at CD diagnosis in newly industrialised nations have decreased over the 1990s and 2000s; China (-19.36%). Never-smokers at UC diagnosis also decreased in China; -15.4%. The former-smoker population at UC diagnosis in China is expanding; 11%(1990–2006) to 34%(2011–2013).

Conclusion

There has been a reduction in the prevalence of smoking in the IBD cohort in the West. This is not consistent globally. Although, smoking prevalence has decreased in the general population of newly industrialised nations, this remains an important risk factor with longer term outcomes awaiting translation in both UC and CD.

Citation: Thomas T, Chandan JS, Li VSW, Lai CY, Tang W, Bhala N, et al. (2019) Global smoking trends in inflammatory bowel disease: A systematic review of inception cohorts. PLoS ONE 14(9): e0221961. https://doi.org/10.1371/journal.pone.0221961

Editor: Stefanos Bonovas, Humanitas University, ITALY

Received: March 19, 2019; Accepted: August 18, 2019; Published: September 23, 2019

Copyright: © 2019 Thomas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supplementary files.

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: (IBD), Inflammatory Bowel Disease; (CD), Crohn’s disease; (UC), ulcerative colitis

Introduction

Our group has extensively reported that inflammatory bowel diseases (IBD) have become a global challenge in the 21st century.[1–5] The rapidly accelerating incidence of both Crohn’s disease (CD) and ulcerative colitis (UC) in the newly industrialized countries in the East mirrors epidemiological patterns of IBD in the West more than 75 years ago.[2] The evolving epidemiology of IBD is thought to be associated with the industrialisation of society. The rise of IBD incidence in newly industrialised nations combined with reports of comparable rates of IBD in migrant and native populations in the West[6] support the theory that environmental triggers and Western lifestyle have an integral role in the pathogenesis of IBD. [3,4]

The dichotomous relationship between smoking and the development of IBD has been the subject of intense scrutiny and is a complex interplay of genetics, immunology and environment. In the West, smoking has been consistently reported as a risk factor for developing CD and adversely affects disease course[7–9], whereas former smokers and non-smokers are at increased risk of developing UC in comparison to current smokers.[10,11] In contrast, studies in non-Western populations have been unable to replicate this association between CD and smoking.[12] The interaction between smoking and the NOD-2 gene and their effect on the risk of CD has been postulated to be specific to the 1007 fs mutation and a negative association between NOD-2 mutation and smoking could be explained by their inverse relationship.[13]

An understanding of global smoking prevalence trends specific to the IBD cohort is required as the foundation for further investigation of the heterogeneous influence of this risk factor in IBD pathogenesis and disease course across different regions. In addition, this is increasingly important in light of the identification of smoking as a key risk factor for non-response to anti-TNF agents in patients with CD.[14] However, the global prevalence of smoking associated with IBD have not been collated and reported. We conducted a systematic review to assess the prevalence of smoking in all population based IBD inception cohort studies. We examined smoking prevalence specific to individual IBD cohorts across time and geography.

Materials and methods

Search strategy and selection criteria

This systematic review was conducted according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines.[15] A systematic literature search (S1 Table) was conducted on Medline (01 January 1946 to April 5th 2018) and Embase (01 January 1947 to April 5th 2018) for studies assessing the prevalence of smoking at diagnosis in inception IBD cohorts. All studies from our previous systematic review on IBD epidemiology[1],[5] as well as the reference lists of all relevant articles were included. We also obtained data outside of the search strategy using expert knowledge of active studies as with the Asia-Pacific Crohn’s and Colitis Epidemiologic Study Group [ACCESS]).

All stages of the systematic review were independently conducted by two teams; the first from the United Kingdom (TT and JSC) and the second from Hong Kong (SCN, VSWL and CYL). The first stage consisted of an initial screening of abstracts and titles of search results. Studies were excluded if they were not observational in design and did not report original data (i.e. review articles). Studies were considered for final inclusion in the review if their study participants consisted of a population-based inception cohort of CD and/or UC with raw numbers reported to enable the calculation of ever and/or never smoking proportion at time of IBD diagnosis. Studies could also be included if they expressed the frequency of smokers or non-smokers. A study was considered to be population-based if the sample was representative of geographical region. Smoking data had to be reported separately in CD and UC cohorts for inclusion. Studies that did not report smoking data from time of diagnosis or did not have the year of IBD diagnosis were excluded. Discrepancies between the reviewers were resolved in conjunction with GGK, SG and SCN. The flow chart for the above process is presented in Fig 1.

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Fig 1. Study selection.

https://doi.org/10.1371/journal.pone.0221961.g001

Data analysis

The data extracted included: author, geographical location, study period, size of CD or UC cohort, frequency of current, former and never-smokers including unknown smoking status. Study quality was ascertained using a modified version of the Newcastle-Ottawa Scale (S2 Table). The modified scale addressed aspects of quality relevant to population-based inception cohorts as well as ascertainment of smoking exposure.

We classified geographic regions according to proximity and economic similarity based upon the United Nations classification of economic region as in our previous work.[1],[5] The regions included are: North America, South America, Eastern Europe, Northern Europe, Southern Europe, Western Europe, Asia and Oceania.

Scatter plots (created using Plotly (Montreal, Canada) were used to display time trends across geography in the proportion of never and ever smokers in inception cohorts of CD (Fig 2) and UC (Fig 3) between 1980 to 2013. The earliest and latest years for which smoking data was available was 1980 and 2013 respectively. Smoking prevalence in local jurisdictions/regions were extrapolated to the entire country. In studies that reported smoking prevalence across a range of years, the median year was selected. Where studies reported former smokers, these patients were pooled with current smokers to formulate an ever-smoker category. In studies that reported only current and former category or an ever smoker category, the remainder of the population were designated as never-smokers. In UC, we sought to assess the former smoker population as this is considered the at-risk population. However, the former smoker population was also incorporated into the ever smoker population and reported for consistency. Studies with a total sample size of less than 10 subjects were excluded from these graphs. Further analysis in the form of meta-analysis or time trend analyses were not deemed appropriate due to paucity of data and heterogeneity in study design. Apart from ever smoking and never smoking data, quantitation of smoking in terms of average number of cigarettes smoked or duration of smoking were not available from the population based epidemiological data.

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Fig 2. The proportion of never smokers at diagnosis in global population based inception cohorts of Crohn’s disease stratified by region, country and year (1946–2018).

https://doi.org/10.1371/journal.pone.0221961.g002

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Fig 3. The proportion of never smokers at diagnosis in global population based inception cohorts of ulcerative colitis stratified by region, country and year (1946–2018).

https://doi.org/10.1371/journal.pone.0221961.g003

Results

We identified 41 records from our previous research on IBD inception cohorts1. Our search strategy identified 3152 additional records from MEDLINE and Embase from January 1948 to April 31st 2018. Fig 1 demonstrates the number of records eligible for and removed prior to full text review. 56 studies were eligible for final inclusion in the systematic review. These included 44 studies in CD and 46 studies in UC (Fig 1). Characteristics of all included studies are presented in Tables 1 and 2.

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Table 1. Smoking prevalence in global population-based inception cohorts of Crohn’s disease stratified by region, country and year (1946–2018).

https://doi.org/10.1371/journal.pone.0221961.t001

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Table 2. Smoking prevalence in global population-based inception cohorts of ulcerative colitis stratified by region, country and year (1946–2018).

https://doi.org/10.1371/journal.pone.0221961.t002

Smoking prevalence figures were reported for: North America (2 studies), South America (1 study), Eastern Europe (3 studies), Northern Europe (16 studies), Southern Europe (12 studies), Western Europe (4 studies), Asia (15 studies), and Oceania (3 studies). Scatter plots representing never-smoker prevalence in the CD and UC cohorts from 1980 to 2018 stratified by geographic region are presented in Figs 2 and 3 respectively. Smoking prevalence varied greatly according to geographic region. Fig 2 shows that an increasing number of the newly diagnosed CD population over the last two decades in the West particularly in the UK have never smoked. In contrast, a decrease in the proportion of never-smokers over the 1990s and 2000s is seen in newly industrialised nations such as China. Fig 3 is suggestive of significant heterogeneity in the trend of the never-smoker group in the newly diagnosed UC population in the West. Data from the United Kingdom and Sweden over the 1980s and 1990s suggest a decrease in this group whilst data from Iceland and Italy show an increase in the never-smoking proportion. Fig 3 shows that the proportion of people who have never smoked at UC diagnosis in newly industrialised nations particularly China has been decreasing over the last two decades. Tables 3 and 4 displays these ranges stratified according to geographic region.

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Table 3. Prevalence of never-smokers in global population-based inception cohorts of Crohn’s disease and ulcerative colitis stratified by range and region (1946–2018).

https://doi.org/10.1371/journal.pone.0221961.t003

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Table 4. Prevalence of ever-smokers in global population-based inception cohorts of Crohn’s disease and ulcerative colitis stratified by range and region (1946–2018).

https://doi.org/10.1371/journal.pone.0221961.t004

Crohn’s disease

Smoking prevalence data at diagnosis of CD was collected from twenty countries. The western world particularly Europe has demonstrated an overall increase in the prevalence of never smokers in the newly diagnosed CD cohort over the last three decades.

In Sweden (Northern Europe), the proportion of never-smokers increased from 31.6%[16] in the 1980s to 42.8% (2007)[17]. In the early 1990s, the proportion of never-smokers in the newly diagnosed CD cohort in the UK was 38%.[18] A large population-based inception cohort study (1989–2009)[19] in the UK estimated that 64.6% of newly diagnosed CD patients were never-smokers. This trend is replicated in Western Europe, Southern Europe and Eastern Europe. The proportion of never-smokers in the CD cohort in the Netherlands ranged from 29.7%[20] to 31%[21] in the 1990s however France and Germany demonstrated a never-smoker proportion of 65%[22] and 63.1%[23] in the 2000s respectively. In Italy (Southern Europe), there was a steady increase in the never-smoker population at CD diagnosis over the course of the 1980s[24] and 1990s.[25] Similarly, Spain showed consistent trends with the ever-smoker group steadily declining from 66%(1980 and 1990s)[26] to 46%(2001)[27] in the newly-diagnosed CD cohort. Similarly, in Hungary (Eastern Europe), the proportion of never smokers in the newly diagnosed CD cohort increased from 44.3%[8] to 50.2%[28] over the course of 30 years.

In contrast to Europe, smoking prevalence in inception CD cohorts in Asia appears to be increasing over time. The majority of CD subjects in Asia were never-smokers. The proportion of subjects who had never smoked range from 75%[29] (Hong Kong, China;1985–2001) to 92.6%[30] (Hong Kong, China;1991–2006). However, in a more recent inception cohort from Asia from 2011-2013(ACCESS), 73.2% of CD subjects were never smokers. Nine out of 44 studies did not report former smokers. Never-smoker populations were assumed to be the remainder of the population if ever smoker data was provided.

Ulcerative colitis

Smoking prevalence data at diagnosis of UC was collected from twenty-five countries. Smoking trends in Europe for the newly diagnosed UC cohort showed more heterogeneity than in CD. Data from the United Kingdom appear to suggest a decrease in the never-smoker proportion in the UC cohort during the 1990s; 66.2%(1993)[31] to 58.6%(1995–1997)[32] and 37.5% (1999)[33]. The former smoker population appears to have decreased in the same decade from 21.6%[31] to 18.8%[33]. Data from Sweden demonstrate reduction in the never smoker population from 52.4%(1984–1987)[16] to 32.5%(2005–2009)[34]. An increase in the proportion of former smokers at diagnosis from 17.9%(1984–1987)[16] to 24.7%(2005–2009)[34] was noted. Other Scandinavian regions such as Denmark showed only a slightly higher proportion of never smokers in their UC cohorts; 45%(2004)[35]. In contrast to the remainder of Northern Europe in the 1980s and 1990s, Iceland demonstrated an increase in the never-smoker proportion from 13.5%[36] to 35.8%[37] across this period. The percentage of former smokers at UC diagnosis also rose from 11.7% to 20% across those two decades. These results co-relate with a decrease in the ever-smoker proportion down to 48%[38] in the 21st century.

In Southern Europe, Spain demonstrated an increase in their ever-smoker proportion from 12.5%[26] in the 1980s and 1990s to 48%[39] in the 2000s. In Italy, the never-smoker proportion varied by geographic region; 42% (Milan; early 1980s)[24] to 33% (Bologna; late 1980s)[40] and 44% (Crema and Cremona; early 1990s)[25]. Former-smoker proportions were similarly varied across these regions and time periods: 37.1%, 43% and 39% respectively. In Eastern Europe, Veszprem (Hungary) demonstrated a reduction in the never-smoker population in the UC cohort; 67.5%(1977–2008)[8] to 65.5%(2002–2006)[28]. The former smoker population in the newly diagnosed UC cohort during those periods were 17.6% and 20.9% respectively. In contrast to the rest of Europe, never-smoker proportions increased over the late 1990s and early 2000s in Western Europe from 44.3%[20] (Netherlands; 1996) to 77.55% (France; 2003)[22] and 58.09%(Germany;2005)[23].

The proportion of newly diagnosed UC subjects who have never smoked has decreased in China over the last two decades. The proportion who had never smoked were 84.9%[41] in China in the late 1990s. By 2012 these figures had decreased to 69.5% (ACCESS Cohort;2011–2013). The proportion of former smoker patients in the newly diagnosed UC cohort in China appears to be increasing from 11%(1990–2006)[42] to 34% (Hong Kong ACCESS cohort).

Data from major cities in Australia suggest that the proportion of never-smokers in the newly diagnosed UC cohort has increased from 58.8%(Sydney;1992)[43] to 77%(Victoria; 2007–2013)[44]. The former smoker proportion of patients at diagnosis also decreased from 29.4% to 18% across the same regions and time periods respectively. The impact of missing smoking data regarding the participants vary due to heterogeneity in reporting. Four out of the 46 studies included for UC did not report former smokers at diagnosis. Never-smoker populations were assumed to be the remainder of the population if ever smoker data was provided.

Discussion

We present a comprehensive review of smoking trends over time in inception IBD cohorts worldwide. In the West, the proportion of newly diagnosed CD subjects who have never smoked has increased over time. The proportion of newly diagnosed UC subjects who have never smoked has declined in the 1980s and 1990s in Europe although an increase was noted in Western Europe from the late 1990s. In contrast, the proportion of subjects who have never smoked at IBD diagnosis has decreased in Asia, particularly in China. Thus, we demonstrate that trends in smoking prevalence specific to the IBD cohort do not mirror global trends in smoking discerned from the general population.[45]

The incidence of IBD in newly industrialised countries is accelerating whilst the incidence of IBD is stabilising in the West.[1] The effect of smoking on the incidence of IBD across the globe likely varies due to heterogeneity in genetic susceptibility and the presence of other risk factors. Public health measures in the 1980s and 1990s led to a reduction of smoking prevalence in the general population in many Western countries.[46] The higher proportion of never smokers at diagnosis of CD over time may be explained by adolescents who decided not to smoke in the 1990s. This could have potentially contributed to the stabilization, and in certain regions decrease, in the incidence of adult-onset CD in some Western countries. This ecological trend could also explain the decrease in the former smoker population in the UK over the 1990s and could have contributed to the recent stabilisation of UC incidence.[1]

In contrast, we are at the infancy of the IBD ‘epidemic’ in newly industrialized countries in Asia, especially in areas of high smoking prevalence[46]; hence ever-smoker trends at IBD diagnosis are on the increase. The rapid expansion of the former smoker population at UC diagnosis in China is suggestive of a rapid expansion of the at-risk population. The Global Burden of Disease Study 2015 identified China as one of the leading countries in the world for the total number of smokers.[46] In line with the Lopez model[47], these newly industrialised nations are rapidly moving towards Stage IV where smoking prevalence in the general population will decrease as societal attitudes shift and government anti-smoking policy becomes comprehensive. This could potentially foreshadow a protracted course of high UC incidence in comparison to CD. Similar to the West, we hypothesise that a ‘lag effect’ can be expected in future epidemiological studies particularly in CD based in newly industrialised nations. However, due to the complex interplay between genetics and environment in the development of IBD, this effect may not be as pronounced as in the West[12] although in contrast to CD, there is some evidence to suggest that the role of smoking in UC is uniform across the East and West.[12,48,49]

The concurrent decrease of the never-smoker population in both CD and UC cohorts in newly industrialised nations is potentially suggestive of significant heterogeneity in the interaction between smoking and the process of IBD development across geographic regions. Even in the West, the incidence of CD had been high in relatively low smoking prevalence populations i.e. Israeli Jews[50], Canada, and Sweden. Multiple studies[12],[29],[51] in the Asia-Pacific region have demonstrated that active smoking does not confer an increased risk of CD in this population as it does in the West. The relative absence of the NOD-2 mutation in CD cases in Japan suggests that the role of smoking in IBD is subject to underlying genetic heterogeneity.[52] Environmental factors such as air pollution[53], diet and a Western lifestyle as demonstrated in migrant sub-populations[6] as well as evolving early life feeding patterns and improved hygiene as part of socioeconomic development[12] could be more potent mediators of IBD development.[54,55]

Our study has several limitations predominantly due to lack of available data. We were unable to perform a meta-analysis or ecological trend analysis due to study heterogeneity. Small sample sizes in some studies have also increased the risk of imprecise estimates for smoking prevalence. A paucity of gender-specific, age-category specific smoking prevalence data, data relating to quantification of smoking habits or breakdown of rural vs. urban data in the IBD cohort did not allow for further sub-group analysis. Although, it is possible studies that included children and adolescents would have a higher prevalence of never-smokers, summary statistics from included studies suggest this is not the case. The exposure to smoking was reported inconsistently; some studies reported current and former smokers whilst others reported ever and never smokers. Twenty three out of ninety-five included cohorts reported missing smoking data on participants (Tables 1 and 2). No data was available regarding second-hand smoking exposure. Due to differing study periods and the generalisation of regions to represent countries, smoking data was not fully homogenous. The inequalities in healthcare access across the globe can also affect data collection and reporting. In addition, we acknowledge that the attributable risk of smoking on IBD is low (i.e. most IBD patients do not have a history of smoking [current or former] prior to their diagnosis), however it remains an important risk mediator in the development of IBD.

Despite these limitations, this study provides a comprehensive overview of the prevalence of smoking in the global IBD cohort across time and geography. The proportion of never-smokers in IBD cohorts from newly industrialised countries appears to be decreasing over time in contrast to the IBD cohorts in the West. In light of our previous work and this study, it appears that IBD epidemiological patterns globally can be modelled along geographical and development lines within a context of genetic heterogeneity and environmental ecological exposures. It remains of clinical importance for medical practitioners to record information and act on smoking status for patients with IBD regardless of geography and ethnicity, especially in light of data suggesting smoking confers an adverse disease course in CD and is a risk factor in non-response to anti-TNF therapy.[14] Large-scale prospective inception cohorts assessing the associations of smoking for both UC and CD in Eastern and Western populations will add to the available data.

This is the first systematic review to assess trends in the prevalence of smoking in the IBD cohort worldwide. It provides a foundation for future work assessing the prevalence of this important risk mediator in a global setting as well as highlighting some of the challenges surrounding this data. A deeper understanding of IBD aetiology in relation to diet and other environmental factors across geographic regions and ethnicities is urgently required in order to formulate strategies to slow the global increase in the incidence of IBD.

Supporting information

S1 Table. Detailed MEDLINE and EMBASE search strategy for article selection (1 January 1947 to April 5 2018).

https://doi.org/10.1371/journal.pone.0221961.s001

(DOCX)

S2 Table. Quality assessment of manuscripts (modified Newcastle Ottawa scale).

https://doi.org/10.1371/journal.pone.0221961.s002

(DOCX)

Acknowledgments

SG is supported by the NIHR Biomedical Research Centre, Birmingham.

References

  1. 1. Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet (London, England) [Internet]. 2018 Dec 23 [cited 2018 Apr 15];390(10114):2769–78. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29050646
  2. 2. Kaplan GG, Ng SC. Understanding and Preventing the Global Increase of Inflammatory Bowel Disease. Gastroenterology [Internet]. 2017 Jan [cited 2018 Jul 21];152(2):313-321.e2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27793607
  3. 3. Kaplan GG, Ng SC. Globalisation of inflammatory bowel disease: perspectives from the evolution of inflammatory bowel disease in the UK and China. Lancet Gastroenterol Hepatol [Internet]. 2016 Dec [cited 2018 Aug 21];1(4):307–16. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28404201 pmid:28404201
  4. 4. Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol [Internet]. 2015 Dec 1 [cited 2018 Aug 21];12(12):720–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26323879 pmid:26323879
  5. 5. Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al. Increasing Incidence and Prevalence of the Inflammatory Bowel Diseases With Time, Based on Systematic Review. Gastroenterology [Internet]. 2012 Jan [cited 2017 Sep 12];142(1):46-54.e42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22001864
  6. 6. Probert CSJ, Jayanthi V, Pinder D, Wicks AC, Mayberry JF, Probert J, et al. Epidemiological study of ulcerative proctocolitis in Indian migrants and the indigenous population of Leicestershire Hindus and Sikhs have a significantly higher incidence of UC than Europeans in Leicestershire. Gut [Internet]. 1992 [cited 2018 Jul 18];33:687–93. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1379303/pdf/gut00572-0137.pdf pmid:1307684
  7. 7. Lawrance IC, Murray K, Batman B, Gearry RB, Grafton R, Krishnaprasad K, et al. Crohn’s disease and smoking: Is it ever too late to quit? J Crohn’s Colitis [Internet]. 2013 Dec 15 [cited 2018 Jul 21];7(12):e665–71. Available from: https://academic.oup.com/ecco-jcc/article-lookup/doi/10.1016/j.crohns.2013.05.007
  8. 8. Lakatos PL, Vegh Z, Lovasz BD, David G, Pandur T, Erdelyi Z, et al. Is Current smoking still an important environmental factor in inflammatory bowel diseases? Results from a population-based incident cohort. Inflamm Bowel Dis. 2013;19(4):1010–7.
  9. 9. Nunes T, Etchevers MJ, Domènech E, García-Sánchez V, Ber Y, Peñalva M, et al. Smoking does influence disease behaviour and impacts the need for therapy in Crohn′s disease in the biologic era. Aliment Pharmacol Ther [Internet]. 2013 Oct [cited 2018 Jul 21];38(7):752–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23980933 pmid:23980933
  10. 10. Calkins BM. A meta-analysis of the role of smoking in inflammatory bowel disease. Dig Dis Sci [Internet]. 1989 Dec [cited 2018 Jul 17];34(12):1841–54. Available from: http://link.springer.com/10.1007/BF01536701 pmid:2598752
  11. 11. Mahid SS, Minor KS, Soto RE, Hornung CA, Galandiuk S. Smoking and Inflammatory Bowel Disease: A Meta-analysis. Mayo Clin Proc [Internet]. 2006 Nov [cited 2018 Jul 17];81(11):1462–71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17120402 pmid:17120402
  12. 12. Ng SC, Tang W, Leong RW, Chen M, Ko Y, Studd C, et al. Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific. Gut [Internet]. 2015 Jul [cited 2018 May 21];64(7):1063–71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25217388 pmid:25217388
  13. 13. Kuenzig ME, Yim J, Coward S, Eksteen B, Seow CH, Barnabe C, et al. The NOD2 -Smoking Interaction in Crohn’s Disease is likely Specific to the 1007 fs Mutation and may be Explained by Age at Diagnosis: A Meta-Analysis and Case-Only Study. EBioMedicine [Internet]. 2017 Jul [cited 2017 Sep 12];21:188–96. Available from: http://linkinghub.elsevier.com/retrieve/pii/S2352396417302475 pmid:28668336
  14. 14. Kennedy NA, Heap GA, Green HD, Hamilton B, Bewshea C, Walker GJ, et al. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: a prospective, multicentre, cohort study. lancet Gastroenterol Hepatol. 2019 May;4(5):341–53. pmid:30824404
  15. 15. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA [Internet]. 2000 Apr 19 [cited 2018 Jul 22];283(15):2008–12. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10789670 pmid:10789670
  16. 16. Persson PG, Ahlbom A, Hellers G. Inflammatory bowel disease and tobacco smoke—a case-control study. Gut [Internet]. 1990;31(12):1377–81. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1378760&tool=pmcentrez&rendertype=abstract%5Cnhttp://gut.bmj.com/cgi/doi/10.1136/gut.31.12.1377 pmid:2265777
  17. 17. Sjöberg D, Holmström T, Larsson M, Nielsen AL, Holmquist L, Ekbom A, et al. Incidence and clinical course of Crohn’s disease during the first year—Results from the IBD Cohort of the Uppsala Region (ICURE) of Sweden 2005–2009. J Crohn’s Colitis [Internet]. 2014;8(3):215–22. Available from: https://doi.org/10.1016/j.crohns.2013.08.009
  18. 18. Yapp TR, Stenson R, Thomas GA, Lawrie BW, Williams GT HB. Crohn’s disease incidence in Cardiff from 1930: an update for 1991-1995.pdf. Eur J Gastroenterol Hepatol [Internet]. 2000;12(8). Available from: https://journals.lww.com/eurojgh/Abstract/2000/12080/Crohn_s_disease_incidence_in_Cardiff_from_1930__an.10.aspx
  19. 19. Chhaya V, Saxena S, Cecil E, Subramanian V, Curcin V, Majeed A, et al. Emerging trends and risk factors for perianal surgery in Crohn’s disease. Eur J Gastroenterol Hepatol [Internet]. 2016 Aug [cited 2018 Apr 11];28(8):890–5. Available from: https://insights.ovid.com/crossref?an=00042737-201608000-00006 pmid:27128719
  20. 20. van der Heide F, Wassenaar M, van der Linde K, Spoelstra P, Kleibeuker JH, Dijkstra G. Effects of active and passive smoking on Crohnʼs disease and ulcerative colitis in a cohort from a regional hospital. Eur J Gastroenterol Hepatol [Internet]. 2011;23(3):255–61. Available from: https://insights.ovid.com/crossref?an=00042737-201103000-00010 pmid:21191306
  21. 21. Romberg-Camps MJL, Hesselink-van de Kruijs MAM, Schouten LJ, Dagnelie PC, Limonard CB, Kester ADM, et al. Inflammatory Bowel Disease in South Limburg (the Netherlands) 1991–2002: Incidence, diagnostic delay, and seasonal variations in onset of symptoms. J Crohn’s Colitis [Internet]. 2009;3(2):115–24. Available from: https://doi.org/10.1016/j.crohns.2008.12.002
  22. 22. Abakar-Mahamat A, Filippi J, Pradier C, Dozol A, Hébuterne X. Incidence of inflammatory bowel disease in Corsica from 2002 to 2003. Gastroenterol Clin Biol. 2007;31(12):1098–103. pmid:18176365
  23. 23. Ott C, Obermeier F, Thieler S, Kemptner D, Bauer A, Schölmerich J, et al. The incidence of inflammatory bowel disease in a rural region of Southern Germany: a prospective population-based study. Eur J Gastroenterol Hepatol [Internet]. 2008;20(9):917–23. Available from: https://insights.ovid.com/crossref?an=00042737-200809000-00016 pmid:18794607
  24. 24. Franceschi S, Panza E, Vecchia C La, Parazzini F, Decarli A, Porro GB. Nonspecific inflammatory bowel disease and smoking. Am J Epidemiol. 1987;125(3):445–52. pmid:3812450
  25. 25. Ranzi T, Bodini P, Zambelli A, Politi P, Lupinacci G, Campanini MC, et al. Epidemiological aspects of inflammatory bowel disease in a north Italian population: a 4-year prospective study. Eur J Gastroenterol Hepatol [Internet]. 1996 Jul [cited 2018 Aug 4];8(7):657–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8853254 pmid:8853254
  26. 26. Garrido a, Martínez MJ, Ortega J a, Lobato a, Rodríguez MJ, Guerrero FJ. Epidemiology of chronic inflammatory bowel disease in the Northern area of Huelva. Rev Esp Enferm Dig [Internet]. 2004;96(10):687–91; 691–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15537375 pmid:15537375
  27. 27. Rodrigo L, Riestra S, Nino P, Cadahia V, Tojo R, Fuentes D, et al. A population-based study on the incidence of inflammatory bowel disease in Oviedo (Northern Spain). Rev Esp Enferm Dig. 2004;96(5):296–305. pmid:15180441
  28. 28. Lakatos L, Kiss LS, David G, Pandur T, Erdelyi Z, Mester G, et al. Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002–2006. Inflamm Bowel Dis. 2011;17(12):2558–65. pmid:22072315
  29. 29. Leong RWL, Lau JY, Sung JJY. The epidemiology and phenotype of Crohn’s disease in the Chinese population. Inflamm Bowel Dis [Internet]. 2004 Sep [cited 2018 Jul 18];10(5):646–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15472528 pmid:15472528
  30. 30. Lok KH, Hung HG, Ng CH, Li KK, Li KF, Szeto ML. The epidemiology and clinical characteristics of Crohn’s disease in the Hong Kong Chinese population: experiences from a regional hospital. Hong Kong Med J [Internet]. 2007;13(6):436–41. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18057431 pmid:18057431
  31. 31. Carr I, Mayberry JF. The effects of migration on ulcerative colitis: A three-year prospective study among Europeans and first- and second-generation South Asians in Leicester (1991–1994). Am J Gastroenterol. 1999;94(10):2918–22. pmid:10520845
  32. 32. García-Fontana B, Morales-Santana S, Longobardo V, Reyes-García R, Rozas-Moreno P, García-Salcedo J, et al. Relationship between Proinflammatory and Antioxidant Proteins with the Severity of Cardiovascular Disease in Type 2 Diabetes Mellitus. Int J Mol Sci [Internet]. 2015 Apr 27 [cited 2016 Dec 27];16(5):9469–83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25923078 pmid:25923078
  33. 33. Tsironi E, Feakins RM, Roberts CSJ, Rampton DS. Incidence of inflammatory bowel disease is rising and abdominal tuberculosis is falling in Bangladeshis in East London, United Kingdom. Am J Gastroenterol. 2004;99(9):1749–55. pmid:15330914
  34. 34. Sjöberg D, Holmström T, Larsson M, Nielsen AL, Holmquist L, Ekbom A, et al. Incidence and natural history of ulcerative colitis in the Uppsala Region of Sweden 2005–2009—Results from the IBD Cohort of the Uppsala Region (ICURE). J Crohn’s Colitis [Internet]. 2013;7(9):e351–7. Available from: https://doi.org/10.1016/j.crohns.2013.02.006
  35. 35. Vind I, Riis L, Jess T, Knudsen E, Pedersen N, Elkjær M, et al. Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen City and County, 2003–2005: A population-based study from the Danish Crohn colitis database. Am J Gastroenterol. 2006;101(6):1274–82. pmid:16771949
  36. 36. BJÖRNSSON S., JOHANNSSON J. H., JHJEO E. Inflammatory Bowel Disease in Iceland, 1980–89: A Retrospective Nationwide Epidemiologic Study. Scand J Gastroenterol [Internet]. 1998 Jan 8 [cited 2018 Aug 3];33(1):71–7. Available from: http://www.tandfonline.com/doi/full/10.1080/00365529850166239 pmid:9489911
  37. 37. JH BS and J. Inflammatory bowel disease in Iceland, 1990–1994: a prospective, nationwide, epidemiological study.pdf. Eur J Gastroenterol Hepatol. 2000;12:31–8. pmid:10656207
  38. 38. Björnsson S, Tryggvason FP, Jónasson JG, Cariglia N, Örvar K, Kristjánsdóttir S, et al. Incidence of inflammatory bowel disease in Iceland 1995–2009. A nationwide population-based study. Scand J Gastroenterol. 2015;50(11):1368–75. pmid:25979112
  39. 39. Fraga XF, Vergara M, Medina C, Casellas F, Bermejo B MJ. Effects of smoking on the presentation and clinical course of inflammatory bowel disease.pdf. Eur J Gastroenterol Hepatol. 1997;9(7):683–7. pmid:9262977
  40. 40. Tragnone A, Hanau C, Bazzocchi G, Lanfranchi GA. Epidemiological characteristics of inflammatory bowel disease in Bologna, Italy—incidence and risk factors. Digestion [Internet]. 1993;54(3):183–8. Available from: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med3&AN=8359562%5Cnhttp://openurl.ac.uk/athens:lee/?sid=OVID:medline&id=pmid:8359562&id=doi:&issn=0012-2823&isbn=&volume=54&issue=3&spage=183&pages=183-8&date=1993&title=Digestion&atitle pmid:8359562
  41. 41. Chow DKL, Leong RWL, Tsoi KKF, Ng SSM, Leung W, Wu JCY, et al. Long-term Follow-up of Ulcerative Colitis in the Chinese Population. Am J Gastroenterol [Internet]. 2009;104(3):647–54. Available from: http://www.nature.com/doifinder/10.1038/ajg.2008.74 pmid:19262521
  42. 42. Lok K-H, Hung H-G, Ng C-H, Kwong KC, Yip W-M, Lau S-F, et al. Epidemiology and clinical characteristics of ulcerative colitis in Chinese population: Experience from a single center in Hong Kong. J Gastroenterol Hepatol [Internet]. 2008;23(3):406–10. Available from: http://doi.wiley.com/10.1111/j.1440-1746.2007.05079.x pmid:17623033
  43. 43. Abraham N, Selby W, Lazarus R, Solomon M. Is smoking an indirect risk factor for the development of ulcerative colitis? An age- and sex-matched case-control study. J Gastroenterol Hepatol. 2003;18(2):139–46. pmid:12542596
  44. 44. Vegh Z, Burisch J, Pedersen N, Kaimakliotis I, Duricova D, Bortlik M, et al. Incidence and initial disease course of inflammatory bowel diseases in 2011 in Europe and Australia: Results of the 2011 ECCO-EpiCom inception cohort. J Crohn’s Colitis. 2014;8(11):1506–15.
  45. 45. Reitsma MB, Fullman N, Ng M, Salama JS, Abajobir A, Hassen Abate K, et al. Articles Smoking prevalence and attributable disease burden in 195 countries and territories, 1990–2015: a systematic analysis from the Global Burden of Disease Study 2015. Lancet [Internet]. 2017 [cited 2018 Jul 17];389:1885–906. Available from: https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)30819-X.pdf
  46. 46. Reitsma MB, Fullman N, Ng M, Salama JS, Abajobir A, Abate KH, et al. Smoking prevalence and attributable disease burden in 195 countries and territories, 1990–2015: a systematic analysis from the Global Burden of Disease Study 2015. Lancet [Internet]. 2017 May [cited 2017 Sep 12];389(10082):1885–906. Available from: http://linkinghub.elsevier.com/retrieve/pii/S014067361730819X pmid:28390697
  47. 47. Lopez AD, Collishaw NE, Piha T. A descriptive model of the cigarette epidemic in developed countries. Tob Control [Internet]. 1994 Sep 1 [cited 2018 Aug 25];3(3):242–7. Available from: http://tobaccocontrol.bmj.com/cgi/doi/10.1136/tc.3.3.242
  48. 48. The Epidemiology Group of the Research Committee of Inflammatory Bowel Disease in Japan. A case-control study of ulcerative colitis in relation to dietary and other factors in Japan. J Gastroenterol [Internet]. 1995 Nov [cited 2018 Jul 18];30 Suppl 8:9–12. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8563901
  49. 49. Jiang L, Xia B, Li J, Ye M, Deng C, Ding Y, et al. Risk Factors for Ulcerative Colitis in a Chinese Population. J Clin Gastroenterol [Internet]. 2007 Mar [cited 2018 Jul 18];41(3):280–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17426467 pmid:17426467
  50. 50. Reif S, Klein I, Arber N, Gilat T. Lack of association between smoking and inflammatory bowel disease in Jewish patients in Israel. Gastroenterology [Internet]. 1995 Jun [cited 2018 Jul 17];108(6):1683–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7768372 pmid:7768372
  51. 51. Prideaux L, Kamm MA, De Cruz P, Williams J, Bell SJ, Connell WR, et al. Comparison of clinical characteristics and management of inflammatory bowel disease in Hong Kong versus Melbourne. J Gastroenterol Hepatol [Internet]. 2012 May [cited 2018 Jul 18];27(5):919–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22098103 pmid:22098103
  52. 52. Inoue N, Tamura K, Kinouchi Y, Fukuda Y, Takahashi S, Ogura Y, et al. Lack of common NOD2 variants in Japanese patients with Crohn’s disease. Gastroenterology [Internet]. 2002 Jul [cited 2018 Jul 18];123(1):86–91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12105836 pmid:12105836
  53. 53. Kaplan GG, Hubbard J, Korzenik J, Sands BE, Panaccione R, Ghosh S, et al. The inflammatory bowel diseases and ambient air pollution: a novel association. Am J Gastroenterol [Internet]. 2010 Nov [cited 2018 Jul 18];105(11):2412–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20588264 pmid:20588264
  54. 54. Shoda R, Matsueda K, Yamato S, Umeda N. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr [Internet]. 1996 May 1 [cited 2018 Jul 18];63(5):741–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8615358 pmid:8615358
  55. 55. Sakamoto N, Kono S, Wakai K, Fukuda Y, Satomi M, Shimoyama T, et al. Dietary risk factors for inflammatory bowel disease: a multicenter case-control study in Japan. Inflamm Bowel Dis [Internet]. 2005 Feb [cited 2018 Jul 18];11(2):154–63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15677909 pmid:15677909
  56. 56. R.W.L. L, J.Y. L, Leong RWL, Lau JY, Sung JJY. The epidemiology and phenotype of Crohn’s disease in the Chinese population. Inflamm Bowel Dis [Internet]. 2004;10(5):646–51. Available from: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=med5&NEWS=N&AN=15472528%5Cnhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emed6&NEWS=N&AN=2004409340 pmid:15472528
  57. 57. Zhao J, Ng SC, Lei Y, Yi F, Li J, Yu L, et al. First prospective, population-based inflammatory bowel disease incidence study in mainland of China: The emergence of “western” disease. Inflamm Bowel Dis. 2013;19(9):1839–45. pmid:23669403
  58. 58. Zeng Z, Zhu Z, Yang Y, Ruan W, Peng X, Su Y, et al. Incidence and clinical characteristics of inflammatory bowel disease in a developed region of Guangdong Province, China: A prospective population-based study. J Gastroenterol Hepatol [Internet]. 2013;28(7):1148–53. Available from: http://doi.wiley.com/10.1111/jgh.12164 pmid:23432198
  59. 59. Yang H, Li Y, Wu W, Sun Q, Zhang Y, Zhao W, et al. The incidence of inflammatory bowel disease in Northern China: A prospective population-based study. PLoS One. 2014;9(7):5–10.
  60. 60. Zahedi MJ, Darvish Moghadam S, Hayat Bakhsh Abbasi M, Dehghani M, Shafiei Pour S, Zydabady Nejad H, et al. The incidence rate of inflammatory bowel disease in an urban area of iran: a developing country. Middle East J Dig Dis [Internet]. 2014;6(1):32–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24829703%5Cnhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4005476 pmid:24829703
  61. 61. Tozun N, Atug O, Imeryuz N, Hamzaoglu HO, Tiftikci A, Parlak E, et al. Clinical characteristics of inflammatory bowel disease in Turkey: A multicenter epidemiologic survey. J Clin Gastroenterol. 2009;43(1):51–7. pmid:18724251
  62. 62. Gheorghe C, Pascu O, Gheorghe L, Iacob R, Dumitru E, Tantau M, et al. Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: A multicentre study. Eur J Gastroenterol Hepatol. 2004;16(11):1153–9. pmid:15489575
  63. 63. Ramadas A V., Gunesh S, Thomas GAO, Williams GT, Hawthorne AB. Natural history of Crohn’s disease in a population-based cohort from Cardiff (1986–2003): a study of changes in medical treatment and surgical resection rates. Gut [Internet]. 2010 Sep 1 [cited 2018 Apr 15];59(9):1200–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20650924 pmid:20650924
  64. 64. GARCIA RODRIGUEZ LA, GONZALEZ-PEREZ A, JOHANSSON S, WALLANDER M-A. Risk factors for inflammatory bowel disease in the general population. Aliment Pharmacol Ther [Internet]. 2005;22(4):309–15. Available from: http://doi.wiley.com/10.1111/j.1365-2036.2005.02564.x pmid:16097997
  65. 65. Gunesh S, Thomas GAO, Williams GT, Roberts A, Hawthorne AB. The incidence of Crohn’s disease in Cardiff over the last 75 years: An update for 1996–2005. Aliment Pharmacol Ther. 2008;27(3):211–9. pmid:18005244
  66. 66. Kiudelis G, Jonaitis L, Adamonis K, Žvirbliene A, Tamelis A, Kregždyte R, et al. Incidence of inflammatory bowel disease in kaunas region, lithuania. Med. 2012;48(8):431–5.
  67. 67. Björnsson S, Tryggvason FÞ, Jónasson JG, Cariglia N, Örvar K, Kristjánsdóttir S, et al. Incidence of inflammatory bowel disease in Iceland 1995–2009. A nationwide population-based study. Scand J Gastroenterol [Internet]. 2015 Nov 2 [cited 2018 Aug 3];50(11):1368–75. Available from: http://www.tandfonline.com/doi/full/10.3109/00365521.2015.1047792 pmid:25979112
  68. 68. Hammer T, Nielsen KR, Munkholm P, Burisch J, Lynge E. The Faroese IBD study: Incidence of inflammatory bowel diseases across 54 years of population-based data. J Crohn’s Colitis. 2016;10(8):934–42.
  69. 69. Vucelic B*, Korac B, Sentic M, Milicic D HN, Juresa V BJ. Epidemiology of Crohn’s Disease in Zagreb, Yugoslavia. Int J Epidemiol. 2018;20(1):216–20.
  70. 70. Manousos ON, Koutroubakis I, Potamianos S, Roussomoustakaki M, Gourtsoyiannis N, Vlachonikolis IG. A prospective epidemiologic study of Crohn’s disease in Heraklion, Crete: Incidence over a 5-year period. Scand J Gastroenterol. 1996;31(6):599–603. pmid:8789900
  71. 71. Cottone M, Renda MC, Mattaliano A, Oliva L, Fries W, Criscuoli V, et al. Incidence of Crohn’s disease and CARD15 mutation in a small township in Sicily. Eur J Epidemiol. 2006;21(12):887–92. pmid:17160430
  72. 72. Niewiadomski O, Studd C, Hair C, Wilson J, Ding NS, Heerasing N, et al. Prospective population-based cohort of inflammatory bowel disease in the biologics era: Disease course and predictors of severity. J Gastroenterol Hepatol. 2015;30(9):1346–53. pmid:25867770
  73. 73. Edwards CN, Griffith SG, Hennis AJ, Hambleton IR. Inflammatory bowel disease: Incidence, prevalence, and disease characteristics in Barbados, West Indies. Inflamm Bowel Dis. 2008;14(10):1419–24. pmid:18484668
  74. 74. Parente JML, Coy CSR, Campelo V, Parente MPPD, Costa LA, Da Silva RM, et al. Inflammatory bowel disease in an underdeveloped region of Northeastern Brazil. World J Gastroenterol. 2015;21(4):1197–206. pmid:25632193
  75. 75. Zhai H, Huang W, Liu A, Li Q, Hao Q, Ma L, et al. Current smoking improves ulcerative colitis patients’ disease behaviour in the northwest of China. Gastroenterol Rev [Internet]. 2017;4(4):286–90. Available from: https://www.termedia.pl/doi/10.5114/pg.2017.72104
  76. 76. Nakamura Y, Labarthe DR. A case-control study of ulcerative colitis with relation to smoking habits and alcohol consumption in Japan. Am J Epidemiol. 1994;140(10):902–11. pmid:7977277
  77. 77. Radhakrishnan S, Zubaidi G, Daniel M, Sachdev GK MA. Ulcerative colitis in Oman: A prospective study of incidence and disease pattern from 1987 to 1994. Diges. 1997;58:266–70.
  78. 78. Song EM, Lee H-S, Park SH, Kim GU, Seo MS, Hwang SW, et al. Clinical Characteristics and Long-term Prognosis of Elderly-onset Ulcerative Colitis. J Gastroenterol Hepatol [Internet]. 2017; Available from: http://doi.wiley.com/10.1111/jgh.13826
  79. 79. Tezel A, Dökmeci G, Eskiocak M, Ümit H, Soylu AR. Epidemiological features of ulcerative colitis in Trakya, Turkey. J Int Med Res. 2003;31(2):141–8. pmid:12760318
  80. 80. Vuceljć B, Korać B, Sentić M, Millličlć D, Hadžić N, Jureša V, et al. Ulcerative colitis in Zagreb, Yugoslavia: Incidence and prevalence 1980–1989. Int J Epidemiol. 1991;20(4):1043–7. pmid:1800402
  81. 81. Ladas SD, Mallas E, Giorgiotis K, Karamanolis G, Trigonis D, Markadas A, et al. Incidence of ulcerative colitis in Central Greece: A prospective study. World J Gastroenterol. 2005;11(12):1785–7. pmid:15793864
  82. 82. Manousos ON, Giannadaki E, Mouzas IA, Tzardi M, Koutroubakis I, Skordilis P, et al. Ulcerative colitis is as common in Crete as in northern Europe: a 5-year prospective study. Eur J Gastroenterol Hepatol. 1996;8(9):893–8. pmid:8889457
  83. 83. Yamamoto-Furusho JK. Clinical Epidemiology of Ulcerative Colitis in Mexico. J Clin Gastroenterol [Internet]. 2009;43(3):221–4. Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00004836-200903000-00004 pmid:19057395